PAI-1 Regulates the Cytoskeleton and Intrinsic Stiffness of Vascular Smooth Muscle Cells.

BACKGROUND: Plasma concentration of PAI-1 (plasminogen activator inhibitor-1) correlates with arterial stiffness. Vascular smooth muscle cells (SMCs) express PAI-1, and the intrinsic stiffness of SMCs is a major determinant of total arterial stiffness. We hypothesized that PAI-1 promotes SMC stiffness by regulating the cytoskeleton and that pharmacological inhibition of PAI-1 decreases SMC and aortic stiffness. METHODS: PAI-039, a specific inhibitor of PAI-1, and small interfering RNA were used to inhibit PAI-1 expression in cultured human SMCs. Effects of PAI-1 inhibition on SMC stiffness, F-actin (filamentous actin) content, and cytoskeleton-modulating enzymes were assessed. WT (wild-type) and PAI-1-deficient murine SMCs were used to determine PAI-039 specificity. RNA sequencing was performed to determine the effects of PAI-039 on SMC gene expression. In vivo effects of PAI-039 were assessed by aortic pulse wave velocity. RESULTS: PAI-039 significantly reduced intrinsic stiffness of human SMCs, which was accompanied by a significant decrease in cytoplasmic F-actin content. PAI-1 gene knockdown also decreased cytoplasmic F-actin. PAI-1 inhibition significantly increased the activity of cofilin, an F-actin depolymerase, in WT murine SMCs, but not in PAI-1-deficient SMCs. RNA-sequencing analysis suggested that PAI-039 upregulates AMPK (AMP-activated protein kinase) signaling in SMCs, which was confirmed by Western blotting. Inhibition of AMPK prevented activation of cofilin by PAI-039. In mice, PAI-039 significantly decreased aortic stiffness and tunica media F-actin content without altering the elastin or collagen content. CONCLUSIONS: PAI-039 decreases intrinsic SMC stiffness and cytoplasmic stress fiber content. These effects are mediated by AMPK-dependent activation of cofilin. PAI-039 also decreases aortic stiffness in vivo. These findings suggest that PAI-1 is an important regulator of the SMC cytoskeleton and that pharmacological inhibition of PAI-1 has the potential to prevent and treat cardiovascular diseases involving arterial stiffening.

Neuraminidase-induced externalization of phosphatidylserine activates ADAM17 and impairs insulin signaling in endothelial cells.

Endothelial insulin resistance represents a causal factor in the pathogenesis of type 2 diabetes (T2D) and vascular disease, thus the need to identify molecular mechanisms underlying defects in endothelial insulin signaling. We previously have shown that a disintegrin and metalloproteinase-17 (ADAM17) is increased while insulin receptor α-subunit (IRα) is decreased in the vasculature of patients with T2D, leading to impaired insulin-induced vasodilation. We have also demonstrated that ADAM17 sheddase activity targets IRα; however, the mechanisms driving endothelial ADAM17 activity in T2D are largely unknown. Herein, we report that externalization of phosphatidylserine (PS) to the outer leaflet of the plasma membrane causes ADAM17-mediated shedding of IRα and blunting of insulin signaling in endothelial cells. Furthermore, we demonstrate that endothelial PS externalization is mediated by the phospholipid scramblase anoctamin-6 (ANO6) and that this process can be stimulated by neuraminidase, a soluble enzyme that cleaves sialic acid residues. Of note, we demonstrate that men and women with T2D display increased levels of neuraminidase activity in plasma, relative to age-matched healthy individuals, and this occurs in conjunction with increased ADAM17 activity and impaired leg blood flow responses to endogenous insulin. Collectively, this work reveals the neuraminidase-ANO6-ADAM17 axis as a novel potential target for restoring endothelial insulin sensitivity in T2D.NEW & NOTEWORTHY This work provides the first evidence that neuraminidase, an enzyme increased in the circulation of men and women with type 2 diabetes (T2D), promotes anoctamin-6 (ANO6)-dependent externalization of phosphatidylserine in endothelial cells, which in turn leads to activation of a disintegrin and metalloproteinase-17 (ADAM17) and consequent shedding of the insulin receptor-α from the cell surface. Hence, this work supports that consideration should be given to the neuraminidase-ANO6-ADAM17 axis as a novel potential target for restoring endothelial insulin sensitivity in T2D.

Neuraminidase inhibition improves endothelial function in diabetic mice.

Neuraminidases cleave sialic acids from glycocalyx structures and plasma neuraminidase activity is elevated in type 2 diabetes (T2D). Therefore, we hypothesize circulating neuraminidase degrades the endothelial glycocalyx and diminishes flow-mediated dilation (FMD), whereas its inhibition restores shear mechanosensation and endothelial function in T2D settings. We found that compared with controls, subjects with T2D have higher plasma neuraminidase activity, reduced plasma nitrite concentrations, and diminished FMD. Ex vivo and in vivo neuraminidase exposure diminished FMD and reduced endothelial glycocalyx presence in mouse arteries. In cultured endothelial cells, neuraminidase reduced glycocalyx coverage. Inhalation of the neuraminidase inhibitor, zanamivir, reduced plasma neuraminidase activity, enhanced endothelial glycocalyx length, and improved FMD in diabetic mice. In humans, a single-arm trial (NCT04867707) of zanamivir inhalation did not reduce plasma neuraminidase activity, improved glycocalyx length, or enhanced FMD. Although zanamivir plasma concentrations in mice reached 225.8 ± 22.0 ng/mL, in humans were only 40.0 ± 7.2 ng/mL. These results highlight the potential of neuraminidase inhibition for ameliorating endothelial dysfunction in T2D and suggest the current Food and Drug Administration-approved inhaled dosage of zanamivir is insufficient to achieve desired outcomes in humans.NEW & NOTEWORTHY This work identifies neuraminidase as a key mediator of endothelial dysfunction in type 2 diabetes that may serve as a biomarker for impaired endothelial function and predictive of development and progression of cardiovascular pathologies associated with type 2 diabetes (T2D). Data show that intervention with the neuraminidase inhibitor zanamivir at effective plasma concentrations may represent a novel pharmacological strategy for restoring the glycocalyx and ameliorating endothelial dysfunction.

ADAM17 cleaves the insulin receptor ectodomain on endothelial cells and causes vascular insulin resistance.

Inflammation and vascular insulin resistance are hallmarks of type 2 diabetes (T2D). However, several potential mechanisms causing abnormal endothelial insulin signaling in T2D need further investigation. Evidence indicates that the activity of ADAM17 (a disintegrin and metalloproteinase-17) and the presence of insulin receptor (IR) in plasma are increased in subjects with T2D. Accordingly, we hypothesized that in T2D, increased ADAM17 activity sheds the IR ectodomain from endothelial cells and impairs insulin-induced vasodilation. We used small visceral arteries isolated from a cross-sectional study of subjects with and without T2D undergoing bariatric surgery, human cultured endothelial cells, and recombinant proteins to test our hypothesis. Here, we demonstrate that arteries from subjects with T2D had increased ADAM17 expression, reduced presence of tissue inhibitor of metalloproteinase-3 (TIMP3), decreased extracellular IRα, and impaired insulin-induced vasodilation versus those from subjects without T2D. In vitro, active ADAM17 cleaved the ectodomain of the IRß subunit. Endothelial cells with ADAM17 overexpression or exposed to the protein kinase-C activator, PMA, had increased ADAM17 activity, decreased IRα presence on the cell surface, and increased IR shedding. Moreover, pharmacological inhibition of ADAM17 with TAPI-0 rescued PMA-induced IR shedding and insulin-signaling impairments in endothelial cells and insulin-stimulated vasodilation in human arteries. In aggregate, our findings suggest that ADAM17-mediated shedding of IR from the endothelial surface impairs insulin-mediated vasodilation. Thus, we propose that inhibition of ADAM17 sheddase activity should be considered a strategy to restore vascular insulin sensitivity in T2D.NEW & NOTEWORTHY To our knowledge, this is the first study to investigate the involvement of ADAM17 in causing impaired insulin-induced vasodilation in T2D. We provide evidence that ADAM17 activity is increased in the vasculature of patients with T2D and support the notion that ADAM17-mediated shedding of endothelial IRα ectodomains is a novel mechanism causing vascular insulin resistance. Our results highlight that targeting ADAM17 activity may be a potential therapeutic strategy to correct vascular insulin resistance in T2D.

Computer Vision and Machine Learning-Based Gait Pattern Recognition for Flat Fall Prediction.

BACKGROUND: Gait recognition has been applied in the prediction of the probability of elderly flat ground fall, functional evaluation during rehabilitation, and the training of patients with lower extremity motor dysfunction. Gait distinguishing between seemingly similar kinematic patterns associated with different pathological entities is a challenge for the clinician. How to realize automatic identification and judgment of abnormal gait is a significant challenge in clinical practice. The long-term goal of our study is to develop a gait recognition computer vision system using artificial intelligence (AI) and machine learning (ML) computing. This study aims to find an optimal ML algorithm using computer vision techniques and measure variables from lower limbs to classify gait patterns in healthy people. The purpose of this study is to determine the feasibility of computer vision and machine learning (ML) computing in discriminating different gait patterns associated with flat-ground falls. METHODS: We used the Kinect® Motion system to capture the spatiotemporal gait data from seven healthy subjects in three walking trials, including normal gait, pelvic-obliquity-gait, and knee-hyperextension-gait walking. Four different classification methods including convolutional neural network (CNN), support vector machine (SVM), K-nearest neighbors (KNN), and long short-term memory (LSTM) neural networks were used to automatically classify three gait patterns. Overall, 750 sets of data were collected, and the dataset was divided into 80% for algorithm training and 20% for evaluation. RESULTS: The SVM and KNN had a higher accuracy than CNN and LSTM. The SVM (94.9 ± 3.36%) had the highest accuracy in the classification of gait patterns, followed by KNN (94.0 ± 4.22%). The accuracy of CNN was 87.6 ± 7.50% and that of LSTM 83.6 ± 5.35%. CONCLUSIONS: This study revealed that the proposed AI machine learning (ML) techniques can be used to design gait biometric systems and machine vision for gait pattern recognition. Potentially, this method can be used to remotely evaluate elderly patients and help clinicians make decisions regarding disposition, follow-up, and treatment.

Novel Multi-Modal Analgesia Protocol Significantly Decreases Opioid Requirements in Inflatable Penile Prosthesis Patients.

BACKGROUND: Inflatable penile prosthesis (IPP) surgery is associated with significant perioperative pain that may reduce patient satisfaction. Though various pain management strategies have been proposed, most implanters manage postoperative patients with only prescription opioids. No protocol to date has been implemented and reported for pain management in IPP patients throughout the entire recovery process following surgery. AIM: Develop a multimodal analgesic (MMA) regimen consisting of perioperative administration of acetaminophen, meloxicam, and gabapentin with intraoperative local anesthetic injections, and compare post-operative pain control to a matched cohort of patients managed with an opioid-based (OB) regimen. METHODS: We retrospectively analyzed our prospectively maintained IPP database from November 2015-January 2018. The MMA protocol was instituted for all patients beginning June 2017, and these patients were matched in a 1:2 ratio to a cohort of eligible IPP patients managed through an OB protocol. Only patients receiving a 3-piece IPP were included; those with a history of narcotic dependence, neuropathy, or chronic non-steroidal anti-inflammatory drug use were excluded. Postoperative pain scores (visual analog scale) and opioid usage (total morphine equivalents [TME] in milligrams) were compared temporally in the post-anesthesia care unit, postoperative day (POD) 0, POD 1, and following discharge. OUTCOMES: The primary outcomes of the study are postoperative pain scores and narcotic usage. RESULTS: 57 patients were eligible for analysis: 19 (33%) and 38 (66%) in the MMA and OB groups, respectively. Groups were similar in demographics. MMA patients had significantly lower visual analog scale scores in post-anesthesia care unit, POD 0, or POD 1 (mean 0.84 vs 2.97, P = .01; 2.62 vs 4.73, P = .003; and 2.26 vs 4.0, P = .01, respectively) and used fewer narcotics on POD 0 (mean 4.08 vs 13.8 mg TME, P < .001) and POD 1 (mean 5.05 vs 25.1 mg TME, P < .001). MMA patients were discharged home with fewer narcotics (mean 12.7 vs 51.3 tabs, P < .001), and despite this, the MMA group needed less narcotic medication refills (11% vs 49%, P = .007). Neither group experienced a medication-related postoperative adverse event. CLINICAL IMPLICATIONS: Multimodal pain management allows for effective pain control with minimal side effects, enhancing recovery. STRENGTHS & LIMITATIONS: This is the first report to assess use of a multi-modal pain regimen on IPP recipients with demonstration of tangible benefit throughout the recovery process. Limitations include a single-surgeon and retrospective study design. CONCLUSION: In our rigorous assessment of IPP patients, implementation of a novel MMA protocol achieved equivalent and effective pain control, while resulting in substantially fewer narcotics throughout the entire post-operative period following IPP implantation. Tong CMC, Lucas J, Shah A, et al. Novel Multi-Modal Analgesia Protocol Significantly Decreases Opioid Requirements in Inflatable Penile Prosthesis Patients. J Sex Med 2018;15:1187-1194.

BMC ecology image competition 2017: the winning images.

For the fifth year, BMC Ecology is proud to present the winning images from our annual image competition. The 2017 edition received entries by talented shutterbug-ecologists from across the world, showcasing research that is increasing our understanding of ecosystems worldwide and the beauty and diversity of life on our planet. In this editorial we showcase the winning images, as chosen by our Editorial Board and guest judge Chris Darimont, as well as our selection of highly commended images. Enjoy!

Brief serotonin exposure initiates arteriolar inward remodeling processes in vivo that involve transglutaminase activation and actin cytoskeleton reorganization.

Inward remodeling of the resistance vasculature is strongly associated with life-threatening cardiovascular events. Previous studies have demonstrated that both actin polymerization and the activation of transglutaminases mediate early stages of the transition from a structurally normal vessel to an inwardly remodeled one. Ex vivo studies further suggest that a few hours of exposure to vasoconstrictor agonists induces inward remodeling in the absence of changes in intraluminal pressure. Here we report that a short, 10-min, topical exposure to serotonin (5-HT) + N(ω)-nitro-l-arginine methyl ester hydrochloride (l-NAME) was sufficient to initiate inward remodeling processes in rat cremasteric feed arterioles (100-200 µm lumen diameter), in vivo. Addition of the transglutaminase inhibitor, cystamine, blocked the in vivo remodeling. We further demonstrate that, in isolated arterioles, 5-HT + l-NAME activates transglutaminases and modulates the phosphorylation state of cofilin, a regulator of actin depolymerization. The 5-HT + l-NAME-induced remodeling process in isolated arterioles was also inhibited by an inhibitor of Lim Kinase, the kinase that phosphorylates and inactivates cofilin. Therefore, our results indicate that a brief vasoconstriction induced by 5-HT + l-NAME is able to reduce the passive structural diameter of arterioles through processes that are dependent on the activation of transglutaminases and Lim kinase, and the subsequent phosphorylation of cofilin.

An open future for ecological and evolutionary data?

As part of BioMed Central's open science mission, we are pleased to announce that two of our journals have integrated with the open data repository Dryad. Authors submitting their research to either BMC Ecology or BMC Evolutionary Biology will now have the opportunity to deposit their data directly into the Dryad archive and will receive a permanent, citable link to their dataset. Although this does not affect any of our current data deposition policies at these journals, we hope to encourage a more widespread adoption of open data sharing in the fields of ecology and evolutionary biology by facilitating this process for our authors. We also take this opportunity to discuss some of the wider issues that may concern researchers when making their data openly available. Although we offer a number of positive examples from different fields of biology, we also recognise that reticence to data sharing still exists, and that change must be driven from within research communities in order to create future science that is fit for purpose in the digital age. This editorial was published jointly in both BMC Ecology and BMC Evolutionary Biology.

The obligatory role of the actin cytoskeleton on inward remodeling induced by dithiothreitol activation of endogenous transglutaminase in isolated arterioles.

Inward remodeling is the most prevalent structural change found in the resistance arteries and arterioles of hypertensive individuals. Separate studies have shown that the inward remodeling process requires transglutaminase activation and the polymerization of actin. Therefore, we hypothesize that inward remodeling induced via endogenous transglutaminase activation requires and depends on actin cytoskeletal structures. To test this hypothesis, isolated and cannulated rat cremaster arterioles were exposed to dithiothreitol (DTT) to activate endogenous transglutaminases. DTT induced concentration-dependent vasoconstriction that was suppressed by coincubation with cystamine or cytochalasin-D to inhibit tranglutaminase activity or actin polymerization, respectively. Prolonged (4 h) exposure to DTT caused arteriolar inward remodeling that was also blocked by the presence of cystamine or cytochalasin-D. DTT inwardly remodeled arterioles had reduced passive diameters, augmented wall thickness-to-lumen ratios and altered elastic characteristics that were reverted upon disruption of the actin cytoskeleton with mycalolide-B. In freshly isolated arterioles, exposure to mycalolide-B caused no changes in their passive diameters or their elastic characteristics. These results suggest that, in arterioles, the early stages of the inward remodeling process induced by prolonged endogenous transglutaminase activation require actin dynamics and depend on changes in actin cytoskeletal structures.

Mechanisms of the inward remodeling process in resistance vessels: is the actin cytoskeleton involved?

The resistance arteries and arterioles are the vascular components of the circulatory system where the greatest drop in blood pressure takes place. Consequently, these vessels play a preponderant role in the regulation of blood flow and the modulation of blood pressure. For this reason, the inward remodeling process of the resistance vasculature, as it occurs in hypertension, has profound consequences on the incidence of life-threatening cardiovascular events. In this manuscript, we review some of the most prominent characteristics of inwardly remodeled resistance arteries including their changes in vascular passive diameter, wall thickness, and elastic properties. Then, we explore the known contribution of the different components of the vascular wall to the characteristics of inwardly remodeled vessels, and pay particular attention to the role the vascular smooth muscle actin cytoskeleton may play on the initial stages of the remodeling process. We end by proposing potential ways by which many of the factors and mechanisms known to participate in the inward remodeling process may be associated with cytoskeletal modifications and participate in reducing the passive diameter of resistance vessels.

Effects of the use of assisted reproduction and high-caloric diet consumption on body weight and cardiovascular health of juvenile mouse offspring.

Maternal obesity and the use of assisted reproductive technologies (ART) are two suboptimal developmental environments that can lead to offspring obesity and cardiovascular disease. We hypothesized that these environments independently and synergistically adversely affect the offspring's weight and cardiovascular performance at ~7 weeks of age. Mice were fed either 24% fat and 17.5% high-fructose (HF) corn syrup or maintenance chow (5% fat; low-fat, no-fructose (LF)). Dams were subdivided into no ART and ART groups. ART embryos were cultured in Whitten's medium and transferred into pseudopregnant recipients consuming the same diet as the donor. Offspring were fed the same diet as the mother. Body weights (BW) were measured weekly and mean arterial pressure (MAP) was collected through carotid artery catheterization at killing (55±0.5 days old). Expression of genes involved in cardiovascular remodeling was measured in thoracic aorta using qRT-PCR, and levels of reactive oxygen species (ROS) were measured intracellularly and extracellularly in mesenteric resistance arteries. ART resulted in increased BW at weaning. This effect decreased over time and diet was the predominant determinant of BW by killing. Males had greater MAP than females (P=0.002) and HF consumption was associated with greater MAP regardless of sex (P<0.05). Gene expression was affected by sex (P<0.05) and diet (P<0.1). Lastly, the use of ART resulted in offspring with increased intracellular ROS (P=0.05). In summary, exposure to an obesogenic diet pre- and/or post-natally affects weight, MAP, and gene expression while ART increases oxidative stress in mesenteric resistance arteries of juvenile offspring, no synergistic effects were observed.

An open future for ecological and evolutionary data?

As part of BioMed Central's open science mission, we are pleased to announce that two of our journals have integrated with the open data repository Dryad. Authors submitting their research to either BMC Ecology or BMC Evolutionary Biology will now have the opportunity to deposit their data directly into the Dryad archive and will receive a permanent, citable link to their dataset. Although this does not affect any of our current data deposition policies at these journals, we hope to encourage a more widespread adoption of open data sharing in the fields of ecology and evolutionary biology by facilitating this process for our authors. We also take this opportunity to discuss some of the wider issues that may concern researchers when making their data openly available. Although we offer a number of positive examples from different fields of biology, we also recognise that reticence to data sharing still exists, and that change must be driven from within research communities in order to create future science that is fit for purpose in the digital age. This editorial was published jointly in both BMC Ecology and BMC Evolutionary Biology.

The role of reactive oxygen species in microvascular remodeling.

The microcirculation is a portion of the vascular circulatory system that consists of resistance arteries, arterioles, capillaries and venules. It is the place where gases and nutrients are exchanged between blood and tissues. In addition the microcirculation is the major contributor to blood flow resistance and consequently to regulation of blood pressure. Therefore, structural remodeling of this section of the vascular tree has profound implications on cardiovascular pathophysiology. This review is focused on the role that reactive oxygen species (ROS) play on changing the structural characteristics of vessels within the microcirculation. Particular attention is given to the resistance arteries and the functional pathways that are affected by ROS in these vessels and subsequently induce vascular remodeling. The primary sources of ROS in the microcirculation are identified and the effects of ROS on other microcirculatory remodeling phenomena such as rarefaction and collateralization are briefly reviewed.

Operative Management Improves Near-term Survival of Patients With Odontoid Type II Fractures: A Propensity-matched National Registry Analysis.

STUDY DESIGN: National Trauma Data Bank (NTDB) review and propensity-matched analysis. OBJECTIVE: To evaluate differences in clinical outcomes by operative management. SUMMARY OF BACKGROUND DATA: Odontoid type II fractures are the most prevalent cervical fracture. Operative intervention on these fractures is frequently debated; surgical risks are compounded by clinical severity, patient age, and comorbidities. METHODS: This registry review included index admissions for odontoid type II fractures [International Classification of Diseases (ICD)-10 codes beginning with S12.11] from 1/1/2017 to 1/1/2020; patients who died in the emergency department (ED) were excluded. Propensity score techniques were used to match patients 1:1 by surgical management, using a caliper distance of 0.05, after matching on the following covariates that differed significantly between surgical and nonsurgical patients: age, sex, race, cause of injury, transfer status, injury severity score, ED Glasgow coma score, ED systolic blood pressure, presence of transverse ligamentous injury, cervical dislocation, and 8 comorbidities. The following outcomes were analyzed with McNemar tests and Wilcoxon signed-rank tests: near-term survival (discharged from the hospital to locations other than morgue or hospice), intensive care unit (ICU) admission, hospital complications, median hospital length of stay (LOS), and median ICU LOS. RESULTS: There were 16,607 patients, 2916 (17.6%) were operatively managed and 13,691 were nonoperatively managed. Before matching, survival was greater for patients managed operatively compared with nonoperatively (95.0% vs. 88.2%). The matched population consisted of 5334 patients: 2667 patients in the operative group (91.5% of this population) and 2667 well-matched patients in the nonoperative group. After matching, there was a survival benefit for patients who were operatively managed compared with nonoperative management (94.8% vs. 91.4% P <0.001). However, operative management was associated with greater development of complications, ICU admission, and longer hospital and ICU LOS. CONCLUSION: Compared with nonoperative management, operative management demonstrated a significant near-term survival benefit for patients with odontoid type II fractures in select patients. LEVEL OF EVIDENCE: III.

Plasma syndecan-1 concentration as a biomarker for endothelial glycocalyx degradation in septic adult horses.

BACKGROUND: Limited information is available regarding endothelial glycocalyx degradation during sepsis in horses. Plasma syndecan-1 concentrations are increased in consequence of sepsis in other species and have been useful for prognostication. OBJECTIVES: To determine whether plasma syndecan-1 levels are increased in adult horses affected with sepsis. STUDY DESIGN: Retrospective cohort study. METHODS: Adult horses were assigned to one of three groups based on results of physical and laboratory examinations, clinical diagnosis, and results of previously described SIRS classification: Group 1 horses included healthy, nonseptic horses; Group 2 included horses in which clinical illness was identified but that were not considered to be septic; Group 3 included horses with a clinical diagnosis of sepsis. Plasma syndecan-1 concentration was determined in blood obtained at admission into the hospital for each horse, using an equine specific ELISA. Data were analysed using ANOVA and linear regression (p ≤ 0.05). RESULTS: One hundred and ninety-one horses were included and divided into three groups. Scores for SIRS were highest for Group 3 horses and lowest in Groups 1 and 2. Plasma syndecan-1 concentrations in Group 3 horses (50.73 ± 84.24 µg/ml; n = 42) were greater than those for Group 1 (15.69 ± 11.28 µg/ml; n = 66) and Group 2 (16.88 ± 15.30 µg/ml; n = 83). There was no difference regarding syndecan concentrations between Groups 1 and 2. MAIN LIMITATIONS: Retrospective study design, solitary time point of measurement for each patient, and lack of a widely accepted consensus regarding definitive diagnosis of sepsis in adult horses. CONCLUSIONS: Circulating plasma levels of syndecan-1, a biochemical marker of endothelial glycocalyx damage, are increased in septic adult horses.

Border-fence falls versus domestic falls at a South Texas trauma center.

Objectives: Falling from height may lead to significant injuries and time hospitalized; however, there are few studies comparing the specific mechanism of fall. The purpose of this study was to compare injuries from falls after attempting to cross the USA-Mexico border fence (intentional) with injuries from domestic falls (unintentional) of comparable height. Methods: This retrospective cohort study included all patients admitted after a fall from a height of 15-30 ft to a level II trauma center between April 2014 and November 2019. Patient characteristics were compared by falls from the border fence with those who fell domestically. Fisher's exact test, χ2 test and Wilcoxon Mann-Whitney U test were used as appropriate. A significance level of α<0.05 was used. Results: Of the 124 patients included, 64 (52%) were falls from the border fence while 60 (48%) were domestic falls. Patients sustaining injuries from border falls were on average younger than patients who had domestic falls (32.6 (10) vs 40.0 (16), p=0.002), more likely males (58% vs 41%, p<0.001), fell from a significantly higher distance (20 (20-25) vs 16.5 (15-25), p<0.001), and had a significantly lower median injury severity score (ISS) (5 (4-10) vs 9 (5-16.5), p=0.001). Additionally, compared with domestic falls, border falls had fewer injuries to the head (3% vs 25%, p=0.004) and chest (5% vs 27%, p=0.007), yet more extremity injuries (73% vs 42%, p=0.003), and less had an intensive care unit (ICU) stay (30% vs 63%, p=0.002). No significant differences in mortality were found. Conclusion: Patients sustaining injuries from border crossing falls were slightly younger, and although fell from higher, had a lower ISS, more extremity injuries, and fewer were admitted to the ICU compared with patients sustaining falls domestically. There was no difference in mortality between groups. Level of evidence: Level III, retrospective study.

Registered Reports: A new chapter at Ecology & Evolution.

Ecology & Evolution has published its first Registered Report and offers the perspective of the editor, author, and student on the publication process.

Reproducibility in ecology and evolution: Minimum standards for data and code.

We call for journals to commit to requiring open data be archived in a format that will be simple and clear for readers to understand and use. If applied consistently, these requirements will allow contributors to be acknowledged for their work through citation of open data, and facilitate scientific progress.