Publications by authors named "Juan P Hernandez"

Few studies have analyzed the role of the lung microbiome in the diagnosis of pulmonary coinfection in ventilated ICU COVID-19 patients. We characterized the lung microbiota in COVID-19 patients with severe pneumonia on invasive mechanical ventilation using full-length 16S rRNA gene sequencing and established its relationship with coinfections, mortality, and the need for mechanical ventilation for more than 7 days. This study included 67 COVID-19 ICU patients.

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Detection and epidemiologic characterization of infectious disease outbreaks are key for early identification and response to potential pandemic threats. The rapid global spread of severe SARS-CoV-2 in 2020 highlighted the critical role of diagnostics in understanding the epidemiology of the virus early in the pandemic. As a natural extension of Abbott's work in diagnostics, virus discovery, and virus surveillance, the Abbott Pandemic Defense Coalition (APDC) was launched in early 2021.

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Arrhythmogenic cardiomyopathy (ACM) encompasses a group of inherited cardiomyopathies including arrhythmogenic right ventricular cardiomyopathy (ARVC) whose molecular disease mechanism is associated with dysregulation of the canonical WNT signalling pathway. Recent evidence indicates that ARVC and ACM caused by pathogenic variants in the FLNC gene encoding filamin C, a major cardiac structural protein, may have different molecular mechanisms of pathogenesis. We sought to identify dysregulated biological pathways in FLNC-associated ACM.

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Background: Pathogenic variants in the filamin C (FLNC) gene are associated with inherited cardiomyopathies including dilated cardiomyopathy with an arrhythmogenic phenotype. We evaluated FLNC variants in arrhythmogenic cardiomyopathy (ACM) and investigated the disease mechanism at a molecular level.

Methods: 120 gene-elusive ACM patients who fulfilled diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC) were screened by whole exome sequencing.

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Targeted mutant models are common in mechanistic toxicology experiments investigating the absorption, metabolism, distribution, or elimination (ADME) of chemicals from individuals. Key models include those for xenosensing transcription factors and cytochrome P450s (CYP). Here we investigated changes in transcript levels, protein expression, and steroid hydroxylation of several xenobiotic detoxifying CYPs in constitutive androstane receptor (CAR)-null and two CYP-null mouse models that have subfamily members regulated by CAR; the Cyp3a-null and a newly described Cyp2b9/10/13-null mouse model.

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Article Synopsis
  • 2'-3-dimethyl-4-aminoazobenzene (OAT) is an azo dye identified as a potential human carcinogen by IARC, but its mechanism of action is not well understood.
  • Research indicates that OAT activates the Constitutive Androstane Receptor (CAR) in mice, leading to an increase in the expression of several CAR target genes in a dose-dependent manner.
  • CAR plays a crucial role in mediating the effects of OAT, as mice lacking CAR did not show the same gene expression changes, and while OAT did not immediately induce liver cell proliferation, it later caused a CAR-dependent proliferative response.
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Nonylphenol (NP), a by-product of alkylphenol ethoxylates, is a pervasive surfactant that activates the xenosensing nuclear receptor, the pregnane X-receptor (PXR) in transactivation assays in vitro. We are interested in determining if NP activates PXR in vivo, determining if hPXR and mPXR act similarly, and investigating the role of PXR in protecting individuals from NP. Wild-type (WT), PXR-null, and humanized PXR (hPXR) mice were treated with NP at 0, 50 or 75mg/kg/day for one week, and cytochrome P450 (CYP) induction, liver histopathology, and serum NP concentrations were examined.

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Constitutive androstane receptor [corrected](CAR) is activated by several chemicals and in turn regulates multiple detoxification genes. Our research demonstrates that parathion is one of the most potent, environmentally relevant CAR activators with an EC(50) of 1.43 microM.

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The aim of this study was to determine the effect of diet supplemented with Saccharomyces cerevisiae (SC), on the liver morphology, serum activities of aspartateaminotrasferase (AST) and alanineaminotransferase (ALT), and the serum concentration of total proteins, albumin and the different fractions (alpha, beta, gamma) of globulin in chickens. Two groups of Hubbar x Hubbar strain chickens (each = 16), were fed with a diet T1 (commercial food without SC) and T2 (commercial food with SC) for 42 days. Thereafter, animals were sacrificed and samples of blood and liver were obtained.

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Nonylphenol (NP) and its parent compounds, the nonylphenol ethoxylates are some of the most prevalent chemicals found in U.S. waterways.

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Nonylphenol (NP) is a breakdown product of nonylphenol ethoxylates, which are used in a variety of industrial, agricultural, household cleaning, and beauty products. NP is one of the most commonly found toxicants in the United States and Europe and is considered a toxicant of concern because of its long half-life. NP is an environmental estrogen that also activates the pregnane X-receptor (PXR) and in turn induces P450s.

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Background: Early interaction of dengue virus and monocyte/macrophages could be an important feature for virus dissemination after its initial entry via the mosquito vector. Since ultrastructural analysis of this interaction has not been reported, dengue type 2 (DEN2) virus-infected human monocyte cultures were studied at 1, 2, 4 and 6 hours after infection.

Results: Typical dengue particles and fuzzy coated viral particles were 35 to 42 nm and 74 to 85 nm respectively.

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