Publications by authors named "G E Hernandez"

1,114 Publications

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How can assessing hemodynamics help to assess volume status?

Intensive Care Med 2022 Aug 10. Epub 2022 Aug 10.

AP-HP, Service de médecine intensive-réanimation, Hôpital de Bicêtre, DMU 4 CORREVE, Inserm UMR S_999, FHU SEPSIS, CARMAS, Université Paris-Saclay, 78 rue du Général Leclerc, 94270, Le Kremlin-Bicêtre, France.

In critically ill patients, fluid infusion is aimed at increasing cardiac output and tissue perfusion. However, it may contribute to fluid overload which may be harmful. Thus, volume status, risks and potential efficacy of fluid administration and/or removal should be carefully evaluated, and monitoring techniques help for this purpose. Central venous pressure is a marker of right ventricular preload. Very low values indicate hypovolemia, while extremely high values suggest fluid harmfulness. The pulmonary artery catheter enables a comprehensive assessment of the hemodynamic profile and is particularly useful for indicating the risk of pulmonary oedema through the pulmonary artery occlusion pressure. Besides cardiac output and preload, transpulmonary thermodilution measures extravascular lung water, which reflects the extent of lung flooding and assesses the risk of fluid infusion. Echocardiography estimates the volume status through intravascular volumes and pressures. Finally, lung ultrasound estimates lung edema. Guided by these variables, the decision to infuse fluid should first consider specific triggers, such as signs of tissue hypoperfusion. Second, benefits and risks of fluid infusion should be weighted. Thereafter, fluid responsiveness should be assessed. Monitoring techniques help for this purpose, especially by providing real time and precise measurements of cardiac output. When decided, fluid resuscitation should be performed through fluid challenges, the effects of which should be assessed through critical endpoints including cardiac output. This comprehensive evaluation of the risk, benefits and efficacy of fluid infusion helps to individualize fluid management, which should be preferred over a fixed restrictive or liberal strategy.
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http://dx.doi.org/10.1007/s00134-022-06808-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9363272PMC
August 2022

The mechanism of RNA capping by SARS-CoV-2.

Nature 2022 Aug 9. Epub 2022 Aug 9.

Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

The SARS-CoV-2 RNA genome contains a 5'-cap that facilitates translation of viral proteins, protection from exonucleases and evasion of the host immune response. How this cap is made in SARS-CoV-2 is not completely understood. Here, we reconstitute the SARS-CoV-2 GpppA-RNA cap using virally encoded non-structural proteins (nsps). We show that the kinase-like NiRAN domain of nsp12 transfers RNA to the amino terminus of nsp9, forming a covalent RNA-protein intermediate (a process termed RNAylation). Subsequently, the NiRAN domain transfers RNA to GDP, forming the core cap structure GpppA-RNA. The nsp14 and nsp16 methyltransferases then add methyl groups to form functional cap structures. Structural analyses of the replication-transcription complex bound to nsp9 identified key interactions that mediate the capping reaction. Furthermore, we demonstrate in a reverse genetics system that the N-terminus of nsp9 and the kinase-like active site residues in the NiRAN domain are required for successful SARS-CoV-2 replication. Collectively, our results reveal an unconventional mechanism by which SARS-CoV-2 caps its RNA genome, thus exposing a new target in the development of antivirals to treat COVID-19.
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http://dx.doi.org/10.1038/s41586-022-05185-zDOI Listing
August 2022

Oral health status and dental care for individuals with visual impairment. A narrative review.

Spec Care Dentist 2022 Aug 8. Epub 2022 Aug 8.

Department of Dental Clinical Specialties, ORALMED Research Group, Complutense University, Madrid, Spain.

Visual impairment is a highly prevalent condition worldwide. Oral health care in this group of patients is not always adequate. This is due to the low awareness of the importance of oral health in this population group and the fact that these patients prioritize their general health over oral health. Therefore, caries and periodontal disease are frequent in this population group. Especially, periodontal status is worse in patients with acquired visual impairment compared to patients with congenital visual impairment. On the other hand, the proportion of treated caries in this group is very low. This may be due to the poorer access of this population to dental care, which is limited by physical, social, and information barriers. Dental phobia and the lack of dental professionals capable of treating this population group have been identified as one of the most important factors. Therefore, establishing oral hygiene routines that are adapted to individuals' skills and needs is essential to achieve good oral health and improve patient's quality of life. This narrative review also updates those dental treatment considerations, depending on each dental specialty, that can help improve patient satisfaction when they come to the dental office.
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http://dx.doi.org/10.1111/scd.12764DOI Listing
August 2022

Patient-Reported Reasons for Switching or Discontinuing Statin Therapy: A Mixed Methods Study Using Social Media.

Drug Saf 2022 Aug 7. Epub 2022 Aug 7.

Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Introduction: Statin discontinuation can have major negative health consequences. Studying the reasons for discontinuation can be challenging as traditional data collection methods have limitations. We propose an alternative approach using social media.

Methods: We used natural language processing and machine learning to extract mentions of discontinuation of statin therapy from an online health forum, WebMD ( http://www.webmd.com ). We then extracted data according to themes and identified key attributes of the people posting for themselves.

Results: We identified 2121 statin reviews that contained information on discontinuing at least one named statin. Sixty percent of people posting declared themselves as female and the most common age category was 55-64 years. Over half the people taking statins did so for < 6 months. By far the most common reason given (90%) was patient experience of adverse events, the most common of which were musculoskeletal and connective tissue disorders. The rank order of adverse events reported in WebMD was largely consistent with those reported to regulatory agencies in the US and UK. Data were available on age, sex, duration of statin use, and, in some instances, adverse event resolution and rechallenge. In some instances, details were presented on resolution of the adverse event and rechallenge.

Conclusion: Social media may provide data on the reasons for switching or discontinuation of a medication, as well as unique patient perspectives that may influence continuation of a medication. This information source may provide unique data for novel interventions to reduce medication discontinuation.
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http://dx.doi.org/10.1007/s40264-022-01212-0DOI Listing
August 2022

Fic-mediated AMPylation tempers the unfolded protein response during physiological stress.

Proc Natl Acad Sci U S A 2022 Aug 1;119(32):e2208317119. Epub 2022 Aug 1.

Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390.

The proper balance of synthesis, folding, modification, and degradation of proteins, also known as protein homeostasis, is vital to cellular health and function. The unfolded protein response (UPR) is activated when the mechanisms maintaining protein homeostasis in the endoplasmic reticulum become overwhelmed. However, prolonged or strong UPR responses can result in elevated inflammation and cellular damage. Previously, we discovered that the enzyme filamentation induced by cyclic-AMP (Fic) can modulate the UPR response via posttranslational modification of binding immunoglobulin protein (BiP) by AMPylation during homeostasis and deAMPylation during stress. Loss of in leads to vision defects and altered UPR activation in the fly eye. To investigate the importance of Fic-mediated AMPylation in a mammalian system, we generated a conditional null allele of in mice and characterized the effect of loss on the exocrine pancreas. Compared to controls, mice exhibit elevated serum markers for pancreatic dysfunction and display enhanced UPR signaling in the exocrine pancreas in response to physiological and pharmacological stress. In addition, both flies and mice show reduced capacity to recover from damage by stress that triggers the UPR. These findings show that Fic-mediated AMPylation acts as a molecular rheostat that is required to temper the UPR response in the mammalian pancreas during physiological stress. Based on these findings, we propose that repeated physiological stress in differentiated tissues requires this rheostat for tissue resilience and continued function over the lifetime of an animal.
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http://dx.doi.org/10.1073/pnas.2208317119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9371680PMC
August 2022
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