Intranasal respiratory syncytial virus vaccine attenuated by codon-pair deoptimization of seven open reading frames is genetically stable and elicits mucosal and systemic immunity and protection against challenge virus replication in hamsters.

Respiratory syncytial virus (RSV) is the most important viral agent of severe pediatric respiratory illness worldwide, but there is no approved pediatric vaccine. Here, we describe the development of the live-attenuated RSV vaccine candidate Min AL as well as engineered derivatives. Min AL was attenuated by codon-pair deoptimization (CPD) of seven of the 11 RSV open reading frames (ORFs) (NS1, NS2, N, P, M, SH and L; 2,073 silent nucleotide substitutions in total). Min AL replicated efficiently in vitro at the permissive temperature of 32°C but was highly temperature sensitive (shut-off temperature of 36°C). When serially passaged at increasing temperatures, Min AL retained greater temperature sensitivity compared to previous candidates with fewer CPD ORFs. However, whole-genome deep-sequencing of passaged Min AL revealed mutations throughout its genome, most commonly missense mutations in the polymerase cofactor P and anti-termination transcription factor M2-1 (the latter was not CPD). Reintroduction of selected mutations into Min AL partially rescued its replication in vitro at temperatures up to 40°C, confirming their compensatory effect. These mutations restored the accumulation of positive-sense RNAs to wild-type (wt) RSV levels, suggesting increased activity by the viral transcriptase, whereas viral protein expression, RNA replication, and virus production were only partly rescued. In hamsters, Min AL and derivatives remained highly restricted in replication in the upper and lower airways, but induced serum IgG and IgA responses to the prefusion form of F (pre F) that were comparable to those induced by wt RSV, as well as robust mucosal and systemic IgG and IgA responses against RSV G. Min AL and derivatives were fully protective against challenge virus replication. The derivatives had increased genetic stability compared to Min AL. Thus, Min AL and derivatives with selected mutations are stable, attenuated, yet highly-immunogenic RSV vaccine candidates that are available for further evaluation.

Mucosal prime-boost immunization with live murine pneumonia virus-vectored SARS-CoV-2 vaccine is protective in macaques.

Immunization via the respiratory route is predicted to increase the effectiveness of a SARS-CoV-2 vaccine. Here, we evaluate the immunogenicity and protective efficacy of one or two doses of a live-attenuated murine pneumonia virus vector expressing SARS-CoV-2 prefusion-stabilized spike protein (MPV/S-2P), delivered intranasally/intratracheally to male rhesus macaques. A single dose of MPV/S-2P is highly immunogenic, and a second dose increases the magnitude and breadth of the mucosal and systemic anti-S antibody responses and increases levels of dimeric anti-S IgA in the airways. MPV/S-2P also induces S-specific CD4+ and CD8+ T-cells in the airways that differentiate into large populations of tissue-resident memory cells within a month after the boost. One dose induces substantial protection against SARS-CoV-2 challenge, and two doses of MPV/S-2P are fully protective against SARS-CoV-2 challenge virus replication in the airways. A prime/boost immunization with a mucosally-administered live-attenuated MPV vector could thus be highly effective in preventing SARS-CoV-2 infection and replication.

Intranasal murine pneumonia virus-vectored SARS-CoV-2 vaccine induces mucosal and serum antibodies in macaques.

Next-generation SARS-CoV-2 vaccines are needed that induce systemic and mucosal immunity. Murine pneumonia virus (MPV), a murine homolog of respiratory syncytial virus, is attenuated by host-range restriction in nonhuman primates and has a tropism for the respiratory tract. We generated MPV vectors expressing the wild-type SARS-CoV-2 spike protein (MPV/S) or its prefusion-stabilized form (MPV/S-2P). Both vectors replicated similarly in cell culture and stably expressed S. However, only S-2P was associated with MPV particles. After intranasal/intratracheal immunization of rhesus macaques, MPV/S and MPV/S-2P replicated to low levels in the airways. Despite its low-level replication, MPV/S-2P induced high levels of mucosal and serum IgG and IgA to SARS-CoV-2 S or its receptor-binding domain. Serum antibodies from MPV/S-2P-immunized animals efficiently inhibited ACE2 receptor binding to S proteins of variants of concern. Based on its attenuation and immunogenicity in macaques, MPV/S-2P will be further evaluated as a live-attenuated vaccine for intranasal immunization against SARS-CoV-2.

Aplicações móveis de apoio à autogestão da diabetes tipo 2: experiências, necessidades e preferências do cliente / Mobile applications to support type 2 diabetes self-management: patient experiences, needs, and preferences / Aplicaciones móviles de apoyo a la autogestión de la diabetes tipo 2: experiencias, necesidades y preferencias del cliente

Resumo Enquadramento: As aplicações móveis podem ser úteis para a autogestão da diabetes. Conhecer as necessidades e preferências dos utilizadores é fundamental para que estas ferramentas sejam um suporte efetivo neste processo. Objetivos: Conhecer as experiências, identificar as necessidades e explorar as preferências de pessoas com diabetes mellitus tipo 2 relativamente a aplicações móveis de apoio à autogestão da doença e regime terapêutico. Metodologia: Estudo descritivo, de natureza qualitativa, com 12 participantes recrutados por técnica amostral de bola de neve. Dados recolhidos por entrevistas semiestruturadas e analisados pela técnica de análise de conteúdo. Resultados: Emergiram seis categorias (funções e características técnicas, conteúdos de informação, autodeterminação, gestão de emoções, profissional de saúde e fatores facilitadores). Os dados sugerem baixas competências digitais, necessidade de acesso à informação e a preferência por aplicações multifuncionais e interativas. Conclusão: Apesar da utilização parca de aplicações relacionadas com a saúde, as pessoas assumem interesse e percecionam o benefício de utilizar estas ferramentas para gerir a sua diabetes.

Abstract Background: Mobile applications can be useful in diabetes self-management. Knowing the needs and preferences of users is essential for these tools to provide effective support in this process. Objective: To learn about the experiences, identify needs, and explore the preferences of people with type 2 diabetes mellitus regarding mobile applications to support diabetes self-management. Methodology: Qualitative descriptive study with 12 participants selected using the snowball sampling technique. Data was collected through semi-structured interviews and analyzed using the content analysis technique. Results: Six categories emerged from the analysis: functions and technical characteristics, informative content, self-determination, emotional management, health professional, and facilitating factors. The results suggest poor digital skills, need for access to information, and preference for multifunctional and interactive applications. Conclusion: Despite the limited use of health-related apps, people are interested and realize the benefit of using these tools to manage their diabetes.

Resumen Marco contextual: Las aplicaciones móviles pueden ser útiles para el autocontrol de la diabetes. Conocer las necesidades y preferencias de los usuarios es esencial para que estas herramientas sean un apoyo eficaz en este proceso. Objetivos: Conocer las experiencias, identificar las necesidades y explotar las preferencias de personas con diabetes mellitus tipo 2 relacionadas con las aplicaciones móviles de apoyo a la autogestión de la enfermedad y al régimen terapéutico. Metodología: Estudio descriptivo, de naturaleza cualitativa, con 12 participantes seleccionados por la técnica de muestra de bola de nieve. Datos recogidos por entrevistas semiestructuradas y analizados por la técnica de análisis de contenido. Resultados: Surgieron seis categorías (funciones y características técnicas, contenidos de información, autodeterminación, gestión de emociones, profesional sanitario y factores facilitadores). Los datos sugieren bajas competencias digitales, necesidad de acceso a la información y preferencia por aplicaciones multifuncionales e interactivas. Conclusión: A pesar de la escasa utilización de aplicaciones relacionadas con la salud, las personas muestran interés y perciben el beneficio de utilizar estas herramientas para gestionar su diabetes.

The Influence of Sex, Age, and Race on Coronary Artery Disease: A Narrative Review.

Cardiovascular disease has remained one of the leading causes of mortality in the world. The basic pathophysiology of coronary artery disease (CAD) is a reduction of the blood flow in coronary vessels, leading to restricted blood flow to the heart muscle. Both modifiable and non-modifiable risk factors contribute to its multifactorial etiology. The clinical presentation ranges from asymptomatic to typical symptoms like chest pain, shortness of breath, and left arm or jaw pain. The purpose of this review is to investigate and analyze the variation of CAD depending on the biological sex, age, race, or ethnicity and how it might differ in the studied population while comparing the symptoms and prognosis of CAD. For this research, PubMed's database was used. A total of 926 articles were selected using pre-determined inclusion and exclusion criteria, with 74 articles eligible to be included in the narrative review. Studies were selected from the general population of patients with CAD, regardless of their severity, stage of diagnosis, and treatment plan. The scale for the assessment of non-systematic review articles (SANRA) was used to assess the quality of the study. As humans age, the incidence of CAD increases, and people over 75 are more likely to have multiple-vessel CAD. It has been observed that South Asians have the highest rate of CAD at 24%, while the White population has the lowest at 8%. The prevalence of CAD also depends on race, with the White population having the lowest rate at 3.2%, followed by Hispanics at 5%, Black women at 5.2%, and Black men at 5.7%. Younger Black women tend to have more chest pain. Men with CAD commonly experience chest pain, and women are more likely to present with atypical symptoms. Modifiable risk factors such as smoking and alcoholism are more commonly observed in young men than in young women. Coronary artery disease in the elderly, female, minority, and Black patients is associated with a higher mortality rate. Acknowledging the prevalence of certain risk factors, signs, results, and responses to treatment in certain socio-demographic groups, as well as the provision and accessibility of diagnosis and treatment, would lead to a better outcome for all individuals. The impact of this shift can range from an earlier diagnosis of CAD to a faster and more customized treatment plan tailored to each patient's individual requirements.

Mucosal prime-boost immunization with live murine pneumonia virus-vectored SARS-CoV-2 vaccine is protective in macaques.

Immunization via the respiratory route is predicted to increase the effectiveness of a SARS-CoV-2 vaccine. We evaluated the immunogenicity and protective efficacy of one or two doses of a live-attenuated murine pneumonia virus vector expressing SARS-CoV-2 prefusion-stabilized spike protein (MPV/S-2P), delivered intranasally/intratracheally to rhesus macaques. A single dose of MPV/S-2P was highly immunogenic, and a second dose increased the magnitude and breadth of the mucosal and systemic anti-S antibody responses and increased levels of dimeric anti-S IgA in the airways. MPV/S-2P also induced S-specific CD4+ and CD8+ T-cells in the airways that differentiated into large populations of tissue-resident memory cells within a month after the boost. One dose induced substantial protection against SARS-CoV-2 challenge, and two doses of MPV/S-2P were fully protective against SARS-CoV-2 challenge virus replication in the airways. A prime/boost immunization with a mucosally-administered live-attenuated MPV vector could thus be highly effective in preventing SARS-CoV-2 infection and replication.

Experiencia de adultos mayores «PT4Ageing». Un programa de autogestión de enfermedades crónicas / Older person's experience of PT4Ageing—A programme on self-management «support» in chronic illness

Objetivo: Este estudio buscó describir la experiencia de un grupo de adultos mayores que participaron en un programa de autogestión de enfermedades crónicas. Métodos: El estudio empleó un enfoque fenomenológico cualitativo. Los participantes fueron ocho ancianos y los datos se recogieron mediante entrevistas semiestructuradas. Los datos se analizaron mediante análisis temático. Resultados: Del análisis surgieron cinco temas: 1) Consejos para mejorar nuestra vida diaria, 2) siempre estaba motivado, 3) compartir y ayuda mutua, 4) nos hicieron creer que éramos capaces, 5) sería estupendo que esto no acabara aquí. Globalmente, los participantes en el programa describieron su experiencia como muy positiva. Identificaron beneficios derivados de la participación en el programa, como el aprendizaje de estrategias que les ayudarán a afrontar sus problemas de salud, la mejora de su capacidad para gestionar sus enfermedades de forma más autónoma y el refuerzo del apoyo social, que incluso persistieron tras la conclusión de la intervención. Conclusiones: Los resultados de este estudio proporcionan una visión de cómo los adultos mayores experimentan un programa para la autogestión de enfermedades crónicas. Para el desarrollo de futuros programas, debe tenerse en cuenta la creación de apoyo. Los adultos mayores que participan en programas de autogestión muestran una mayor autoeficacia con relación a la gestión de sus enfermedades crónicas y una mayor autonomía en el autocuidado.(AU)

Objective: This study sought to describe the experience of a group of older adults who participated in a chronic illness self-management programme. Methods: The study employed a qualitative phenomenological approach. Participants were eight elders and data collected using semi-structured interviews. Data was analysed using thematic analysis. Results: Five themes emerged from the analysis: 1) tips to improve our daily lives, 2) I was always motivated, 3) sharing and mutual help, 4) they made us believe we were capable, 5) It would be great if it did not end here. Globally, the participants of the programme described their experience as very positive. They identified gains from participating in the programme, such as learning strategies to help them cope with their health problems, improving their ability to manage their illnesses more autonomously and building social support, that even persisted after the conclusion of the intervention. Conclusion: The findings of this study provide insight into how older adults experience a programme for the self-management of chronic illness. For the development of future programmes, support building must be considered. Older adults who participate in self-management programmes exhibit improved self-efficacy in relation to the management their chronic illnesses and greater autonomy in self-care.(AU)

Older person's experience of PT4Ageing-A programme on self-management «support¼ in chronic illness.

OBJECTIVE: This study sought to describe the experience of a group of older adults who participated in a chronic illness self-management program. METHODS: The study employed a qualitative phenomenological approach. Participants were eight elders and data collected using semi-structured interviews Data was analysed using thematic analysis. RESULTS: Five themes emerged from the analysis: (1) Tips to improve our daily lives, (2) I was always motivated, (3) Sharing and mutual help, (4) They made us believe we were capable (5). It would be great if it did not end here. Globally, the participants of the program described their experience as very positive. They identified gains from participating in the program, such as learning strategies to help them cope with their health problems, improving their ability to manage their illnesses more autonomously and building social support, that even persisted after the conclusion of the intervention. CONCLUSION: The findings of this study provide insight into how older adults experience a program for the self-management of chronic illness. For the development of future programs, support building must be considered. Older adults who participate in self-management programmes exhibit improved self-efficacy in relation to the management their chronic illnesses and greater autonomy in self-care.

A situação da violência doméstica durante a pandemia de covid-19: estudo quantitativo na cidade de Bauru-SP / The situation of domestic violence during the covid-19 pandemic: a quantitative study in the city of Bauru-SP / La situación de la violencia doméstica durante la pandemia de covid-19: un estudio cuantitativo en la ciudad de Bauru-SP

Este artigo é parte do relatório de pesquisa de opinião, quantitativa, executada pela Unesp em parceria com o Conselho Municipal de Políticas para Mulheres, de Bauru-SP, sobre a violência doméstica, de junho a agosto de 2020. A investigação não probabilística, de caráter descritivo, teve como método de coleta de dados o questionário on-line. Seu objetivo foi levantar opiniões de mulheres, de modo a oferecer parâmetros para subsidiar ações de comunicação e publicitação dos serviços promovidos pela Rede de Enfrentamento à violência contra a mulher nessa cidade. Seus resultados constituíram um insumo fundamental para a divulgação de direitos, leis, medidas protetivas, campanhas e informativos de prevenção, e de visibilidade aos serviços dessa Rede. Eles permitiram orientar estratégias de comunicação balizadas na opinião da comunidade, adequadas às demandas e às necessidades de cada região observada na pesquisa, que possibilitaram monitorar e avaliar a Rede de Enfrentamento

This article is part of a report based on a survey carried out by Unesp in partnership with the Municipal Council of Policies for Women, Bauru-SP on domestic violence, from June to August 2020. The non-prob-abilistic research, of descriptive nature, used the online questionnaire to collect data. The survey was con-ducted to find out woman opinions, in order to offer parameters to support communication and publicity actions for the service provided by a network for combating violence against women in that city. Its results enerated fundamental information for dissemination of rights, laws, protective measures, campaigns and prevention, among other ways of giving visibility to the service provided by that network. They made possi-ble to plan communication strategies based on the community opinion, appropriate to demands and pecu-liar needs for each region approached by the survey, which enabled to monitor and evaluate that network

Este artículo es parte del informe cuantitativo de encuesta de opinión realizada por la Unesp en alianza con el Consejo Municipal de Políticas para Mujeres, Bauru-SP, sobre violencia intrafamiliar, desde junio hasta agosto de 2020. La investigación no probabilística, de naturaleza descriptiva, utilizó el cuestionario online para obtener datos. Su objetivo fue conocer la opinión de mujeres, con el fin de ofrecer parámetros para auxiliar acciones de comunicación y divulgar los servicios promovidos por una red de afrontamiento a la violencia contra las mujeres en aquella ciudad. Sus resultados generaron informaciones fundamentales para la difusión de derechos, leyes, medidas de protección, campañas y prevención, y visibilidad a los servicios de esa red. Permitieron orientar estrategias de comunicación basadas en la opinión de la comunidad, adecuadas a las demandas y necesidades de cada región observada en la encuesta, que posibilitaron monitorizar y evaluar aquella red

EVC-EVC2 complex stability and ciliary targeting are regulated by modification with ubiquitin and SUMO.

Ellis van Creveld syndrome and Weyers acrofacial dysostosis are two rare genetic diseases affecting skeletal development. They are both ciliopathies, as they are due to malfunction of primary cilia, microtubule-based plasma membrane protrusions that function as cellular antennae and are required for Hedgehog signaling, a key pathway during skeletal morphogenesis. These ciliopathies are caused by mutations affecting the EVC-EVC2 complex, a transmembrane protein heterodimer that regulates Hedgehog signaling from inside primary cilia. Despite the importance of this complex, the mechanisms underlying its stability, targeting and function are poorly understood. To address this, we characterized the endogenous EVC protein interactome in control and Evc-null cells. This proteomic screen confirmed EVC's main known interactors (EVC2, IQCE, EFCAB7), while revealing new ones, including USP7, a deubiquitinating enzyme involved in Hedgehog signaling. We therefore looked at EVC-EVC2 complex ubiquitination. Such ubiquitination exists but is independent of USP7 (and of USP48, also involved in Hh signaling). We did find, however, that monoubiquitination of EVC-EVC2 cytosolic tails greatly reduces their protein levels. On the other hand, modification of EVC-EVC2 cytosolic tails with the small ubiquitin-related modifier SUMO3 has a different effect, enhancing complex accumulation at the EvC zone, immediately distal to the ciliary transition zone, possibly via increased binding to the EFCAB7-IQCE complex. Lastly, we find that EvC zone targeting of EVC-EVC2 depends on two separate EFCAB7-binding motifs within EVC2's Weyers-deleted peptide. Only one of these motifs had been characterized previously, so we have mapped the second herein. Altogether, our data shed light on EVC-EVC2 complex regulatory mechanisms, with implications for ciliopathies.

Percepção de enfermeiros sobre as 3S ­ Smart Safe Shoes: meias para prevenção de quedas / Nurses perception of the 3S - Smart Safe Shoes: socks to prevent falls / Percepción de enfermeros sobre los 3S - Smart Safe Shoes: calcetines para prevenir caídas

Objetivo: analisar a percepção dos enfermeiros sobre o uso das 3S - Smart Safe Shoes na sua fase de protótipo e os resultados da avaliação do seu uso por idosos internados. Método: estudo de carater exploratório, descritivo e misto, entre novembro de 2021 e março de 2022. Incluiu idosos internados com capacidade de deambulação e identificados com risco de queda; e enfermeiros especialistas. Os dados quantitativos foram analisados por estatística descritiva e os qualitativos a partir de análise temática. Resultados: participaram 28 idosos e sete enfermeiros, ambos concordaram que as 3S ­ Smart Safe Shoes são confortáveis. Os enfermeiros consideram que as meias se adaptaram perfeitamente às diferentes regiões anatômicas do pé e que apresentam propriedades antiderrapantes nos pisos testados; e na maioria das situações, permitem uma boa mobilidade dos dedos, em todos os movimentos tibiotársicos (86%). Todos os enfermeiros destacam a facilidade de calçar as meias e consideram que estas devem ser incluídas como um elemento em estratégia de prevenção de quedas. Conclusão: as 3S - Smart Safe Shoes reunem as características necessárias para garantir uma marcha segura em idosos internados e o seu uso deve ser considerado em outros contextos.

Objective: to analyse nurse's perception about 3S - Smart Safe Shoes use in their prototype phase and describe their evaluation about this use by hospitalized elderly patients. Method: exploratory, descriptive and mixed study, between November 2021 and March 2022. It included hospitalized elderly people who were able to walk and identified as being at risk of falling; and specialist nurses. Quantitative data were analyzed using descriptive statistics and qualitative data using thematic analysis. Results: 28 seniors and seven nurses participated, both agreed that the 3S ­ Smart Safe Shoes are comfortable. The nurses consider that the socks adapt perfectly to the different anatomical regions of the foot and that they have non-slip properties on the tested floors; and in most situations, they allow good mobility of the fingers, in all tibiotarsal movements (86%). All nurses highlight the ease of putting on stockings and consider that these should be included as an element in a fall prevention strategy. Conclusion: 3S - Smart Safe Shoes have the necessary characteristics to guarantee a safe gait in hospitalized elderly patients and their use should be considered in other contexts.

Live-attenuated pediatric parainfluenza vaccine expressing 6P-stabilized SARS-CoV-2 spike protein is protective against SARS-CoV-2 variants in hamsters.

The pediatric live-attenuated bovine/human parainfluenza virus type 3 (B/HPIV3)-vectored vaccine expressing the prefusion-stabilized SARS-CoV-2 spike (S) protein (B/HPIV3/S-2P) was previously evaluated in vitro and in hamsters. To improve its immunogenicity, we generated B/HPIV3/S-6P, expressing S further stabilized with 6 proline mutations (S-6P). Intranasal immunization of hamsters with B/HPIV3/S-6P reproducibly elicited significantly higher serum anti-S IgA/IgG titers than B/HPIV3/S-2P; hamster sera efficiently neutralized variants of concern (VoCs), including Omicron variants. B/HPIV3/S-2P and B/HPIV3/S-6P immunization protected hamsters against weight loss and lung inflammation following SARS-CoV-2 challenge with the vaccine-matched strain WA1/2020 or VoCs B.1.1.7/Alpha or B.1.351/Beta and induced near-sterilizing immunity. Three weeks post-challenge, B/HPIV3/S-2P- and B/HPIV3/S-6P-immunized hamsters exhibited a robust anamnestic serum antibody response with increased neutralizing potency to VoCs, including Omicron sublineages. B/HPIV3/S-6P primed for stronger anamnestic antibody responses after challenge with WA1/2020 than B/HPIV3/S-2P. B/HPIV3/S-6P will be evaluated as an intranasal vaccine to protect infants against both HPIV3 and SARS-CoV-2.

Intervenção educacional em enfermagem para promover a adaptação nos sobreviventes de câncer: protocolo para estudo-piloto / Educational nursing intervention to promote adaptation in cancer survivors: protocol for pilot study / Intervención educativa de enfermería para promover la adaptación en supervivientes de cáncer: protocolo de estudio piloto

RESUMO Objetivo: apresentar o protocolo de um estudo-piloto que visa avaliar a viabilidade e a aceitabilidade de uma intervenção educacional em enfermagem para promover a adaptação dos sobreviventes de câncer, focado no coping e na ansiedade. Método: este protocolo foi desenvolvido com base no Protocol Items: Recommendations for Interventional Trials 2013 (SPIRIT2013) Statement, na cidade do Porto - Portugal, em 2022. Resultados: foram definidos o desenho, a estrutura, o conteúdo, as estratégias e os instrumentos de avaliação da intervenção a serem implementados. Conclusão: este artigo fornece detalhadamente a estrutura e o conteúdo de uma intervenção educacional em enfermagem para promover a adaptação dos sobreviventes de câncer passível de integrar os procedimentos da fase de pilotagem. Pode, ainda, ser considerado um estímulo ao desenvolvimento de novas intervenções e programas de intervenções nesta fase da doença oncológica.

ABSTRACT Objective: to present the protocol of a pilot study that aims to evaluate the feasibility and acceptability of an educational nursing intervention to promote the adaptation of cancer survivors, focused on coping and anxiety. Method: this protocol was developed based on the Protocol Items: Recommendations for Interventional Trials 2013 (SPIRIT2013) Statement, in the city of Porto - Portugal, in 2022. Results: the design, structure, content, strategies, and evaluation instruments of the intervention to be implemented were defined. Conclusion: This article provides in detail the structure and content of an educational nursing intervention to promote the adaptation of cancer survivors that can be integrated into the piloting phase procedures. It can also be considered a stimulus for the development of new interventions and intervention programs in this phase of the cancer disease.

RESUMEN Objetivo: Presentar el protocolo de un estudio piloto destinado a evaluar la viabilidad y aceptabilidad de una intervención educativa de enfermería para promover la adaptación de los supervivientes de cáncer, centrándose en el afrontamiento y la ansiedad. Método: Este protocolo fue desarrollado con base en el Protocol Items: Recommendations for Interventional Trials 2013 (SPIRIT2013) Statement, en la ciudad de Porto - Portugal, en 2022. Resultados: Se definieron el diseño, la estructura, el contenido, las estrategias y las herramientas de evaluación de la intervención que se iba a llevar a cabo. Conclusión: Este artículo detalla la estructura y el contenido de una intervención educativa de enfermería para promover la adaptación de los supervivientes de cáncer que puede integrarse en los procedimientos de la fase de pilotaje. También puede considerarse un estímulo para el desarrollo de nuevas intervenciones y programas de intervención en esta fase de la enfermedad oncológica.

The use of residual serum samples to perform serological surveillance of severe acute respiratory syndrome coronavirus 2 in Dili and regional areas of Timor-Leste.

BACKGROUND: Lack of access to diagnostic testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can limit disease surveillance in remote areas. Serological surveillance can indicate the true extent and distribution of infections in such settings. METHODS: This study monitored SARS-CoV-2 seroprevalence in residual serum samples salvaged from laboratories at five healthcare facilities across Timor-Leste from March to October 2021. RESULTS: Seroprevalence increased from 8.3% to 87.0% during the study period. Potential immunity gaps were identified among children aged 0-15 y (who had not been eligible for vaccination) and individuals aged >60 y. CONCLUSIONS: Efforts to vaccinate vulnerable individuals including older people should be maintained. Residual serum samples can be analysed to give local, contemporary information about the extent and distribution of antibodies to infections, especially SARS-CoV-2, in areas where epidemiological information is limited.

From the Discovery of ADAMTS13 to Current Understanding of Its Role in Health and Disease.

ADAMTS13 (a disintegrin-like metalloprotease domain with thrombospondin type 1 motif, member 13) is a protease of crucial importance in the regulation of the size of von Willebrand factor multimers. Very low ADAMTS13 activity levels result in thrombotic thrombocytopenic purpura, a rare and life-threatening disease. The mechanisms involved can either be acquired (immune-mediated thrombotic thrombocytopenic purpura [iTTP]) or congenital (cTTP, Upshaw-Schulman syndrome) caused by the autosomal recessive inheritance of disease-causing variants (DCVs) located along the ADAMTS13 gene, which is located in chromosome 9q34. Apart from its role in TTP, and as a regulator of microthrombosis, ADAMTS13 has begun to be identified as a prognostic and/or diagnostic marker of other diseases, such as those related to inflammatory processes, liver damage, metastasis of malignancies, sepsis, and different disorders related to angiogenesis. Since its first description almost 100 years ago, the improvement of laboratory tests and the description of novel DCVs along the ADAMTS13 gene have contributed to a better and faster diagnosis of patients under critical conditions. The ability of ADAMTS13 to dissolve platelet aggregates in vitro and its antithrombotic properties makes recombinant human ADAMTS13 treatment a potential therapeutic approach targeting not only patients with cTTP but also other medical conditions.

Avaliação da viabilidade e aceitabilidade de uma intervenção educacional em enfermagem: protocolo de um estudo piloto / Evaluation of the feasibility and acceptability of an educational intervention in nursing: protocol of a pilot study

RESUMO: Objetivo: explanar o protocolo de um estudo piloto cujo finalidade é projetar a avaliação da viabilidade e aceitabilidade de uma intervenção educacional em enfermagem para promover os comportamentos de saúde nos sobreviventes de cancro. Método: o protocolo foi desenvolvido com base no Standard Protocol Items: Recommendations for Interventional Trials de 2013 - SPIRIT 2013 Statement, no Porto, Portugal em 2022. Resultados: o protocolo suportará a implementação do estudo piloto, de forma a avaliar a viabilidade e aceitabilidade dos procedimentos definidos para a intervenção, estimar o recrutamento e retenção dos participantes e definir o tamanho da amostra, de modo a que se possa considerar possíveis reformulações da intervenção educacional e se possa prosseguir para a fase de avaliação. Conclusão: este estudo definiu as bases estruturais e conteúdos para a realização de um estudo piloto e, posteriormente, poderá influenciar a decisão da concretização de um estudo randomizado controlado.

ABSTRACT Objective: to explain the protocol of a pilot study that aims to evaluate the feasibility and acceptability of a nursing educational intervention to promote health behaviors in cancer survivors. Method: the protocol was developed based on the Standard Protocol Items: Recommendations for Interventional Trials 2013 - SPIRIT 2013 Statement, in Porto, Portugal in 2022. Results: the protocol would support the implementation of the pilot study in order to assess the feasibility and acceptability of the procedures defined for the intervention, estimate the recruitment and retention of participants, and define the sample size so that possible reformulations of the educational intervention could be considered and proceed to the evaluation phase. Conclusion: this study has laid the structural foundations and content for conducting a pilot study and may later influence the decision to conduct a randomized controlled trial.

Live-attenuated pediatric parainfluenza vaccine expressing 6P-stabilized SARS-CoV-2 spike protein is protective against SARS-CoV-2 variants in hamsters.

The pediatric live-attenuated bovine/human parainfluenza virus type 3 (B/HPIV3)-vectored vaccine expressing the prefusion-stabilized SARS-CoV-2 spike (S) protein (B/HPIV3/S-2P) was previously evaluated in vitro and in hamsters. To improve its immunogenicity, we generated B/HPIV3/S-6P, expressing S further stabilized with 6 proline mutations (S-6P). Intranasal immunization of hamsters with B/HPIV3/S-6P reproducibly elicited significantly higher serum anti-S IgA/IgG titers than B/HPIV3/S-2P; hamster sera efficiently neutralized variants of concern (VoCs), including Omicron variants. B/HPIV3/S-2P and B/HPIV3/S-6P immunization protected hamsters against weight loss and lung inflammation following SARS-CoV-2 challenge with the vaccine-matched strain WA1/2020 or VoCs B.1.1.7/Alpha or B.1.351/Beta and induced near-sterilizing immunity. Three weeks post-challenge, B/HPIV3/S-2P- and B/HPIV3/S-6P-immunized hamsters exhibited a robust anamnestic serum antibody response with increased neutralizing potency to VoCs, including Omicron sublineages. B/HPIV3/S-6P primed for stronger anamnestic antibody responses after challenge with WA1/2020 than B/HPIV3/S-2P. B/HPIV3/S-6P will be evaluated as an intranasal vaccine to protect infants against both HPIV3 and SARS-CoV-2. AUTHOR SUMMARY: SARS-CoV-2 infects and causes disease in all age groups. While injectable SARS-CoV-2 vaccines are effective against severe COVID-19, they do not fully prevent SARS-CoV-2 replication and transmission. This study describes the preclinical comparison in hamsters of B/HPIV3/S-2P and B/HPIV3/S-6P, live-attenuated pediatric vector vaccine candidates expressing the "2P" prefusion stabilized version of the SARS-CoV-2 spike protein, or the further-stabilized "6P" version. B/HPIV3/S-6P induced significantly stronger anti-S serum IgA and IgG responses than B/HPIV3/S-2P. A single intranasal immunization with B/HPIV3/S-6P elicited broad systemic antibody responses in hamsters that efficiently neutralized the vaccine-matched isolate as well as variants of concern, including Omicron. B/HPIV3/S-6P immunization induced near-complete airway protection against the vaccine-matched SARS-CoV-2 isolate as well as two variants. Furthermore, following SARS-CoV-2 challenge, immunized hamsters exhibited strong anamnestic serum antibody responses. Based on these data, B/HPIV3/S-6P will be further evaluated in a phase I study.

Validação de uma intervenção educacional em enfermagem para promover a adaptação dos sobreviventes de cancro / Validation of an educational nursing intervention to promote the adaptation of cancer survivors / Validación de una intervención educativa de enfermería para promover la adaptación de los supervivientes de cáncer

Resumo Enquadramento: Os sobreviventes de cancro representam um grande desafio para os sistemas de saúde, pela escassez de planos assistenciais a estas pessoas. Objetivo: Validar a estrutura e o conteúdo de uma intervenção educacional em enfermagem (intervenção complexa) para promover a adaptação dos sobreviventes de cancro. Metodologia: Utilizou-se a técnica e-Delphi modificada, ao longo de três rondas, através de questionários online. Resultados: Um conjunto de 27 peritos validaram a inclusão de 33 itens relativos à estrutura e 177 itens relativos ao conteúdo. A intervenção educacional deve ser realizada ao longo de cinco a oito sessões, individualmente, com a possibilidade de integrar um familiar significativo, e de dinâmicas de grupo, integrando os quatro domínios propostos: Adaptação, Atitude/Coping, Emoção/Ansiedade e Recursos. Conclusão: O consenso alcançado é essencial para evidenciar o papel dos enfermeiros nesta fase da doença oncológica e para viabilizar a avaliação da eficácia da intervenção educacional em desenvolvimento.

Abstract Background: Cancer survivors represent a major challenge for health systems due to the lack of care plans for these patients. Objective: To validate the structure and content of an educational nursing intervention (complex intervention) to promote the adaptation of cancer survivors. Methodology: The modified e-Delphi technique consisted of three rounds of online questionnaires. Results: A group of 27 experts validated the inclusion of 33 items related to the structure and 177 items related to the content. The educational intervention should consist of five to eight individual (with the possibility of including a significant family member) and group sessions and focus on the four domains proposed: Adaptation, Attitude/Coping, Emotion/Anxiety, and Resources. Conclusion: The consensus reached is essential to highlight nurses' role in this stage of cancer and assess the effectiveness of this educational intervention.

Resumen Marco contextual: Los supervivientes de cáncer representan un gran reto para los sistemas sanitarios, debido a la escasez de planes de atención para estas personas. Objetivo: Validar la estructura y el contenido de una intervención educativa de enfermería (intervención compleja) para promover la adaptación de los supervivientes de cáncer. Metodología: Se utilizó la técnica e-Delphi modificada, a lo largo de tres rondas, mediante cuestionarios en línea. Resultados: Un conjunto de 27 expertos validó la inclusión de 33 ítems relacionados con la estructura y 177 ítems relacionados con el contenido. La intervención educativa debe realizarse a lo largo de cinco a ocho sesiones, de forma individual, con la posibilidad de incluir a un familiar significativo y en dinámicas de grupo, integrando los cuatro dominios propuestos: Adaptación, Actitud/Coping, Emoción/Ansiedad y Recursos. Conclusión: El consenso alcanzado es esencial para destacar el papel de los enfermeros en esta fase del cáncer y para permitir la evaluación de la eficacia de la intervención educativa que se está desarrollando.