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Neutrophils exacerbate pulmonary ischemia-reperfusion injury (IRI) resulting in poor short and long-term outcomes for lung transplant recipients. Glycolysis powers neutrophil activation, but it remains unclear if neutrophil-specific targeting of this pathway will inhibit IRI. Lipid nanoparticles containing the glycolysis flux inhibitor 2-deoxyglucose (2-DG) were conjugated to neutrophil-specific Ly6G antibodies (NP-Ly6G[2-DG]). Intravenously administered NP-Ly6G(2-DG) to mice exhibited high specificity for circulating neutrophils. NP-Ly6G(2-DG)-treated neutrophils were unable to adapt to hypoglycemic conditions of the lung airspace environment as evident by the loss of demand-induced glycolysis, reductions in glycogen and ATP content, and an increased vulnerability to apoptosis. NP-Ly6G(2-DG) treatment inhibited pulmonary IRI following hilar occlusion and orthotopic lung transplantation. IRI protection was associated with less airspace neutrophil extracellular trap generation, reduced intragraft neutrophilia, and enhanced alveolar macrophage efferocytotic clearance of neutrophils. Collectively, our data show that pharmacologically targeting glycolysis in neutrophils inhibits their activation and survival leading to reduced pulmonary IRI., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

During July 7-11, 2023, CDC received reports of two patients in different states with a tuberculosis (TB) diagnosis following spinal surgical procedures that used bone allografts containing live cells from the same deceased donor. An outbreak associated with a similar product manufactured by the same tissue establishment (i.e., manufacturer) occurred in 2021. Because of concern that these cases represented a second outbreak, CDC and the Food and Drug Administration worked with the tissue establishment to determine that this product was obtained from a donor different from the one implicated in the 2021 outbreak and learned that the bone allograft product was distributed to 13 health care facilities in seven states. Notifications to all seven states occurred on July 12. As of December 20, 2023, five of 36 surgical bone allograft recipients received laboratory-confirmed TB disease diagnoses; two patients died of TB. Whole-genome sequencing demonstrated close genetic relatedness between positive Mycobacterium tuberculosis cultures from surgical recipients and unused product. Although the bone product had tested negative by nucleic acid amplification testing before distribution, M. tuberculosis culture of unused product was not performed until after the outbreak was recognized. The public health response prevented up to 53 additional surgical procedures using allografts from that donor; additional measures to protect patients from tissue-transmitted M. tuberculosis are urgently needed., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Saroj Rai reports uncompensated service as the Association of Immunization Managers’ (AIM) liaison to CDC’s Advisory Committee on Immunization Practices – Chikungunya Workgroup and on the Legacy Council for AIM; and retirement stocks at Novartis Pharmaceuticals. Jeffrey M. Percak reports travel support from the County of San Diego and from the California Tuberculosis Controller’s Association for attendance at the California Tuberculosis Controller’s Association fall meeting. Lisa Y. Armitige reports support from the Texas Department of State Health Services, consulting fees (paid to institution) from the Kansas Health Department, and honoraria (forwarded to institution) from the American Academy of HIV Medicine. No other potential conflicts of interest were disclosed.

Objectives: Deep venous thrombosis (DVT) causes significant morbidity and mortality after trauma. Recently, we have shown that blood flow patterns at vein valves induce oscillatory stress genes, which maintain an anticoagulant endothelial phenotype that inhibits spontaneous clotting at vein valves and sinuses, is lost in the presence of DVT in human pathological samples, and is dependent on expression of the transcription factor FOXC2. We describe an assay, modifying our mouse multiple injury system, which shows evidence of clinically relevant microthrombosis and hypercoagulability applicable to the study of spontaneous DVT in trauma without requiring direct vascular injury or ligation. Finally, we investigated whether these model findings are relevant to a human model of critical illness by examining gene expression changes by quantitative polymerase chain reaction and immunofluorescence in veins collected from critically ill., Methods: C57/Bl6 mice were subjected to a modified mouse multiple injury model with liver crush injury, crush and pseudofracture of a single lower extremity, and 15% total blood volume hemorrhage. Serum was assayed for d-dimer at 2, 6, 24, and 48 hours after injury by enzyme-linked immunosorbent assay. For the thrombin clotting assay, veins of the leg were exposed, 100 μL of 1 mM rhodamine (6 g) was injected retro-orbitally, and 450 μg/mL thrombin was then applied to the surface of the vein with examination of real-time clot formation via in vivo immunofluorescence microscopy. Images were then examined for percentage area of clot coverage of visible mouse saphenous and common femoral vein. Vein valve specific knockout of FOXC2 was induced with tamoxifen treatment in PROX1 Ert2Cre FOXC2 fl/fl mice as previously described. Animals were then subjected to a modified mouse multiple injury model with liver crush injury, crush and pseudofracture of a single lower extremity, and 15% total blood volume hemorrhage. Twenty-four hours after injury, we examined the valve phenotype in naive versus multiple injury animals, with and without loss of the FOXC2 gene from the vein valve (FOXC2 del ) via the thrombin assay. Images were then examined for proximity of clot formation to the valve present at the junction of the mouse saphenous, tibial, and superficial femoral vein and presence of spontaneous microthrombi present in the veins before exposure to thrombin. Human vein samples were obtained from excess tissue preserved after harvest for elective cardiac surgery and from organ donors after organ procurement. Sections were submitted for paraffin embedding and then assayed by immunofluorescence for PROX1, FOXC2, thrombomodulin, endothelial protein C receptor, and von Willebrand's factor. All animal studies were reviewed and approved by the Institutional Animal Care and Use Committee, and all human studies reviewed and approved by the institutional review board., Results: After mouse multiple injuries, enzyme-linked immunosorbent assay for d-dimer showed evidence of products of fibrin breakdown consistent with formation of clot related to injury, fibrinolysis, and/or microthrombosis. The thrombin clotting assay demonstrated higher percentage area of vein covered with clot when exposed to thrombin in the multiple injury animals compared with uninjured (45% vs. 27% p = 0.0002) consistent with a phenotype of hypercoagulable state after trauma in our model system. Unmanipulated FoxC2 knockout mice manifest increased clotting at the vein valve as compared with unmanipulated wild type animals. After multiple injuries, wild type mice manifest increase clotting at the vein after thrombin exposure ( p = 0.0033), and equivalent to that of valvular knockout of FoxC2 (FoxC2del), recapitulating the phenotype seen in FoxC2 knockout animals. The combination of multiple injuries and FoxC2 knockout resulted in spontaneous microthrombi in 50% of the animals, a phenotype not observed with either multiple injuries or FoxC2 deficiency alone (χ 2 , p = 0.017). Finally, human vein samples demonstrated the protective vein valve phenotype of increased FOXC2 and PROX1 and showed decreased expression in the critically ill organ donor population by immunofluorescence imaging in organ donor samples., Conclusion: We have established a novel model of posttrauma hypercoagulation that does not require direct restriction of venous flow or direct injury to the vessel endothelium to assay for hypercoagulability and can generate spontaneous microthrombosis when combined with valve-specific FOXC2 knockout. We find that multiple injuries induce a procoagulant phenotype that recapitulates the valvular hypercoagulability seen in FOXC2 knockout and, in critically ill human specimens, find evidence for loss of oscillatory shear stress-induced gene expression of FOXC2 and PROX1 in the valvular endothelium consistent with potential loss of DVT-protective valvular phenotype., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Several surgically relevant conditions are directly or indirectly influenced by the human microbiome. Different microbiomes may be found within, or along, specific organs and intra-organ variation is common. Such variations include those found along the course of the gastrointestinal tract as well as those on different regions of the skin. A variety of physiologic stressors and care interventions may derange the native microbiome. A deranged microbiome is termed a dysbiome and is characterized by decreased diversity and an increase in the proportion of potentially pathogenic organisms; the elaboration of virulence factors coupled with clinical consequences defines a pathobiome. Specific conditions such as Clostridium difficile colitis, inflammatory bowel disease, obesity, and diabetes mellitus are tightly linked to a dysbiome or pathobiome. Additionally, massive transfusion after injury appears to derange the gastrointestinal microbiome as well. This review explores what is known about these surgically relevant clinical conditions to chart how non-surgical interventions may support surgical undertakings or potentially reduce the need for operation.

The recognition that a resident community of microbes contributes substantially to human health and disease is one of the emerging great discoveries in modern medicine. This collection of bacteria, archaea, fungi, viruses, and eukaryotes are referred to as microbiota, which together with the individual tissues they inhabit is defined as our individual microbiome. Recent advances in modern DNA sequencing technologies permit the identification, description, and characterization of these microbial communities as well as their variations within and between individuals and groups. This complex understanding of the human microbiome is supported by a rapidly expanding field of inquiry and offers the potential to significantly impact the treatment of a wide variety of disease states. This review explores the recent findings associated with the various components of the human microbiome, and the geodiversity of microbial communities between different tissue types, individuals, and clinical conditions.

The global COVID-19 pandemic has claimed the lives of more than 750,000 US citizens. Dysregulation of the immune system underlies the pathogenesis of COVID-19, with inflammation mediated tissue injury to the lung in the setting of suppressed systemic immune function. To define the molecular mechanisms of immune dysfunction in COVID-19 we utilized a systems immunology approach centered on the circulating leukocyte phosphoproteome measured by mass cytometry. We find that although COVID-19 is associated with wholesale activation of a broad set of signaling pathways across myeloid and lymphoid cell populations, STAT3 phosphorylation predominated in both monocytes and T cells. STAT3 phosphorylation was tightly correlated with circulating IL-6 levels and high levels of phospho-STAT3 was associated with decreased markers of myeloid cell maturation/activation and decreased ex-vivo T cell IFN-γ production, demonstrating that during COVID-19 dysregulated cellular activation is associated with suppression of immune effector cell function. Collectively, these data reconcile the systemic inflammatory response and functional immunosuppression induced by COVID-19 and suggest STAT3 signaling may be the central pathophysiologic mechanism driving immune dysfunction in COVID-19., Competing Interests: IRT, RSH, KER and MBM have pending intellectual property related to the ELISpot assay. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

A 9-year-old boy presented with a 2-day history of vomiting, ataxia and reduced consciousness. He had vomited intermittently in the two preceding months, without headaches, visual disturbance or early morning symptoms. He had autism spectrum disorder, and restricted eating since aged 2 years, eating only corn-crisps, Rich Tea biscuits and chips (French fries), and drinking Coca-Cola (containing 10% glucose; figure 1). Recently a dietician had prescribed a multivitamin., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Genome and proteome data predict the presence of both the reductive citric acid cycle (rCAC; also called the reductive tricarboxylic acid cycle) and the Calvin-Benson-Bassham cycle (CBB) in " Candidatus Endoriftia persephonae," the autotrophic sulfur-oxidizing bacterial endosymbiont from the giant hydrothermal vent tubeworm Riftia pachyptila. We tested whether these cycles were differentially induced by sulfide supply, since the synthesis of biosynthetic intermediates by the rCAC is less energetically expensive than that by the CBB. R. pachyptila was incubated under in situ conditions in high-pressure aquaria under low (28 to 40 μmol · h -1 ) or high (180 to 276 μmol · h -1 ) rates of sulfide supply. Symbiont-bearing trophosome samples excised from R. pachyptila maintained under the two conditions were capable of similar rates of CO 2 fixation. Activities of the rCAC enzyme ATP-dependent citrate lyase (ACL) and the CBB enzyme 1,3-bisphosphate carboxylase/oxygenase (RubisCO) did not differ between the two conditions, although transcript abundances for ATP-dependent citrate lyase were 4- to 5-fold higher under low-sulfide conditions. δ 13 C values of internal dissolved inorganic carbon (DIC) pools were varied and did not correlate with sulfide supply rate. In samples taken from freshly collected R. pachyptila , δ 13 C values of lipids fell between those collected for organisms using either the rCAC or the CBB exclusively. These observations are consistent with cooccurring activities of the rCAC and the CBB in this symbiosis. IMPORTANCE Previous to this study, the activities of the rCAC and CBB in R. pachyptila had largely been inferred from "omics" studies of R. pachyptila without direct assessment of in situ conditions prior to collection. In this study, R. pachyptila was maintained and monitored in high-pressure aquaria prior to measuring its CO 2 fixation parameters. Results suggest that ranges in sulfide concentrations similar to those experienced in situ do not exert a strong influence on the relative activities of the rCAC and the CBB. This observation highlights the importance of further study of this symbiosis and other organisms with multiple CO 2 -fixing pathways, which recent genomics and biochemical studies suggest are likely to be more prevalent than anticipated.

Background: Forty percent of critically ill trauma patients will develop an infectious complication. Pneumonia is the most common cause of death of trauma patients surviving their initial insult. We previously demonstrated that polytrauma (PT), defined as two or more severe injuries in at least two areas of the body, induces emergency hematopoiesis characterized by accelerated myelopoiesis in the bone marrow and increased myeloid cell frequency in the peripheral tissues. We hypothesized that PT alone induces priming of neutrophils, resulting in hyperactivation upon secondary exposure to bacteria and causing acute lung injury and increased susceptibility to secondary exposure to Pseudomonas aeruginosa pneumonia., Methods: C57BL/6 mice were subjected to PT consisting of a lower extremity pseudofracture, liver crush injury, and 15% blood-volume hemorrhage. Pneumonia was induced by intratracheal injection of 5 × 106 CFU live P. aeruginosa or 1 × 107 of heat-killed P. aeruginosa (HKPA). For reactive oxygen species (ROS), studies polymorphonuclear neutrophils (PMNs) were isolated by immunomagnetic bead negative selection and stimulated ex-vivo with HKPA. Reactive oxygen species production was measured by immunofluorescence. For histology, lung sections were stained by hematoxylin-eosin and analyzed by a blinded grader., Results: Polytrauma induced persistent changes in immune function at baseline and to secondary infection. Pneumonia after injury resulted in increased mortality (60% vs. 5% p < 0.01). Blood neutrophils from PT mice had higher resting (unstimulated) ROS production than in naive animals (p < 0.02) demonstrating priming of the neutrophils following PT. After intratracheal HKPA injection, bronchoalveolar lavage PMNs from injured mice had higher ROS production compared with naive mice (p < 0.01), demonstrating an overexuberant immunopathologic response of neutrophils following PT., Conclusion: Polytrauma primes neutrophils and causes immunopathologic PMN ROS production, increased lung injury and susceptibility to secondary bacterial pneumonia. These results suggest that trauma-induced immune dysfunction can cause immunopathologic response to secondary infection and suggests neutrophil-mediated pulmonary damage as a therapeutic target for posttrauma pneumonia., (Copyright © 2021 American Association for the Surgery of Trauma.)

A nonimmunocompromised patient developed life-threatening soft tissue infection with Trichosporon asahii , Fusarium , and Saksenaea that progressed despite maximum antifungal therapies and aggressive debridement. Interleukin-7 immunotherapy resulted in clinical improvement, fungal clearance, reversal of lymphopenia, and improved T-cell function. Immunoadjuvant therapies to boost host immunity may be efficacious in life-threatening fungal infections., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Successful trauma resuscitation relies on multi-disciplinary collaboration. In most academic programs, general surgery (GS) and emergency medicine (EM) residents rarely train together before functioning as a team., Methods: In our Multi-Disciplinary Trauma Evaluation and Management Simulation (MD-TEAMS), EM and GS residents completed manikin-based trauma scenarios and were evaluated on resuscitation and communication skills. Residents were surveyed on confidence surrounding training objectives., Results: Residents showed improved confidence running trauma scenarios in multi-disciplinary teams. Residents received lower communication scores from same-discipline vs cross-discipline faculty. EM residents scored higher in evaluation and planning domains; GS residents scored higher in action processes; groups scored equally in team management. Strong correlation existed between team leader communication and resuscitative skill completion., Conclusion: MD-TEAMS demonstrated correlation between communication and resuscitation checklist item completion and communication differences by resident specialty. In the future, we plan to evaluate training-related resident behavior changes and specialty-specific communication differences by residents., Competing Interests: Declaration of competing interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Salary support for KEC was provided by the Washington University School of Medicine Surgical Oncology Basic Science and Translational Research Training Program grant T32CA009621, from the National Cancer Institute (NCI). All other authors declare no relevant conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Fungal infections are associated with increased morbidity and death. Few studies have examined risk factors associated with post-operative fungal intra-abdominal infections (FIAIs) in trauma patients after exploratory laparotomy. In this study, we evaluated potential risk factors for acquiring post-operative FIAIs and their impact on clinical outcomes. Methods: This was a retrospective analysis of trauma patients admitted from 2005 to 2018 who underwent exploratory laparotomy and subsequently had development of intra-abdominal infection (IAI). Demographics, comorbidities, culture data, antimicrobial usage, Injury Severity Scores (ISS), and clinical outcomes were abstracted. All post-operative IAIs were evaluated and stratified as either bacterial, fungal, combined, and with or without colonization. All groups were compared. Risk factors for the development of post-operative IAI and clinical outcomes were analyzed by Student t test and chi-square test. Multi-variable logistic regression was used to determine independent predictors of post-operative FIAIs. Results: There were 1675 patients identified as having undergone exploratory laparotomy in the setting of traumatic injury, 161 of whom were suspected of having IAI. A total of 105 (6.2%) patients had a diagnosis of IAI. Of these patients, 40 (38%) received a diagnosis of FIAI. The most common fungal pathogens were unspeciated yeast (48.3%), followed by Candida albicans (42.7%), C. glabrata (4.5%) , C. dubliniensis (2.25%), and C. tropicalis (2.25%). There were no significant differences in demographics, comorbidities, and percentage of gastric perforations between FIAI and bacterial IAI (BIAI) groups. Patients with FIAIs, however, had a 75% temporary abdominal closure (TAC) rate compared with 51% in BIAIs (p = 0.01). The FIAI group had higher ISS (27 vs. 22, p = 0.03), longer hospital days (34 vs. 25, p = 0.02), and longer intensive care unit (ICU) days (17 vs. 9, p = 0.006) when compared with BIAI. The FIAI group also had a five-fold greater mortality rate. Logistic regression identified TAC as an independent risk factor for the development of post-operative FIAIs (odds ratio [OR] 6.16, confidence interval [CI] 1.14-28.0, p = 0.02). Conclusions: An FIAI after exploratory laparotomy was associated with greater morbidity and death. A TAC was associated independently with increased risk of FIAI after exploratory laparotomy in the setting of traumatic injury. Clinicians should suspect fungal infections in trauma patients in whom post-operative IAI develops after undergoing exploratory laparotomy using TAC techniques.

We investigate the shape of near-Earth asteroid (101955) Bennu by constructing a high-resolution (20 cm) global digital terrain model from laser altimeter data. By modeling the northern and southern hemispheres separately, we find that longitudinal ridges previously identified in the north extend into the south but are obscured there by surface material. In the south, more numerous large boulders effectively retain surface materials and imply a higher average strength at depth to support them. The north has fewer large boulders and more evidence of boulder dynamics (toppling and downslope movement) and surface flow. These factors result in Bennu's southern hemisphere being rounder and smoother, whereas its northern hemisphere has higher slopes and a less regular shape. We infer an originally asymmetric distribution of large boulders followed by a partial disruption, leading to wedge formation in Bennu's history., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)

The gravity field of a small body provides insight into its internal mass distribution. We used two approaches to measure the gravity field of the rubble-pile asteroid (101955) Bennu: (i) tracking and modeling the spacecraft in orbit about the asteroid and (ii) tracking and modeling pebble-sized particles naturally ejected from Bennu's surface into sustained orbits. These approaches yield statistically consistent results up to degree and order 3, with the particle-based field being statistically significant up to degree and order 9. Comparisons with a constant-density shape model show that Bennu has a heterogeneous mass distribution. These deviations can be modeled with lower densities at Bennu's equatorial bulge and center. The lower-density equator is consistent with recent migration and redistribution of material. The lower-density center is consistent with a past period of rapid rotation, either from a previous Yarkovsky-O'Keefe-Radzievskii-Paddack cycle or arising during Bennu's accretion following the disruption of its parent body., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

The OSIRIS-REx mission has observed multiple instances of particles being ejected from the surface of near-Earth asteroid (101955) Bennu. The ability to quickly identify the particle trajectories and origins is necessary following a particle ejection event. Using proven initial orbit determination techniques, we can rapidly estimate particle trajectories and ejection locations. We present current results pertaining to the identification of particle tracks, an evaluation of the estimated orbits and the excess velocity necessary to induce the particle ejection from the surface, and the uncertainty quantification of the ejection location. We estimate energies per particle ranging from 0.03 to 11.03 mJ for the largest analyzed events and velocities ranging from 5 to 90 cm/s, though we exclude the highest-velocity particles in this technique. We estimate ejection times for eight events and constrain six of the analyzed ejection events to have occurred between about 16:30 and 19:00 local solar time, with the largest events occurring between 16:30 and 18:05., (©2020. The Authors.)

OSIRIS-REx began observing particle ejection events shortly after entering orbit around near-Earth asteroid (101955) Bennu in January 2019. For some of these events, the only observations of the ejected particles come from the first two images taken immediately after the event by OSIRIS-REx's NavCam 1 imager. Without three or more observations of each particle, traditional orbit determination is not possible. However, by assuming that the particles all ejected at the same time and location for a given event, and approximating that their velocities remained constant after ejection (a reasonable approximation for fast-moving particles, i.e., with velocities on the order of 10 cm/s or greater, given Bennu's weak gravity), we show that it is possible to estimate the particles' states from only two observations each. We applied this newly developed technique to reconstruct the particle ejection events observed by the OSIRIS-REx spacecraft during orbit about Bennu. Particles were estimated to have ejected with inertial velocities ranging from 7 cm/s to 3.3 m/s, leading to a variety of trajectory types. Most (>80%) of the analyzed events were estimated to have originated from midlatitude regions and to have occurred after noon (local solar time), between 12:44 and 18:52. Comparison with higher-fidelity orbit determination solutions for the events with sufficient observations demonstrates the validity of our approach and also sheds light on its biases. Our technique offers the capacity to meaningfully constrain the properties of particle ejection events from limited data., (©2020. The Authors.)

Use of hydrogen gas (H 2 ) as an electron donor is common among free-living chemolithotrophic microorganisms. Given the presence of this dissolved gas at deep-sea hydrothermal vents, it has been suggested that it may also be a major electron donor for the free-living and symbiotic chemolithoautotrophic bacteria that are the primary producers at these sites. Giant Riftia pachyptila siboglinid tubeworms and their symbiotic bacteria (" Candidatus Endoriftia persephone") dominate many vents in the Eastern Pacific, and their use of sulfide as a major electron donor has been documented. Genes encoding hydrogenase are present in the " Ca Endoriftia persephone" genome, and proteome data suggest that these genes are expressed. In this study, high-pressure respirometry of intact R. pachyptila and incubations of trophosome homogenate were used to determine whether this symbiotic association could also use H 2 as a major electron donor. Measured rates of H 2 uptake by intact R. pachyptila in high-pressure respirometers were similar to rates measured in the absence of tubeworms. Oxygen uptake rates in the presence of H 2 were always markedly lower than those measured in the presence of sulfide, as was the incorporation of 13 C-labeled dissolved inorganic carbon. Carbon fixation by trophosome homogenate was not stimulated by H 2 , nor was hydrogenase activity detectable in these samples. Though genes encoding [NiFe] group 1e and [NiFe] group 3b hydrogenases are present in the genome and transcribed, it does not appear that H 2 is a major electron donor for this system, and it may instead play a role in intracellular redox homeostasis. IMPORTANCE Despite the presence of hydrogenase genes, transcripts, and proteins in the " Ca Endoriftia persephone" genome, transcriptome, and proteome, it does not appear that R. pachyptila can use H 2 as a major electron donor. For many uncultivable microorganisms, omic analyses are the basis for inferences about their activities in situ However, as is apparent from the study reported here, there are dangers in extrapolating from omics data to function, and it is essential, whenever possible, to verify functions predicted from omics data with physiological and biochemical measurements., (Copyright © 2019 American Society for Microbiology.)

Active asteroids are those that show evidence of ongoing mass loss. We report repeated instances of particle ejection from the surface of (101955) Bennu, demonstrating that it is an active asteroid. The ejection events were imaged by the OSIRIS-REx (Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer) spacecraft. For the three largest observed events, we estimated the ejected particle velocities and sizes, event times, source regions, and energies. We also determined the trajectories and photometric properties of several gravitationally bound particles that orbited temporarily in the Bennu environment. We consider multiple hypotheses for the mechanisms that lead to particle ejection for the largest events, including rotational disruption, electrostatic lofting, ice sublimation, phyllosilicate dehydration, meteoroid impacts, thermal stress fracturing, and secondary impacts., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Introduction: Many injured patients or their families make the difficult decision to withdraw life-sustaining therapies (WLST) following severe injury. While this population has been studied in the setting of severe traumatic brain injury (TBI), little is known about patients who undergo WLST without TBI. We sought to describe patients who may benefit from early involvement of end-of-life resources., Methods: Trauma Quality Improvement Program (2013-2014) patients who underwent WLST were identified. WLST patients were compared to those who died with full supportive care (FSC). Patients were excluded for death within 24 h of admission, or head AIS > 3. Intergroup comparisons were by student's t tests or Wilcoxon rank sum tests; significance for p < 0.05., Results: We identified 3471 total injured patients without major TBI who died > 24 h after admission. Of these death after WLST occurred in 2301 (66% of total). This group had a mean age of 66.8 years; 35.7% were women, and 95.4% sustained blunt injury. WLST patients had a higher ISS (21.6 vs. 12.5, p = 0.001), more in-hospital complications (71.4% vs. 41.6%, p = < 0.0001), and a longer ICU length of stay (8.9 days vs. 7.5 days, p = <0.0001) compared to patients who died with FSC., Conclusion: WLST occurs in two-thirds of injured patients without severe TBI who die in the hospital. In-hospital complications are more frequent in this patient group than those who die with FSC. Early palliative care consultation may improve patient and family satisfaction after acute injury when the timeframe to leverage such services is significantly condensed., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The top-shape morphology of asteroid (101955) Bennu is commonly found among fast-spinning asteroids and binary asteroid primaries, and might have contributed significantly to binary asteroid formation. Yet a detailed geophysical analysis of this morphology for a fast-spinning asteroid has not been possible prior to the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission. Combining the measured Bennu mass and shape obtained during the Preliminary Survey phase of OSIRIS-REx, we find a significant transition in Bennu's surface slopes within its rotational Roche lobe, defined as the region where material is energetically trapped to the surface. As the intersection of the rotational Roche lobe with Bennu's surface has been most recently migrating towards its equator (given Bennu's increasing spin rate), we infer that Bennu's surface slopes have been changing across its surface within the last million years. We also find evidence for substantial density heterogeneity within this body, suggesting that its interior has a distribution of voids and boulders. The presence of such heterogeneity and Bennu's top-shape is consistent with spin-induced failure at some point in its past, although the manner of its failure cannot be determined yet. Future measurements by the OSIRIS-REx spacecraft will give additional insights and may resolve questions regarding the formation and evolution of Bennu's top-shape morphology and its link to the formation of binary asteroids.

Members of the genera Hydrogenovibrio , Thiomicrospira , and Thiomicrorhabdus fix carbon at hydrothermal vents, coastal sediments, hypersaline lakes, and other sulfidic habitats. The genome sequences of these ubiquitous and prolific chemolithoautotrophs suggest a surprising diversity of mechanisms for the uptake and fixation of dissolved inorganic carbon (DIC); these mechanisms are verified here. Carboxysomes are apparent in the transmission electron micrographs of most of these organisms but are lacking in Thiomicrorhabdus sp. strain Milos-T2 and Thiomicrorhabdus arctica , and the inability of Thiomicrorhabdus sp. strain Milos-T2 to grow under low-DIC conditions is consistent with the absence of carboxysome loci in its genome. For the remaining organisms, genes encoding potential DIC transporters from four evolutionarily distinct families (Tcr&#95;0853 and Tcr&#95;0854, Chr, SbtA, and SulP) are located downstream of carboxysome loci. Transporter genes collocated with carboxysome loci, as well as some homologs located elsewhere on the chromosomes, had elevated transcript levels under low-DIC conditions, as assayed by reverse transcription-quantitative PCR (qRT-PCR). DIC uptake was measureable via silicone oil centrifugation when a representative of each of the four types of transporter was expressed in Escherichia coli The expression of these genes in the carbonic anhydrase-deficient E. coli strain EDCM636 enabled it to grow under low-DIC conditions, a result consistent with DIC transport by these proteins. The results from this study expand the range of DIC transporters within the SbtA and SulP transporter families, verify DIC uptake by transporters encoded by Tcr&#95;0853 and Tcr&#95;0854 and their homologs, and introduce DIC as a potential substrate for transporters from the Chr family. IMPORTANCE Autotrophic organisms take up and fix DIC, introducing carbon into the biological portion of the global carbon cycle. The mechanisms for DIC uptake and fixation by autotrophic Bacteria and Archaea are likely to be diverse but have been well characterized only for " Cyanobacteria " Based on genome sequences, members of the genera Hydrogenovibrio , Thiomicrospira , and Thiomicrorhabdus have a variety of mechanisms for DIC uptake and fixation. We verified that most of these organisms are capable of growing under low-DIC conditions, when they upregulate carboxysome loci and transporter genes collocated with these loci on their chromosomes. When these genes, which fall into four evolutionarily independent families of transporters, are expressed in E. coli , DIC transport is detected. This expansion in known DIC transporters across four families, from organisms from a variety of environments, provides insight into the ecophysiology of autotrophs, as well as a toolkit for engineering microorganisms for carbon-neutral biochemistries of industrial importance., (Copyright © 2019 American Society for Microbiology.)

Introduction: Severely injured patients should receive definitive care at high acuity trauma centers. The purposes of this study were to determine the undertriage (UT) rate within a national sample of trauma centers and to identify characteristics of UT patients., Methods: Severely injured adults ≥16 years were identified from the 2010-2012 NTDB. UT was defined as those who received definitive care or died at hospitals without state or ACS level I or II verification. Risk factors for UTT and the impact of UT on mortality were determined., Results: Of 348,394 severely injured patients, 11,578 (3.3%) were UT. Older, less severely injured, and certain minority patients were most likely to be UT. After risk adjustment, predictors of UT included increased age and minority race. Increased injury severity and comorbidity were protective (all p < .05). Mortality was greater in UT patients regardless of ISS (OR = 1.32, p < .001)., Conclusion: The low UT rate in this study demonstrates the effectiveness of triage practices amongst ACS and state verified centers however age, race, and insurance disparities in UT should be improved., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Treatment for acute myeloid leukemia (AML) has remained relatively unchanged over the past few decades. Although recent drug approvals have provided an increase in the number of treatment options in AML, further optimization of standard induction therapy is still necessary. The most commonly utilized induction options have been well studied, but there is a paucity of literature comparing the combination of idarubicin with cytarabine and cladribine., Objective: To assess the clinical effectiveness of the addition of cladribine to idarubicin and cytarabine (7+3 IA) induction therapy in the treatment of AML., Methods: This retrospective, propensity score-matched cohort study evaluated 37 patients with previously untreated AML who received either 7+3 IA or idarubicin, cytarabine, and cladribine (7+3+5 IAC) as induction therapy. The primary end point of this study was complete response (CR), with secondary end points including hospital length of stay (LOS), and adverse event rates., Results: After propensity score matching, odds of reaching CR in the 7+3+5 IAC cohort were increased by 33% (95% CI = 1.09-1.55; P < 0.01) compared with the 7+3 IA cohort. Patients who received cladribine were also found to have a reduction in hospital LOS by 3.5 days (95% CI = 0.07-6.85; P = 0.045) without an increase in adverse event rates., Conclusion: The addition of cladribine to the 7+3 IA regimen may improve clinical outcomes when used as initial induction therapy, without increasing the incidence of adverse event rates.

Central nervous system tuberculosis (CNS-TB) takes three clinical forms: meningitis (TBM), intracranial tuberculoma, and spinal arachnoiditis. TBM predominates in the western world and presents as a subacute to chronic meningitis syndrome with a prodrome of malaise, fever, and headache progressing to altered mentation and focal neurologic signs, followed by stupor, coma, and death within five to eight weeks of onset. The CSF formula typically shows a lymphocytic pleocytosis, and low glucose and high protein concentrations. Diagnosis rests on serial samples of CSF for smear and culture, combined with CSF PCR. Brain CT and MRI aid in diagnosis, assessment for complications, and monitoring of the clinical course. In a patient with compatible clinical features, the combination of meningeal enhancement and any degree of hydrocephalus is strongly suggestive of TBM. Vasculitis leading to infarcts in the basal ganglia occurs commonly and is a major determinant of morbidity and mortality. Treatment is most effective when started in the early stages of disease, and should be initiated promptly on the basis of strong clinical suspicion without waiting for laboratory confirmation. The initial 4 drug regimen (isoniazid, rifampin, pyrazinamide, ethambutol) covers the possibility of infection with a resistant strain, maximizes antimicrobial impact, and reduces the likelihood of emerging resistance on therapy. Adjunctive corticosteroid therapy has been shown to reduce morbidity and mortality in all but late stage disease.

Generating a contiguous, ordered reference sequence of a complex genome such as hexaploid wheat (2n = 6x = 42; approximately 17 GB) is a challenging task due to its large, highly repetitive, and allopolyploid genome. In wheat, ordering of whole-genome or hierarchical shotgun sequencing contigs is primarily based on recombination and comparative genomics-based approaches. However, comparative genomics approaches are limited to syntenic inference and recombination is suppressed within the pericentromeric regions of wheat chromosomes, thus, precise ordering of physical maps and sequenced contigs across the whole-genome using these approaches is nearly impossible. We developed a whole-genome radiation hybrid (WGRH) resource and tested it by genotyping a set of 115 randomly selected lines on a high-density single nucleotide polymorphism (SNP) array. At the whole-genome level, 26 299 SNP markers were mapped on the RH panel and provided an average mapping resolution of approximately 248 Kb/cR1500 with a total map length of 6866 cR1500 . The 7296 unique mapping bins provided a five- to eight-fold higher resolution than genetic maps used in similar studies. Most strikingly, the RH map had uniform bin resolution across the entire chromosome(s), including pericentromeric regions. Our research provides a valuable and low-cost resource for anchoring and ordering sequenced BAC and next generation sequencing (NGS) contigs. The WGRH developed for reference wheat line Chinese Spring (CS-WGRH), will be useful for anchoring and ordering sequenced BAC and NGS based contigs for assembling a high-quality, reference sequence of hexaploid wheat. Additionally, this study provides an excellent model for developing similar resources for other polyploid species., (© 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.)

Background: Triticum monococcum (2n) is a close ancestor of T. urartu, the A-genome progenitor of cultivated hexaploid wheat, and is therefore a useful model for the study of components regulating photomorphogenesis in diploid wheat. In order to develop genetic and genomic resources for such a study, we constructed genome-wide transcriptomes of two Triticum monococcum subspecies, the wild winter wheat T. monococcum ssp. aegilopoides (accession G3116) and the domesticated spring wheat T. monococcum ssp. monococcum (accession DV92) by generating de novo assemblies of RNA-Seq data derived from both etiolated and green seedlings., Principal Findings: The de novo transcriptome assemblies of DV92 and G3116 represent 120,911 and 117,969 transcripts, respectively. We successfully mapped ∼90% of these transcripts from each accession to barley and ∼95% of the transcripts to T. urartu genomes. However, only ∼77% transcripts mapped to the annotated barley genes and ∼85% transcripts mapped to the annotated T. urartu genes. Differential gene expression analyses revealed 22% more light up-regulated and 35% more light down-regulated transcripts in the G3116 transcriptome compared to DV92. The DV92 and G3116 mRNA sequence reads aligned against the reference barley genome led to the identification of ∼500,000 single nucleotide polymorphism (SNP) and ∼22,000 simple sequence repeat (SSR) sites., Conclusions: De novo transcriptome assemblies of two accessions of the diploid wheat T. monococcum provide new empirical transcriptome references for improving Triticeae genome annotations, and insights into transcriptional programming during photomorphogenesis. The SNP and SSR sites identified in our analysis provide additional resources for the development of molecular markers.

This study empirically examines the extent of environmental management practiced by US chemical manufacturing facilities, as reflected in the number of environmental internal audits conducted annually. As its focus, this study analyzes the effects of firm-level organizational structure on facility-level environmental management practices. For this empirical analysis, the study exploits unique data from a survey distributed to all U.S. chemical manufacturing permitted to discharge wastewater in 2001; the data reflect internal audits conducted during the years 1999-2001. Empirical results reveal differences in auditing behavior based on whether facilities are owned by publicly held or non-publicly held firms, owned by U.S.-based or non-U.S.-based firms, and owned by larger or smaller firms., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

There has been limited application of sapflow technology to small-stemmed species and across co-existing functional types, restricting its use in diverse floras such as the Mediterranean-type shrubland in South Africa. Our main objective was to test whether sapflow may provide an alternative to traditional gas-exchange measurements, which would permit comparative evaluation of transpiration at a previously unattained temporal resolution. We tested miniature external heat ratio method (HRM) sapflow gauges on three co-occurring functional types with contrasting stem or culm anatomies and examined the relationship between sapflow and shoot- and leaf-level water loss in both a controlled and field environment. Our sapflow gauges captured dynamic patterns of transpiration in both settings for all three functional types. In a controlled environment the relationship between sapflow and transpiration was linear in all three species with r2 values ranging from 0.78 for Cannomois congesta Mast. (Restionaceae) to 0.96 for Protea repens (L.) L. (Proteaceae) and Erica monsoniana L.f. (Ericaceae). In the field, r2 values were lower, ranging from 0.59 for C. congesta to 0.74 for P. repens. We discuss the efficacy and potential of this methodology to cast light on patterns of community ecology in functionally diverse shrublands by capturing continuous variation in transpiration.

Lysine acetylation is an important posttranslational modification that regulates microtubules and microfilaments, but its effects on intermediate filament proteins (IFs) are unknown. We investigated the regulation of keratin 8 (K8), a type II simple epithelial IF, by lysine acetylation. K8 was basally acetylated and the highly conserved Lys-207 was a major acetylation site. K8 acetylation regulated filament organization and decreased keratin solubility. Acetylation of K8 was rapidly responsive to changes in glucose levels and was up-regulated in response to nicotinamide adenine dinucleotide (NAD) depletion and in diabetic mouse and human livers. The NAD-dependent deacetylase sirtuin 2 (SIRT2) associated with and deacetylated K8. Pharmacologic or genetic inhibition of SIRT2 decreased K8 solubility and affected filament organization. Inhibition of K8 Lys-207 acetylation resulted in site-specific phosphorylation changes of K8. Therefore, K8 acetylation at Lys-207, a highly conserved residue among type II keratins and other IFs, is up-regulated upon hyperglycemia and down-regulated by SIRT2. Keratin acetylation provides a new mechanism to regulate keratin filaments, possibly via modulating keratin phosphorylation.

Pseudohypoaldosteronism type 1 (PHA-1) is a rare salt-wasting syndrome caused by a peripheral resistance to aldosterone. Here, we describe an unusual presentation of the autosomal dominant PHA-1 featuring bilateral pneumothoraces at birth, thrombocytosis in infancy, and hypercalcemia in addition to the well-described findings of hyponatremia, hyperkalemia, and failure to thrive. These findings contribute to the limited case descriptions of PHA-1 and may suggest additional diagnostic considerations in a neonate presenting with hyperkalemia, hyponatremia, and failure to thrive.

Kernel hardness or texture, used to classify wheat (Triticum aestivum L.) into soft and hard classes, is a major determinant of milling and baking quality. Wheat genotypes in the soft class that are termed 'extra-soft' (with kernel hardness in the lower end of the spectrum) have been associated with superior end-use quality. In order to better understand the relationship between kernel hardness, milling yield, and various agronomic traits, we performed quantitative trait mapping using a recombinant inbred line population derived from a cross between a common soft wheat line and a genotype classified as an 'extra-soft' line. A total of 47 significant quantitative trait loci (QTL) (LOD ≥ 3.0) were identified for nine traits with the number of QTL affecting each trait ranging from three to nine. The percentage of phenotypic variance explained by these QTL ranged from 3.7 to 50.3%. Six QTL associated with kernel hardness and break flour yield were detected on chromosomes 1BS, 4BS, 5BS, 2DS, 4DS, and 5DL. The two most important QTL were mapped onto orthologous regions on chromosomes 4DS (Xbarc1118-Rht-D1) and 4BS (Xwmc617-Rht-B1). These results indicated that the 'extra-soft' characteristic was not controlled by the Hardness (Ha) locus on chromosome 5DS. QTL for eight agronomic traits occupied two genomic regions near semi-dwarf genes Rht-D1 on chromosome 4DS and Rht-B1 on chromosome 4BS. The clustering of these QTL is either due to the pleiotropic effects of single genes or tight linkage of genes controlling these various traits.

Physical mapping and genome sequencing are underway for the ≈17 Gb wheat genome. Physical mapping methods independent of meiotic recombination, such as radiation hybrid (RH) mapping, will aid precise anchoring of BAC contigs in the large regions of suppressed recombination in Triticeae genomes. Reports of endosperm development following pollination with irradiated pollen at dosages that cause embryo abortion prompted us to investigate endosperm as a potential source of RH mapping germplasm. Here, we report a novel approach to construct RH based physical maps of all seven D-genome chromosomes of the hexaploid wheat 'Chinese Spring', simultaneously. An 81-member subset of endosperm samples derived from 20-Gy irradiated pollen was genotyped for deletions, and 737 markers were mapped on seven D-genome chromosomes. Analysis of well-defined regions of six chromosomes suggested a map resolution of ∼830 kb could be achieved; this estimate was validated with assays of markers from a sequenced contig. We estimate that the panel contains ∼6,000 deletion bins for D-genome chromosomes and will require ∼18,000 markers for high resolution mapping. Map-based deletion estimates revealed a majority of 1-20 Mb interstitial deletions suggesting mutagenic repair of double-strand breaks in pollen provides a useful resource for RH mapping and map based cloning studies.

Genetic factors impact liver injury susceptibility and disease progression. Prominent histological features of some chronic human liver diseases are hepatocyte ballooning and Mallory-Denk bodies. In mice, these features are induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) in a strain-dependent manner, with the C57BL and C3H strains showing high and low susceptibility, respectively. To identify modifiers of DDC-induced liver injury, we compared C57BL and C3H mice using proteomic, biochemical, and cell biological tools. DDC elevated reactive oxygen species (ROS) and oxidative stress enzymes preferentially in C57BL livers and isolated hepatocytes. C57BL livers and hepatocytes also manifested significant down-regulation, aggregation, and nuclear translocation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH). GAPDH knockdown depleted bioenergetic and antioxidant enzymes and elevated hepatocyte ROS, whereas GAPDH overexpression decreased hepatocyte ROS. On the other hand, C3H livers had higher expression and activity of the energy-generating nucleoside-diphosphate kinase (NDPK), and knockdown of hepatocyte NDPK augmented DDC-induced ROS formation. Consistent with these findings, cirrhotic, but not normal, human livers contained GAPDH aggregates and NDPK complexes. We propose that GAPDH and NDPK are genetic modifiers of murine DDC-induced liver injury and potentially human liver disease.