Diet-enhanced LRG1 expression promotes insulin hypersecretion and ER stress in pancreatic beta cells.

Aims/hypothesis: Upregulation of serum leucine-rich α-2-glycoprotein 1 (LRG1) has been implicated in diet-induced obesity and metabolic disorders. However, its specific hormonal actions remain unclear. This study aimed to determine whether diet-enhanced serum LRG1 levels promote hyperinsulinaemia by directly stimulating insulin secretion from pancreatic beta cells.

Evaluation of Inhaled Nitric Oxide Generation Systems at Altitude.

Introduction: Inhaled nitric oxide (INO) is a selective pulmonary vasodilator delivered from compressed gas cylinders filled to 2,200 psig (137.8 bar) with 800 ppm of NO in a balance of nitrogen. NO is currently FDA-approved for use in term or near-term infants with hypoxemia and signs of pulmonary hypertension in the absence of cardiac disease.

Need for Blood Transfusion Volume Is Associated With Increased Mortality in Severe Traumatic Brain Injury.

Introduction: Many patients suffering from isolated severe traumatic brain injury (sTBI) receive blood transfusion on hospital arrival due to hypotension. We hypothesized that increasing blood transfusions in isolated sTBI patients would be associated with an increase in mortality.

Methods: We performed a trauma quality improvement program (TQIP) (2017-2019) and single-center (2013-2021) database review filtering for patients with isolated sTBI (Abbreviated Injury Scale head ≥3 and all other areas ≤2).

Evaluation of a Rebreathing System for Use with Portable Mechanical Ventilators.

Introduction: Maximizing the capabilities of available lowflow oxygen is key to providing adequate oxygen to prevent/treat hypoxemia and conserve oxygen. We designed a closed-circuit system that allows rebreathing of gases while scrubbing carbon dioxide (CO2) in conjunction with portable mechanical ventilators in a bench model.

Methods: We evaluated the system using two portable mechanical ventilators currently deployed by the Department of Defense-Zoll 731 and AutoMedx SAVe II-over a range of ventilator settings and lung models, using 1 and 3L/min low-flow oxygen into a reservoir bag.

Identifying and Reducing Insulin Errors in the Simulated Military Critical Care Air Transport Environment: A Human Factors Approach.

Introduction: During high-fidelity simulations in the Critical Care Air Transport (CCAT) Advanced course, we identified a high frequency of insulin medication errors and sought strategies to reduce them using a human factors approach.

Materials And Methods: Of 169 eligible CCAT simulations, 22 were randomly selected for retrospective audio-video review to establish a baseline frequency of insulin medication errors. Using the Human Factors Analysis Classification System, dosing errors, defined as a physician ordering an inappropriate dose, were categorized as decision-based; administration errors, defined as a clinician preparing and administering a dose different than ordered, were categorized as skill-based.

Re-evaluating the Use of High Sensitivity Troponin to Diagnose Blunt Cardiac Injury.

Introduction: Blunt cardiac injury (BCI) can be challenging diagnostically, and if misdiagnosed, can lead to life-threatening complications. Our institution previously evaluated BCI screening with troponin and electrocardiogram (EKG) during a transition from troponin I to high sensitivity troponin (hsTnI), a more sensitive troponin I assay. The previous study found an hsTnI of 76 ng/L had the highest capability of accurately diagnosing a clinically significant BCI.

Systemic Inflammatory Effect of Hypobaria During Aeromedical Evacuation after Porcine Traumatic Brain Injury.

Background: Traumatic brain injury (TBI)-related morbidity is caused largely by secondary injury resulting from hypoxia, excessive sympathetic drive, and uncontrolled inflammation. Aeromedical evacuation (AE) is used by the military for transport of wounded soldiers to higher levels of care. We hypothesized that the hypobaric, hypoxic conditions of AE may exacerbate uncontrolled inflammation after TBI that could contribute to more severe TBI-related secondary injury.

Just Say NO: Inhaled Nitric Oxide Effect on Respiratory Parameters Following Traumatic Brain Injury in Humans and a Porcine Model.

Introduction: The mechanism of post-traumatic brain injury (TBI) hypoxemia involves ventilation/perfusion mismatch and loss of pulmonary hypoxic vasoconstriction. Inhaled nitric oxide (iNO) has been studied as an adjunct treatment to avoid the use of high positive end-expiratory pressure and inspired oxygen in treatment-refractory hypoxia. We hypothesized that iNO treatment following TBI would improve systemic and cerebral oxygenation via improved matching of pulmonary perfusion and ventilation.

Validation of Preload Assessment Technologies at Altitude in a Porcine Model of Hemorrhage.

Introduction: Dynamic preload assessment measures including pulse pressure variation (PPV), stroke volume variation (SVV), pleth variability index (PVI), and hypotension prediction index (HPI) have been utilized clinically to guide fluid management decisions in critically ill patients. These values aid in the balance of correcting hypotension while avoiding over-resuscitation leading to respiratory failure and increased mortality. However, these measures have not been previously validated at altitude or in those with temporary abdominal closure (TAC).

Predictive Value of Early Inflammatory Markers in Trauma Patients Based on Transfusion Status.

Introduction: Seven key inflammatory biomarkers were recently found to be associated with the risk of mortality in a multicenter study of massively transfused patients. The aim of this prospective single-center study was to determine which of these early inflammatory markers could predict 30-d mortality among all critically injured trauma patients.

Methods: Serum samples were collected at 6, 24, and 72 h from 238 consecutive patients admitted to the intensive care unit following traumatic injury.

The Ability of Military Critical Care Air Transport Members to Visually Estimate Percent Systolic Pressure Variation.

Introduction: Inappropriate fluid management during patient transport may lead to casualty morbidity. Percent systolic pressure variation (%SPV) is one of several technologies that perform a dynamic assessment of fluid responsiveness (FT-DYN). Trained anesthesia providers can visually estimate and use %SPV to limit the incidence of erroneous volume management decisions to 1-4%.

LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing monoclonal antibodies (mAbs) can reduce the risk of hospitalization from coronavirus disease 2019 (COVID-19) when administered early. However, SARS-CoV-2 variants of concern (VOCs) have negatively affected therapeutic use of some authorized mAbs. Using a high-throughput B cell screening pipeline, we isolated LY-CoV1404 (bebtelovimab), a highly potent SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody.

Change in country-level COVID-19 lethality is associated with improved testing: no apparent role of medical care or disease-specific knowledge.

Aim: Reductions in the case fatality rate of COVID-19 in the unvaccinated have been credited to improvements in medical care. Here I test whether either of these factors predicts reductions in the case fatality rate, and whether observed reductions are better explicable by improved ascertainment of mild cases.

Methods: Using weighted log-log regression, I compute the association between changes in the case fatality rate and test density between 3 July 2020 and 5 January 2021 in 162 countries; and check whether case fatality rate change is associated with either per capita medical spending (proxy for critical care access) or timing of the pandemic (proxy for COVID-specific knowledge).

Estimating total morbidity burden of COVID-19: relative importance of death and disability.

Objective: Calculations of disease burden of COVID-19, used to allocate scarce resources, have historically considered only mortality. However, survivors often develop postinfectious 'long-COVID' similar to chronic fatigue syndrome; physical sequelae such as heart damage, or both. This paper quantifies relative contributions of acute case fatality, delayed case fatality, and disability to total morbidity per COVID-19 case.

Cardioprotective effects of resistance training add to those of total activity in Americans.

Background: Resistance training is cardioprotective independent of total activity in experimental research and is prescribed to clinical populations, but is often largely neglected at population scale. Here we determine whether these benefits are relevant to general practice.

Methods: A total of 6947 Americans over 20 years old (51% male) from NHANES 2003-2006 reported resistance training and objectively tracked 1-week total activity.

LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants.

Unlabelled: SARS-CoV-2 neutralizing monoclonal antibodies (mAbs) can reduce the risk of hospitalization when administered early during COVID-19 disease. However, the emergence of variants of concern has negatively impacted the therapeutic use of some authorized mAbs. Using a high throughput B-cell screening pipeline, we isolated a highly potent SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody called LY-CoV1404 (also known as bebtelovimab).

Role of Ascertainment Bias in Determining Case Fatality Rate of COVID-19.

Case fatality rate (CFR) is used to calculate mortality burden of COVID-19 under different scenarios, thus informing risk-benefit balance of interventions both pharmaceutical and nonpharmaceutical. However, observed CFR is driven by testing: as more low-risk cases are identified, observed CFR will decline. This report quantifies test bias by modeling observed CFR as log-log-linear function of test density (tests per population) in 163 countries.

The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a public health threat for which preventive and therapeutic agents are urgently needed. Neutralizing antibodies are a key class of therapeutics that may bridge widespread vaccination campaigns and offer a treatment solution in populations less responsive to vaccination. Here, we report that high-throughput microfluidic screening of antigen-specific B cells led to the identification of LY-CoV555 (also known as bamlanivimab), a potent anti-spike neutralizing antibody from a hospitalized, convalescent patient with coronavirus disease 2019 (COVID-19).

Self-estimated BMI, but not self-perceived body size, accurately identifies unhealthy weight in US adults.

Background: Self-perceptions of health and disease can be a major driver of health behaviors. Improving accuracy of self-ascertainment of obesity may prompt uptake of weight-control behaviors in those with obesity.

Methods: We assess performance of self-perceived body size ('too small', 'about right' or 'too large'), self-estimated BMI in kg/m, and sociodemographics in detecting measured BMI category (under-, normal-, overweight and obese; BMI cutpoints 18.

LY-CoV555, a rapidly isolated potent neutralizing antibody, provides protection in a non-human primate model of SARS-CoV-2 infection.

Unlabelled: SARS-CoV-2 poses a public health threat for which therapeutic agents are urgently needed. Herein, we report that high-throughput microfluidic screening of antigen-specific B-cells led to the identification of LY-CoV555, a potent anti-spike neutralizing antibody from a convalescent COVID-19 patient. Biochemical, structural, and functional characterization revealed high-affinity binding to the receptor-binding domain, ACE2 binding inhibition, and potent neutralizing activity.

Phylogenetic relationships and diversity of bat-associated Leptospira and the histopathological evaluation of these infections in bats from Grenada, West Indies.

Bats can harbor zoonotic pathogens, but their status as reservoir hosts for Leptospira bacteria is unclear. During 2015-2017, kidneys from 47 of 173 bats captured in Grenada, West Indies, tested PCR-positive for Leptospira. Sequence analysis of the Leptospira rpoB gene from 31 of the positive samples showed 87-91% similarity to known Leptospira species.

Clonal Decomposition and DNA Replication States Defined by Scaled Single-Cell Genome Sequencing.

Accurate measurement of clonal genotypes, mutational processes, and replication states from individual tumor-cell genomes will facilitate improved understanding of tumor evolution. We have developed DLP+, a scalable single-cell whole-genome sequencing platform implemented using commodity instruments, image-based object recognition, and open source computational methods. Using DLP+, we have generated a resource of 51,926 single-cell genomes and matched cell images from diverse cell types including cell lines, xenografts, and diagnostic samples with limited material.

Better lung function with increased handgrip strength, as well as maximum oxygen uptake, in congenital heart disease across the lifespan.

Background: The respiratory benefits of muscle strength are well-known in heart-healthy populations, but recommendations and research often focus instead on aerobic fitness (peak oxygen uptake) or total activity. Independent benefits of strength thus may be underestimated, especially in congenital heart disease where perceived dangers of certain types of exercise may outweigh perceived benefits. To assess whether it is plausible that pulmonary benefits of strength in heart-healthy populations also apply in congenital heart disease, we simultaneously correlated these patients' lung function with fitness, strength, and cardiac diagnosis.

Uni- and triaxial accelerometric signals agree during daily routine, but show differences between sports.

Accelerometers objectively monitor physical activity, and ongoing research suggests they can also detect patterns of body movement. However, different types of signal (uniaxial, captured by older studies, vs. the newer triaxial) and or/device (validated Actigraph used by older studies, vs.