RESUMO
Aneurysmal subarachnoid hemorrhage can be a devastating disease, with an in-hospital mortality rate of up to 20%. The American Heart Association/American Stroke Association 2023 Aneurysmal Subarachnoid Hemorrhage Guidelines provide a comprehensive update to the 2012 Guidelines based on a systematic review of the intervening evidence. The guidelines are broad in scope, covering prehospital care, aneurysm treatment modality, medical complications, detection and treatment of delayed cerebral ischemia, and recovery. Here, we comment on salient aspects of aneurysmal subarachnoid hemorrhage care, compare these guidelines with the 2023 Neurocritical Care aneurysmal subarachnoid hemorrhage guidelines, and review relevant updates.
Assuntos
Isquemia Encefálica , Aneurisma Intracraniano , Hemorragia Subaracnóidea , Vasoespasmo Intracraniano , Humanos , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/terapia , Hemorragia Subaracnóidea/complicações , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/diagnóstico , Aneurisma Intracraniano/terapia , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/terapia , Isquemia Encefálica/complicações , Infarto Cerebral/complicações , Vasoespasmo Intracraniano/complicaçõesAssuntos
Catatonia/imunologia , Infecções por Coronavirus/imunologia , Inflamação/imunologia , Pneumonia Viral/imunologia , Idoso , Fibrilação Atrial/complicações , Gânglios da Base/metabolismo , Betacoronavirus , Proteína C-Reativa/imunologia , COVID-19 , Catatonia/complicações , Catatonia/tratamento farmacológico , Catatonia/metabolismo , Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Diabetes Mellitus Tipo 2/complicações , Tremor Essencial/complicações , Ferritinas/metabolismo , Hospitalização , Humanos , Hipertensão/complicações , Hipnóticos e Sedativos/uso terapêutico , Hiponatremia/etiologia , Lorazepam/uso terapêutico , Doenças Pulmonares Intersticiais/complicações , Linfopenia/etiologia , Masculino , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Doença Pulmonar Obstrutiva Crônica/complicações , SARS-CoV-2 , Esquizofrenia/complicações , Trombocitopenia/etiologia , Ácido gama-Aminobutírico/metabolismoRESUMO
Many Gram-negative pathogens encode type 3 secretion systems, sophisticated nanomachines that deliver proteins directly into the cytoplasm of mammalian cells. These systems present attractive opportunities for therapeutic protein delivery applications; however, their utility has been limited by their inherent pathogenicity. Here, we report the reengineering of a laboratory strain of Escherichia coli with a tunable type 3 secretion system that can efficiently deliver heterologous proteins into mammalian cells, thereby circumventing the need for virulence attenuation. We first introduced a 31 kB region of Shigella flexneri DNA that encodes all of the information needed to form the secretion nanomachine onto a plasmid that can be directly propagated within E. coli or integrated into the E. coli chromosome. To provide flexible control over type 3 secretion and protein delivery, we generated plasmids expressing master regulators of the type 3 system from either constitutive or inducible promoters. We then constructed a Gateway-compatible plasmid library of type 3 secretion sequences to enable rapid screening and identification of sequences that do not perturb function when fused to heterologous protein substrates and optimized their delivery into mammalian cells. Combining these elements, we found that coordinated expression of the type 3 secretion system and modified target protein substrates produces a nonpathogenic strain that expresses, secretes, and delivers heterologous proteins into mammalian cells. This reengineered system thus provides a highly flexible protein delivery platform with potential for future therapeutic applications.