Recent tropical Andean glacier retreat is unprecedented in the Holocene.

Tropical glaciers have retreated over recent decades, but whether the magnitude of this retreat exceeds the bounds of Holocene fluctuations is unclear. We measured cosmogenic beryllium-10 and carbon-14 concentrations in recently exposed bedrock at the margin of four glaciers spanning the tropical Andes to reconstruct their past extents relative to today. Nuclide concentrations are near zero in almost all samples, suggesting that these locations were never exposed during the Holocene. Our data imply that many glaciers in the tropics are probably now smaller than they have been in at least 11,700 years, making the tropics the first large region where this milestone has been documented.

ACG Clinical Guideline: Focal Liver Lesions.

Focal liver lesions (FLLs) have become an increasingly common finding on abdominal imaging, especially asymptomatic and incidental liver lesions. Gastroenterologists and hepatologists often see these patients in consultation and make recommendations for management of multiple types of liver lesions, including hepatocellular adenoma, focal nodular hyperplasia, hemangioma, and hepatic cystic lesions including polycystic liver disease. Malignancy is important to consider in the differential diagnosis of FLLs, and healthcare providers must be familiar with the diagnosis and management of FLLs. This American College of Gastroenterology practice guideline uses the best evidence available to make diagnosis and management recommendations for the most common FLLs.

Taking the sting out of scorpions: Electrophysiological investigation of the relative efficacy of three antivenoms against medically significant Centruroides species.

In this study, we report the innovative application of whole-cell patch-clamp electrophysiology in assessing broad-spectrum neutralisation by three different antivenoms, of venoms from the medically significant scorpion genus Centruroides. Envenomations by as many as 21 species from the Centruroides genus result in up to 300,000 envenomations per year in Mexico, which poses significant and potentially life-threatening pathophysiology. We first evaluated the in vitro manifestation of envenomation against two human voltage-gated sodium (hNaV) channel subtypes: hNaV1.4 and hNaV1.5, which are primarily expressed in skeletal muscles and cardiomyocytes, respectively. The neutralisation of venom activity was then characterised for three different antivenoms using a direct competition model against the more potent target, hNaV1.4. While broad-spectrum neutralisation was identified, variation in neutralisation arose for Centruroides elegans, C. limpidus, C. noxius and C. suffusus venoms, despite the presence of a number of these venoms within the immunising mixture. This raises questions regarding the truly "broad" neutralisation capacity of the antivenoms. This study not only extends previous validation of the in vitro investigation of antivenom efficacy utilising the whole-cell patch-clamp technique but also underscores the potential of this animal-free model in exploring cross-reactivity, experimental scalability, and most importantly, informing clinical management practices regarding the administration of antivenom in Mexico.

A Measure of the Impact on Real-Time Patient Care of Evidence-based Medicine Logs.

Introduction: Evidence-based medicine (EBM) is a critical skill for physicians, and EBM competency has been shown to increase implementation of best medical practices, reduce medical errors, and increase patient-centered care. Like any skill, EBM must be practiced, receiving iterative feedback to improve learners' comprehension. Having residents document patient interactions in logbooks to allow for residency program review, feedback, and documentation of competency has been previously described as a best practice within emergency medicine (EM) to document practice-based learning (PBL) competency. Quantifying how residents use the information they query, locate, evaluate, and apply while providing direct patient care can measure the efficacy of EBM education and provide insight into more efficient ways of providing medical care. Methods: Practice-based learning logs were surveys created to record resident EBM activity on-shift and were placed into our residency management software program. Residents were required to submit 3-5 surveys of EBM activity performed during a 28-day rotation during which additional information was sought. This study included all PBL logs completed by EM residents from June 1, 2013-May 11, 2020. Using qualitative methodology, a codebook was created to analyze residents' free-text responses to the prompt: "Based on your research, would you have done anything differently?" The codebook was designed to generate a three-digit code conveying the effect of the researched information on the patient about whom the log was written, as well as whether the information would affect future patient care and whether these decisions were based on scientific evidence. Results: A total of 10,574 logs were included for primary analysis. In total, 1,977 (18.7%) logs indicated that the evidence acquired through research would affect future patient care. Of these, 392 (3.7%) explicitly stated that the EBM activity conducted as part of our project led to real-time changes in patient care in the ED and would change future management of patients as well. Conclusion: We present a proof of concept that PBL log activity can lead to integration of evidence-based medicine into real-time patient care. While a convenience sample, our cohort recorded evidence of both lifelong learning and application to patient care.

Conceptualizations of wellbeing among nonbinary individuals in the Midwestern United States: a photovoice study.

Background: Traditionally, gender has been viewed through an essentialist lens with fixed biology-based traits or polarized gender norms between women and men. As awareness of gender diversity grows, increasingly more people are coming out as nonbinary - or not exclusively a man or woman. Little has been explored regarding experiences unique to nonbinary individuals, particularly beyond a focus on adverse risks and outcomes to understand their wellbeing. This article discusses gendered experiences and the construction of wellbeing among nonbinary individuals. Aim: The purpose of this study was to conceptualize wellbeing as a complex multidimensional phenomenon through nonbinary individuals' perspectives. Methods: A virtual PhotoVoice study was conducted with 17 nonbinary adults in the Midwestern United States who participated in online group discussions and in-depth semi-structured interviews, which were analyzed with thematic analysis. Results: The analysis identified five core dimensions of nonbinary wellbeing: 1) Security, 2) Mental and physical health, 3) Autonomy, 4) Belonging, and 5) Gender positivity. Exemplary definitions of wellbeing are also presented. Discussion: Understanding how nonbinary individuals thrive challenges the framing of gender diverse experiences in adversity and presents a more holistic portrayal that community members and allies can strive toward. This study contributes an intersectional understanding of wellbeing in relation to identities of race, culture, age, disability, neurodiversity, and sociopolitical geographical context. The findings of this study can aid in practice, advocacy, and research to bolster the wellbeing of nonbinary people.

Correction: How to estimate body condition in large lizards? Argentine black and white tegu (Salvator merianae, Duméril and Bibron, 1839) as a case study.

[This corrects the article DOI: 10.1371/journal.pone.0282093.].

An Improved Postprocessing Method to Mitigate the Macroscopic Cross-Slice B0 Field Effect on R2* Measurements in the Mouse Brain at 7T.

The MR transverse relaxation rate, R2*, has been widely used to detect iron and myelin content in tissue. However, it is also sensitive to macroscopic B0 inhomogeneities. One approach to correct for the B0 effect is to fit gradient-echo signals with the three-parameter model, a sinc function-weighted monoexponential decay. However, such three-parameter models are subject to increased noise sensitivity. To address this issue, this study presents a two-stage fitting procedure based on the three-parameter model to mitigate the B0 effect and reduce the noise sensitivity of R2* measurement in the mouse brain at 7T. MRI scans were performed on eight healthy mice. The gradient-echo signals were fitted with the two-stage fitting procedure to generate R2corr_t*. The signals were also fitted with the monoexponential and three-parameter models to generate R2nocorr* and R2corr*, respectively. Regions of interest (ROIs), including the corpus callosum, internal capsule, somatosensory cortex, caudo-putamen, thalamus, and lateral ventricle, were selected to evaluate the within-ROI mean and standard deviation (SD) of the R2* measurements. The results showed that the Akaike information criterion of the monoexponential model was significantly reduced by using the three-parameter model in the selected ROIs (p = 0.0039-0.0078). However, the within-ROI SD of R2corr* using the three-parameter model was significantly higher than that of the R2nocorr* in the internal capsule, caudo-putamen, and thalamus regions (p = 0.0039), a consequence partially due to the increased noise sensitivity of the three-parameter model. With the two-stage fitting procedure, the within-ROI SD of R2corr* was significantly reduced by 7.7-30.2% in all ROIs, except for the somatosensory cortex region with a fast in-plane variation of the B0 gradient field (p = 0.0039-0.0078). These results support the utilization of the two-stage fitting procedure to mitigate the B0 effect and reduce noise sensitivity for R2* measurement in the mouse brain.

Blood Lines: Intraspecific and Interspecific Variations in Anticoagulant Actions of Agkistrodon Viperid Venoms.

This study investigated the intraspecific and interspecific variability in the venom effects of Agkistrodon viperid snake species and subspecies (eleven venoms total) on plasma clotting times, fibrinogen levels, and fibrin clot strength. Significant delays in plasma clotting time were observed for A. conanti, A. contortrix mokasen, A. contortrix phaeogaster, A. howardgloydi, A. piscivorus leucostoma, and A. piscivorus piscivorus. Notably, the phylogenetically disjunct lineages A. conanti, A. contortrix mokasen, and A. howardgloydi exhibited the most potent anticoagulant effects, indicating the independent amplification of a basal trait. Inhibition assays with the activated clotting enzymes Factors XIa, IXa, Xa, and IIa (thrombin) revealed that FXa inhibition is another basal trait amplified independently on multiple occasions within the genus, but with A. howardgloydi, notably more potent than all others. Phospholipid degradation and zymogen destruction were identified as mechanisms underlying the variability in venom effects observed experimentally and in previous clinical reports. Thromboelastography demonstrated that the venoms did not clot fibrinogen directly but affected fibrin clot strength by damaging fibrinogen and that thrombin was subsequently only able to cleave into weak, unstable clots. The ability to activate Protein C, an endogenous anticoagulant enzyme, varied across species, with some venoms exceeding that of A. contortrix contortrix, which previously yielded the protein diagnostic agent Protac®. Phylogenetic analysis suggested that both fibrinogen degradation and Protein C activation were each amplified multiple times within the genus, albeit with negative correlation between these two modes of action. This study highlights the evolutionary, clinical, and biodiscovery implications of venom variability in the Agkistrodon species, underscoring their dynamic evolution, emphasising the need for tailored clinical approaches, and highlighting the potential for novel diagnostic and therapeutic developments inspired by the unique properties of snake venoms.

Early safety of endoscopic sleeve gastroplasty in super obesity (body mass index > 50).

BACKGROUND: The prevalence of super obesity (body mass index [BMI] > 50) continues to rise. However, the adoption of bariatric surgery in this population remains very low. There are limited studies evaluating the utility of endoscopic sleeve gastroplasty (ESG) in super obesity. OBJECTIVES: The purpose of this study is to evaluate the short-term safety profile of ESG in patients with super obesity using data from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database. SETTING: United States. METHODS: We retrospectively analyzed patients who underwent ESG and sleeve gastrectomy (SG) from 2016 to 2021. Patients with BMI >50 who underwent ESG were compared to ESG patients with BMI <50 and also SG patients with BMI >50. Primary outcomes included the incidence of severe adverse events (AEs), hospital readmission, reintervention, and reoperation within 30 days of the primary procedure. Secondary outcomes included procedure time, hospital length of stay, and total body weight loss at 30 days. RESULTS: There were no significant differences in AE, reoperations, hospital readmissions, or reinterventions for patients with super obesity undergoing ESG, compared to patients with BMI below 50. Mean total body weight loss was greater in patients with super obesity. There were no significant differences in AEs for patients with super obesity who underwent ESG versus SG, although ESG patients had more hospital readmissions, reinterventions, and reoperations. CONCLUSIONS: ESG may be performed safely, with comparable safety to SG, in patients with BMI as high as 70. However, further studies are needed to validate the feasibility and long-term efficacy prior to clinical implementation.

The Clot Thickens: Differential Coagulotoxic and Cardiotoxic Activities of Anguimorpha Lizard Venoms.

Despite their evolutionary novelty, lizard venoms are much less studied in comparison to the intense research on snake venoms. While the venoms of helodermatid lizards have long been assumed to be for defensive purposes, there is increasing evidence of toxic activities more useful for predation than defence (such as paralytic neurotoxicity). This study aimed to ascertain the effects of Heloderma, Lanthanotus, and Varanus lizard venoms on the coagulation and cardiovascular systems. Anticoagulant toxicity was demonstrated for the Varanus species studied, with the venoms prolonging clotting times in human and bird plasma due to the destructive cleavage of fibrinogen. In contrast, thromboelastographic analyses on human and bird plasmas in this study demonstrated a procoagulant bioactivity for Heloderma venoms. A previous study on Heloderma venom using factor-depleted plasmas as a proxy model suggested a procoagulant factor was present that activated either Factor XI or Factor XII, but could not ascertain the precise target. Our activation studies using purified zymogens confirmed FXII activation. Comparisons of neonate and adult H. exasperatum, revealed the neonates to be more potent in the ability to activate FXII, being more similar to the venom of the smaller species H. suspectum than the adult H. exasperatum. This suggests potent FXII activation a basal trait in the genus, present in the small bodied last common ancestor. This also indicates an ontogenetic difference in prey preferences in the larger Heloderma species paralleing the change in venom biochemistry. In addition, as birds lack Factor XII, the ability to clot avian plasma suggested an additional procoagulant site of action, which was revealed to be the activation of Factor VII, with H. horridum being the most potent. This study also examined the effects upon the cardiovascular system, including the liberation of kinins from kininogen, which contributes to hypotension induction. This form of toxicity was previously described for Heloderma venoms, and was revealed in this study was to also be a pathophysiological effect of Lanthanotus and Varanus venoms. This suggests that this toxic activity was present in the venom of the last common ancestor of the anguimorph lizards, which is consistent with kallikrein enzymes being a shared toxin trait. This study therefore uncovered novel actions of anguimorph lizard venoms, not only contributing to the evolutionary biology body of knowledge but also revealing novel activities to mine for drug design lead compounds.

Comparative accuracy of four guidelines to predict high-grade dysplasia or malignancy in surgically resected pancreatic intraductal papillary mucinous neoplasms: Small nuances between guidelines lead to vastly different results.

Backgrounds/Aims: The guidelines regarding the management of intraductal papillary mucinous neoplasms (IPMNs) all have slightly different surgical indications for high-risk lesions. We aim to retrospectively compare the accuracy of four guidelines in recommending surgery for high-risk IPMNs, and assess the accuracy of elevated CA-19-9 levels and imaging characteristics of IPMNs considered high-risk in predicting malignancy or high-grade dysplasia (HGD). Methods: The final histopathological diagnosis of surgically resected high-risk IPMNs during 2013-2020 were compared to preoperative surgical indications, as enumerated in four guidelines: the 2015 American Gastroenterological Association (AGA), 2017 International Consensus, 2018 European Study Group, and 2018 American College of Gastroenterology (ACG). Surgery was considered "justified" if histopathology of the surgical specimen showed HGD/malignancy, or there was postoperative symptomatic improvement. Results: Surgery was postoperatively justified in 26/65 (40.0%) cases. All IPMNs with HGD/malignancy were detected by the 2018 ACG and the combined (absolute and relative criteria) 2018 European guidelines. The combined ("high-risk stigmata" and "worrisome features") 2017 International guideline missed 1/19 (5.3%) IPMNs with HGD/malignancy. The 2015 AGA guideline missed the most cases (11/19, 57.9%) of IPMNs with HGD/malignancy. We found the features most-associated with HGD/malignancy were pancreatic ductal dilation, and elevated CA-19-9 levels. Conclusions: Following the 2015 AGA guideline results in the highest rate of missed HGD/malignancy, but the lowest rate of operating on IPMNs without these features; meanwhile, the 2018 ACG and the combined (absolute and relative criteria) 2018 European guidelines result in more operations for IPMNs without HGD/malignancy, but the lowest rates of missed HGD/malignancy in IPMNs.

Early, rapidly progressive vasculopathy in a transplanted heart: A possible complication of COVID-19.

The epidemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has had a significant global impact, especially on immunosuppressed populations such as heart transplant recipients. While SARS-CoV-2 initially infects the respiratory system, cardiovascular complications induced by coronavirus disease 2019 (COVID-19) include cardiac arrest, myocardial infarction, heart failure, myocarditis, arrhythmia, acute myocyte injury, thrombotic events, and cardiogenic shock. Here, we present a case of a 45-year-old African American male who tested positive for COVID-19 infection six months after receiving a heart transplant. The patient was asymptomatic initially, but two weeks later he developed dyspnea, early satiety, and abdominal bloating. The patient was admitted to the hospital for acute renal failure and subsequently diagnosed with moderate acute T cell-mediated allograft rejection (Grade 2R) by endomyocardial biopsy. Three months after testing positive for COVID-19, the patient suffered a sudden cardiac death. At autopsy, the epicardium was diffusely edematous and showed vascular congestion. The coronary arteries showed a striking concentric narrowing of lumens and diffusely thickened arterial walls of all major extramural arteries deemed consistent with a rapidly progressive form of cardiac allograft vasculopathy (CAV). SARS-CoV-2 nucleocapsid protein was localized by immunohistochemistry (IHC) in endothelial cells of venules and capillaries within the epicardium. Our localization of SARS-CoV-2 in coronary vessel endothelial cells by IHC suggests that endothelial cell infection, endotheliitis, and immune-related inflammation may be a primary mechanism of vascular injury. The present case represents an early onset rapidly progressive form of CAV. This case may be the first case of post-transplant arteriopathy occurring in such a short time that includes corresponding autopsy, surgical pathology, and IHC data.

Fangs and foliage: Unearthing the haemotoxic secrets of cannabis-dwelling rattlesnakes.

Despite a recent surge in high-throughput venom research that has enabled many species to be studied, some snake venoms remain understudied. The long-tailed rattlesnakes (Crotalus ericsmithi, C. lannomi, and C. stejnegeri) are one group where such research lags, largely owing to the rarity of these snakes and the hazardous areas, ripe with drug (marijuana and opium) production, they inhabit in Mexico. To fill this knowledge gap, we used multiple functional assays to examine the coagulotoxic (including across different plasma types), neurotoxic, and myotoxic activity of the venom of the long-tailed rattlesnakes. All crude venoms were shown to be potently anticoagulant on human plasma, which we discovered was not due to the destruction of fibrinogen, except for C. stejnegeri displaying minor fibrinogen destruction activity. All venoms exhibited anticoagulant activity on rat, avian, and amphibian plasmas, with C. ericsmithi being the most potent. We determined the mechanism of anticoagulant activity by C. ericsmithi and C. lannomi venoms to be phospholipid destruction and inhibition of multiple coagulation factors, leading to a net disruption of the clotting cascade. In the chick biventer assay, C. ericsmithi and C. lannomi did not exhibit neurotoxic activity but displayed potential weak myotoxic activity. BIRMEX® (Faboterápico Polivalente Antiviperino) antivenom was not effective in neutralising this venom effect. Overall, this study provides an in-depth investigation of venom function of understudied long-tailed rattlesnakes and provides a springboard for future venom and ecology research on the group.

Red-on-Yellow Queen: Bio-Layer Interferometry Reveals Functional Diversity Within Micrurus Venoms and Toxin Resistance in Prey Species.

Snakes in the family Elapidae largely produce venoms rich in three-finger toxins (3FTx) that bind to the α 1 subunit of nicotinic acetylcholine receptors (nAChRs), impeding ion channel activity. These neurotoxins immobilize the prey by disrupting muscle contraction. Coral snakes of the genus Micrurus are specialist predators who produce many 3FTx, making them an interesting system for examining the coevolution of these toxins and their targets in prey animals. We used a bio-layer interferometry technique to measure the binding interaction between 15 Micrurus venoms and 12 taxon-specific mimotopes designed to resemble the orthosteric binding region of the muscular nAChR subunit. We found that Micrurus venoms vary greatly in their potency on this assay and that this variation follows phylogenetic patterns rather than previously reported patterns of venom composition. The long-tailed Micrurus tend to have greater binding to nAChR orthosteric sites than their short-tailed relatives and we conclude this is the likely ancestral state. The repeated loss of this activity may be due to the evolution of 3FTx that bind to other regions of the nAChR. We also observed variations in the potency of the venoms depending on the taxon of the target mimotope. Rather than a pattern of prey-specificity, we found that mimotopes modeled after snake nAChRs are less susceptible to Micrurus venoms and that this resistance is partly due to a characteristic tryptophan → serine mutation within the orthosteric site in all snake mimotopes. This resistance may be part of a Red Queen arms race between coral snakes and their prey.

Ocular screening for chronic graft-versus-host disease in patients with allogeneic hematopoietic stem cell transplant.

OBJECTIVE: This study investigates ocular manifestations of graft-versus-host disease in patients following allogeneic hematopoietic stem cell transplantation (HSCT) at the University of Texas Medical Branch (UTMB). Preferred practice pattern guidelines are proposed for ocular graft-versus-host disease (oGHVD) detection. METHODS: The Epic electronic medical record database at UTMB was screened using International Classification of Diseases, Tenth Revision (ICD-10), codes for bone marrow transplants, stem cell transplants, and complications of bone marrow transplants and stem cell transplants. We identified 50 patients with the ICD-10 codes that were seen at UTMB between 2000 and 2021. Patients who received an HSCT and follow-up care with UTMB were included in this study. Thirty-eight patients met the inclusion criteria, whereas 12 patients were excluded because they had no diagnosis of HSCT or did not follow-up with UTMB. RESULTS: Of the 38 patients in our cohort, 23.7% (n = 9) were noted to have oGVHD. As many as 89% of the patients with oGVHD presented with an ocular surface disease including keratoconjunctivitis sicca, meibomian gland dysfunction, and dry eye syndrome. Systemic GVHD also was found in 44% of the patients with oGVHD. Only 29% (n = 11) of the study population had referrals to ophthalmology. Most referrals (55%) were made within 1 year of getting the HSCT. None of the patients in our cohort received an ocular screening before HSCT. CONCLUSIONS: Many post-HSCT patients lack routine ophthalmic care. Regularly assessing post-HSCT patients for early signs and symptoms of oGVHD may limit adverse outcomes. Management of oGVHD should involve a multidisciplinary team approach.

Emerging Trends in the Prevalence of Military Medicine Interest Groups and Specialty Tracks at U.S. Medical Schools.

INTRODUCTION: A challenge confronting health care is the national physician shortage, notably impacting the DoD's recruitment of military physicians. To address this, the Health Professions Scholarship Program is annually awarded to medical students to facilitate their transition into the U.S. Armed Forces. There is a glaring absence of military medical education in civilian schools to accommodate the unique interests of these students. While medical schools have adapted with interest groups and specialty tracks, the current presence of military medicine interest groups (MMIGs) and military medicine specialty tracks (MMSTs) remains under-explored. This study aimed to (1) update the prevalence of MMIGs in U.S. medical institutions, (2) identify the presence of MMSTs, and (3) compare military medicine involvement between allopathic and osteopathic programs. METHODS: The study was approved for exempt status from the Kansas City University Institutional Review Board (study number 20,211,568-1). In a cross-sectional analysis, surveys were sent to 208 U.S. medical schools, with responses from student services or available public data from 200 institutions included in the final analysis. A secondary survey was sent to respondents who provided MMIG or MMST contacts. RESULTS: Results indicated that 62% (n = 124/200) of schools currently have an established MMIG, a modest growth from 56% (n = 70/125) in 2015 (p = .14). MMST prevalence, however, is minimal at 2.5% (5/200). Osteopathic institutions demonstrated a significantly greater engagement in military medicine education (88.7%) compared to allopathic schools (52.4%) (p < .001). CONCLUSION: This research underscores the need for comprehensive military medical training in medical schools to meet the interests and career aspirations of their students. Future studies should also evaluate the efficacy of MMIGs and MMSTs in preparing students for military medical roles.

Superoxide Dismutase Mimetic Avasopasem Manganese Enhances Radiation Therapy Effectiveness in Soft Tissue Sarcomas and Accelerates Wound Healing.

Soft tissue sarcomas (STSs) are mesenchymal malignant lesions that develop in soft tissues. Despite current treatments, including radiation therapy (RT) and surgery, STSs can be associated with poor patient outcomes and metastatic recurrences. Neoadjuvant radiation therapy (nRT), while effective, is often accompanied by severe postoperative wound healing complications due to damage to the surrounding normal tissues. Thus, there is a need to develop therapeutic approaches to reduce nRT toxicities. Avasopasem manganese (AVA) is a selective superoxide dismutase mimetic that protects against IR-induced oral mucositis and lung fibrosis. We tested the efficacy of AVA in enhancing RT in STSs and in promoting wound healing. Using colony formation assays and alkaline comet assays, we report that AVA selectively enhanced the STS (liposarcoma, fibrosarcoma, leiomyosarcoma, and MPNST) cellular response to radiation compared to normal dermal fibroblasts (NDFs). AVA is believed to selectively enhance radiation therapy by targeting differential hydrogen peroxide clearance in tumor cells compared to non-malignant cells. STS cells demonstrated increased catalase protein levels and activity compared to normal fibroblasts. Additionally, NDFs showed significantly higher levels of GPx1 activity compared to STSs. The depletion of glutathione using buthionine sulfoximine (BSO) sensitized the NDF cells to AVA, suggesting that GPx1 may, in part, facilitate the selective toxicity of AVA. Finally, AVA significantly accelerated wound closure in a murine model of wound healing post RT. Our data suggest that AVA may be a promising combination strategy for nRT therapy in STSs.

Endotyping in ARDS: one step forward in precision medicine.

BACKGROUND: The Berlin definition of acute respiratory distress syndrome (ARDS) includes only clinical characteristics. Understanding unique patient pathobiology may allow personalized treatment. We aimed to define and describe ARDS phenotypes/endotypes combining clinical and pathophysiologic parameters from a Canadian ARDS cohort. METHODS: A cohort of adult ARDS patients from multiple sites in Calgary, Canada, had plasma cytokine levels and clinical parameters measured in the first 24 h of ICU admission. We used a latent class model (LCM) to group the patients into several ARDS subgroups and identified the features differentiating those subgroups. We then discuss the subgroup effect on 30 day mortality. RESULTS: The LCM suggested three subgroups (n1 = 64, n2 = 86, and n3 = 30), and 23 out of 69 features made these subgroups distinct. The top five discriminating features were IL-8, IL-6, IL-10, TNF-a, and serum lactate. Mortality distinctively varied between subgroups. Individual clinical characteristics within the subgroup associated with mortality included mean PaO2/FiO2 ratio, pneumonia, platelet count, and bicarbonate negatively associated with mortality, while lactate, creatinine, shock, chronic kidney disease, vasopressor/ionotropic use, low GCS at admission, and sepsis were positively associated. IL-8 and Apache II were individual markers strongly associated with mortality (Area Under the Curve = 0.84). PERSPECTIVE: ARDS subgrouping using biomarkers and clinical characteristics is useful for categorizing a heterogeneous condition into several homogenous patient groups. This study found three ARDS subgroups using LCM; each subgroup has a different level of mortality. This model may also apply to developing further trial design, prognostication, and treatment selection.

Augmented Stress Weight-bearing CT for Evaluation of Subtle Lisfranc Injuries in the Elite Athlete.

BACKGROUND: Lisfranc injuries refer to a disruption or displacement of the tarsometatarsal joint of the foot. Subtle Lisfranc injuries can go undiagnosed on conventional imaging leading to devastating consequences and poor functional outcomes for elite athletes. Objective. The objective of this case study is to present a novel imaging technique using weight-bearing computed tomography (CT) with enhanced stress to identify subtle, dynamically unstable Lisfranc injuries. We illustrate this with a case presentation of an elite athlete who ultimately required surgical fixation for a subtle Lisfranc injury. MATERIALS AND METHODS: To perform an augmented stress weight-bearing CT, the patient was positioned standing, with their feet facing forward, and weight equally distributed. The patient was then coached to symmetrically raise both heels from the scanner platform. This plantarflexion provided augmented stress on the midfoot, allowing for more sensitive imaging of the Lisfranc injury. The weight-bearing CT and augmented stress images undergo 3D reconstruction and postprocessing to render coronal and sagittal images, allowing for comparison of the standard weight-bearing and augmented stress images. RESULTS: We present the case of a 22-year-old collegiate football lineman sustaining a Lisfranc injury. The injury diagnosis was made by magnetic resonance imaging (MRI) and clinical examination, without evidence of injury on weight-bearing XR or standard weight-bearing CT. With augmented stress CT imaging, the Lisfranc instability was noted, leading to surgical fixation, and return to sport the next season. CONCLUSION: We propose this technique for diagnosing subtle, unstable Lisfranc injuries where clinical suspicion persists despite inconclusive imaging, particularly in elite athletes. Further research is needed with larger sample sizes to investigate the sensitivity of this novel imaging technique for the detection of Lisfranc injury. LEVELS OF EVIDENCE: Level 4: Case Report.

The Evolution of Agrarian Landscapes in the Tropical Andes.

Changes in land-use practices have been a central element of human adaptation to Holocene climate change. Many practices that result in the short-term stabilization of socio-natural systems, however, have longer-term, unanticipated consequences that present cascading challenges for human subsistence strategies and opportunities for subsequent adaptations. Investigating complex sequences of interaction between climate change and human land-use in the past-rather than short-term causes and effects-is therefore essential for understanding processes of adaptation and change, but this approach has been stymied by a lack of suitably-scaled paleoecological data. Through a high-resolution paleoecological analysis, we provide a 7000-year history of changing climate and land management around Lake Acopia in the Andes of southern Peru. We identify evidence of the onset of pastoralism, maize cultivation, and possibly cultivation of quinoa and potatoes to form a complex agrarian landscape by c. 4300 years ago. Cumulative interactive climate-cultivation effects resulting in erosion ended abruptly c. 2300 years ago. After this time, reduced sedimentation rates are attributed to the construction and use of agricultural terraces within the catchment of the lake. These results provide new insights into the role of humans in the manufacture of Andean landscapes and the incremental, adaptive processes through which land-use practices take shape.