Influência da Pressão Hidrostática Em saccharomyces Cerevisiae: Correlação Com estresses Químicos e Físicos

RESUMO Leveduras são organismos unicelulares expostos a ambientes altamente variáveis, acerca de viabilidade de nutrientes, temperatura, pH, radiação, acesso ao oxigênio e, especialmente, atividade da água. A evolução tem selecionado leveduras tolerantes, até certo ponto, a estes estresses ambientais. Altas pressões hidrostáticas (HHP) exercem um amplo efeito sobre células de leveduras, interferindo nas membranas celulares, arquitetura celular e em processos de polimerização e desnaturação de proteínas. O padrão de expressão gênica de S. cerevisiae em resposta a HHP revelou um perfil de resposta ao estresse. A maioria dos genes induzidos estão envolvidos na defesa ao estresse e metabolismo de carboidratos, enquanto a maioria dos genes reprimidos pertencem a categoria de progressão do ciclo celular e síntese de proteínas (Fernandes et al., 2004). O óxido nítrico (NO) é uma molécula simples e única que possui diversas funções em organismos, incluindo a de mensageiro intracelular e intercelular. A influência do NO no crescimento de Saccharomyces cerevisiae e como molécula sinalizadora em resposta ao estresse de HHP foi avaliada. Células respirando foram mais sensíveis a um aumento na concentração intracelular de NO que células crescendo fermentativamente. Baixos níveis de NO demonstraram um efeito citoprotetor durante o estresse causado pela pressão hidrostática. A indução da NO sintase foi isoforma-específica e dependente do estado metabólico da célula e da via de resposta ao estresse. Estes resultados suportam a hipótese que um aumento na concentração intracelular do NO leva à proteção contra o estresse de HHP. Além disso, a aquisição de tolerância a alta pressão hidrostática de 220 MPa em resposta ao pré-tratamento com 0,4 mM de peróxido de hidrogênio, 6 % de etanol ou choque frio de 10 ºC por diferentes intervalos de tempo foi estudado na levedura S. cerevisiae. A proteção conferida por estes diferentes tratamentos foi similar, aproximadamente 3 log, e dependente do tempo. A análise da indução dos principais genes induzidos pela pressão sobre estas condições foi investigada por RT-PCR. Nossos resultados revelaram que a resposta celular a HHP possui características comuns com os estresses de peróxido de hidrogênio e etanol, mas difere em alguns aspectos ao choque frio. Também, foi observado que média pressão induz parada no ciclo celular e proteção contra estresses severos, como alta temperatura, alta pressão e congelamento. Entretanto, esta proteção foi significante apenas quando as células eram incubadas à pressão atmosférica após o tratamento com HHP. A expressão dos genes que são induzidos por HHP e são relacionados à resistência a este estresse também foi analisada, e, para a maioria destes, a maior indução foi atingida após 15 min póspressurização. Juntos estes resultados implicam em uma interconexão entre estes estresse

Implementing psychological support for health and social care staff affected by the COVID-19 pandemic: a qualitative exploration of staff well-being hubs ('Resilience Hubs') using normalisation process theory

Objectives Evaluate the implementation of Hubs providing access to psychological support for health and social care keyworkers affected by the COVID-19 pandemic. Design Qualitative interviews informed by normalisation process theory to understand how the Hub model became embedded into normal practice, and factors that disrupted normalisation of this approach. Setting Three Resilience Hubs in the North of England. Participants Hub staff, keyworkers who accessed Hub support (Hub clients), keyworkers who had not accessed a Hub, and wider stakeholders involved in the provision of staff support within the health and care system (N=63). Results Hubs were generally seen as an effective way of supporting keyworkers, and Hub clients typically described very positive experiences. Flexibility and adaptability to local needs were strongly valued. Keyworkers accessed support when they understood the offer, valuing a confidential service that was separate from their organisation. Confusion about how Hubs differed from other support prevented some from enrolling. Beliefs about job roles, unsupportive managers, negative workplace cultures and systemic issues prevented keyworkers from valuing mental health support. Lack of support from managers discouraged keyworker engagement with Hubs. Black, Asian and minority ethnic keyworkers impacted by racism felt that the Hubs did not always meet their needs. Conclusions Hubs were seen as a valuable, responsive and distinct part of the health and care system. Findings highlight the importance of improving promotion and accessibility of Hubs, and continuation of confidential Hub support. Policy implications for the wider health and care sector include the central importance of genuine promotion of and value placed on mental health support by health and social care management, and the creation of psychologically safe work environments. Diversity and cultural competency training is needed to better reach under-represented communities. Findings are consistent with the international literature, therefore, likely to have applicability outside of the current context

A service mapping exercise of four health and social care staff mental health and wellbeing services, Resilience Hubs, to describe health service provision and interventions

Background: NHS England funded 40 Mental Health and Wellbeing Hubs to support health and social care staff affected by the COVID-19 pandemic. We aimed to document variations in how national guidance was adapted to the local contexts of four Hubs in the North of England.Methods: We used a modified version of Price’s (2019) service mapping methodology. Service level data were used to inform the analysis. A mapping template was adapted from a range of tools, including the European Service Mapping Schedule, and reviewed by Hub leads. Key data included service model; staffing; and interventions. Data were collected between March 2021 – March 2022 by site research assistants. Findings were accuracy-checked by Hub leads, and a logic model developed to theorise how the Hubs may effect change.Results: Hub goals and service models closely reflected guidance; offering: proactive outreach; team-based support; clinical assessment; onward referral, and rapid access to mental health support (in-house and external). Implementation reflected a service context of a client group with high mental health need, and high waiting times at external mental health services. Hubs were predominantly staffed by experienced clinicians, to manage these mental health presentations and organisational working. Formulation-based psychological assessment and the provision of direct therapy were not core functions of the NHS England model, however all Hubs incorporated these adaptations into their service models in response to local contexts, such as extensive waiting lists within external services, and/or client presentations falling between gaps in existing service provision. Finally, a standalone clinical records system was seen as important to reassure Hub users of confidentiality. Other more nuanced variation depended on localised contexts.Conclusion: This study provides a map for setting up services, emphasising early understandings of how new services will integrate within existing systems. Local and regional contexts led to variation in service configuration. Whilst additional Hub functions are supported by available literature, further research is needed to determine whether these functions should comprise essential components of staff wellbeing services moving forward. Future research should also determine the comparative effectiveness of service components, and the limits of permissible variation.Study registration: researchregistry6303.</p

A service mapping exercise of four health and social care staff mental health and wellbeing services, Resilience Hubs, to describe health service provision and interventions

Background: NHS England funded 40 Mental Health and Wellbeing Hubs to support health and social care staff affected by the COVID-19 pandemic. We aimed to document variations in how national guidance was adapted to the local contexts of four Hubs in the North of England. Methods: We used a modified version of Price’s (2019) service mapping methodology. Service level data were used to inform the analysis. A mapping template was adapted from a range of tools, including the European Service Mapping Schedule, and reviewed by Hub leads. Key data included service model; staffing; and interventions. Data were collected between March 2021 – March 2022 by site research assistants. Findings were accuracy-checked by Hub leads, and a logic model developed to theorise how the Hubs may effect change. Results: Hub goals and service models closely reflected guidance; offering: proactive outreach; team-based support; clinical assessment; onward referral, and rapid access to mental health support (in-house and external). Implementation reflected a service context of a client group with high mental health need, and high waiting times at external mental health services. Hubs were predominantly staffed by experienced clinicians, to manage these mental health presentations and organisational working. Formulation-based psychological assessment and the provision of direct therapy were not core functions of the NHS England model, however all Hubs incorporated these adaptations into their service models in response to local contexts, such as extensive waiting lists within external services, and/or client presentations falling between gaps in existing service provision. Finally, a standalone clinical records system was seen as important to reassure Hub users of confidentiality. Other more nuanced variation depended on localised contexts. Conclusion: This study provides a map for setting up services, emphasising early understandings of how new services will integrate within existing systems. Local and regional contexts led to variation in service configuration. Whilst additional Hub functions are supported by available literature, further research is needed to determine whether these functions should comprise essential components of staff wellbeing services moving forward. Future research should also determine the comparative effectiveness of service components, and the limits of permissible variation. Study registration: researchregistry6303

187 Expert-developed ICD-AIS map for measuring serious road traffic injuries

This is a conference abstract. The author accepted manuscript version is entitled ICD-AIS MAP FOR SERIOUS MAIS 3+ INJURIES. It has been published in the journal Injury Prevention Vol 22 Supp 2 as part of the Safety 2016 World Conference, 18–21 September 2016, Tampere, Finland. The definitive version is available at: http://dx.doi.org/10.1136/injuryprev-2016-042156.18

Infection and Fever in Pregnancy and Autism Spectrum Disorders: Findings from the Study to Explore Early Development

Maternal infection and fever during pregnancy have been implicated in the etiology of autism spectrum disorder (ASD); however, studies have not been able to separate the effects of fever itself from the impact of a specific infectious organism on the developing brain. We utilized data from the Study to Explore Early Development (SEED), a case-control study among 2- to 5-year-old children born between 2003 and 2006 in the United States, to explore a possible association between maternal infection and fever during pregnancy and risk of ASD and other developmental disorders (DDs). Three groups of children were included: children with ASD (N = 606) and children with DDs (N = 856), ascertained from clinical and educational sources, and children from the general population (N = 796), randomly sampled from state birth records. Information about infection and fever during pregnancy was obtained from a telephone interview with the mother shortly after study enrollment and maternal prenatal and labor/delivery medical records. ASD and DD status was determined by an in-person standardized developmental assessment of the child at 3-5 years of age. After adjustment for covariates, maternal infection anytime during pregnancy was not associated with ASD or DDs. However, second trimester infection accompanied by fever elevated risk for ASD approximately twofold (aOR = 2.19, 95% confidence interval 1.14-4.23). These findings of an association between maternal infection with fever in the second trimester and increased risk of ASD in the offspring suggest that the inflammatory response to the infectious agent may be etiologically relevant. Autism Res 2019, 12: 1551-1561. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Using data from a large multisite study in the United States-the Study to Explore Early Development-we found that women who had an infection during the second trimester of pregnancy accompanied by a fever are more likely to have children with ASD. These findings suggest the possibility that only more severe infections accompanied by a robust inflammatory response increase the risk of ASD

Effect of cancer pain guideline implementation on pain outcomes among adult outpatients with cancer-related plain: A Stepped Wedge Cluster randomized trial

Importance An evidence-practice gap exists for cancer pain management, and cancer pain remains prevalent and disabling. Objectives To evaluate the capacity of 3 cancer pain guideline implementation strategies to improve pain-related outcomes for patients attending oncology and palliative care outpatient services. Design, Setting, and Participants A pragmatic, stepped wedge, cluster-randomized, nonblinded, clinical trial was conducted between 2014 and 2019. The clusters were cancer centers in Australia providing oncology and palliative care outpatient clinics. Participants included a consecutive cohort of adult outpatients with advanced cancer and a worst pain severity score of 2 or more out of 10 on a numeric rating scale (NRS). Data were collected between August 2015 and May 2019. Data were analyzed July to October 2019 and reanalyzed November to December 2021. Interventions Guideline implementation strategies at the cluster, health professional, and patient levels introduced with the support of a clinical champion. Main Outcomes and Measures The primary measure of effect was the percentage of participants initially screened as having moderate to severe worst pain (NRS ≥ 5) who experienced a clinically important improvement of 30% or more 1 week later. Secondary outcomes included mean average pain, patient empowerment, fidelity to the intervention, and quality of life and were measured in all participants with a pain score of 2 or more 10 at weeks 1, 2, and 4. Results Of 8099 patients screened at 6 clusters, 1564 were eligible, and 359 were recruited during the control phase (mean [SD] age, 64.2 [12.1] years; 196 men [55%]) and 329 during the intervention phase (mean [SD] age, 63.6 [12.7] years; 155 men [47%]), with no significant differences between phases on baseline measures. The mean (SD) baseline worst pain scores were 5.0 (2.6) and 4.9 (2.6) for control and intervention phases, respectively. The mean (SD) baseline average pain scores were 3.5 (2.1) for both groups. For the primary outcome, the proportions of participants with a 30% or greater reduction in a pain score of 5 or more of 10 at baseline were similar in the control and intervention phases (31 of 280 participants [11.9%] vs 30 of 264 participants [11.8%]; OR, 1.12; 95% CI, 0.79-1.60; P = .51). No significant differences were found in secondary outcomes between phases. Fidelity to the intervention was low. Conclusions and Relevance A suite of implementation strategies was insufficient to improve pain-related outcomes for outpatients with cancer-related pain. Further evaluation is needed to determine the required clinical resources needed to enable wide-scale uptake of the fundamental elements of cancer pain care. Ongoing quality improvement activities should be supported to improve sustainability

Effect of Cancer Pain Guideline Implementation on Pain Outcomes among Adult Outpatients with Cancer-Related Pain A SteppedWedge Cluster Randomized Trial

IMPORTANCE: An evidence-practice gap exists for cancer pain management, and cancer pain remains prevalent and disabling. OBJECTIVES: To evaluate the capacity of 3 cancer pain guideline implementation strategies to improve pain-related outcomes for patients attending oncology and palliative care outpatient services. DESIGN, SETTING, AND PARTICIPANTS: A pragmatic, stepped wedge, cluster-randomized, nonblinded, clinical trial was conducted between 2014 and 2019. The clusters were cancer centers in Australia providing oncology and palliative care outpatient clinics. Participants included a consecutive cohort of adult outpatients with advanced cancer and a worst pain severity score of 2 or more out of 10 on a numeric rating scale (NRS). Data were collected between August 2015 and May 2019. Data were analyzed July to October 2019 and reanalyzed November to December 2021. INTERVENTIONS Guideline implementation strategies at the cluster, health professional, and patient levels introduced with the support of a clinical champion. MAIN OUTCOMES AND MEASURES: The primary measure of effect was the percentage of participants initially screened as having moderate to severe worst pain (NRS ≥ 5) who experienced a clinically important improvement of 30% or more 1week later. Secondary outcomes included mean average pain, patient empowerment, fidelity to the intervention, and quality of life and were measured in all participants with a pain score of 2 or more 10 at weeks 1, 2, and 4. RESULTS: Of 8099 patients screened at 6 clusters, 1564 were eligible, and 359 were recruited during the control phase (mean [SD] age, 64.2 [12.1] years; 196 men [55%]) and 329 during the intervention phase (mean [SD] age, 63.6 [12.7] years; 155 men [47%]), with no significant differences between phases on baseline measures. The mean (SD) baselineworst pain scoreswere 5.0 (2.6) and 4.9 (2.6) for control and intervention phases, respectively. The mean (SD) baseline average pain scores were 3.5 (2.1) for both groups. For the primary outcome, the proportions of participants with a 30% or greater reduction in a pain score of 5 or more of 10 at baseline were similar in the control and intervention phases (31 of 280 participants [11.9%] vs 30 of 264 participants [11.8%]; OR, 1.12; 95%CI, 0.79-1.60; P = .51). No significant differences were found in secondary outcomes between phases. Fidelity to the intervention was low. CONCLUSIONS AND RELEVANCE: A suite of implementation strategies was insufficient to improve pain-related outcomes for outpatients with cancer-related pain. Further evaluation is needed to determine the required clinical resources needed to enable wide-scale uptake of the fundamental elements of cancer pain care. Ongoing quality improvement activities should be supported to improve sustainability