Evaluation of Lateral Radar Positioning for Vital Sign Monitoring: An Empirical Study.

Vital sign monitoring is dominated by precise but costly contact-based sensors. Contactless devices such as radars provide a promising alternative. In this article, the effects of lateral radar positions on breathing and heartbeat extraction are evaluated based on a sleep study. A lateral radar position is a radar placement from which multiple human body zones are mapped onto different radar range sections. These body zones can be used to extract breathing and heartbeat motions independently from one another via these different range sections. Radars were positioned above the bed as a conventional approach and on a bedside table as well as at the foot end of the bed as lateral positions. These positions were evaluated based on six nights of sleep collected from healthy volunteers with polysomnography (PSG) as a reference system. For breathing extraction, comparable results were observed for all three radar positions. For heartbeat extraction, a higher level of agreement between the radar foot end position and the PSG was found. An example of the distinction between thoracic and abdominal breathing using a lateral radar position is shown. Lateral radar positions could lead to a more detailed analysis of movements along the body, with the potential for diagnostic applications.

Transfer Learning for Automatic Sleep Staging Using a Pre-Gelled Electrode Grid.

Novel sensor solutions for sleep monitoring at home could alleviate bottlenecks in sleep medical care as well as enable selective or continuous observation over long periods of time and contribute to new insights in sleep medicine and beyond. Since especially in the latter case the sensor data differ strongly in signal, number and extent of sensors from the classical polysomnography (PSG) sensor technology, an automatic evaluation is essential for the application. However, the training of an automatic algorithm is complicated by the fact that the development phase of the new sensor technology, extensive comparative measurements with standardized reference systems, is often not possible and therefore only small datasets are available. In order to circumvent high system-specific training data requirements, we employ pre-training on large datasets with finetuning on small datasets of new sensor technology to enable automatic sleep phase detection for small test series. By pre-training on publicly available PSG datasets and finetuning on 12 nights recorded with new sensor technology based on a pre-gelled electrode grid to capture electroencephalography (EEG), electrooculography (EOG) and electromyography (EMG), an F1 score across all sleep phases of 0.81 is achieved (wake 0.84, N1 0.62, N2 0.81, N3 0.87, REM 0.88), using only EEG and EOG. The analysis additionally considers the spatial distribution of the channels and an approach to approximate classical electrode positions based on specific linear combinations of the new sensor grid channels.

Nondental Invasive Procedures and Risk of Infective Endocarditis: Time for a Revisit: A Science Advisory From the American Heart Association.

There have been no published prospective randomized clinical trials that have: (1) established an association between invasive dental and nondental invasive procedures and risk of infective endocarditis; or (2) defined the efficacy and safety of antibiotic prophylaxis administered in the setting of invasive procedures in the prevention of infective endocarditis in high-risk patients. Moreover, previous observational studies that examined the association of nondental invasive procedures with the risk of infective endocarditis have been limited by inadequate sample size. They have typically focused on a few potential at-risk surgical and nonsurgical invasive procedures. However, recent investigations from Sweden and England that used nationwide databases and demonstrated an association between nondental invasive procedures, and the subsequent development of infective endocarditis (in particular, in high-risk patients with infective endocarditis) prompted the development of the current science advisory.

PHARMACOKINETICS OF MELOXICAM AFTER SINGLE ORAL AND INTRAMUSCULAR ADMINISTRATION IN CHINA ROCKFISH (SEBASTES NEBULOSUS).

Fish species are important for various purposes including aquaculture stock and display animals, but there are significant gaps in the medical knowledge regarding pharmacological parameters and effective pain management. Meloxicam is a nonsteroidal anti-inflammatory drug (NSAID) that has been studied in few teleost species and with several administration routes. However, these species were typically freshwater or euryhaline fish, and evaluation in marine species is lacking. The pharmacokinetic properties of meloxicam were determined in nine adult China rockfish (Sebastes nebulosus), presumed healthy based on physical examination and benign medical histories. Based on a pilot study, China rockfish were given 1 mg/kg meloxicam via IM injection in the epaxial musculature, and, after a 48-h washout period, 1 mg/kg meloxicam was given by PO gavage. Blood samples were collected from the caudal vein at baseline and at nine time intervals over a 48-h time period following administration of meloxicam. Plasma meloxicam concentrations were determined by reverse phase high-performance liquid chromatography, and noncompartmental analysis was performed. The mean peak plasma concentration after IM injection was 4.9 µg/ml, and the mean terminal half-life was 5.0 h. The mean peak plasma concentration after PO administration was 0.07 µg/ml. Based on these findings, IM injected meloxicam reaches plasma levels consistent with therapeutic concentrations in select mammals, and peak levels were maintained for ≤12 h. Single-dose PO administration failed to achieve similar concentrations, and clinical practicality is unknown. Further studies evaluating NSAID multidose regimes and their pharmacodynamic effects may provide additional dosing information.

The Eyes Have It-for Idiopathic Pulmonary Fibrosis: a Preliminary Observation.

INTRODUCTION: The disease origins of idiopathic pulmonary fibrosis (IPF), which occurs at higher rates in certain races/ethnicities, are not understood. The highest rates occur in white persons of European descent, particularly those with light skin, who are also susceptible to lysosomal organelle dysfunction of the skin leading to fibroproliferative disease . We had observed clinically that the vast majority of patients with IPF had light-colored eyes, suggesting a phenotypic characteristic. METHODS: We pursued this observation through a research database from the USA Veterans Administration, a population that has a high occurrence of IPF due to predominance of elderly male smokers. Using this medical records database, which included facial photos, we compared the frequency of light (blue, green, hazel) and dark (light brown, brown) eyes among white patients diagnosed with IPF compared with a control group of lung granuloma only (no other radiologic evidence of interstitial lung disease). RESULTS: Light eye color was significantly more prevalent in patients with IPF than in the control group with lung granuloma [114/147 (77.6%) versus 129/263 (49.0%], p < 0.001), indicating that light-colored eyes are a phenotype associated with IPF . CONCLUSION: We provide evidence that light eye color is predominant among white persons with IPF.

Pre-gelled Electrode Grid for Self-Applied EEG Sleep Monitoring at Home.

The need for diagnostic capabilities for sleep disorders such as sleep apnea and insomnia far exceeds the capacity of inpatient sleep laboratories. Some home monitoring systems omit electroencephalography (EEG) because trained personnel may be needed to apply EEG sensors. Since EEG is essential for the detailed evaluation of sleep, better systems supporting the convenient and robust recording of sleep EEG at home are desirable. Recent advances in EEG acquisition with flex-printed sensors promise easier application of EEG sensor arrays for chronic recordings, yet these sensor arrays were not designed for sleep EEG. Here we explored the self-applicability of a new sleep EEG sensor array (trEEGrid) without prior training. We developed a prototype with pre-gelled neonatal ECG electrodes placed on a self-adhesive grid shape that guided the fast and correct positioning of a total of nine electrodes on the face and around the ear. Positioning of the sensors was based on the results of a previous ear-EEG sleep study (da Silva Souto et al., 2021), and included electrodes around the ear, one eye, and the chin. For comparison, EEG and electrooculogram channels placed according to the American Academy of Sleep Medicine criteria, as well as respiratory inductance plethysmography on thorax and abdomen, oxygen saturation, pulse and body position were included with a mobile polysomnography (PSG) system. Two studies with 32 individuals were conducted to compare the signal quality of the proposed flex-printed grid with PSG signals and to explore self-application of the new grid at home. Results indicate that the new array is self-applicable by healthy participants without on-site hands-on support. A comparison of the hypnogram annotations obtained from the data of both systems revealed an overall substantial agreement on a group level (Cohen's κ = 0.70 ± 0.01). These results suggest that flex-printed pre-gelled sensor arrays designed for sleep EEG acquisition can facilitate self-recording at home.

RETROSPECTIVE MORTALITY REVIEW OF TUFTED PUFFINS (FRATERCULA CIRRHATA) AT A SINGLE INSTITUTION (1982-2017).

Tufted puffins (Fratercula cirrhata) are commonly exhibited in zoologic institutions across the world, yet there is a paucity of information on causes of mortality in managed populations. This retrospective review reports the pathologic findings associated with 91 tufted puffins at a single institution over 35 years from 1982 to 2017. Common pathologic findings were evaluated by age at death, sex, year, and season. With the exception of neonates, the leading pathologic finding across all age classes was aspergillosis, particularly in adults. Hemoparasitism, predation, and trauma were also frequent causes of mortality. Neonatal mortality was common and primarily caused by omphalitis, yolk sac disease, and bacterial septicemia, with most cultures revealing Escherichia coli. This study also provides documentation of mortality in tufted puffins secondary to avian pox and suspected toxoplasmosis. Understanding morbidity and mortality trends within a population allows institutions to form management plans and implement practices to improve outcomes and survival.

Nuclear respiratory factor-1 negatively regulates TGF-ß1 and attenuates pulmonary fibrosis.

The preclinical model of bleomycin-induced lung fibrosis is useful to study mechanisms related to human pulmonary fibrosis. Using BLM in mice, we find low HO-1 expression. Although a unique Rhenium-CO-releasing molecule (ReCORM) up-regulates HO-1, NRF-1, CCN5, and SMAD7, it reduces TGFß1, TGFßr1, collagen, α-SMA, and phosphorylated Smad2/3 levels in mouse lung and in human lung fibroblasts. ChIP assay studies confirm NRF-1 binding to the promoters of TGFß1 repressors CCN5 and Smad7. ReCORM did not blunt lung fibrosis in Hmox1-deficient alveolar type 2 cell knockout mice, suggesting this gene participates in lung protection. In human lung fibroblasts, TGFß1-dependent production of α-SMA is abolished by ReCORM or by NRF-1 gene transfection. We demonstrate effective HO-1/NRF-1 signaling in lung AT2 cells protects against BLM induced lung injury and fibrosis by maintaining mitochondrial health, function, and suppressing the TGFß1 pathway. Thus, protection of AT2 cell mitochondrial integrity via HO-1/NRF-1 presents an innovative therapeutic target.

Flex-Printed Ear-EEG Sensors for Adequate Sleep Staging at Home.

A comfortable, discrete and robust recording of the sleep EEG signal at home is a desirable goal but has been difficult to achieve. We investigate how well flex-printed electrodes are suitable for sleep monitoring tasks in a smartphone-based home environment. The cEEGrid ear-EEG sensor has already been tested in the laboratory for measuring night sleep. Here, 10 participants slept at home and were equipped with a cEEGrid and a portable amplifier (mBrainTrain, Serbia). In addition, the EEG of Fpz, EOG_L and EOG_R was recorded. All signals were recorded wirelessly with a smartphone. On average, each participant provided data for M = 7.48 h. An expert sleep scorer created hypnograms and annotated grapho-elements according to AASM based on the EEG of Fpz, EOG_L and EOG_R twice, which served as the baseline agreement for further comparisons. The expert scorer also created hypnograms using bipolar channels based on combinations of cEEGrid channels only, and bipolar cEEGrid channels complemented by EOG channels. A comparison of the hypnograms based on frontal electrodes with the ones based on cEEGrid electrodes (κ = 0.67) and the ones based on cEEGrid complemented by EOG channels (κ = 0.75) both showed a substantial agreement, with the combination including EOG channels showing a significantly better outcome than the one without (p = 0.006). Moreover, signal excerpts of the conventional channels containing grapho-elements were correlated with those of the cEEGrid in order to determine the cEEGrid channel combination that optimally represents the annotated grapho-elements. The results show that the grapho-elements were well-represented by the front-facing electrode combinations. The correlation analysis of the grapho-elements resulted in an average correlation coefficient of 0.65 for the most suitable electrode configuration of the cEEGrid. The results confirm that sleep stages can be identified with electrodes placement around the ear. This opens up opportunities for miniaturized ear-EEG systems that may be self-applied by users.

Heparin-based blood purification attenuates organ injury in baboons with Streptococcus pneumoniae pneumonia.

Bacterial pneumonia is a major cause of morbidity and mortality worldwide despite the use of antibiotics, and novel therapies are urgently needed. Building on previous work, we aimed to 1) develop a baboon model of severe pneumococcal pneumonia and sepsis with organ dysfunction and 2) test the safety and efficacy of a novel extracorporeal blood filter to remove proinflammatory molecules and improve organ function. After a dose-finding pilot study, 12 animals were inoculated with Streptococcus pneumoniae [5 × 109 colony-forming units (CFU)], given ceftriaxone at 24 h after inoculation, and randomized to extracorporeal blood purification using a filter coated with surface-immobilized heparin sulfate (n = 6) or sham treatment (n = 6) for 4 h at 30 h after inoculation. For safety analysis, four uninfected animals also underwent purification. At 48 h, necropsy was performed. Inoculated animals developed severe pneumonia and septic shock. Compared with sham-treated animals, septic animals treated with purification displayed significantly less kidney injury, metabolic acidosis, hypoglycemia, and shock (P < 0.05). Purification blocked the rise in peripheral blood S. pneumoniae DNA, attenuated bronchoalveolar lavage (BAL) CCL4, CCL2, and IL-18 levels, and reduced renal oxidative injury and classical NLRP3 inflammasome activation. Purification was safe in both uninfected and infected animals and produced no adverse effects. We demonstrate that heparin-based blood purification significantly attenuates levels of circulating S. pneumoniae DNA and BAL cytokines and is renal protective in baboons with severe pneumococcal pneumonia and septic shock. Purification was associated with less severe acute kidney injury, metabolic derangements, and shock. These results support future clinical studies in critically ill septic patients.

An Evaluation of Motion Trackers with Virtual Reality Sensor Technology in Comparison to a Marker-Based Motion Capture System Based on Joint Angles for Ergonomic Risk Assessment.

The reproduction and simulation of workplaces, and the analysis of body postures during work processes, are parts of ergonomic risk assessments. A commercial virtual reality (VR) system offers the possibility to model complex work scenarios as virtual mock-ups and to evaluate their ergonomic designs by analyzing motion behavior while performing work processes. In this study a VR tracking sensor system (HTC Vive tracker) combined with an inverse kinematic model (Final IK) was compared with a marker-based optical motion capture system (Qualisys). Marker-based optical motion capture systems are considered the gold standard for motion analysis. Therefore, Qualisys was used as the ground truth in this study. The research question to be answered was how accurately the HTC Vive System combined with Final IK can measure joint angles used for ergonomic evaluation. Twenty-six subjects were observed simultaneously with both tracking systems while performing 20 defined movements. Sixteen joint angles were analyzed. Joint angle deviations between ±6∘ and ±42∘ were identified. These high deviations must be considered in ergonomic risk assessments when using a VR system. The results show that commercial low-budget tracking systems have the potential to map joint angles. Nevertheless, substantial weaknesses and inaccuracies in some body regions must be taken into account. Recommendations are provided to improve tracking accuracy and avoid systematic errors.

Fatal Meningoencephalitis From a Rhizomucor pusillus Infection in a Juvenile Magellanic Penguin (Spheniscus magellanicus).

A 7-month-old, male Magellanic penguin (Spheniscus magellanicus), housed in an outdoor exhibit, developed acute neurologic signs that progressed to death over 2 days. On gross examination, the bird had congested, edematous lungs, and cerebellar hemorrhage. Histologic examination identified granulomatous pneumonia and encephalitis, with thrombosis and eosinophilic, branching fungal hyphae that had invaded the meningeal vessel walls. Polymerase chain reaction identified the fungus in the brain as Rhizomucor pusillus, an uncommon cause of mucormycosis. This organism has previously been reported in respiratory, skeletal, and sino-orbital lesions of avian species. This clinical report describes meningoencephalitis associated with Rhizomucor pusillus in a penguin.

Interstitial lung disease in a veterans affairs regional network; a retrospective cohort study.

BACKGROUND: The epidemiology of Interstitial Lung Diseases (ILD) in the Veterans Health Administration (VHA) is presently unknown. RESEARCH QUESTION: Describe the incidence/prevalence, clinical characteristics, and outcomes of ILD patients within the Veteran's Administration Mid-Atlantic Health Care Network (VISN6). STUDY DESIGN AND METHODS: A multi-center retrospective cohort study was performed of veterans receiving hospital or outpatient ILD care from January 1, 2008 to December 31st, 2015 in six VISN6 facilities. Patients were identified by at least one visit encounter with a 515, 516, or other ILD ICD-9 code. Demographic and clinical characteristics were summarized using median, 25th and 75th percentile for continuous variables and count/percentage for categorical variables. Characteristics and incidence/prevalence rates were summarized, and stratified by ILD ICD-9 code. Kaplan Meier curves were generated to define overall survival. RESULTS: 3293 subjects met the inclusion criteria. 879 subjects (26%) had no evidence of ILD following manual medical record review. Overall estimated prevalence in verified ILD subjects was 256 per 100,000 people with a mean incidence across the years of 70 per 100,000 person-years (0.07%). The prevalence and mean incidence when focusing on people with an ILD diagnostic code who had a HRCT scan or a bronchoscopic or surgical lung biopsy was 237 per 100,000 people (0.237%) and 63 per 100,000 person-years respectively (0.063%). The median survival was 76.9 months for 515 codes, 103.4 months for 516 codes, and 83.6 months for 516.31. INTERPRETATION: This retrospective cohort study defines high ILD incidence/prevalence within the VA. Therefore, ILD is an important VA health concern.

IL-10 and class 1 histone deacetylases act synergistically and independently on the secretion of proinflammatory mediators in alveolar macrophages.

INTRODUCTION: Anti-inflammatory cytokine IL-10 suppresses pro-inflammatory IL-12b expression after Lipopolysaccharide (LPS) stimulation in colonic macrophages, as part of the innate immunity Toll-Like Receptor (TLR)-NF-κB activation system. This homeostatic mechanism limits excess inflammation in the intestinal mucosa, as it constantly interacts with the gut flora. This effect is reversed with Histone Deacetylase 3 (HDAC3), a class I HDAC, siRNA, suggesting it is mediated through HDAC3. Given alveolar macrophages' prominent role in Acute Lung Injury (ALI), we aim to determine whether a similar regulatory mechanism exists in the typically sterile pulmonary microenvironment. METHODS: Levels of mRNA and protein for IL-10, and IL-12b were determined by qPCR and ELISA/Western Blot respectively in naïve and LPS-stimulated alveolar macrophages. Expression of the NF-κB intermediaries was also similarly assessed. Experiments were repeated with AS101 (an IL-10 protein synthesis inhibitor), MS-275 (a selective class 1 HDAC inhibitor), or both. RESULTS: LPS stimulation upregulated all proinflammatory mediators assayed in this study. In the presence of LPS, inhibition of IL-10 and/or class 1 HDACs resulted in both synergistic and independent effects on these signaling molecules. Quantitative reverse-transcriptase PCR on key components of the TLR4 signaling cascade demonstrated significant diversity in IL-10 and related gene expression in the presence of LPS. Inhibition of IL-10 secretion and/or class 1 HDACs in the presence of LPS independently affected the transcription of MyD88, IRAK1, Rela and the NF-κB p50 subunit. Interestingly, by quantitative ELISA inhibition of IL-10 secretion and/or class 1 HDACs in the presence of LPS independently affected the secretion of not only IL-10, IL-12b, and TNFα, but also proinflammatory mediators CXCL2, IL-6, and MIF. These results suggest that IL-10 and class 1 HDAC activity regulate both independent and synergistic mechanisms of proinflammatory cytokine/chemokine signaling. CONCLUSIONS: Alveolar macrophages after inflammatory stimulation upregulate both IL-10 and IL-12b production, in a highly class 1 HDAC-dependent manner. Class 1 HDACs appear to help maintain the balance between the pro- and anti-inflammatory IL-12b and IL-10 respectively. Class 1 HDACs may be considered as targets for the macrophage-initiated pulmonary inflammation in ALI in a preclinical setting.

MORTALITY TRENDS FOR BUDGERIGARS (MELOPSITTACUS UNDULATUS) HOUSED IN A WALK-THROUGH AVIARY IN A ZOO IN NORTH AMERICA, 2009-2019.

Many zoos in North America feature walk-through exhibits that allow members of the public to interact with psittacine species, as these exhibits are popular with guests and can generate additional revenue. There is limited research available on the life expectancy and common causes of mortality of psittacines when group-housed in aviaries. This study compiled data on 496 budgerigar (Melopsittacus undulatus) mortalities at a walk-through aviary at a North American zoo from March 2009 to March 2019, including histopathology on 62 tissue sets collected post mortem, and gross necropsy data for 163 birds deceased from March 2015 to March 2019. The mean age at death or euthanasia of all fledged birds from 2015 to 2019 was 3.57 ± 1.58 yr. The most common causes of death or euthanasia found on gross necropsy were granulomatous disease (39.2%), trauma (16.0%), and Macrorhabdus ornithogaster (13.5%). The most common histologic finding was M. ornithogaster, described as the primary pathologic finding in 31.7% of submitted tissue sets, and recorded as a secondary pathologic finding in 53.2% of submitted tissue sets. Mycobacterial disease was the primary pathologic finding in 25.3% of submitted tissue sets, and was recorded as an additional pathologic finding in 35.4% of submitted tissue sets.

Peripheral Blood Mononuclear Cells Demonstrate Mitochondrial Damage Clearance During Sepsis.

OBJECTIVES: Metabolic derangements in sepsis stem from mitochondrial injury and contribute significantly to organ failure and mortality; however, little is known about mitochondrial recovery in human sepsis. We sought to test markers of mitochondrial injury and recovery (mitochondrial biogenesis) noninvasively in peripheral blood mononuclear cells from patients with sepsis and correlate serial measurements with clinical outcomes. DESIGN: Prospective case-control study. SETTING: Academic Medical Center and Veterans Affairs Hospital. PATIENTS: Uninfected control patients (n = 20) and septic ICU patients (n = 37). INTERVENTIONS: Blood samples were collected once from control patients and serially with clinical data on days 1, 3, and 5 from septic patients. Gene products for HMOX1, NRF1, PPARGC1A, and TFAM, and mitochondrial DNA ND1 and D-loop were measured by quantitative reverse transcriptase-polymerase chain reaction. Proinflammatory cytokines were measured in plasma and neutrophil lysates. MEASUREMENTS AND MAIN RESULTS: Median (interquartile range) Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores were 21 (8) and 10 (4), respectively, and 90-day mortality was 19%. Transcript levels of all four genes in peripheral blood mononuclear cells were significantly reduced in septic patients on day 1 (p < 0.05), whereas mitochondrial DNA copy number fell and plasma D-loop increased (both p < 0.05), indicative of mitochondrial damage. D-loop content was directly proportional to tumor necrosis factor-α and high-mobility group protein B1 cytokine expression. By day 5, we observed transcriptional activation of mitochondrial biogenesis and restoration of mitochondrial DNA copy number (p < 0.05). Patients with early activation of mitochondrial biogenesis were ICU-free by 1 week. CONCLUSIONS: Our findings support data that sepsis-induced mitochondrial damage is reversed by activation of mitochondrial biogenesis and that gene transcripts measured noninvasively in peripheral blood mononuclear cells can serve as novel biomarkers of sepsis recovery.

Nonhuman primate species as models of human bacterial sepsis.

Sepsis involves a disordered host response to systemic infection leading to high morbidity and mortality. Despite intense research, targeted sepsis therapies beyond antibiotics have remained elusive. The cornerstone of sepsis research is the development of animal models to mimic human bacterial infections and test novel pharmacologic targets. Nonhuman primates (NHPs) have served as an attractive, but expensive, animal to model human bacterial infections due to their nearly identical cardiopulmonary anatomy and physiology, as well as host response to infection. Several NHP species have provided substantial insight into sepsis-mediated inflammation, endothelial dysfunction, acute lung injury, and multi-organ failure. The use of NHPs has usually focused on translating therapies from early preclinical models to human clinical trials. However, despite successful sepsis interventions in NHP models, there are still no FDA-approved sepsis therapies. This review highlights major NHP models of bacterial sepsis and their relevance to clinical medicine.

A phase I trial of low-dose inhaled carbon monoxide in sepsis-induced ARDS.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a prevalent disease with significant mortality for which no effective pharmacologic therapy exists. Low-dose inhaled carbon monoxide (iCO) confers cytoprotection in preclinical models of sepsis and ARDS. METHODS: We conducted a phase I dose escalation trial to assess feasibility and safety of low-dose iCO administration in patients with sepsis-induced ARDS. Twelve participants were randomized to iCO or placebo air 2:1 in two cohorts. Four subjects each were administered iCO (100 ppm in cohort 1 or 200 ppm in cohort 2) or placebo for 90 minutes for up to 5 consecutive days. Primary outcomes included the incidence of carboxyhemoglobin (COHb) level ≥10%, prespecified administration-associated adverse events (AEs), and severe adverse events (SAEs). Secondary endpoints included the accuracy of the Coburn-Forster-Kane (CFK) equation to predict COHb levels, biomarker levels, and clinical outcomes. RESULTS: No participants exceeded a COHb level of 10%, and there were no administration-associated AEs or study-related SAEs. CO-treated participants had a significant increase in COHb (3.48% ± 0.7% [cohort 1]; 4.9% ± 0.28% [cohort 2]) compared with placebo-treated subjects (1.97% ± 0.39%). The CFK equation was highly accurate at predicting COHb levels, particularly in cohort 2 (R2 = 0.9205; P < 0.0001). Circulating mitochondrial DNA levels were reduced in iCO-treated participants compared with placebo-treated subjects. CONCLUSION: Precise administration of low-dose iCO is feasible, well-tolerated, and appears to be safe in patients with sepsis-induced ARDS. Excellent agreement between predicted and observed COHb should ensure that COHb levels remain in the target range during future efficacy trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT02425579. FUNDING: NIH grants P01HL108801, KL2TR002385, K08HL130557, and K08GM102695.

Gastric dilatation and enterotoxemia in ten captive felids.

CASE DESCRIPTION 10 large felids at 8 facilities were determined or suspected to have developed gastric dilatation with or without enterotoxemia over a 20-year period. Four felids were found dead with no premonitory signs. CLINICAL FINDINGS 4 felids (2 male snow leopards [Uncia uncia], 1 male Amur tiger [Panthera tigris altaica], and 1 male Sumatran tiger [Panthera tigris sumatrae]) were found dead or died before they could be evaluated. Six felids had hematemesis (1 male and 1 female African lion [Panthera leo] and 1 male jaguar [Panthera onca]) or abdominal distention and signs of lethargy with or without vomiting (1 male African lion, 1 male Malayan tiger [Panthera tigris jacksoni], and 1 female Sumatran tiger). Gastric dilatation was radiographically and surgically confirmed in the male Malayan and female Sumatran tigers and the jaguar. TREATMENT AND OUTCOME In 3 felids with an antemortem diagnosis, the gastric dilatation resolved with decompressive laparotomy but then recurred in 1 felid, which subsequently died. Three others died at various points during hospitalization. Although Clostridium perfringens type A was recovered from 3 of the 5 felids for which microbial culture was performed, and 2 felids had a recent increase in the amount fed, no single factor was definitively identified that might have incited or contributed to the gastric dilatation. CLINICAL RELEVANCE Gastric dilatation was a life-threatening condition in the large felids of this report, causing sudden death or clinical signs of hematemesis, abdominal distention, or vomiting. Even with rapid diagnosis and surgical decompression, the prognosis was poor. Research is needed into the factors that contribute to this emergent condition in large felids so that preventive measures might be taken.

Ultrasonographic characteristics of the reproductive tract and serum progesterone and estradiol concentrations in captive female red wolves (Canis rufus) with and without reproductive tract disease.

OBJECTIVE To describe ultrasonographic characteristics of the reproductive tract and serum progesterone and estradiol concentrations in captive female red wolves (Canis rufus) with and without reproductive tract disease. DESIGN Prospective study. ANIMALS 13 adult female red wolves. PROCEDURES Wolves with varying parity and history of contraceptive treatment were anesthetized to facilitate ultrasonographic examination and measurement of the reproductive tract and blood collection for determination of serum progesterone and estradiol concentrations in December 2011 and June 2012. Additionally, during the December evaluation, fine-needle aspirate samples of the uterus were obtained for cytologic evaluation. Measurements were compared between wolves with and without reproductive tract disease and between wolves that had and had not received a contraceptive. RESULTS 7 of 13 wolves had or developed reproductive tract disease during the study. Ranges for measurements of reproductive tract structures overlapped between ultrasonographically normal and abnormal tracts, but measurements for abnormal tracts were generally greater than those for normal tracts. The ultrasonographic diagnosis was consistent with the histologic diagnosis for reproductive tracts obtained from wolves that were sterilized, were euthanized, or died during the study. Cytologic results for fine-needle aspirate samples of the uterus and serum progesterone and estradiol concentrations were unable to distinguish wolves with and without reproductive tract disease. Reproductive tract disease was not associated with parity or contraceptive administration. CONCLUSIONS AND CLINICAL RELEVANCE The ultrasonographic images, reproductive tract measurements, and descriptions of reproductive tract lesions provided in this study can be used as diagnostic guidelines for the treatment and management of red wolves with reproductive tract disease.