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1.
Nature ; 592(7852): 122-127, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33636719

RESUMO

During the evolution of SARS-CoV-2 in humans, a D614G substitution in the spike glycoprotein (S) has emerged; virus containing this substitution has become the predominant circulating variant in the COVID-19 pandemic1. However, whether the increasing prevalence of this variant reflects a fitness advantage that improves replication and/or transmission in humans or is merely due to founder effects remains unknown. Here we use isogenic SARS-CoV-2 variants to demonstrate that the variant that contains S(D614G) has enhanced binding to the human cell-surface receptor angiotensin-converting enzyme 2 (ACE2), increased replication in primary human bronchial and nasal airway epithelial cultures as well as in a human ACE2 knock-in mouse model, and markedly increased replication and transmissibility in hamster and ferret models of SARS-CoV-2 infection. Our data show that the D614G substitution in S results in subtle increases in binding and replication in vitro, and provides a real competitive advantage in vivo-particularly during the transmission bottleneck. Our data therefore provide an explanation for the global predominance of the variant that contains S(D614G) among the SARS-CoV-2 viruses that are currently circulating.


Assuntos
COVID-19/transmissão , COVID-19/virologia , Mutação , SARS-CoV-2/genética , SARS-CoV-2/fisiologia , Glicoproteína da Espícula de Coronavírus/genética , Replicação Viral/genética , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Brônquios/citologia , Brônquios/virologia , COVID-19/epidemiologia , Linhagem Celular , Células Cultivadas , Cricetinae , Modelos Animais de Doenças , Células Epiteliais/virologia , Feminino , Furões/virologia , Efeito Fundador , Técnicas de Introdução de Genes , Aptidão Genética , Humanos , Masculino , Mesocricetus , Camundongos , Mucosa Nasal/citologia , Mucosa Nasal/virologia , Ligação Proteica , RNA Viral/análise , Receptores de Coronavírus/metabolismo , SARS-CoV-2/metabolismo , SARS-CoV-2/patogenicidade
2.
Otolaryngol Head Neck Surg ; 163(2): 204-208, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31986975

RESUMO

OBJECTIVE: This course was designed to characterize the impact of a curriculum for training family medicine physicians in advanced airway techniques with respect to intubation performance and learner confidence. METHODS: A training course was introduced into the curriculum in a single-group pretest-posttest model at a community family medicine residency program. Training consisted of a didactic teaching session on airway management and hands-on skill session with direct laryngoscopy (DL) and video-assisted laryngoscopy (VAL) on normal and difficult airway simulators. Participants were scored with the Intubation Difficulty Scale and completed surveys before and after the training. RESULTS: Twenty-eight residents of all levels participated. The mean time to successful intubation was significantly decreased after training from 51.96 to 23.71 seconds for DL and from 27.89 to 17.07 seconds for VAL. Participant scores with the Intubation Difficulty Scale were also significantly improved for DL and VAL. All participants rated their comfort levels with both techniques as high following training. DISCUSSION: Advanced airway management is a critical skill for any physician involved in caring for critically ill patients, though few trainees receive formal training. Addition of an airway training course with simulation and hands-on experience can improve trainee proficiency and comfort with advanced airway techniques. IMPLICATIONS FOR PRACTICE: Training on airway management should be included in the curriculum for trainees who require the requisite skills and knowledge necessary for advanced airway interventions. This introductory project demonstrates the efficacy and feasibility of a relatively brief training as part of a family medicine residency curriculum.


Assuntos
Manuseio das Vias Aéreas , Currículo , Medicina de Família e Comunidade/educação , Internato e Residência , Laringoscopia/educação , Manuseio das Vias Aéreas/métodos , Estudos Prospectivos
3.
Otolaryngol Head Neck Surg ; 153(4): 532-7, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25820589

RESUMO

OBJECTIVES: Airway stabilization is critical in combat maxillofacial injury as normal anatomical landmarks can be obscured. The study objective was to characterize the epidemiology of airway management in maxillofacial trauma. STUDY DESIGN: Retrospective database analysis. SETTING: Military treatment facilities in Iraq and Afghanistan and stateside tertiary care centers. SUBJECTS: In total, 1345 military personnel with combat-related maxillofacial injuries sustained March 2004 to August 2010 were identified from the Expeditionary Medical Encounter Database using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes. METHODS: Descriptive statistics, including basic demographics, injury severity, associated injuries, and airway interventions, were collected. A logistic regression was performed to determine factors associated with the need for tracheostomy. RESULTS: A total of 239 severe maxillofacial injuries were identified. The most common mechanism of injury was improvised explosive devices (66%), followed by gunshot wounds (8%), mortars (5%), and landmines (4%). Of the subjects, 51.4% required intubation on their initial presentation. Of tracheostomies, 30.4% were performed on initial presentation. Of those who underwent bronchoscopy, 65.2% had airway inhalation injury. There was a significant relationship between the presence of head and neck burn and association with airway inhalation injury (P < .0001). There was also a significant relationship between the severity of facial injury and the need for intubation (P = .002), as well as the presence of maxillofacial fracture and the need for tracheostomy (P = .0001). CONCLUSIONS: There is a high incidence of airway injury in combat maxillofacial trauma, which may be underestimated. Airway management in this population requires a high degree of suspicion and low threshold for airway stabilization.


Assuntos
Manuseio das Vias Aéreas/estatística & dados numéricos , Traumatismos Maxilofaciais/terapia , Campanha Afegã de 2001- , Traumatismos por Explosões/epidemiologia , Broncoscopia/estatística & dados numéricos , Queimaduras/complicações , Queimaduras por Inalação/epidemiologia , Feminino , Humanos , Intubação Intratraqueal , Guerra do Iraque 2003-2011 , Masculino , Medicina Militar/estatística & dados numéricos , Estudos Retrospectivos , Traqueostomia/estatística & dados numéricos , Ferimentos por Arma de Fogo/epidemiologia , Adulto Jovem
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