10 research outputs found

    Subclinical infection of macaques and baboons with a baboon simarterivirus

    Get PDF
    Simarteriviruses (Arteriviridae: Simarterivirinae) are commonly found at high titers in the blood of African monkeys but do not cause overt disease in these hosts. In contrast, simarteriviruses cause severe disease in Asian macaques upon accidental or experimental transmission. Here, we sought to better understand the host-dependent drivers of simarterivirus pathogenesis by infecting olive baboons (n = 4) and rhesus monkeys (n = 4) with the simarterivirus Southwest baboon virus 1 (SWBV-1). Surprisingly, none of the animals in our study showed signs of disease following SWBV-1 inoculation. Three animals (two rhesus monkeys and one olive baboon) became infected and sustained high levels of SWBV-1 viremia for the duration of the study. The course of SWBV-1 infection was highly predictable: plasma viremia peaked between 1 × 107 and 1 × 108 vRNA copies/mL at 3–10 days post-inoculation, which was followed by a relative nadir and then establishment of a stable set-point between 1 × 106 and 1 × 107 vRNA copies/mL for the remainder of the study (56 days). We characterized cellular and antibody responses to SWBV-1 infection in these animals, demonstrating that macaques and baboons mount similar responses to SWBV-1 infection, yet these responses are ineffective at clearing SWBV-1 infection. SWBV-1 sequencing revealed the accumulation of non-synonymous mutations in a region of the genome that corresponds to an immunodominant epitope in the simarterivirus major envelope glycoprotein GP5, which likely contribute to viral persistence by enabling escape from host antibodies

    Association of exhaled carbon monoxide with subclinical cardiovascular disease and their conjoint impact on the incidence of cardiovascular outcomes

    No full text
    AIMS: Whereas endogenous carbon monoxide (CO) is cytoprotective at physiologic levels, excess CO concentrations are associated with cardiometabolic risk and may represent an important marker of progression from subclinical to clinical cardiovascular disease (CVD). METHODS AND RESULTS: In 1926 participants of the Framingham Offspring Study (aged 57 +/- 10 years, 46% women), we investigated the relationship of exhaled CO, a surrogate of blood CO concentration, with both prevalent subclinical CVD and incident clinical CVD events. Presence of subclinical CVD was determined using a comprehensive panel of diagnostic tests used to assess cardiac and vascular structure and function. Individuals with the highest ( \u3e 5 p.p.m.) compared with lowest ( \u3c /=4 p.p.m.) CO exposure were more likely to have subclinical CVD [odds ratios (OR): 1.67, 95% CI: 1.32-2.12; P \u3c 0.001]. During the follow-up period (mean 5 +/- 3 years), 193 individuals developed overt CVD. Individuals with both high CO levels and any baseline subclinical CVD developed overt CVD at an almost four-fold higher rate compared with those with low CO levels and no subclinical disease (22.1 vs. 6.3%). Notably, elevated CO was associated with incident CVD in the presence [hazards ration (HR): 1.83, 95% CI: 1.08-3.11; P = 0.026] but not in the absence (HR: 0.80, 95% CI: 0.42-1.53; P = 0.51) of subclinical CVD (P interaction = 0.019). Similarly, subclinical CVD was associated with incident CVD in the presence of high but not low CO exposure. CONCLUSION: Our findings in a community-based sample suggest that elevated CO is a marker of greater subclinical CVD burden and, furthermore, a potential key component in the progression from subclinical to clinical CVD

    Prehospital Point of Care Testing for the Early Detection of Shock and Prediction of Lifesaving Interventions

    No full text
    INTRODUCTION: Early diagnosis and treatment are essential for enhancing outcomes for the traumatically injured. In this prospective prehospital observational study, we hypothesized that a variety of laboratory results measured in the prehospital environment would predict both the presence of early shock and the need for lifesaving interventions (LSIs) for adult patients with traumatic injuries. METHODS: Adult trauma patients flown by a helicopter emergency medical service were prospectively enrolled. Using an i-STAT portable analyzer, data from 16 laboratory tests were collected. Vital signs data were also collected. Outcomes of interest included detection of shock, mortality, and requirement for LSIs. Logistic regression, including a Bayesian analysis, was performed. RESULTS: Among 300 patients screened for enrollment, 261 had complete laboratory data for analysis. The majority of patients were male (75%) with blunt trauma (91.2%). The median injury severity score was 29 (IQR, 25-75) and overall mortality was 4.6%. A total of 170 LSIs were performed. The median lactate for patients who required an LSI was 4.1 (IQR, 3-5.4). The odds of requiring an LSI within the first hour of admission to the trauma center was highly associated with increases in lactate and glucose. A lactate level \u3e 4 mmol/L was statistically associated with greater sensitivity and specificity for predicting the need for a LSI compared with shock index. CONCLUSIONS: In this prospective observational trial, lactate outperformed static vital signs, including shock index, for detecting shock and predicting the need for LSIs. A lactate level \u3e 4 mmol/L was found to be highly associated with the need for LSIs

    mRNA Coronavirus Disease 2019 Vaccine-Associated Myopericarditis in Adolescents: A Survey Study

    No full text
    In this survey study of institutions across the US, marked variability in evaluation, treatment, and follow-up of adolescents 12 through 18 years of age with mRNA coronavirus disease 2019 (COVID-19) vaccine-associated myopericarditis was noted. Only one adolescent with life-threatening complications was reported, with no deaths at any of the participating institutions

    Incidence Rates of Childhood Asthma with Recurrent Exacerbations in the U.S. Environmental influences on Child Health Outcomes (ECHO) Program

    No full text
    BACKGROUND: Descriptive epidemiological data on incidence rates (IRs) of asthma with recurrent exacerbations (ARE) are sparse. OBJECTIVE: We hypothesized that IRs for ARE would vary by time, geography, age, race and ethnicity, irrespective of parental asthma history. METHODS: We leveraged data from 17246 children born after 1990 enrolled in 59 U.S. and one Puerto Rican cohort in the Environmental Influences on Child Health Outcomes consortium to estimate IRs for AREs. RESULTS: The overall crude IR for ARE was 6.07/1000 person-years (95% confidence intervals (CI) 5.63, 6.51) and was highest for children age 2-4 years, for Hispanic and non-Hispanic Black children and for those with a parental history of asthma. ARE IRs were higher for 2-4 year olds in each race and ethnicity category and for both sexes. Multi-variable analysis confirmed higher adjusted ARE IRs (aIRR) for children born 2000-2009 compared to 1990-1999 and 2010-2017, 2-4 versus 10-19 years old (aIRR=15.36; CI 12.09, 2.99), and for males versus females (aIRR=1.34; CI 1.16, 1.55). Black children (non-Hispanic and Hispanic) had higher rates than non-Hispanic White children (aIRR=2.51; CI 2.10, 2.99 and aIRR=2.04; CI 1.22, 3.39, respectively). Children born in the Midwest, Northeast and South had higher rates than the West (p\u3c0.01 for each comparison). Children with a parental history of asthma had rates nearly three times higher than those without such history (aIRR=2.90; CI 2.43-3.46). CONCLUSIONS: Factors associated with time, geography, age, race and ethnicity, sex and parental history appear to influence the inception of ARE among children and adolescents

    mRNA Coronavirus-19 Vaccine-Associated Myopericarditis in Adolescents: A Survey Study

    No full text
    In this survey study of institutions across the US, marked variability in evaluation, treatment, and follow-up of adolescents 12 through 18 years of age with mRNA coronavirus disease 2019 (COVID-19) vaccine-associated myopericarditis was noted. Only one adolescent with life-threatening complications was reported, with no deaths at any of the participating institutions
    corecore