Showing papers by "United States Department of the Army published in 2020"

Broad neutralization of SARS-related viruses by human monoclonal antibodies.

Abstract: Broadly protective vaccines against known and preemergent human coronaviruses (HCoVs) are urgently needed. To gain a deeper understanding of cross-neutralizing antibody responses, we mined the memory B cell repertoire of a convalescent severe acute respiratory syndrome (SARS) donor and identified 200 SARS coronavirus 2 (SARS-CoV-2) binding antibodies that target multiple conserved sites on the spike (S) protein. A large proportion of the non-neutralizing antibodies display high levels of somatic hypermutation and cross-react with circulating HCoVs, suggesting recall of preexisting memory B cells elicited by prior HCoV infections. Several antibodies potently cross-neutralize SARS-CoV, SARS-CoV-2, and the bat SARS-like virus WIV1 by blocking receptor attachment and inducing S1 shedding. These antibodies represent promising candidates for therapeutic intervention and reveal a target for the rational design of pan-sarbecovirus vaccines.

Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2.

Abstract: The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds angiotensin-converting enzyme 2 (ACE2) on host cells to initiate entry, and soluble ACE2 is a therapeutic candidate that neutralizes infection by acting as a decoy. By using deep mutagenesis, mutations in ACE2 that increase S binding are found across the interaction surface, in the asparagine 90-glycosylation motif and at buried sites. The mutational landscape provides a blueprint for understanding the specificity of the interaction between ACE2 and S and for engineering high-affinity decoy receptors. Combining mutations gives ACE2 variants with affinities that rival those of monoclonal antibodies. A stable dimeric variant shows potent SARS-CoV-2 and -1 neutralization in vitro. The engineered receptor is catalytically active, and its close similarity with the native receptor may limit the potential for viral escape.

Understanding and managing connected extreme events

Abstract: Extreme weather and climate events and their impacts can occur in complex combinations, an interaction shaped by physical drivers and societal forces. In these situations, governance, markets and other decision-making structures—together with population exposure and vulnerability—create nonphysical interconnections among events by linking their impacts, to positive or negative effect. Various anthropogenic actions can also directly affect the severity of events, further complicating these feedback loops. Such relationships are rarely characterized or considered in physical-sciences-based research contexts. Here, we present a multidisciplinary argument for the concept of connected extreme events, and we suggest vantage points and approaches for producing climate information useful in guiding decisions about them. The impacts of extreme weather and climate can be amplified by physical interactions among events and across a complex set of societal factors. This Perspective discusses the concept and challenge of connected extreme events, exploring research approaches and decision-making strategies.

COVID-19: Facts, Cultural Considerations, and Risk of Stigmatization.

Abstract: Data on COVID-19 supports targeted social distancing could be an effective way to reduce morbidity and mortality, but could inadvertently increase stigma for affected populations. As health care providers we must be aware of the facts of COVID-19, cultural implications, and potential for stigmatization of populations affected by COVID-2019. It is important to consider the real economic impact related to lost workdays due to quarantine and social isolation efforts as well as travel restrictions that may negatively impact access to care and ability to pay for care. Efforts geared towards general education about the disease and the rationale for quarantine and public health information provided to the general public can reduce stigmatization. Countries who are successful at aggressive screening, early identification, patient isolation, contact tracing, quarantine, and infection control methods should also address the risk of stigmatization among populations and the negative effects which could occur. The cases of COVID-19 will continue to rise and the virus will be sustainable for future infections. Timely and appropriate public health interventions addressing cultural impact and risk for stigmatization along with proper screening, treatment, and follow up for affected individuals and close contacts can reduce the number of infections, serious illness, and deaths.

Association of Prehospital Plasma Transfusion With Survival in Trauma Patients With Hemorrhagic Shock When Transport Times Are Longer Than 20 Minutes: A Post Hoc Analysis of the PAMPer and COMBAT Clinical Trials.

Abstract: Importance Both military and civilian clinical practice guidelines include early plasma transfusion to achieve a plasma to red cell ratio approaching 1:1 to 1:2. However, it was not known how early plasma should be given for optimal benefit. Two recent randomized clinical trials were published, with apparently contradictory results. The Prehospital Air Medical Plasma (PAMPer) clinical trial showed a nearly 30% reduction in mortality with plasma transfusion in the prehospital environment, while the Control of Major Bleeding After Trauma (COMBAT) clinical trial showed no survival improvement. Objective To facilitate a post hoc combined analysis of the COMBAT and PAMPer trials to examine questions that could not be answered by either clinical trial alone. We hypothesized that prehospital transport time influenced the effects of prehospital plasma on 28-day mortality. Design, Setting, and Participants A total of 626 patients in the 2 clinical trials were included. Patients with trauma and hemorrhagic shock were randomly assigned to receive either standard care or 2 U of thawed plasma followed by standard care in the prehospital environment. Data analysis was performed between September 2018 and January 2019. Interventions Prehospital transfusion of 2 U of plasma compared with crystalloid-based resuscitation. Main Outcomes and Measures The main outcome was 28-day mortality. Results In this post hoc analysis of 626 patients (467 men [74.6%] and 159 women [25.4%]; median [interquartile range] age, 42 [27-57] years) who had trauma with hemorrhagic shock, a Cox regression analysis showed a significant overall survival benefit for plasma (hazard ratio [HR], 0.65; 95% CI, 0.47-0.90;P = .01) after adjustment for injury severity, age, and clinical trial cohort (COMBAT or PAMPer). A significant association with prehospital transport time was detected (from arrival on scene to arrival at the trauma center). Increased mortality was observed in patients in the standard care group when prehospital transport was longer than 20 minutes (HR, 2.12; 95% CI, 1.05-4.30;P = .04), while increased mortality was not observed in patients in the prehospital plasma group (HR, 0.78; 95% CI, 0.40-1.51;P = .46). No serious adverse events were associated with prehospital plasma transfusion. Conclusions and Relevance These data suggest that prehospital plasma is associated with a survival benefit when transport times are longer than 20 minutes and that the benefit-risk ratio is favorable for use of prehospital plasma. Trial Registration ClinicalTrials.gov identifiers:NCT01838863(COMBAT) andNCT01818427(PAMPer)

Spaceflight associated neuro-ocular syndrome (SANS) and the neuro-ophthalmologic effects of microgravity: a review and an update.

Abstract: Prolonged microgravity exposure during long-duration spaceflight (LDSF) produces unusual physiologic and pathologic neuro-ophthalmic findings in astronauts. These microgravity associated findings collectively define the “Spaceflight Associated Neuro-ocular Syndrome” (SANS). We compare and contrast prior published work on SANS by the National Aeronautics and Space Administration’s (NASA) Space Medicine Operations Division with retrospective and prospective studies from other research groups. In this manuscript, we update and review the clinical manifestations of SANS including: unilateral and bilateral optic disc edema, globe flattening, choroidal and retinal folds, hyperopic refractive error shifts, and focal areas of ischemic retina (i.e., cotton wool spots). We also discuss the knowledge gaps for in-flight and terrestrial human research including potential countermeasures for future study. We recommend that NASA and its research partners continue to study SANS in preparation for future longer duration manned space missions.

Isothermally crystallized perovskites at room-temperature

Abstract: The solution processability of photoactive halide perovskites differentiates them from traditional inorganic semiconducting materials that require multiple post-processing steps such as thermal/vacuum/blowing- and solvent-assisted treatment. Here we report a technical breakthrough of isothermally crystallizing high-quality perovskite films at room-temperature (RT) without the necessity of any post-processing. This process takes advantage of our discovery of a metastable intermediate of lower-dimensionality formed by amine-assisted crystallographic lattice expansion from an initial three-dimensional perovskite. Using in situ optoelectrical/chemical and ex situ structural characterizations, a detailed understanding of the low-dimensional metastable intermediate is developed. In conjunction with the metastable intermediate, the rapid evaporation of the solvent and amine facilitates ultra-fast crystallization at RT within seconds. This RT rapidly synthesized perovskite film exhibits a carrier diffusion length of 2.9 μm and {00} preferred orientation with an ultrahigh Lotgering factor of 97%. These films are highly compatible to conventional or inverted devices, demonstrating 22.3% and 23.1% power conversion efficiencies, respectively.

Recommendations from the CSO-HNS taskforce on performance of tracheotomy during the COVID-19 pandemic.

Abstract: The performance of tracheotomy is a common procedural request by critical care departments to the surgical services of general surgery, thoracic surgery and otolaryngology - head & neck surgery. A Canadian Society of Otolaryngology – Head & Neck Surgery (CSO-HNS) task force was convened with multi-specialty involvement from otolaryngology-head & neck surgery, general surgery, critical care and anesthesiology to develop a set of recommendations for the performance of tracheotomies during the COVID-19 pandemic. The tracheotomy procedure is highly aerosol generating and directly exposes the entire surgical team to the viral aerosol plume and secretions, thereby increasing the risk of transmission to healthcare providers. As such, we believe extended endotracheal intubation should be the standard of care for the entire duration of ventilation in the vast majority of patients. Pre-operative COVID-19 testing is highly recommended for any non-emergent procedure. The set of recommendations in this document highlight the importance of avoiding tracheotomy procedures in patients who are COVID-19 positive if at all possible. Recommendations for appropriate PPE and environment are made for COVID-19 positive, negative and unknown patients requiring consideration of tracheotomy. The safety of healthcare professionals who care for ill patients and who keep critical infrastructure operating is paramount.

Impact of Asparaginase Discontinuation on Outcome in Childhood Acute Lymphoblastic Leukemia: A Report From the Children’s Oncology Group

Abstract: PURPOSEAsparaginase (ASNase) is an important component of acute lymphoblastic leukemia (ALL) treatment, but is often discontinued because of toxicity. Erwinia chrysanthemi ASNase (Erwinia) substitu...

Convalescent Plasma Therapy for COVID-19: State of the Art.

Abstract: Convalescent plasma (CP) therapy has been used since the early 1900s to treat emerging infectious diseases; its efficacy was later associated with the evidence that polyclonal neutralizing antibodies can reduce the duration of viremia. Recent large outbreaks of viral diseases for which effective antivirals or vaccines are still lacking has renewed the interest in CP as a life-saving treatment. The ongoing COVID-19 pandemic has led to the scaling up of CP therapy to unprecedented levels. Compared with historical usage, pathogen reduction technologies have now added an extra layer of safety to the use of CP, and new manufacturing approaches are being explored. This review summarizes historical settings of application, with a focus on betacoronaviruses, and surveys current approaches for donor selection and CP collection, pooling technologies, pathogen inactivation systems, and banking of CP. We additionally list the ongoing registered clinical trials for CP throughout the world and discuss the trial results published thus far.

Musculoskeletal Injuries and United States Army Readiness Part I: Overview of Injuries and their Strategic Impact.

Abstract: Introduction Noncombat injuries ("injuries") greatly impact soldier health and United States (U.S.) Army readiness; they are the leading cause of outpatient medical encounters (more than two million annually) among active component (AC) soldiers. Noncombat musculoskeletal injuries ("MSKIs") may account for nearly 60% of soldiers' limited duty days and 65% of soldiers who cannot deploy for medical reasons. Injuries primarily affect readiness through increased limited duty days, decreased deployability rates, and increased medical separation rates. MSKIs are also responsible for exorbitant medical costs to the U.S. government, including service-connected disability compensation. A significant subset of soldiers develops chronic pain or long-term disability after injury; this may increase their risk for chronic disease or secondary health deficits potentially associated with MSKIs. The authors will review trends in U.S. Army MSKI rates, summarize MSKI readiness-related impacts, and highlight the importance of standardizing surveillance approaches, including injury definitions used in injury surveillance. Materials/methods This review summarizes current reports and U.S. Department of Defense internal policy documents. MSKIs are defined as musculoskeletal disorders resulting from mechanical energy transfer, including traumatic and overuse injuries, which may cause pain and/or limit function. This review focuses on various U.S. Army populations, based on setting, sex, and age; the review excludes combat or battle injuries. Results More than half of all AC soldiers sustained at least one injury (MSKI or non-MSKI) in 2017. Overuse injuries comprise at least 70% of all injuries among AC soldiers. Female soldiers are at greater risk for MSKI than men. Female soldiers' aerobic and muscular fitness performances are typically lower than men's performances, which could account for their higher injury rates. Older soldiers are at greater injury risk than younger soldiers. Soldiers in noncombat arms units tend to have higher incidences of reported MSKIs, more limited duty days, and higher rates of limited duty days for chronic MSKIs than soldiers in combat arms units. MSKIs account for 65% of medically nondeployable AC soldiers. At any time, 4% of AC soldiers cannot deploy because of MSKIs. Once deployed, nonbattle injuries accounted for approximately 30% of all medical evacuations, and were the largest category of soldier evacuations from both recent major combat theaters (Iraq and Afghanistan). More than 85% of service members medically evacuated for MSKIs failed to return to the theater. MSKIs factored into (1) nearly 70% of medical disability discharges across the Army from 2011 through 2016 and (2) more than 90% of disability discharges within enlisted soldiers' first year of service from 2010 to 2015. MSKI-related, service-connected (SC) disabilities account for 44% of all SC disabilities (more than any other body system) among compensated U.S. Global War on Terrorism veterans. Conclusions MSKIs significantly impact soldier health and U.S. Army readiness. MSKIs also figure prominently in medical disability discharges and long-term, service-connected disability costs. MSKI patterns and trends vary between trainees and soldiers in operational units and among military occupations and types of operational units. Coordinated injury surveillance efforts are needed to provide standardized metrics and accurately measure temporal changes in injury rates.

A review of transfusion- and trauma-induced hypocalcemia: Is it time to change the lethal triad to the lethal diamond?

Abstract: The understanding of trauma management and damage control resuscitation is constantly changing as new research becomes available. While poor outcomes in hemorrhagic shock have traditionally been attributed to the "lethal triad" of hypothermia, coagulopathy, and acidosis, research has suggested that hypocalcemia may also play an integrated part in this interaction. Studies have shown a prevalence of hypocalcemia in trauma patients, as well as greater mortality associated with severe hypocalcemia in trauma. Given that whole blood is becoming the fluid of choice in resuscitation and that the citrate used to preserve blood products can worsen existing hypocalcemia, prompt management of hypocalcemia becomes even more of a concern. For these reasons, the authors of this paper suggest hypocalcemia in trauma patients may be of greater importance than originally believed and propose creating the "lethal diamond" of trauma comprised of hypocalcemia, acidosis, coagulopathy, and hypothermia. It is hoped that this increased focus on hypocalcemia in trauma can lead to research regarding early administration of calcium with the hopes of improving trauma patient outcomes.Level of Evidence: Therapeutic/care management Level IV. Study Type: Review article.

Deployable CRISPR-Cas13a diagnostic tools to detect and report Ebola and Lassa virus cases in real-time.

Abstract: Recent outbreaks of viral hemorrhagic fevers (VHFs), including Ebola virus disease (EVD) and Lassa fever (LF), highlight the urgent need for sensitive, deployable tests to diagnose these devastating human diseases. Here we develop CRISPR-Cas13a-based (SHERLOCK) diagnostics targeting Ebola virus (EBOV) and Lassa virus (LASV), with both fluorescent and lateral flow readouts. We demonstrate on laboratory and clinical samples the sensitivity of these assays and the capacity of the SHERLOCK platform to handle virus-specific diagnostic challenges. We perform safety testing to demonstrate the efficacy of our HUDSON protocol in heat-inactivating VHF viruses before SHERLOCK testing, eliminating the need for an extraction. We develop a user-friendly protocol and mobile application (HandLens) to report results, facilitating SHERLOCK’s use in endemic regions. Finally, we successfully deploy our tests in Sierra Leone and Nigeria in response to recent outbreaks. Outbreaks of viral hemorrhagic fevers highlight the need for sensitive, field-deployable diagnostics. Here the authors present a CRISPR-based SHERLOCK platform with field protocol and mobile app for Ebola and Lassa fever outbreaks.

Protective Fabrics: Metal-Organic Framework Textiles for Rapid Photocatalytic Sulfur Mustard Simulant Detoxification

Abstract: Summary Metal-organic frameworks (MOFs) can catalyze toxic chemical decontamination, but new MOF materials and synthesis strategies are needed to improve performance, particularly in field-usable MOF-textile formats. This article reports for the first time the exceptional photocatalytic reactivity of Al-PMOF (Al-porphyrin-based MOF), composed of an earth-abundant metal-containing Al(OH)O4 cluster bridged by H2TCPP (5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin) chromophores, against the toxic sulfur mustard simulant 2-chloroethyl ethyl sulfide (CEES) under visible-light irradiation. Furthermore, Al-PMOF is strongly immobilized into polymeric fibers via well-controlled Al2O3 solid film conversion using dimethylformamide/water cosolvent. The approach enables a secure integration of conformal Al-PMOF films onto polymer fibers at a relatively low synthesis temperature (120°C). In addition, on a per-unit mass of MOF basis, the surface-bound Al-PMOF films enable extremely rapid CEES detoxification turnover frequency, up to 170 mol CEES mol chromophore − 1 min − 1 , more than 10-fold faster than the best MOF powders and 2-fold better than MOF films reported to date.

On the Design of Multi-Spectrally Constrained Constant Modulus Radar Signals

Abstract: This paper deals with the synthesis of constant modulus waveforms that optimize radar performance while satisfying multiple spectral compatibility constraints. For each shared band, a precise control is imposed on the injected interference energy. Furthermore, the compliance with amplifiers operating in saturation is ensured at the design stage where phase-only waveforms are considered. To tackle the resulting NP-hard optimization problem, an iterative procedure based on the coordinate descent method is introduced. The overall computational burden of the algorithm is linear with respect to the code length as well as the number of iterations and less then cubic with reference to the number of spectral constraints. Hence, some case studies are reported to highlight the effectiveness of the technique.

Structural Diversity of Zirconium Metal-Organic Frameworks and Effect on Adsorption of Toxic Chemicals.

Abstract: While linkers with various conformations pose challenges in the design and prediction of metal-organic framework (MOF) structures, they ultimately provide great opportunities for the discovery of novel structures thereby enriching structural diversity. Tetratopic carboxylate linkers, for example, have been widely used in the formation of Zr-based MOFs due to the ability to target diverse topologies, providing a promising platform to explore their mechanisms of formation. However, it remains a challenge to control the resulting structures when considering the complex assembly of linkers with unpredicted conformations and diverse Zr6 node connectivities. Herein, we systematically explore how solvents and modulators employed during synthesis influence the resulting topologies of Zr-MOFs, choosing H4TCPB-Br2 (1,4-dibromo-2,3,5,6-tetrakis(4-carboxyphenyl)benzene) as a representative tetratopic carboxylate linker. By modulating the reaction conditions, the conformations of the linker and the connectivities of the Zr6 node can be simultaneously tuned, resulting in four types of structures: a new topology (NU-500), she (NU-600), scu (NU-906), and csq (NU-1008). Importantly, we have synthesized the first 5-connected Zr6 node to date with the (4,4,4,5)-connected framework, NU-500. We subsequently performed detailed structural analyses to uncover the relationship between the structures and topologies of these MOFs and demonstrated the crucial role that the flexible linker played to access varied structures by different degrees of linker deformation. Due to a variety of pore structures ranging from micropores to hierarchical micropores and mesopores, the resulting MOFs show drastically different behaviors for the adsorption of n-hexane and dynamic adsorption of 2-chloroethyl ethyl sulfide (CEES) under dry and humid conditions.

Advanced Digital Health Technologies for COVID-19 and Future Emergencies.

Abstract: Background: Coronavirus disease 2019 (COVID-19) has led to a national health care emergency in the United States and exposed resource shortages, particularly of health care providers trained to pro...

Thread-based multiplexed sensor patch for real-time sweat monitoring

Abstract: Sensor platforms that exploit the fibrous textile threads as substrates offer great promise since they can be directly sewn, woven or stitched on to any clothing. They can also be placed directly in intimate contact with the skin. In this work, we present a thread-based sensing platform in the form of a multiplexed sensing patch for continuous simultaneous on-skin monitoring of sweat. The patch performs real-time, on-body measurements of important biomarkers present in sweat such as electrolytes (sodium and ammonium ions), metabolites (lactate) and acidity (pH). Flexible threads coated with conductive inks were used as sensing electrodes. Selective potentiometric detection of electrolytes and pH was made possible through ion-selective membrane deposition and pH-sensitive polyaniline coating on threads, respectively. An amperometric enzymatic sensing scheme with lactate oxidase was used for the detection of lactate. An array of the thread sensors is integrated onto a patch with connectivity to a miniaturized circuit module containing a potentiostat, microprocessor and wireless circuitry for wireless smartphone readout. Extensive in vitro validation and an in vivo human pilot study involving a maximal exertion test show the promise of this platform for real-time physiological monitoring of human performance/fitness under stress, as well as diagnostic monitoring through sweat analysis.

Generating Biologically Stable TNA Aptamers that Function with High Affinity and Thermal Stability.

Abstract: Aptamers are often prone to nuclease digestion, which limits their utility in many biomedical applications. Here we describe a xeno-nucleic acid system based on α-l-threofuranosyl nucleic acid (TNA) that is completely refractory to nuclease digestion. The use of an engineered TNA polymerase permitted the isolation of functional TNA aptamers that bind to HIV reverse transcriptase (HIV RT) with KD's of ∼0.4-4.0 nM. The aptamers were identified using a display strategy that provides a powerful genotype-phenotype linkage. The TNA aptamers remain active in the presence of nuclease and exhibit markedly higher thermal stability than monoclonal antibodies. The combined properties of biological stability, high binding affinity, and thermal stability make TNA aptamers a powerful system for the development of diagnostic and therapeutic agents.

Multi-omic biomarker identification and validation for diagnosing warzone-related post-traumatic stress disorder

Abstract: Post-traumatic stress disorder (PTSD) impacts many veterans and active duty soldiers, but diagnosis can be problematic due to biases in self-disclosure of symptoms, stigma within military populations, and limitations identifying those at risk. Prior studies suggest that PTSD may be a systemic illness, affecting not just the brain, but the entire body. Therefore, disease signals likely span multiple biological domains, including genes, proteins, cells, tissues, and organism-level physiological changes. Identification of these signals could aid in diagnostics, treatment decision-making, and risk evaluation. In the search for PTSD diagnostic biomarkers, we ascertained over one million molecular, cellular, physiological, and clinical features from three cohorts of male veterans. In a discovery cohort of 83 warzone-related PTSD cases and 82 warzone-exposed controls, we identified a set of 343 candidate biomarkers. These candidate biomarkers were selected from an integrated approach using (1) data-driven methods, including Support Vector Machine with Recursive Feature Elimination and other standard or published methodologies, and (2) hypothesis-driven approaches, using previous genetic studies for polygenic risk, or other PTSD-related literature. After reassessment of ~30% of these participants, we refined this set of markers from 343 to 28, based on their performance and ability to track changes in phenotype over time. The final diagnostic panel of 28 features was validated in an independent cohort (26 cases, 26 controls) with good performance (AUC = 0.80, 81% accuracy, 85% sensitivity, and 77% specificity). The identification and validation of this diverse diagnostic panel represents a powerful and novel approach to improve accuracy and reduce bias in diagnosing combat-related PTSD.

3D printed self-supporting elastomeric structures for multifunctional microfluidics.

Abstract: Microfluidic devices fabricated via soft lithography have demonstrated compelling applications such as lab-on-a-chip diagnostics, DNA microarrays, and cell-based assays. These technologies could be further developed by directly integrating microfluidics with electronic sensors and curvilinear substrates as well as improved automation for higher throughput. Current additive manufacturing methods, such as stereolithography and multi-jet printing, tend to contaminate substrates with uncured resins or supporting materials during printing. Here, we present a printing methodology based on precisely extruding viscoelastic inks into self-supporting microchannels and chambers without requiring sacrificial materials. We demonstrate that, in the submillimeter regime, the yield strength of the as-extruded silicone ink is sufficient to prevent creep within a certain angular range. Printing toolpaths are specifically designed to realize leakage-free connections between channels and chambers, T-shaped intersections, and overlapping channels. The self-supporting microfluidic structures enable the automatable fabrication of multifunctional devices, including multimaterial mixers, microfluidic-integrated sensors, automation components, and 3D microfluidics.

Effect of Stellate Ganglion Block Treatment on Posttraumatic Stress Disorder Symptoms: A Randomized Clinical Trial.

Abstract: Importance This is the first multisite, randomized clinical trial of stellate ganglion block (SGB) outcomes on posttraumatic stress disorder (PTSD) symptoms. Objective To determine whether paired SGB treatments at 0 and 2 weeks would result in improvement in mean Clinician-Administered PTSD Scale forDSM-5(CAPS-5) total symptom severity scores from baseline to 8 weeks. Design, Setting, and Participants This multisite, blinded, sham-procedure, randomized clinical trial used a 2:1 SGB:sham ratio and was conducted from May 2016 through March 2018 in 3 US Army Interdisciplinary Pain Management Centers. Only anesthesiologists performing the procedures and the procedure nurses were aware of the intervention (but not the participants or assessors); their interactions with the participants were scripted and limited to the 2 interventions. Active-duty service members on stable psychotropic medication dosages who had a PTSD Checklist–Civilian Version (PCL-C) score of 32 or more at screening were included. Key exclusion criteria included a prior SGB treatment, selected psychiatric disorders or substance use disorders, moderate or severe traumatic brain injury, or suicidal ideation in the prior 2 months. Interventions Paired right-sided SGB or sham procedures at weeks 0 and 2. Main Outcomes and Measures Improvement of 10 or more points on mean CAPS-5 total symptom severity scores from baseline to 8 weeks, adjusted for site and baseline total symptom severity scores (planned a priori). Results Of 190 screened individuals, 113 (59.5%; 100 male and 13 female participants; mean [SD] age, 37.3 [6.7] years) were eligible and randomized (74 to SGB and 39 to sham treatment), and 108 (95.6% of 113) completed the study. Baseline characteristics were similar in the SGB and sham treatment groups, with mean (SD) CAPS-5 scores of 37.6 (11.2) and 39.8 (14.4), respectively (on a scale of 0-80); 91 (80.0%) met CAPS-5 PTSD criteria. In an intent-to-treat analysis, adjusted mean total symptom severity score change was −12.6 points (95% CI, −15.5 to −9.7 points) for the group receiving SGB treatments, compared with −6.1 points (95% CI, −9.8 to −2.3 points) for those receiving sham treatment (P = .01). Conclusions and Relevance In this trial of active-duty service members with PTSD symptoms (at a clinical threshold and subthreshold), 2 SGB treatments 2 weeks apart were effective in reducing CAPS-5 total symptom severity scores over 8 weeks. The mild-moderate baseline level of PTSD symptom severity and short follow-up time limit the generalizability of these findings, but the study suggests that SGB merits further trials as a PTSD treatment adjunct. Trial Registration ClinicalTrials.gov identifier:NCT03077919

Ancestral Absence of Electron Transport Chains in Patescibacteria and DPANN.

Abstract: Recent discoveries suggest that the candidate superphyla Patescibacteria and DPANN constitute a large fraction of the phylogenetic diversity of Bacteria and Archaea Their small genomes and limited coding potential have been hypothesized to be ancestral adaptations to obligate symbiotic lifestyles To test this hypothesis, we performed cell-cell association, genomic, and phylogenetic analyses on 4,829 individual cells of Bacteria and Archaea from 46 globally distributed surface and subsurface field samples This confirmed the ubiquity and abundance of Patescibacteria and DPANN in subsurface environments, the small size of their genomes and cells, and the divergence of their gene content from other Bacteria and Archaea Our analyses suggest that most Patescibacteria and DPANN in the studied subsurface environments do not form specific physical associations with other microorganisms These data also suggest that their unusual genomic features and prevalent auxotrophies may be a result of ancestral, minimal cellular energy transduction mechanisms that lack respiration, thus relying solely on fermentation for energy conservation

Association of Long-Duration Spaceflight With Anterior and Posterior Ocular Structure Changes in Astronauts and Their Recovery.

Abstract: Importance During long-duration spaceflights, nearly all astronauts exhibit some change in ocular structure within the spectrum of spaceflight-associated neuro-ocular syndrome. Objective To quantitatively determine in a prospective study whether changes in ocular structures hypothesized to be associated with the development of spaceflight-associated neuro-ocular syndrome occur during 6-month missions on board the International Space Station (ISS). Design, Setting, and Participants The Ocular Health ISS Study of astronauts is a longitudinal prospective cohort study that uses objective quantitative imaging modalities. The present cohort study investigated the ocular structure of 11 astronauts before, during, and after a 6-month mission on board the ISS. Main Outcomes and Measures Changes in ocular structure (peripapillary edema, axial length, anterior chamber depth, and refraction) hypothesized to be associated with the development of spaceflight-associated neuro-ocular syndrome during 6-month missions on board the ISS were assessed. Statistical analyses were conducted from August 2018 to January 2019. Results Before launch, the 11 astronauts were a mean (SD) age of 45 (5) years, a mean (SD) height of 1.76 (0.05) m, and a mean (SD) weight of 75.3 (7.1) kg. Six astronauts did not have prior spaceflight experience, 3 had completed short-duration missions on board the Space Shuttle, and 2 had previous long-duration spaceflight missions on board the ISS. Their mean (SD) duration on board the ISS in the present study was 170 (19) days. Optic nerve head rim tissue and peripapillary choroidal thickness increased from preflight values during early spaceflight, with maximal change typically near the end of the mission (mean change in optic nerve head rim tissue thickness on flight day 150: 35.7 μm; 95% CI, 28.5-42.9 μm;P Conclusions and Relevance This study found that spaceflight-associated peripapillary optic disc edema and choroid thickening were observed bilaterally and occurred in both sexes. In addition, this study documented substantial peripapillary choroid thickening during spaceflight, which has never been reported in a prospective study cohort population and which may be a contributing factor in spaceflight-associated neuro-ocular syndrome. Data collection on spaceflight missions longer than 6 months will help determine whether the duration of the mission is associated with exacerbating these observed changes in ocular structure or visual function.