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Fibrillar protein aggregates are the major pathological hallmark of several incurable, age-related, neurodegenerative disorders. These aggregates typically contain aggregation-prone pathogenic proteins, such as amyloid-beta in Alzheimer's disease and alpha-synuclein in Parkinson's disease. It is, however, poorly understood how these aggregates are formed during cellular aging. Here we identify an evolutionarily highly conserved modifier of aggregation, MOAG-4, as a positive regulator of aggregate formation in C. elegans models for polyglutamine diseases. Inactivation of MOAG-4 suppresses the formation of compact polyglutamine aggregation intermediates that are required for aggregate formation. The role of MOAG-4 in driving aggregation extends to amyloid-beta and alpha-synuclein and is evolutionarily conserved in its human orthologs SERF1A and SERF2. MOAG-4/SERF appears to act independently from HSF-1-induced molecular chaperones, proteasomal degradation, and autophagy. Our results suggest that MOAG-4/SERF regulates age-related proteotoxicity through a previously unexplored pathway, which will open up new avenues for research on age-related, neurodegenerative diseases.
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Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Senescência Celular , Proteínas do Tecido Nervoso/metabolismo , Doenças Neurodegenerativas/metabolismo , Proteínas/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Proteínas de Caenorhabditis elegans/química , Linhagem Celular , Linhagem Celular Tumoral , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Camundongos , Proteínas do Tecido Nervoso/química , Peptídeos/metabolismo , Proteínas/química , alfa-Sinucleína/metabolismoRESUMO
Gender dysphoria and autism spectrum disorder (ASD) co-occur at high rates. Yet, it is unknown whether gender dysphoria and ASD are associated with common or distinct neurobiological correlates or how they relate to experiences of gender-related body incongruence. Using the Social Responsiveness Scale, we assessed autistic traits in 99 transgender and 99 cisgender individuals and investigated their associations with gender-related body incongruence, measured via a visually based "Body Morph" test, and with cortical thickness in the brain. Autistic traits were significantly higher among transgender individuals, and those with higher autistic traits had higher body incongruence scoring. Among transgender individuals, higher autistic traits were linked with a thinner cortex bilaterally in the temporal pole and the superior and inferior temporal gyri. Autistic traits were only partly associated with cortical morphology patterns previously reported in transgender individuals; instead, they were primarily linked to temporal lobe areas mediating social cognition. While replicating the previous literature on the increased prevalence of autistic traits among transgender individuals, this study reports specific regions in the brains of transgender individuals where cortical thickness is associated with autistic traits.
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Transtorno do Espectro Autista , Disforia de Gênero , Pessoas Transgênero , Humanos , Feminino , Masculino , Adulto , Transtorno do Espectro Autista/psicologia , Disforia de Gênero/psicologia , Pessoas Transgênero/psicologia , Imageamento por Ressonância Magnética , Adulto Jovem , Encéfalo/diagnóstico por imagem , Imagem Corporal/psicologia , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologia , Adolescente , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Transexualidade/psicologia , Transtorno Autístico/psicologiaRESUMO
AIM: To explore frontline decision-making, adaptation, and learning in ambulance care during the evolving COVID-19 pandemic. DESIGN: Descriptive and interpretative qualitative study. METHODS: Twenty-eight registered nurses from the Swedish ambulance services described 56 critical incidents during the COVID-19 pandemic through free-text questionnaires. The material was analysed using the Critical Incident Technique and Interpretive Description through the lens of potential for resilient performance. RESULTS: The findings were synthesized into four themes: 'Navigating uncharted waters under never-ending pressure', 'Balancing on the brink of an abyss', 'Sacrificing the few to save the many' and 'Bracing for the next wave'. Frontline decision-making during a pandemic contribute to ethical dilemmas while necessitating difficult prioritizations to adapt and respond to limited resources. Learning was manifested through effective information sharing and the identification of successful adaptations as compared to maladaptations. CONCLUSIONS: During pandemics or under other extreme conditions, decisions must be made promptly, even amidst emerging chaos, potentially necessitating the use of untested methods and ad-hoc solutions due to initial lack of knowledge and guidelines. Within ambulance care, dynamic leadership becomes imperative, combining autonomous frontline decision-making with support from management. Strengthening ethical competence and fostering ethical discourse may enhance confidence in decision-making, particularly under ethically challenging circumstances. IMPACT: Performance under extreme conditions can elevate the risk of suboptimal decision-making and adverse outcomes, with older adults being especially vulnerable. Thus, requiring targeted decision support and interventions. Enhancing patient safety in ambulance care during such conditions demands active participation and governance from management, along with decision support and guidelines. Vertical communication and collaboration between management and frontline professionals are essential to ensure that critical information, guidelines, and resources are effectively disseminated and implemented. Further research is needed into management and leadership in ambulance care, alongside the ethical challenges in frontline decision-making under extreme conditions. REPORTING METHOD: Findings are reported per consolidated criteria for reporting qualitative research (COREQ). PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.
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AIM: To illuminate from the perspective of nurses in ambulance services the experiences of using a web-based advisory decision support system to assess care needs and refer patients. DESIGN: Inductive and descriptive approaches. METHOD: Thirteen semi-structured interviews were conducted in the spring of 2020. The data were analysed through the reflexive thematic analysis. RESULTS: The Swedish web-based advisory decision support system (ADSS) was found to strengthen nurses' feelings of security when they assess patients' care needs, promote their competence and professional pride, and help them manage stress. However, the system also generated difficulties for nurses to adjust to the dynamic ambulance team and revealed a discrepancy between their professional roles and responsibilities to refer patients and provide self-care advice. The nurses thought that the support system facilitated their increased participation and helped them understand patients and significant others by offering transparency in assessment and decision making. Thus, the support system provides nurses with an opportunity to strengthen patients' independence through information and education. However, in the care relationship, nurses worked to overcome patients' expectations. CONCLUSION: Nurses using the ADSS increased their security while performing assessments and referrals and found new opportunities to provide information and promote understanding of their decisions. However, nursing care values can be threatened when new support systems are introduced, especially as ambulance services become increasingly protocol-driven. IMPLICATIONS FOR PROFESSION AND/OR PATIENT CARE: These findings have implications for nurses' work environments and help them maintain consistency in making medical assessments and in providing equivalent self-care advice when referring patients to the different levels of care. The findings will also impact researchers and policymakers who formulate decision support systems. REPORTING METHOD: Consolidated criteria for reporting qualitative research (COREQ). PATIENT OR PUBLIC CONTRIBUTION: None.
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BACKGROUND: Patient participation is considered to promote well-being and is, therefore, central in care contexts. Care-dependent older persons living at home constitute a vulnerable population with increased ambulance care needs. Care transfers risk challenging participation in care, a challenge that can be accentuated in situations involving acute illness. AIM: To illuminate meanings of older persons' participation in ambulance care in the presence of municipal care personnel from the perspective of ambulance personnel. METHOD: A phenomenological hermeneutical method was used to analyse transcripts of narrative interviews with 11 ambulance personnel. RESULTS: The ambulance personnel's lived experience of older persons' participation includes passive and active dimensions and involves a balancing act between an exercise of power that impedes participation and equalisation of power that empowers participation. The main theme 'Balancing dignity in relation to manipulating the body' included the themes Providing a safe haven and Complying with bodily expressions, which means shouldering responsibility for existential well-being and being guided by reactions. The main theme 'Balancing influence in relation to perceived health risks' included the themes Agreeing on a common perspective, Directing decision-making mandate, and Sharing responsibility for well-being, which means shouldering responsibility for health focusing on risks. Influence is conditional and includes performance requirements for both the older person and municipal care personnel. CONCLUSION: Care-dependent older persons' participation in care from the perspective of ambulance personnel means recognising passive and active dimensions involving human dignity, the ability to influence care, and optimising care efforts through collaboration. This study provides a deepened understanding of the balancing of power involved in ambulance care determining participation, where power is equalised or exercised depending on personal engagement, health risks, and available care options. The knowledge provided holds the potential to improve ambulance care to benefit older persons in critical life situations.
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Ambulâncias , Pessoal de Saúde , Idoso , Humanos , Narração , Participação do PacienteRESUMO
BACKGROUND: Participation in care is considered to promote safe and qualitative care. Care-dependent older persons ageing in place have increased emergency care needs, which initiate inter-organisational collaboration involving municipal home care and ambulance services. Previous research concludes that uncertainties exist regarding what participation in care means in clinical practice, which necessitates the need to illuminate the phenomenon for older persons in critical life situations. AIM: This study aimed to illuminate meanings of participation in prehospital emergency care from the perspective of care-dependent older persons experiencing acute illness at home. DESIGN: This study has a qualitative design with a lifeworld approach. METHOD: A phenomenological hermeneutical method was used to analyse transcribed telephone interviews with eleven care-dependent persons aged 70-93 years. RESULTS: Care-dependent older persons' participation in prehospital emergency care means 'Entrusting life to professional caregivers' when being in helpless solitude and existentially unsafe, which emphasises a deepened interpersonal dependence. Meanings of participation in care from the perspective of older persons involve Being reassured in togetherness, Being pliant in trust of emergency expertise, Being enabled through the agency of professional caregivers, and Encountering readiness in the emergency care chain. CONCLUSION: Care-dependent older persons' participation in prehospital emergency care is existential and involves interpersonal dependence. Togetherness brings reassurance, safety and opportunity for emotional rest while accessing the professional caregivers' power, competence and abilities which provide opportunities for existence and movement towards well-being and continued living. IMPLICATIONS FOR PRACTICE: Prehospital emergency care from the perspective of care-dependent older persons transcends organisational boundaries and includes the municipal mobile safety alarm service. The involved municipal and regional organisations need to provide support by implementing lifeworld-led care models and care alternatives that enable professionals to recognise the existential dimension of participation in care.
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BACKGROUND: Older patients are often vulnerable and highly dependent on healthcare professionals' assessment in the event of acute illness. In the context of ambulance services, this poses challenges as the assessment is normally conducted with a focus on identifying life-threatening conditions. Such assessment is not fully satisfactory in a patient relationship that also aims to promote and protect patient autonomy. AIM: To describe ambulance clinicians' understanding of older patients' self-determination when the patient's decision-making ability is impaired. RESEARCH DESIGN: A qualitative design with an inductive approach, guided by descriptive phenomenology. PARTICIPANTS: In total, 30 ambulance clinicians, comprised of 25 prehospital emergency nurses, 1 nurse and 4 emergency medical technicians participated in 15 dyadic interviews. ETHICAL CONSIDERATIONS: The research was conducted in accordance with the Declaration of Helsinki, and permission was granted by the Swedish Ethical Review Authority. FINDINGS: The findings are presented in two themes: (1) Movement between explicit and implicit will; and (2) Contradictions about the patient's best interests. The clinicians' interpretations are based on an understanding of the patient's situation using substitute decision-making in emergency situations and conversations that reveal the patient's explicit wishes. Sometimes the clinicians collaborate to validate the patient's implicit will, while they at other times subordinate themselves to others' opinions. The clinicians find themselves in conflict between personal values and organisational values as they try to protect the patient's self-determination. CONCLUSION: The results indicate that older patients with an impaired decision-making ability risk losing the right to self-determination in the context of ambulance services. The clinicians face challenges that significantly affect their ability to handle the older patient's unique needs based on a holistic perspective and their ability to be autonomous.
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BACKGROUND: Even though the traditional focus in emergency care is on life-threatening medical crisis, ambulance clinicians frequently encounter patients with mental illness, including suicidal ideation. A suicide is preceded by a complex process where most of the suicidal ideation is invisible to others. However, as most patients seek healthcare in the year before suicide, ambulance clinicians could have an important part to play in preventing suicide, as they encounter patients in different phases of the suicidal process. AIM: The aim of this study was to describe ambulance clinicians' conceptions of responsibility when encountering patients in a suicidal process. RESEARCH DESIGN: A qualitative inductive design using a phenomenographic approach was used. PARTICIPANTS AND RESEARCH CONTEXT: Twenty-seven ambulance clinicians from two regions in southern Sweden were interviewed. ETHICAL CONSIDERATIONS: The study was approved by the Swedish Ethical Review Authority. FINDINGS: Three categories of descriptions captured a movement from responding to a biological being to responding to a social being. Conventional responsibility was perceived as a primary responsibility for emergency care. In conditional responsibility, the patient's mental illness was given only limited importance and only if certain conditions were met. Ethical responsibility was perceived to have its primary focus on the encounter with the patient and listening to the patient's life story. CONCLUSIONS: An ethical responsibility is favourable regarding suicide prevention in ambulance care, and competence development in mental illness and conversation skills could enable ambulance clinicians to have conversations with patients about suicidal ideation.
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Serviços Médicos de Emergência , Transtornos Mentais , Suicídio , Humanos , Ambulâncias , Ideação SuicidaRESUMO
BACKGROUND: Ethical problems in everyday healthcare work emerge for many reasons and constitute threats to ethical values. If these threats are not managed appropriately, there is a risk that the patient may be inflicted with moral harm or injury, while healthcare professionals are at risk of feeling moral distress. Therefore, it is essential to support the learning and development of ethical competencies among healthcare professionals and students. The aim of this study was to explore the available literature regarding ethics education that promotes ethical competence learning for healthcare professionals and students undergoing training in healthcare professions. METHODS: In this integrative systematic review, literature was searched within the PubMed, CINAHL, and PsycInfo databases using the search terms 'health personnel', 'students', 'ethics', 'moral', 'simulation', and 'teaching'. In total, 40 articles were selected for review. These articles included professionals from various healthcare professions and students who trained in these professions as subjects. The articles described participation in various forms of ethics education. Data were extracted and synthesised using thematic analysis. RESULTS: The review identified the need for support to make ethical competence learning possible, which in the long run was considered to promote the ability to manage ethical problems. Ethical competence learning was found to be helpful to healthcare professionals and students in drawing attention to ethical problems that they were not previously aware of. Dealing with ethical problems is primarily about reasoning about what is right and in the patient's best interests, along with making decisions about what needs to be done in a specific situation. CONCLUSIONS: The review identified different designs and course content for ethics education to support ethical competence learning. The findings could be used to develop healthcare professionals' and students' readiness and capabilities to recognise as well as to respond appropriately to ethically problematic work situations.
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Ética em Enfermagem , Atenção à Saúde , Pessoal de Saúde , Humanos , Princípios MoraisRESUMO
BACKGROUND: Older patients in emergency care often have complex needs and may have limited ability to make their voices heard. Hence, there are ethical challenges for healthcare professionals in establishing a trustful relationship to determine the patient's preferences and then decide and act based on these preferences. With this comes further challenges regarding how the patient's autonomy can be protected and promoted. AIM: To describe nurses' experiences of dealing with older patients' autonomy when cared for in emergency departments (EDs). RESEARCH DESIGN: This study adopted reflective lifeworld theory and a phenomenological design. PARTICIPANTS AND RESEARCH CONTEXT: A total of 13 open-ended interviews were performed with nurses working at two EDs in Sweden. ETHICAL CONSIDERATIONS: The study was reviewed by the Ethical Advisory Board in South East Sweden and conducted according to the Declaration of Helsinki. All participants gave consent. FINDINGS: Nurses' experiences of dealing with older patients' autonomy in EDs are characterized by moving in a conflicting uphill struggle, indicating obscure thoughts on how patient autonomy can be protected in an ethically challenging context. The phenomenon is further described with its meaning constituents: 'Being hampered by prioritization under stress', 'Balancing paternalism and patient autonomy', 'Making decisions without consent in the patient's best interests' and 'Being trapped by notions of legitimate care needs'. CONCLUSION: Stressful work conditions and lacking organizational strategies in EDs contribute to nurses maintaining unjustified paternalistic care, regardless of the patient's ability and medical condition, and questioning who has legitimacy for participating in decisions about care. The nurses' protection and promotion of older patients' autonomy is dependent on the opportunity, ability and willingness to create a patient relationship where the patient's voice and preferences are valued as important. Consequently, strategies are needed to improve patient autonomy in EDs based on the idea of 'relational autonomy'.
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Tomada de Decisões , Autonomia Relacional , Serviço Hospitalar de Emergência , Humanos , Paternalismo , Pesquisa QualitativaRESUMO
AIM AND OBJECTIVES: The aim of the study was to describe Emergency Medical Services (EMS) nurses' experiences of and coping with critical incidents, when providing nursing care as a member of a dyadic team. BACKGROUND: Nursing care in EMS is a complex task, taking into account the physical, psychological as well as existential dimensions of the patient's suffering. In this, EMS nurses are dependent on the dyadic team. Teams in EMS are described as essential for providing safe medical care. However, nursing care also comprises relationships with patients as a means of reducing patient suffering. DESIGN: The study has an inductive descriptive qualitative design, in adherence to the COREQ-checklist. METHODS: A critical incident technique was used. Thirty-five EMS nurses were interviewed individually, with a focus on dyadic teams providing nursing care. The interviews were analysed with the aim of defining main areas, categories and sub-categories. RESULTS: The experiences of critical incidents emerged to form two main areas: "Functional co-operation" and "Dysfunctional co-operation," comprising seven categories and sixteen sub-categories. Their coping with critical incidents encompassed two main areas: "Adapting oneself" and "Adapting nursing care and the colleague," comprising four categories and eight sub-categories. CONCLUSIONS: Reflection as part of the daily practice emerges as important for the development of nursing care both in relation to individual team members and also the dyadic team as a unit. In addition, the results highlight consensus within dyadic teams regarding the objectives of nursing care, as well as the importance of defined roles. RELEVANCE TO CLINICAL PRACTICE: This study underlines the importance of strengthening the dyadic EMS team's ability to co-operate using common goals and knowledge within clinical nursing care. The individual team members' different roles have to be explicit. In addition, clinical care has to be organised to generate preconditions for mutual performance monitoring through collegial feedback and reflection.
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Serviços Médicos de Emergência , Adaptação Psicológica , Humanos , Pesquisa QualitativaRESUMO
BACKGROUND: Since the vast majority of older adults in Sweden live in their private homes throughout life, the emergency medical services need to adapt accordingly. Hence, we aimed to describe characteristic patterns of dyadic staffed emergency ambulance assignments for older adults aged > 70 years compared with adults aged 18-69 years requiring emergency care at home in Sweden. METHODS: A descriptive retrospective study was performed using anonymized registry data from the emergency medical services in a region of Sweden during 2017-2018. One-sample χ2 test, one-way analysis of variance, and binary logistic regression models were used for investigating group differences. Variables for analysis were age, gender, clinical assessments, on-scene time, priority levels, result of response, and temporal patterns. RESULTS: Of all included emergency ambulance assignments (n = 28,533), 59.9% involved older adults, of which 53.8% were women. The probability for older adults to receive the highest priority was decreased for both dispatch (p < 0.001, odds ratio [OR] 0.63, 95% confidence interval [CI] 0.59-0.66), and transport priorities (p < 0.001, OR 0.74, 95% CI 0.68-0.80). Older adults were more likely to receive dispatch priority levels 2 (p < 0.001, OR 1.48, 95% CI 1.40-1.56), and 3 (p < 0.001, OR 1.73, 95% CI 1.46-2.06). The older adults were similarly more likely to receive transport priority level 3 (p < 0.001, OR 1.40, 95% CI 1.28-1.52) compared with adults. Age had a small but additive effect in relation to on-scene time (p < 0.001, R2 = 0.01, F = 53.82). Distinguishing initial clinical assessments for older adults were circulatory, respiratory, trauma, infection, and nonspecific assessments. Emergency ambulance assignments for older adults were more frequently occurring on Mondays (p < 0.001, χ2 = 232.56), and in the 08:00-11:59 interval (p < 0.001, χ2 = 1224.08). CONCLUSION: The issues of the lower priority level preponderance, and the decreased probability for receiving the highest priority warrant further attention in future research and clinical practice.
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Ambulâncias/estatística & dados numéricos , Serviços Médicos de Emergência/estatística & dados numéricos , Serviços de Assistência Domiciliar/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SuéciaRESUMO
BACKGROUND: Working as an ambulance nurse involves facing ethically problematic situations with multi-dimensional suffering, requiring the ability to create a trustful relationship. This entails a need to be clinically trained in order to identify ethical conflicts. AIM: To describe ethical conflicts in patient relationships as experienced by ambulance nursing students during clinical studies. RESEARCH DESIGN: An exploratory and interpretative design was used to inductively analyse textual data from examinations in clinical placement courses. PARTICIPANTS: The 69 participants attended a 1-year educational programme for ambulance nurses at a Swedish university. ETHICAL CONSIDERATIONS: The research was conducted in accordance with the Declaration of Helsinki. Participants gave voluntary informed consent for this study. FINDINGS: The students encountered ethical conflicts in patient relationships when they had inadequate access to the patient's narrative. Doubts regarding patient autonomy were due to uncertainty regarding the patient's decision-making ability, which forced students to handle patient autonomy. Conflicting assessments of the patient's best interest added to the conflicts and also meant a disruption in patient focus. The absence of trustful relationships reinforced the ethical conflicts, together with an inadequacy in meeting different needs, which limited the possibility of providing proper care. DISCUSSION: Contextual circumstances add complexity to ethical conflicts regarding patient autonomy, dependency and the patient's best interest. Students felt they were fluctuating between paternalism and letting the patient choose, and were challenged by considerations regarding the patient's communication and decision-making ability, the views of third parties, and the need for prioritisation. CONCLUSION: The essence of the patient relationship is a struggle to preserve autonomy while focusing on the patient's best interest. Hence, there is a need for education and training that promotes ethical knowledge and ethical reflection focusing on the core nursing and caring values of trust and autonomy, particularly in situations that affect the patient's decision-making ability.
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Tomada de Decisões/ética , Serviços Médicos de Emergência/ética , Relações Enfermeiro-Paciente/ética , Autonomia Pessoal , Autonomia Relacional , Estudantes de Enfermagem/psicologia , Adulto , Ambulâncias , Comunicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Suécia , ConfiançaRESUMO
Transgender persons experience incongruence between their gender identity and birth-assigned sex. The resulting gender dysphoria (GD), is frequently treated with cross-sex hormones. However, very little is known about how this treatment affects the brain of individuals with GD, nor do we know the neurobiology of GD. We recently suggested that disconnection of fronto-parietal networks involved in own-body self-referential processing could be a plausible mechanism, and that the anatomical correlate could be a thickening of the mesial prefrontal and precuneus cortex, which is unrelated to sex. Here, we investigate how cross-sex hormone treatment affects cerebral tissue in persons with GD, and how potential changes are related to self-body perception. Longitudinal MRI measurements of cortical thickness (Cth) were carried out in 40 transgender men (TrM), 24 transgender women (TrW) and 19 controls. Cth increased in the mesial temporal and insular cortices with testosterone treatment in TrM, whereas anti-androgen and oestrogen treatment in TrW caused widespread cortical thinning. However, after correction for treatment-related changes in total grey and white matter volumes (increase with testosterone; decrease with anti-androgen and oestrogen), significant Cth decreases were observed in the mesial prefrontal and parietal cortices, in both TrM and TrW (vs. controls) - regions showing greater pre-treatment Cth than in controls. The own body - self congruence ratings increased with treatment, and correlated with a left parietal cortical thinning. These data confirm our hypothesis that GD may be associated with specific anatomical features in own-body/self-processing circuits that reverse to the pattern of cisgender controls after cross-sex hormone treatment.
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Encéfalo/efeitos dos fármacos , Encéfalo/diagnóstico por imagem , Disforia de Gênero/diagnóstico por imagem , Disforia de Gênero/tratamento farmacológico , Hormônios Esteroides Gonadais/uso terapêutico , Procedimentos de Readequação Sexual , Adulto , Imagem Corporal , Encéfalo/patologia , Feminino , Disforia de Gênero/patologia , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Tamanho do Órgão , Pessoas Transgênero , Resultado do Tratamento , Adulto JovemRESUMO
Aberrant protein aggregation underlies a variety of age-related neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Little is known, however, about the molecular mechanisms that modulate the aggregation process in the cellular environment. Recently, MOAG-4/SERF has been identified as a class of evolutionarily conserved proteins that positively regulates aggregate formation. Here, by using nuclear magnetic resonance (NMR) spectroscopy, we examine the mechanism of action of MOAG-4 by characterizing its interaction with α-synuclein (α-Syn). NMR chemical shift perturbations demonstrate that a positively charged segment of MOAG-4 forms a transiently populated α-helix that interacts with the negatively charged C terminus of α-Syn. This process interferes with the intramolecular interactions between the N- and C-terminal regions of α-Syn, resulting in the protein populating less compact forms and aggregating more readily. These results provide a compelling example of the complex competition between molecular and cellular factors that protect against protein aggregation and those that promote it.
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Proteínas de Caenorhabditis elegans/química , Caenorhabditis elegans/química , Proteínas do Tecido Nervoso/química , Agregados Proteicos , alfa-Sinucleína/química , Doença de Alzheimer , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Humanos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Doença de Parkinson , Eletricidade Estática , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismoRESUMO
BACKGROUND: To decrease the morbidity burden of cardiovascular disease and to avoid the development of potentially preventable complications, early assessment and treatment of acute coronary syndrome (ACS) are important. The aim of this study has therefore been to explore the possible association between patients' estimated intensity of chest pain when first seen by the ambulance crew in suspected ACS, and the subsequent outcome before and after arrival in hospital. METHODS: Data was collected both prospectively and retrospectively. The inclusion criteria were chest pain raising suspicion of ACS and a reported intensity of pain ≥4 on the visual analogue scale. RESULTS: All in all, 1603 patients were included in the study. Increased intensity of chest pain was related to: 1) more heart-related complications before hospital admission; 2) a higher proportion of heart failure, anxiety and chest pain after hospital admission; 3) a higher proportion of acute myocardial infarction and 4) a prolonged hospitalisation. However, there was no significant association with mortality neither in 30 days nor in three years. Adjustment for possible confounders including age, a history of smoking and heart failure showed similar results. CONCLUSION: The estimated intensity of chest pain reported by the patients on admission by the ambulance team was associated with the risk of complications prior to hospital admission, heart failure, anxiety and chest pain after hospital admission, the final diagnosis and the number of days in hospital. TRIAL REGISTRATION: ClinicalTrials.gov 151:2008/4564 Identifier: NCT00792181. Registred 17 November 2008 'retrospectively registered'.
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Síndrome Coronariana Aguda/diagnóstico , Angina Pectoris/diagnóstico , Serviços Médicos de Emergência , Medição da Dor , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/terapia , Idoso , Idoso de 80 Anos ou mais , Ambulâncias , Angina Pectoris/etiologia , Angina Pectoris/mortalidade , Angina Pectoris/terapia , Ansiedade/diagnóstico , Ansiedade/etiologia , Diagnóstico Precoce , Auxiliares de Emergência , Feminino , Nível de Saúde , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de TempoRESUMO
BACKGROUND: The purpose of this observational cohort study was to evaluate the outcome and prognostic factors following salvage radiotherapy (SRT) in a consecutive national cohort. MATERIAL AND METHODS: Between 2006 and 2010, 259 patients received SRT in Denmark. Patient- and cancer-related characteristics were retrospectively retrieved from patient charts. The primary end point was biochemical progression-free survival (b-PFS). RESULTS: At the end of follow-up, 51% of the patients displayed a prostate-specific antigen (PSA) level <0.1 ng/ml. The three-year b-PFS rate for the total cohort was 57.0%. Nearly half of the patients (44%) received androgen deprivation therapy (ADT) in combination with SRT. Positive surgical tumour margins (p = 0.025) and ADT (p = 0.001) were the only markers independently correlated with b-PFS. In patients who received SRT without ADT, both a pre-SRT PSA level ≤0.5 ng/ml (p = 0.003) and pathological tumour stage T1-T2 (p = 0.036) independently correlated with b-PFS. Moreover, a duration between radical prostatectomy (RP) and SRT ≤29 months (p = 0.035) independently correlated with b-PFS in patients treated with ADT in combination with RT. CONCLUSIONS: In patients treated for biochemical failure after RP, positive surgical tumour margins and PSA levels ≤0.5 ng/mL at the time of SRT were associated with a favourable outcome. Despite less favourable tumour characteristics, patients receiving SRT and ADT demonstrated improved b-PFS, and in particular, patients with PSA levels >0.2 ng/ml benefitted from additional ADT.
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Antagonistas de Androgênios/uso terapêutico , Recidiva Local de Neoplasia/radioterapia , Prostatectomia/métodos , Neoplasias da Próstata/radioterapia , Terapia de Salvação/métodos , Idoso , Estudos de Coortes , Dinamarca/epidemiologia , Intervalo Livre de Doença , Seguimentos , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Guias de Prática Clínica como Assunto , Prognóstico , Próstata/diagnóstico por imagem , Próstata/patologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/cirurgia , Radioterapia Adjuvante , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Clinical functional magnetic resonance imaging (fMRI) is still an upcoming diagnostic tool because it is time-consuming to perform the post-scan calculations and interpretations. A standardized and easily used method for the clinical assessment of fMRI scans could decrease the workload and make fMRI more attractive for clinical use. PURPOSE: To evaluate a standardized clinical approach for distance measurement between benign brain tumors and eloquent cortex in terms of the ability to predict pre- and postoperative neurological deficits after intraoperative neuronavigation-assisted surgery. MATERIAL AND METHODS: A retrospective study of 34 patients. The fMRI data were reanalyzed using a standardized distance measurement procedure combining data from both fMRI and three-dimensional T1 MRI scans. The pre- and postoperative neurological status of each patient was obtained from hospital records. Data analysis was performed using logistic regression analysis to determine whether the distance measured between the tumor margin and fMRI activity could serve as a predictor for neurological deficits. RESULTS: An odds ratio of 0.89 mm(-1) (P = 0.03) was found between the risk of preoperative neurological motor deficits and the tumor-fMRI distance. An odds ratio of 0.82 mm(-1) (P = 0.04) was found between the risk of additional postoperative neurological motor deficits and the tumor-fMRI distance. The tumor was radically removed in 10 cases; five patients experienced additional postoperative motor deficits (tumor-fMRI distance <18 mm) and five did not (tumor-fMRI distance >18 mm) (P = 0.008). CONCLUSION: This study indicates that the distance measured between the tumor margin and fMRI activation could serve as a valuable predictor of neurological motor deficits.
Assuntos
Neoplasias Encefálicas/patologia , Imageamento por Ressonância Magnética/métodos , Período Pré-Operatório , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/cirurgia , Criança , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos RetrospectivosRESUMO
BACKGROUND: Current research suggests that nurses can influence the outcome for patients with acute coronary syndrome (ACS). The aim of this study has been to evaluate whether a course in cardiovascular nursing (CVN) can improve ambulance nurses' (ANs') prehospital care of patients experiencing suspected ACS, related to pain intensity. METHODS: This is a cluster randomised controlled trial that was conducted in the ambulance services. Patients were allocated to one of two groups: in the first group, patients were treated by ANs who had attended the CVN course and in the second group patients were treated by ANs without this qualification. Inclusion criteria were: 1/pain raising suspicion of ACS, and 2/pain score ≥4 on a visual analogue scale (VAS). The primary outcome was the estimated intensity of pain or discomfort according to VAS 15 min after randomisation. Secondary outcomes were estimated intensity of pain or discomfort on admission to hospital and further requirement of pain treatment, as well as symptoms such as paleness and/or cold sweat; nausea and/or vomiting; anxiety, dyspnea, degree of alertness, respiratory depression and aggressiveness. A further secondary outcome measured was survival to 30 days. Lastly, a final diagnosis was made. A total of 38 ANs attended the CVN course. There were 1,747 patients who fulfilled the inclusion criteria. RESULTS: The pain score did not differ significantly between the two groups fifteen minutes after randomisation (median value of VAS was 4.0 in both groups). On admission to hospital the pain score was significantly lower for patients treated by an AN who had attended the CVN course (n = 332) compared with those treated by an AN who had not attended the course (n = 1,415) (median 2.5 and 3.0 respectively, p = 0.001). The ANs who had attended the course used higher doses of morphine. CONCLUSIONS: An educational intervention with a CVN course did not relate significantly to more efficient pain relief in suspected ACS during the first 15 min. However, this intervention was associated with more effective pain relief later on in the prehospital setting. Thus, a CVN course for ANs appears to be associated with reduced pain intensity among patients experiencing suspected ACS. This result needs however to be confirmed in further trials. TRIAL REGISTRATION: The ClinicalTrials.gov Protocol Registration System (registration number NCT00792181).