ATG9A facilitates the biogenesis of influenza A virus liquid condensates near the ER by dissociating recycling vesicles from microtubules

Many viruses that threaten public health establish condensates via phase transitions to complete their lifecycles, and knowledge on such processes is key for the design of new antivirals. In the case of influenza A virus, liquid condensates known as viral inclusions are sites dedicated to the assembly of its 8-partite RNA genome. Liquid viral inclusions emerge near the endoplasmic reticulum (ER) exit sites, but we lack the molecular understanding on how the ER contributes to their biogenesis. We show here that viral inclusions develop at remodeled ER sites and display dynamic interactions using the ER, including fusion and fission events and sliding movements. We also uncover a novel role for the host factor, ATG9A, in mediating the exchange of viral inclusions between the ER and microtubules. Depletion of ATG9A arrests viral inclusions at microtubules and prevents their accumulation at the ER, leading to a significantly reduced production of viral genome complexes and infectious virions. In light of our recent findings, we propose that a remodeled ER supports the dynamics of liquid IAV inclusions, with ATG9A acting locally to facilitate their formation. This work advances our current knowledge regarding influenza genome assembly, but also reveals new roles for ATG9A beyond its classical involvement in autophagy.info:eu-repo/semantics/draf

Patient safety culture in nurses' clinical practice

Objective: to assess the psychometric characteristics of the Hospital Survey on Patient Safety Culture, to characterize the patient safety culture, and to assess the influence of the sociodemographic and professional variables on the safety culture dimensions. Method: a methodological, observational, analytical and cross-sectional study conducted with 360 nurses in which the Hospital Survey on Patient Safety Culture questionnaire was used. The data were submitted to descriptive and inferential analysis, as well as to feasibility and validity studies. Results: the nurses’ mean age is 42 years old, their mean time of professional experience is 19 years, and they are mostly female. Good internal consistency was obtained (Cronbach’s alpha: 0.83), as well as acceptable model fit quality indices. Teamwork within units, Supervisor expectations and Feedback and communication about errors were the dimensions that obtained scores above 60%. Non-punitive response to error, Frequency of events reported, Support for patient safety and Staffing presented scores below 40%. These dimensions are influenced by age, schooling level and professional experience. Conclusion: the psychometric properties of the questionnaire certify its good quality. Teamwork can be considered as an enhancing factor for the safety culture. Assessing the safety culture allowed identifying problematic dimensions, thus enabling planning of future interventions

Cultura de segurança do doente na prática clínica dos enfermeiros

Objective: to assess the psychometric characteristics of the Hospital Survey on Patient Safety Culture, to characterize the patient safety culture, and to assess the influence of the sociodemographic and professional variables on the safety culture dimensions. Method: a methodological, observational, analytical and cross-sectional study conducted with 360 nurses in which the Hospital Survey on Patient Safety Culture questionnaire was used. The data were submitted to descriptive and inferential analysis, as well as to feasibility and validity studies. Results: the nurses’ mean age is 42 years old, their mean time of professional experience is 19 years, and they are mostly female. Good internal consistency was obtained (Cronbach’s alpha: 0.83), as well as acceptable model fit quality indices. Teamwork within units, Supervisor expectations and Feedback and communication about errors were the dimensions that obtained scores above 60%. Non-punitive response to error, Frequency of events reported, Support for patient safety and Staffing presented scores below 40%. These dimensions are influenced by age, schooling level and professional experience. Conclusion: the psychometric properties of the questionnaire certify its good quality. Teamwork can be considered as an enhancing factor for the safety culture. Assessing the safety culture allowed identifying problematic dimensions, thus enabling planning of future interventions.info:eu-repo/semantics/publishedVersio

Abstracts

Tradução, para a língua inglesa dos resumos dos artigos incluídos no número 12 da Revista Lusófona de Educação

ATG9A regulates the dissociation of recycling endosomes from microtubules to form liquid influenza A virus inclusions

AU It is:now Pleaseconfirmthatallheadinglevelsarerepresentedcorrectly established that many viruses that threaten public health : establish condensates via phase transitions to complete their lifecycles, and knowledge on such processes may offer new strategies for antiviral therapy. In the case of influenza A virus (IAV), liquid condensates known as viral inclusions, concentrate the 8 distinct viral ribonucleoproteins (vRNPs) that form IAV genome and are viewed as sites dedicated to the assembly of the 8-partite genomic complex. Despite not being delimited by host membranes, IAV liquid inclusions accumulate host membranes inside as a result of vRNP binding to the recycling endocytic marker Rab11a, a driver of the biogenesis of these structures. We lack molecular understanding on how Rab11a-recycling endosomes condensate specifically near the endoplasmic reticulum (ER) exit sites upon IAV infection. We show here that liquid viral inclusions interact with the ER to fuse, divide, and slide. We uncover that, contrary to previous indications, the reported reduction in recycling endocytic activity is a regulated process rather than a competition for cellular resources involving a novel role for the host factor ATG9A. In infection, ATG9A mediates the removal of Rab11a-recycling endosomes carrying vRNPs from microtubules. We observe that the recycling endocytic usage of microtubules is rescued when ATG9A is depleted, which prevents condensation of Rab11a endosomes near the ER. The failure to produce viral inclusions accumulates vRNPs in the cytosol andAU reduces: Pleasecheckandconfirmthattheeditst genome assembly and the release of infectious virions. We propose that the ER supports the dynamics of liquid IAV inclusions, with ATG9A facilitating their formation. This work advances our understanding on how epidemic and pandemic influenza genomes are formed. It also reveals the plasticity of recycling pathway endosomes to undergo condensation in response to infection, disclosing new roles for ATG9A beyond its classical involvement in autophagy.info:eu-repo/semantics/publishedVersio

Self-harm in children and adolescents: a mini-review: Auto-flagelação em crianças e adolescentes: uma mini-revisão

Objective: Our objective was to make a mini review of the evidence and some recommendations about a holistic and compassionate approach for children and adolescents with self-harm. Methods: We performed a PubMed research on reviews, guidelines and trials published in English between 2006 and 2021. The keywords used were: self-harm, child and adolescent.  Results: Self-harm is a common problem in young people with serious consequences. Nevertheless, this problem is underdiagnosed, with only a minority of young people using health services. There is a strong correlation between self-harm behaviors and suicide, with part of suicide deaths occurring in young people with a history of self-harm. These behaviors result from an interaction between genetic, biological, psychological, social and cultural factors, with the relevance of the stress diathesis being increasingly defended. There are several risk factors associated with self-harm, for example the existence of family and child adversities, the presence of family history and the observation of self-harm in others. Conclusion: Despite the importance inherent to self-harm behaviors, there is not a lot of literature with effective approaches and interventions for young people with these behaviors. However, a complete and compassionate observation and approaching of the patients is essential, especially in this age

Assessment of indoor air quality in elderly care centers, 2013-2014: GERIA project

O risco da população idosa desenvolver efeitos adversos em virtude da exposição a contaminantes químicos e microbiológicos do ar interior é mais elevado tanto pelo facto do seu sistema imunitário ser mais débil, como por este grupo etário permanecer no interior de edifícios por períodos mais longos. O objetivo deste estudo foi a caraterização da qualidade do ar interior numa amostra representativa de lares de idosos de modo a estudar a sua relação com a ventilação dos locais e a saúde/qualidade de vida dos utentes. O estudo apresentado incidiu sobre a avaliação da qualidade do ar interior em 18 lares de idosos situados em Lisboa (116 locais avaliados), em duas campanhas, uma no inverno e outra na primavera/verão e incluiu a avaliação de contaminação do ar por agentes químicos - dióxido de carbono (CO2 ), monóxido de carbono (CO), formaldeído (HCHO), compostos orgânicos voláteis totais (COVT), PM10 e PM2,5; por agentes microbiológicos – bactérias e fungos. Os resultados indicam que, de um modo geral a contaminação do ar por compostos orgânicos voláteis totais e formaldeído é baixa. Contudo, os valores de referência são excedidos para o dióxido de carbono, microrganismos e as partículas em 20%, 35% e 25-30% dos locais estudados respetivamente. Assim, há que identificar as fontes de contaminação do ar por partículas por forma e reduzir os efeitos adversos associados à exposição e melhorar a ventilação dos lares, particularmente no inverno, por forma a conseguir ambientes interiores mais saudáveis.Elderly people are at a greater risk for adverse health effects from exposure to indoor air pollutants because their immune system become less effective with age and they stay more than 80% of their time indoors. The aim of this study was to characterize indoor air quality in a representative sample of Elderly Care Centers (ECC) in order to associate it with ventilation, health and comfort. Indoor air quality was performed twice, during winter and summer/spring in 18 ECC located in Lisbon and included the monitoring of chemical agents - carbon dioxide, carbon monoxide, formaldehyde, Total Volatile Organic Compounds (TVOC) and Particulate matter (PM10 and PM2,5) and biological agents – bacteria and fungi. The results obtained for TVOC and formaldehyde indicate a low air contamination. However, reference concentrations of dioxide of carbon, particulate matter and microorganisms were exceeded in 20%, 25-30% and 35% of the rooms respectively. Consequently it is necessary to identify particulate matter contamination sources to reduce related adverse effects and to improve ventilation in ECC, particularly in the Winter, in order to achieve healthier indoor environments.Este projeto foi financiado pela Fundação para a Ciência e Tecnologia (FTC), PTDC/SAU-SAP/116563/2010

Combining inflammatory miRNA molecules as diagnostic biomarkers for depression: a clinical study

BackgroundInflammation has been implicated in core features of depression pathophysiology and treatment resistance. Therefore, new challenges in the discovery of inflammatory mediators implicated in depression have emerged. MicroRNAs (miRNAs) have been found aberrantly expressed in several pathologies, increasing their potential as biomarkers and therapeutical targets. In this study, the aim was to assess the changes and biomarker potential of inflammation-related miRNAs in depression patients.MethodsDepression diagnosis was performed according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). 40 healthy controls and 32 depression patients were included in the study. The levels of inflammatory cytokines were measured in plasma, and expression levels of cytokines and inflammation-related miRNAs were evaluated in peripheral blood mononuclear cells (PBMCs).ResultsDepression patients were found to have a pro-inflammatory profile in plasma, with significantly higher levels of TNF-α and CCL2 compared with controls. In PBMCs of depression patients, TNF-α and IL-6 expression levels were significantly up and downregulated, respectively. Moreover, miR-342 levels were found upregulated, while miR-146a and miR-155 were significantly downregulated. miR-342 expression levels were positively correlated with TNF-α. Importantly, when analyzed as a diagnostic panel, receiver operating characteristics (ROC) analysis of miR-342, miR-146a, miR-155 in combination, showed to be highly specific and sensitive in distinguishing between depression patients and healthy controls.ConclusionIn summary, these findings suggest that inflammation-related miRNAs are aberrantly expressed in depression patients. Moreover, we show evidences on the potential of the combination of dysregulated miRNAs as a powerful diagnostic tool for depression

Cultura de segurança do doente na prática clínica dos enfermeiros

Objetivo: avaliar as caraterísticas psicométricas do Hospital Survey on Patient Safety Culture, caracterizar a cultura de segurança do doente e avaliar a influência das variáveis sociodemográficas e profissionais nas dimensões da cultura de segurança. Método: estudo metodológico, observacional, analítico, transversal, realizado com 360 enfermeiros, utilizando o questionário Hospital Survey on Patient Safety Culture. Os dados foram submetidos à análise descritiva, inferencial e estudos de fiabilidade e validade. Resultados: os enfermeiros possuem em média 42 anos de idade, 19 anos de experiência profissional e são maioritariamente do sexo feminino. Obteve-se boa consistência interna (alfa de Cronbach - 0,83) e índices aceitáveis de qualidade de ajustamento do modelo. O trabalho em equipa dentro das unidades, expetativas do supervisor, feedback e comunicação sobre o erro, foram dimensões que apresentaram scores acima dos 60%. A resposta ao erro não punitiva, frequência da notificação, apoio à segurança pela gestão, dotação de profissionais, apresentaram scores abaixo dos 40%. Estas dimensões são influenciadas pela idade, escolaridade e experiência profissional. Conclusão: as propriedades psicométricas do questionário certificam a sua qualidade. O trabalho em equipa pode ser considerado um fator potenciador da cultura de segurança. Avaliar a cultura de segurança permitiu identificar dimensões problemáticas, possibilitando o planeamento de intervenções futuras.Objective: to assess the psychometric characteristics of the Hospital Survey on Patient Safety Culture, to characterize the patient safety culture, and to assess the influence of the sociodemographic and professional variables on the safety culture dimensions. Method: a methodological, observational, analytical and cross-sectional study conducted with 360 nurses in which the Hospital Survey on Patient Safety Culture questionnaire was used. The data were submitted to descriptive and inferential analysis, as well as to feasibility and validity studies. Results: the nurses’ mean age is 42 years old, their mean time of professional experience is 19 years, and they are mostly female. Good internal consistency was obtained (Cronbach’s alpha: 0.83), as well as acceptable model fit quality indices. Teamwork within units, Supervisor expectations and Feedback and communication about errors were the dimensions that obtained scores above 60%. Non-punitive response to error, Frequency of events reported, Support for patient safety and Staffing presented scores below 40%. These dimensions are influenced by age, schooling level and professional experience. Conclusion: the psychometric properties of the questionnaire certify its good quality. Teamwork can be considered as an enhancing factor for the safety culture. Assessing the safety culture allowed identifying problematic dimensions, thus enabling planning of future interventions.Objetivo: evaluar las características psicométricas de la Hospital Survey on Patient Safety Culture, caracterizar la cultura de seguridad del paciente y evaluar la influencia de variables sociodemográficas y profesionales en las dimensiones de la cultura de seguridad. Método: estudio metodológico, observacional, analítico, transversal, realizado con 360 enfermeros, utilizando el cuestionario Hospital Survey on Patient Safety Culture. Los datos fueron sometidos a análisis descriptivo e inferencial y estudios de confiabilidad y validez. Resultados: los enfermeros tienen en promedio 42 años de edad, 19 años de experiencia profesional y la mayoría es de sexo femenino. Se obtuvo buena consistencia interna (alfa de Cronbach - 0,83) e índices aceptables de bondad de ajuste del modelo. El trabajo en equipo dentro de las unidades, las expectativas del supervisor, el feedback y la comunicación del error fueron las dimensiones que presentaron puntajes superiores al 60%. La respuesta al error no punitiva, la frecuencia de notificación, el apoyo a la seguridad por parte de los gestores, la dotación de personal, presentaron puntajes por debajo del 40%. Estas dimensiones son influenciadas por la edad, la educación y la experiencia profesional. Conclusión: las propiedades psicométricas del cuestionario certifican su calidad. El trabajo en equipo puede considerarse un factor que potencia la cultura de seguridad. La evaluación de la cultura de seguridad permitió identificar las dimensiones que tenían problemas y poder planificar futuras intervenciones

Defining basic rules for hardening influenza A virus liquid condensates

In biological systems, liquid and solid-like biomolecular condensates may contain the same molecules but their behaviour, including movement, elasticity and viscosity, is different on account of distinct physicochemical properties. As such, it is known that phase transitions affect the function of biological condensates and that material properties can be tuned by several factors including temperature, concentration and valency. It is, however, unclear if some factors are more efficient than others at regulating their behaviour. Viral infections are good systems to address this question as they form condensates de novo as part of their replication programmes. Here, we used influenza A virus liquid cytosolic condensates, A.K.A viral inclusions, to provide a proof of concept that liquid condensate hardening via changes in the valency of its components is more efficient than altering their concentration or the temperature of the cell. Liquid IAV inclusions may be hardened by targeting vRNP interactions via the known NP oligomerizing molecule, nucleozin, both in vitro and in vivo without affecting host proteome abundance nor solubility. This study is a starting point for understanding how to pharmacologically modulate the material properties of IAV inclusions and may offer opportunities for alternative antiviral strategies.info:eu-repo/semantics/publishedVersio