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mRNA-1273 vaccine efficacy against SARS-CoV-2 Delta wanes over time; however, there are limited data on the impact of durability of immune responses on protection. Here, we immunized rhesus macaques and assessed immune responses over 1 year in blood and upper and lower airways. Serum neutralizing titers to Delta were 280 and 34 reciprocal ID50 at weeks 6 (peak) and 48 (challenge), respectively. Antibody-binding titers also decreased in bronchoalveolar lavage (BAL). Four days after Delta challenge, the virus was unculturable in BAL, and subgenomic RNA declined by â¼3-log10 compared with control animals. In nasal swabs, sgRNA was reduced by 1-log10, and the virus remained culturable. Anamnestic antibodies (590-fold increased titer) but not T cell responses were detected in BAL by day 4 post-challenge. mRNA-1273-mediated protection in the lungs is durable but delayed and potentially dependent on anamnestic antibody responses. Rapid and sustained protection in upper and lower airways may eventually require a boost.
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SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-matched vaccines would enhance protection. Here, nonhuman primates that received mRNA-1273 at weeks 0 and 4 were boosted at week 41 with mRNA-1273 or mRNA-Omicron. Neutralizing titers against D614G were 4,760 and 270 reciprocal ID50 at week 6 (peak) and week 41 (preboost), respectively, and 320 and 110 for Omicron. 2 weeks after the boost, titers against D614G and Omicron increased to 5,360 and 2,980 for mRNA-1273 boost and 2,670 and 1,930 for mRNA-Omicron, respectively. Similar increases against BA.2 were observed. Following either boost, 70%-80% of spike-specific B cells were cross-reactive against WA1 and Omicron. Equivalent control of virus replication in lower airways was observed following Omicron challenge 1 month after either boost. These data show that mRNA-1273 and mRNA-Omicron elicit comparable immunity and protection shortly after the boost.
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COVID-19 , SARS-CoV-2 , Vacina de mRNA-1273 contra 2019-nCoV , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Macaca , RNA MensageiroRESUMO
B.1.351 is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant most resistant to antibody neutralization. We demonstrate how the dose and number of immunizations influence protection. Nonhuman primates received two doses of 30 or 100 µg of Moderna's mRNA-1273 vaccine, a single immunization of 30 µg, or no vaccine. Two doses of 100 µg of mRNA-1273 induced 50% inhibitory reciprocal serum dilution neutralizing antibody titers against live SARS-CoV-2 p.Asp614Gly and B.1.351 of 3,300 and 240, respectively. Higher neutralizing responses against B.1.617.2 were also observed after two doses compared to a single dose. After challenge with B.1.351, there was ~4- to 5-log10 reduction of viral subgenomic RNA and low to undetectable replication in bronchoalveolar lavages in the two-dose vaccine groups, with a 1-log10 reduction in nasal swabs in the 100-µg group. These data establish that a two-dose regimen of mRNA-1273 will be critical for providing upper and lower airway protection against major variants of concern.
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Vacinas contra COVID-19/imunologia , COVID-19/imunologia , Primatas/imunologia , SARS-CoV-2/imunologia , Vacina de mRNA-1273 contra 2019-nCoV , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/virologia , Linhagem Celular , Chlorocebus aethiops , Feminino , Humanos , Macaca mulatta , Masculino , Mesocricetus , Primatas/virologia , RNA Viral/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinação/métodos , Células Vero , Carga Viral/métodosRESUMO
Vaccine-associated enhanced respiratory disease (VAERD) was previously observed in some preclinical models of severe acute respiratory syndrome (SARS) and MERS coronavirus vaccines. We used the SARS coronavirus 2 (SARS-CoV-2) mouse-adapted, passage 10, lethal challenge virus (MA10) mouse model of acute lung injury to evaluate the immune response and potential for immunopathology in animals vaccinated with research-grade mRNA-1273. Whole-inactivated virus or heat-denatured spike protein subunit vaccines with alum designed to elicit low-potency antibodies and Th2-skewed CD4+ T cells resulted in reduced viral titers and weight loss post challenge but more severe pathological changes in the lung compared to saline-immunized animals. In contrast, a protective dose of mRNA-1273 induced favorable humoral and cellular immune responses that protected from viral replication in the upper and lower respiratory tract upon challenge. A subprotective dose of mRNA-1273 reduced viral replication and limited histopathological manifestations compared to animals given saline. Overall, our findings demonstrate an immunological signature associated with antiviral protection without disease enhancement following vaccination with mRNA-1273.
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Vacinas contra COVID-19/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Interações Hospedeiro-Patógeno/imunologia , SARS-CoV-2/imunologia , Vacinas Sintéticas/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Biópsia , Vacinas contra COVID-19/administração & dosagem , Modelos Animais de Doenças , Humanos , Imunoglobulina G , Imuno-Histoquímica , Camundongos , Avaliação de Resultados em Cuidados de Saúde , RNA Mensageiro , Glicoproteína da Espícula de Coronavírus/imunologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Vacinas Sintéticas/administração & dosagem , Vacinas de mRNARESUMO
BACKGROUND: Large language models such as GPT-4 (Generative Pre-trained Transformer 4) are being increasingly used in medicine and medical education. However, these models are prone to "hallucinations" (ie, outputs that seem convincing while being factually incorrect). It is currently unknown how these errors by large language models relate to the different cognitive levels defined in Bloom's taxonomy. OBJECTIVE: This study aims to explore how GPT-4 performs in terms of Bloom's taxonomy using psychosomatic medicine exam questions. METHODS: We used a large data set of psychosomatic medicine multiple-choice questions (N=307) with real-world results derived from medical school exams. GPT-4 answered the multiple-choice questions using 2 distinct prompt versions: detailed and short. The answers were analyzed using a quantitative approach and a qualitative approach. Focusing on incorrectly answered questions, we categorized reasoning errors according to the hierarchical framework of Bloom's taxonomy. RESULTS: GPT-4's performance in answering exam questions yielded a high success rate: 93% (284/307) for the detailed prompt and 91% (278/307) for the short prompt. Questions answered correctly by GPT-4 had a statistically significant higher difficulty than questions answered incorrectly (P=.002 for the detailed prompt and P<.001 for the short prompt). Independent of the prompt, GPT-4's lowest exam performance was 78.9% (15/19), thereby always surpassing the "pass" threshold. Our qualitative analysis of incorrect answers, based on Bloom's taxonomy, showed that errors were primarily in the "remember" (29/68) and "understand" (23/68) cognitive levels; specific issues arose in recalling details, understanding conceptual relationships, and adhering to standardized guidelines. CONCLUSIONS: GPT-4 demonstrated a remarkable success rate when confronted with psychosomatic medicine multiple-choice exam questions, aligning with previous findings. When evaluated through Bloom's taxonomy, our data revealed that GPT-4 occasionally ignored specific facts (remember), provided illogical reasoning (understand), or failed to apply concepts to a new situation (apply). These errors, which were confidently presented, could be attributed to inherent model biases and the tendency to generate outputs that maximize likelihood.
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Educação Médica , Medicina , Medicina Psicossomática , Humanos , Projetos de PesquisaRESUMO
Generative Artificial Intelligence (GenAI) caught Health Professions Education (HPE) institutions off-guard, and they are currently adjusting to a changed educational environment. On the horizon, however, is Artificial General Intelligence (AGI) which promises to be an even greater leap and challenge. This Guide begins by explaining the context and nature of AGI, including its characteristics of multi-modality, generality, adaptability, autonomy, and learning ability. It then explores the implications of AGI on students (including personalised learning and electronic tutors) and HPE institutions, and considers some of the context provided by AGI in healthcare. It then raises the problems to address, including the impact on employment, social risks, student adaptability, costs, quality, and others. After considering a possible timeline, the Guide then ends by indicating some first steps that HPE institutions and educators can take to prepare for AGI.
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INTRODUCTION: The global trend of legalizing medical cannabis (MC) is on the rise. In Germany, physicians have prescribed MC at the expense of health insurers since 2017. However, the teaching on MC has been scant in medical training. This study investigates medical students' attitudes and perceived competence regarding MC and evaluates how varying materials (videos/articles) impact their opinions. METHODS: Fourth-year medical students were invited to participate in the cross-sectional study. During an online session, students viewed a video featuring a patient with somatoform pain discussing her medical history, plus one of four randomly assigned MC-related materials (each an article and a video depicting a positive or negative perspective on MC). Students' opinions were measured at the beginning [T0] and the end of the course [T1] using a standardized questionnaire with a five-point Likert scale. We assessed the influence of the material on the students' opinions using paired-sample t-tests. One-way analysis of variance and Tukey post-hoc tests were conducted to compare the four groups. Pearson correlations assessed correlations. RESULTS: 150 students participated in the course, the response rate being 75.3% [T0] and 72.7% [T1]. At T0, students felt a little competent regarding MC therapy (M = 1.80 ± 0.82). At T1, students in groups 1 (positive video) and 3 (positive article) rated themselves as more capable in managing MC therapy [Formula: see text], and students in groups 3 (positive article) and 4 (negative article) felt more skilled in treating patients with chronic pain [Formula: see text]. Compared to the other groups, group 2 students (negative video) felt significantly less competent. They perceived cannabis as addictive, hazardous and unsuitable for medical prescription. DISCUSSION: This study showed that medical students lack knowledge and perceived competence in MC therapy. Material influences their opinions in different ways, and they seek more training on MC. This underlines that integrating MC education into medical curricula is crucial to address this knowledge gap.
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Educação Médica , Maconha Medicinal , Estudantes de Medicina , Humanos , Feminino , Maconha Medicinal/uso terapêutico , Estudos Transversais , AtitudeRESUMO
BACKGROUND: Meta-analyses indicate a high prevalence of burnout among medical students. Although studies have investigated different coping strategies and health interventions to prevent burnout, professional experience's influence on burnout resilience as seldom been explored. Therefore, in our study we aimed to examine the self-efficacy's mediating role in the relationship between past vocational training and burnout resilience. In the process, we also analysed the associations between study-related variables and burnout resilience. METHODS: In our cross-sectional study, we analysed the data of 2217 medical students at different stages of their university education (i.e. 1st, 3rd, 6th, 10th semester, and final year) at five medical faculties in Germany. The questionnaire included items addressing variables related to medical school, previous professional and academic qualifications, and validated instruments for measuring burnout and self-efficacy. RESULTS: The overall prevalence of burnout was 19.7%, as defined by high scores for emotional exhaustion and notable values in at least one of the other two dimensions (cynicism or academic efficacy). Higher levels for self-efficacy (p < .001), having children (p = .004), and financing education with personal earnings (p = .03) were positively associated with burnout resilience, whereas having education financed by a partner or spouse (p = .04) had a negative association. In a mediation analysis, self-efficacy exerted a suppressor effect on the relationship between vocational training and burnout resilience (indirect effect = 0.11, 95% CI [0.04, 0.19]). CONCLUSIONS: Self-efficacy's suppressor effect suggests that the positive association between vocational training and burnout resilience identified in the mediation analysis disappears for students who have completed vocational training but do not feel efficacious. Those and other findings provide important insights into the psychological mechanisms underlying the development of burnout resilience in medical students and suggest the promotion of self-efficacy in medical education.
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Esgotamento Profissional , Resiliência Psicológica , Autoeficácia , Estudantes de Medicina , Humanos , Estudos Transversais , Esgotamento Profissional/psicologia , Esgotamento Profissional/epidemiologia , Masculino , Feminino , Estudantes de Medicina/psicologia , Alemanha , Adulto , Adulto Jovem , Inquéritos e Questionários , Educação Médica , Prevalência , Adaptação PsicológicaRESUMO
Background: e-Health interventions are increasing in the field of organ transplantations; however, the literature lacks evidence regarding needs, attitudes, and preferences of organ recipients and donors during the course of an organ transplantation. Methods: In a cross-sectional study, 70 subjects were assessed using self-rated and validated questionnaires, such as the PRIME MD Patient Health Questionnaire (PHQ-D) and the Essen Resource Inventory (ERI). Group differences and a multiple linear regression were also applied. Results: Organ recipients had significantly higher scores for depression (U = 245.00, z = -2.65, p = 0.008, Cohen's d = 0.32), somatoform (U = 224.50, z = -2.99, p = 0.003, Cohen's d = 0.37), and stress syndromes (U = 266.00, z = -2.25, p = 0.008, Cohen's d = 0.27). They also named the internet and apps as resources to find information regarding organ transplants (U = 177.50, z = -2.07, p = 0.017, Cohen's d = 0.28; Z = -2.308, p = 0.021) and preferred to use apps to monitor the physical condition (Z = -2.12, p = 0.034) significantly more than organ donors. Anxiety and somatoform syndromes were significant predictors to search for information regarding the transplant process (F[6,38] = 3.98, p < 0.001; R2 = 0.386). Conclusions: e-Health interventions are promising in accompanying the course of an organ transplant for patients to be informed and educated. Predominantly, potential organ recipients might benefit from apps to record physical parameters. However, anxiety syndromes might hinder patients from searching for information about the transplant process, while somatoform syndromes might enable patients who are searching for such information.
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Depressão , Transplante de Órgãos , Humanos , Uso da Internet , Estudos Transversais , Qualidade de Vida , AnsiedadeRESUMO
Collaboration among healthcare providers is regarded as a promising method to improve care quality and patient outcomes with limited human and financial resources. In Norway, "hospital-at-home" refers to care given by teams from the hospital pediatric wards who provide treatment and care in the family's home. When children need home visits multiple times daily, the hospital-at-home often reaches out to municipality healthcare providers, asking them to share this task. We aimed to explore the collaboration between stakeholders to gain knowledge on matters concerning the transfer of pediatric competence between hospital and home-based care, and to gain insight into how to set up the service for children in the future. We conducted three focus group interviews. The results showed that managing hospital-at-home collaboratively came with various challenges concerning unclear responsibilities between hospitals and homecare services and several obstacles to setting up cooperation across service levels. Thus, positive collaboration experiences between hospital and homecare settings were shared. Formalizing this collaboration was considered important for future collaboration. Building competence and learning from and with each other ensures better conditions for success if the collaboration is organized and facilitated through agreements between the hospital and the municipalities.
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The complex work of addressing intergenerational adversities, like violence, abuse, and neglect through perinatal psychotherapy, is understudied. Especially noticeable is the paucity of studies giving voice to the therapists. This study explored therapeutic processes through the perspectives of seven Norwegian therapists. A qualitative approach was chosen with individual interviews and a follow-up focus group. Data were analyzed using reflexive thematic analysis. We identified one overarching theme: To maintain a reflective therapeutic capacity, and two main themes with associated subthemes: 1) Alliance work when a caring system comes to therapy to fight generations of adversities and 2) The complex therapeutic work of addressing generational adversities in perinatal psychotherapy. Findings from the present study indicate that maintaining a reflective stance is essential yet challenging when addressing intergenerational adversities, requiring a holding environment for the therapists. The primary vehicle of change was perceived as a safe enough therapeutic alliance to explore new ways of being together, contrasting earlier experiences. A key question raised was how to give caregivers enough time to trust the therapist without compromising the safety and development of the child. The essence of the therapeutic work was to reduce risk factors and increase protective factors through multiple ports of entry.
El complejo trabajo de abordar el tema de adversidades intergeneracionales, como violencia, abuso y negligencia a través de la sicoterapia perinatal, no se ha estudiado lo suficiente. Especialmente perceptible es la escasez de estudios que les den voz a los terapeutas. Este estudio exploró los procesos terapéuticos a través de perspectivas de siete terapeutas noruegos. Se escogió un acercamiento cualitativo con entrevistas individuales y un grupo de enfoque como seguimiento. Se analizaron los datos usando un análisis temático reflexivo. Identificamos un tema global: Mantener una capacidad terapéutica reflexiva, así como dos temas principales con subtemas asociados: 1) Trabajo en alianza cuando un sistema de cuidados llega a la terapia, para combatir generaciones de adversidades y 2) El complejo trabajo terapéutico de abordar el tema de adversidades generacionales en la sicoterapia perinatal. Los resultados del presente estudio indicaron que mantener una postura de reflexión es esencial, aunque desafiante, cuando se aborda el tema de adversidades generacionales, lo cual requiere un entorno o espacio favorable para los terapeutas. La percepción es que el vehículo primario para el cambio es una suficientemente segura alianza terapéutica para explorar nuevas maneras de vivir juntos, contrastando las experiencias anteriores. Una pregunta clave que se planteó fue cómo darles a los cuidadores suficiente tiempo para que le tengan confianza al terapeuta sin comprometer la seguridad y el desarrollo del niño. La esencia del trabajo terapéutico fue reducir los factores de riesgo e incrementar los factores de protección por medio de múltiples puertas de entrada.
Le travail complexe qui consiste à s'attaquer aux adversités intergénérationnelles comme la violence, la maltraitance et la négligence au travers de la psychothérapie périnatale est sous-étudié. On constate surtout la rareté d'études donnant la parole aux thérapeutes. Cette étude a exploré les processus thérapeutiques au travers des perspectives de sept thérapeutes norvégiens. Une approche qualitative a été choisie avec des entretiens individuels et un groupe d'étude de suivi. Des données ont été analysées en utilisant une analyse réflective thématique. Nous avons identifié un thème général: maintenir une capacité thérapeutique réflective et deux thèmes principaux avec des sous-thèmes liés: 1) le travail d'alliance quand un système attentif en arrive à la thérapie pour contrecarrer des générations d'adversités et 2) le travail thérapeutique complexe qui consiste à s'attaquer aux adversités intergénérationnelles en psychothérapie périnatale. Les résultats de cette étude ont indiqué que le maintien d'une position de réflexion est essentiel mais pose également un défi lorsqu'on on s'attaque aux adversités intergénérationnelles, exigeant un environnement thérapeutique soutenant pour les thérapeutes. Le principal véhicule de changement a été perçu comme une alliance thérapeutique étant assez sûre pour l'exploration de nouvelles façons d'être ensemble, en contraste avec des expériences précédentes. Une question clé qui a été soulevée était de comment donner aux personnes prenant soin des enfants assez de temps pour avoir confiance au thérapeute sans compromettre la sécurité et le développement de l'enfant. L'essence du travail thérapeutique a consisté à réduire les facteurs de risque et à accroître les facteurs protecteurs au travers de plusieurs ports d'entrée.
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Poder Familiar , Psicoterapia , Gravidez , Feminino , Humanos , Criança , Pais , Pessoal Técnico de Saúde , Pesquisa QualitativaRESUMO
BACKGROUND: Vaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on viral replication in both upper and lower airways is important to evaluate in nonhuman primates. METHODS: Nonhuman primates received 10 or 100 µg of mRNA-1273, a vaccine encoding the prefusion-stabilized spike protein of SARS-CoV-2, or no vaccine. Antibody and T-cell responses were assessed before upper- and lower-airway challenge with SARS-CoV-2. Active viral replication and viral genomes in bronchoalveolar-lavage (BAL) fluid and nasal swab specimens were assessed by polymerase chain reaction, and histopathological analysis and viral quantification were performed on lung-tissue specimens. RESULTS: The mRNA-1273 vaccine candidate induced antibody levels exceeding those in human convalescent-phase serum, with live-virus reciprocal 50% inhibitory dilution (ID50) geometric mean titers of 501 in the 10-µg dose group and 3481 in the 100-µg dose group. Vaccination induced type 1 helper T-cell (Th1)-biased CD4 T-cell responses and low or undetectable Th2 or CD8 T-cell responses. Viral replication was not detectable in BAL fluid by day 2 after challenge in seven of eight animals in both vaccinated groups. No viral replication was detectable in the nose of any of the eight animals in the 100-µg dose group by day 2 after challenge, and limited inflammation or detectable viral genome or antigen was noted in lungs of animals in either vaccine group. CONCLUSIONS: Vaccination of nonhuman primates with mRNA-1273 induced robust SARS-CoV-2 neutralizing activity, rapid protection in the upper and lower airways, and no pathologic changes in the lung. (Funded by the National Institutes of Health and others.).
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Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , Vacinas Virais/imunologia , Vacina de mRNA-1273 contra 2019-nCoV , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Betacoronavirus/fisiologia , Antígenos CD4 , COVID-19 , Vacinas contra COVID-19 , Infecções por Coronavirus/patologia , Infecções por Coronavirus/terapia , Modelos Animais de Doenças , Relação Dose-Resposta Imunológica , Imunização Passiva , Pulmão/patologia , Pulmão/virologia , Macaca mulatta , Pneumonia Viral/patologia , Pneumonia Viral/terapia , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Linfócitos T/imunologia , Carga Viral , Vacinas Virais/administração & dosagem , Replicação Viral , Soroterapia para COVID-19RESUMO
BACKGROUND: Right from the beginning of the SARS-CoV-2 pandemic the general public faced the challenge to find reliable and understandable information in the overwhelming flood of information. To enhance informed decision-making, evidence-based information should be provided. Aim was to explore the general public's information needs and preferences on COVID-19 as well as the barriers to accessing evidence-based information. METHODS: We performed a cross-sectional study. Nine hundred twenty-seven panel members were invited to an online survey (12/2020-02/2021). The HeReCa-online-panel is installed at the Martin Luther University Halle-Wittenberg to assess regularly the general public's view on health issues in five regions in Germany. The survey was set up in LimeSurvey, with nine items, multiple-choice and open-ended questions that allowed to gather qualitative data. Quantitative data were analysed descriptively and a content analysis was carried out to categorise the qualitative data. RESULTS: Six hundred thirty-six panel members provided data; mean age 52 years, 56.2% female, and 64.9% with higher education qualifications. Asked about relevant topics related to COVID-19, most participants selected vaccination (63.8%), infection control (52%), and long-term effects (47.8%). The following 11 categories were derived from the qualitative analysis representing the topics of interest: vaccination, infection control, long-term effects, therapies, test methods, mental health, symptoms, structures for pandemic control, infrastructure in health care, research. Participants preferred traditional media (TV 70.6%; radio 58.5%; newspaper 32.7%) to social media, but also used the internet as sources of information, becoming aware of new information on websites (28.5%) or via email/newsletter (20.1%). The knowledge question (Which European country is most affected by the SARS-CoV-2 pandemic?) was correctly answered by 7.5% of participants. The Robert Koch Institute (93.7%) and the World Health Organization (78%) were well known, while other organisations providing health information were rarely known (< 10%). Barriers to accessing trustworthy information were lack of time (30.7%), little experience (23.1%), uncertainty about how to get access (22.2%), complexity and difficulties in understanding (23.9%), and a lack of target group orientation (15,3%). CONCLUSIONS: There are extensive information needs regarding various aspects on COVID-19 among the general population. In addition, target-specific dissemination strategies are still needed to reach different groups.
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COVID-19 , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , COVID-19/epidemiologia , SARS-CoV-2 , Estudos Transversais , Academias e Institutos , ConscientizaçãoRESUMO
High-affinity iron (Fe) scavenging compounds, or siderophores, are widely employed by soil bacteria to survive scarcity in bioavailable Fe. Siderophore biosynthesis relies on cellular carbon metabolism, despite reported decrease in both carbon uptake and Fe-containing metabolic proteins in Fe-deficient cells. Given this paradox, the metabolic network required to sustain the Fe-scavenging strategy is poorly understood. Here, through multiple 13C-metabolomics experiments with Fe-replete and Fe-limited cells, we uncover how soil Pseudomonas species reprogram their metabolic pathways to prioritize siderophore biosynthesis. Across the three species investigated (Pseudomonas putida KT2440, Pseudomonas protegens Pf-5, and Pseudomonas putida S12), siderophore secretion is higher during growth on gluconeogenic substrates than during growth on glycolytic substrates. In response to Fe limitation, we capture decreased flux toward the tricarboxylic acid (TCA) cycle during the metabolism of glycolytic substrates but, due to carbon recycling to the TCA cycle via enhanced anaplerosis, the metabolism of gluconeogenic substrates results in an increase in both siderophore secretion (up to threefold) and Fe extraction (up to sixfold) from soil minerals. During simultaneous feeding on the different substrate types, Fe deficiency triggers a hierarchy in substrate utilization, which is facilitated by changes in protein abundances for substrate uptake and initial catabolism. Rerouted metabolism further promotes favorable fluxes in the TCA cycle and the gluconeogenesis-anaplerosis nodes, despite decrease in several proteins in these pathways, to meet carbon and energy demands for siderophore precursors in accordance with increased proteins for siderophore biosynthesis. Hierarchical carbon metabolism thus serves as a critical survival strategy during the metal nutrient deficiency.
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Carbono/metabolismo , Ferro/metabolismo , Pseudomonas/metabolismo , Sideróforos/metabolismo , Isótopos de Carbono/análise , Ciclo do Ácido Cítrico , Enzimas/metabolismo , Gluconeogênese , Redes e Vias Metabólicas , Oligopeptídeos/metabolismo , Microbiologia do Solo , Ácido Succínico/metabolismoRESUMO
BACKGROUND: Virtual reality (VR)-based simulation is being increasingly used to train medical students in emergency medicine. However, because the usefulness of VR may depend on various factors, the best practices for implementing this technology in the medical school curriculum are yet to be determined. OBJECTIVE: The overall objective of our study was to assess the perceptions of a large cohort of students toward VR-based training and to identify the associations between these attitudes and individual factors, such as gender and age. METHODS: The authors implemented a voluntary, VR-based teaching session in the emergency medicine course at the Medical Faculty in Tübingen, Germany. Fourth-year medical students were invited to participate on a voluntary basis. Afterward, we asked the students about their perceptions, collected data on individual factors, and assessed the test scores achieved by them in the VR-based assessment scenarios. We used ordinal regression analysis and linear mixed-effects analysis to detect the impact of individual factors on the questionnaire answers. RESULTS: A total of 129 students participated in our study (mean age 24.7, SD 2.9 years; n=51, 39.8% male; n=77, 60.2% female). No student had previously used VR for learning, and only 4.7% (n=6) of the students had prior experience with VR. Most of the students agreed that VR can convey complex issues quickly (n=117, 91%), that VR is a useful addition to mannequin-based courses (n=114, 88%) or could even replace them (n=93, 72%), and that VR simulations should also be used for examinations (n=103, 80%). However, female students showed significantly less agreement with these statements. Most students perceived the VR scenario as realistic (n=69, 53%) and intuitive (n=62, 48%), with a relatively lower agreement for the latter among female respondents. We found high agreement among all participants (n=88, 69%) for immersion but strong disagreement (n=69, 54%) for empathy with the virtual patient. Only 3% (n=4) of the students felt confident regarding the medical content. Responses for the linguistic aspects of the scenario were largely mixed; however, most of the students were confident with the English language (not native) scenarios and disagreed that the scenario should be offered in their native language (female students agreed more strongly than male students). Most of the students would not have felt confident with the scenarios in a real-world context (n=69, 53%). Although physical symptoms during VR sessions were reported by 16% (n=21) of the respondents, this did not lead to the termination of the simulation. The regression analysis revealed that the final test scores were not influenced by gender, age, or prior experience in emergency medicine or with virtual reality. CONCLUSIONS: In this study, we observed a strong positive attitude in medical students toward VR-based teaching and assessment. However, this positivity was comparatively lower among female students, potentially indicating that gender differences need to be addressed when VR is implemented in the curriculum. Interestingly, gender, age, or prior experience did not influence the final test scores. Furthermore, confidence regarding the medical content was low, which suggests that the students may need further training in emergency medicine.
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Medicina de Emergência , Estudantes de Medicina , Realidade Virtual , Feminino , Masculino , Humanos , Adulto Jovem , Adulto , Estudos Prospectivos , Faculdades de MedicinaRESUMO
BACKGROUND: Surgical ward rounds are key element to point-of-care interprofessional postoperative treatment and technical and communicational aspects are relevant for the patient's safety and satisfaction. Due to COVID-19 restrictions, the training opportunity of experiencing a face-to-face surgical ward round was massively hampered and thus, we developed a digital concept. This study aims to investigate the feasibility of video-transmitted ward rounds integrating surgical and communicational aspects with live streaming from wards. Further, medical students were asked for their satisfaction and their subjective learning success. METHODS: The proof-of-concept study consisted of self-reported subjective evaluation of competences in ward round skills. Qualitative feedback was collected to gain deeper insight and students' empathy was rated by using the student version of the Jefferson Empathy Scale (JES). RESULTS: One hundred three medical students participated. The students were satisfied with the video-transmitted ward round (M = 3.54; SD = 1.22). In the subjective evaluation students' ward round competencies rose significantly (p < .001, Mpre = 3.00, SD = 0.77; Mpost = 3.76, SD = 0.75). The surgeon was rated as empathic (M = 119.05; SD = 10.09). In the qualitative feedback they named helpful aspects like including an expert for communication. However, they preferred the face-to-face setting in comparison to the digital concept. CONCLUSIONS: It was feasible to implement a video-transmitted ward round within a pandemic. The format worked technically, was well-accepted and also led to a subjective rise in the students' competencies. Video-transmitted ward rounds may be integrated to support the medical education, though, they cannot replace the face-to-face setting.
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COVID-19 , Cirurgiões , Humanos , Estudo de Prova de Conceito , Estudos de Viabilidade , ComunicaçãoRESUMO
Toxicity safety assessments are a fundamental part of the lifecycle of products and aim to protect human health and the environment from harmful exposures to chemical substances. To make decisions regarding the suitability of testing strategies, the applicability of individual tests or concluding an assessment for an individual chemical requires data. This review outlines how different forms of data sharing, from enhancing publicly-available data to extracting knowledge from commercially-sensitive data, leads to increased quantity and quality of evidence being available for safety assessors to review. This can result in more confident decisions for different use cases in the context of chemical safety assessments. Although a number of challenges remain with progressing the evolution of toxicity safety assessments, data sharing should be considered as a key approach to accelerating the development and uptake of new best practices.
Assuntos
Segurança Química , Humanos , Medição de Risco , Tomada de DecisõesRESUMO
BACKGROUND: Older patients are the most frequent users of initial hospital admissions and readmissions. Both hospital admission and discharge require communication and coordination between healthcare professionals within the hospital, and between professionals in hospitals and primary healthcare. We have identified few studies exploring hospital physicians' perspectives on older patients' pathways in the interface between hospital and primary healthcare services. The aim of this study was to explore hospital physicians' experiences and reflections on their work and role in relation to older patients' pathways between hospital and primary healthcare. Specifically, we focused on the challenges they faced and how they dealt with these in relation to admission and discharge, and their suggestions for service improvements that could facilitate older patients' pathway. METHODS: We used a qualitative approach, conducting individual in-depth interviews with 18 hospital physicians from two hospitals in eastern Norway. Data were analyzed using systematic text condensation, in line with a four-step prosedure developed by Malterud. RESULTS: The participants emphasized challenges in the communication about patients across the two service levels. Moreover, they described being in a squeeze between prioritizing patients and trying to ensure a proper flow of patients through the hospital wards, but with restricted possibilities to influence on the admissions. They also described a frustration regarding the lack of influence on the healthcare delivery after discharge. The participants had various suggestions for service improvements which might be beneficial to older patients. CONCLUSIONS: The results demonstrate that the hospital physicians perceived being squeezed between professional autonomy and limited capacity at the hospital, and between their medical judgement as a specialist and their power to decide on hospital admissions for old patients and also on the delivery of health care services to patients after discharge.
Assuntos
Hospitais , Médicos , Atenção à Saúde , Humanos , Alta do Paciente , Pesquisa QualitativaRESUMO
The Covid-19 pandemic necessitated Emergency Remote Teaching (ERT): the sudden move of educational materials online. While ERT served its purpose, medical teachers are now faced with the long-term and complex demands of formal online teaching. One of these demands is ethical online teaching. Although ethical teaching is practiced in face-to-face situations, online teaching has new ethical issues that must be accommodated, and medical teachers who wish to teach online must be aware of these and need to teach ethically. This Guide leads the medical teacher through this maze of complex ethical issues to transform ERT into ethical online teaching. It begins by setting the context and needs and identifies the relevant fundamental ethical principles and issues. It then guides the medical teacher through the practical application of these ethical principles, covering course design and layout (including the curriculum document, implementation, on-screen layouts, material accessibility), methods of interaction (synchronous and asynchronous), feedback, supervision and counselling, deeper accessibility issues, issues specific to clinical teaching, and assessment. It then discusses course reviews (peer-review and student evaluations), student monitoring and analytics, and archiving. The Guide aims to be a useful tool for medical teachers to solidly ground their online teaching practices in ethical principles.
Assuntos
COVID-19 , Educação a Distância , Educação Médica , Humanos , Pandemias , Educação Médica/métodos , Currículo , EnsinoRESUMO
BACKGROUND: Peer-assisted learning represents a favoured method of teaching in universities. The COVID-19 pandemic has necessitated transferring medical education to digital formats, and subsequently, the question has arisen of whether online tutorials might be effective. This study, thus, investigated the efficacy of online tutorials in a communication course by assessing the interaction, verbal communication, and nonverbal communication of tutors and students. METHODS: Second-year medical students were invited to participate in this longitudinal quantitative study. Validated and self-developed questionnaires (e.g., Jefferson Empathy Scale) including 39 questions (rated on a 7- or 5-point Likert scale) were used to assess the different variables including interaction, verbal and nonverbal communication and students' learning success. RESULTS: Out of 165 medical students, 128 took part in the study. The students as well as tutors reported that they found each other likeable (Mstudents = 4.60±0.71; Mtutors = 4.38±0.53; p > .05). Learning success increased throughout the communication course (Cohen's d = 0.36-0.74). The nonverbal and verbal communication in the simulated patient (SP) encounter was also rated as high by all three groups (Mnonverbal = 3.90±0.83; Mverbal = 4.88±0.35). CONCLUSIONS: Interaction as well as nonverbal and verbal communication occurred in the online format, indicating that online tutorials can be effective. The implementation of SPs increases the efficiency of synchronous online learning as it enhances the simulation of a real patient-physician encounter. Thus, online tutorials are a valuable amendment to medical education.