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1.
Acta Biomed ; 93(1): e2022077, 2022 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-35315386

RESUMO

Water immersion during labour and birth has become increasingly popular and widespread in many countries, in particular in midwifery-led care settings. Nevertheless, there is a dearth of quality data about waterbirth, with currently available findings mostly arising from observational studies and case series. The lack of high-quality evidence and the controversial results reported by different studies determined a "behavioral gap" without clearly objective, consistent indications allowing for a sound and evidence-based decision making process. Although water immersion in the first stage of labour is generally considered a safe and cost-effective method of pain management for women in labor, concerns still linger as to the safety of immersion during the second stage of labor and delivery, particularly in terms of neonatal risks and medico-legal implications.


Assuntos
Trabalho de Parto , Tocologia , Parto Normal , Parto Obstétrico , Feminino , Humanos , Recém-Nascido , Parto Normal/métodos , Parto , Gravidez , Água
2.
Sci Adv ; 7(1)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33187978

RESUMO

Using AI, we identified baricitinib as having antiviral and anticytokine efficacy. We now show a 71% (95% CI 0.15 to 0.58) mortality benefit in 83 patients with moderate-severe SARS-CoV-2 pneumonia with few drug-induced adverse events, including a large elderly cohort (median age, 81 years). An additional 48 cases with mild-moderate pneumonia recovered uneventfully. Using organotypic 3D cultures of primary human liver cells, we demonstrate that interferon-α2 increases ACE2 expression and SARS-CoV-2 infectivity in parenchymal cells by greater than fivefold. RNA-seq reveals gene response signatures associated with platelet activation, fully inhibited by baricitinib. Using viral load quantifications and superresolution microscopy, we found that baricitinib exerts activity rapidly through the inhibition of host proteins (numb-associated kinases), uniquely among antivirals. This reveals mechanistic actions of a Janus kinase-1/2 inhibitor targeting viral entry, replication, and the cytokine storm and is associated with beneficial outcomes including in severely ill elderly patients, data that incentivize further randomized controlled trials.


Assuntos
Antivirais/farmacologia , Azetidinas/farmacologia , COVID-19/mortalidade , Inibidores Enzimáticos/farmacologia , Janus Quinases/antagonistas & inibidores , Fígado/virologia , Purinas/farmacologia , Pirazóis/farmacologia , SARS-CoV-2/patogenicidade , Sulfonamidas/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/metabolismo , COVID-19/virologia , Síndrome da Liberação de Citocina , Citocinas/metabolismo , Avaliação Pré-Clínica de Medicamentos , Feminino , Perfilação da Expressão Gênica , Humanos , Interferon alfa-2/metabolismo , Itália , Janus Quinases/metabolismo , Fígado/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Ativação Plaquetária , Modelos de Riscos Proporcionais , RNA-Seq , Espanha , Internalização do Vírus/efeitos dos fármacos , Tratamento Farmacológico da COVID-19
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