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The diffusion of cations in organic solvent solutions is important for the performance of metal-ion batteries. In this article, pulsed field gradient nuclear magnetic resonance experiments and fully atomistic molecular dynamic simulations were employed to study the temperature-dependent diffusive behavior of various liquid electrolytes representing 1M propylene carbonate solutions of metal salts with bis(trifluoromethylsulfonyl)imide (TFSI-) or hexafluorophosphate (PF6-) anions commonly used in lithium-ion batteries and beyond. The experimental studies revealed the temperature dependence of the diffusion coefficients for the propylene carbonate (PC) solvent and for the anions following an Arrhenius type of behavior. It was observed that the PC molecules are the faster species. For the monovalent cations (Li+, Na+, K+), the PC solvent diffusion was enhanced as the cation size increased, while for the divalent cations (Mg2+, Ca2+, Sr2+, Ba2+), the opposite trend was observed, i.e., the diffusion coefficients decreased as the cation size increased. The anion diffusion in LiTFSI and NaTFSI solutions was found to be similar, while in electrolytes with divalent cations, a decrease in anion diffusion with increasing cation size was observed. It was shown that non-polarizable charge-scaled force fields could correspond perfectly to the experimental values of the anion and PC solvent diffusion coefficients in salt solutions of both monovalent (Li+, Na+, K+) and divalent (Mg2+, Ca2+, Sr2+, Ba2+) cations at a range of operational temperatures. Finally, after calculating the radial distribution functions between cations, anions, and solvent molecules, the increase in the PC diffusion coefficient established with the increase in cation size for monovalent cations was clearly explained by the large hydration shell of small Li+ cations, due to their strong interaction with the PC solvent. In solutions with larger monovalent cations, such as Na+, and with a smaller solvation shell of PC, the PC diffusion is faster due to more liberated solvent molecules. In the salt solutions with divalent cations, both the anion and the PC diffusion coefficients decreased as the cation size increased due to an enhanced cation-anion coordination, which was accompanied by an increase in the amount of PC in the cation solvation shell due to the presence of anions.
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The first-in-human clinical trial of the CD28-specific monoclonal antibody (mAb) TGN1412 resulted in a life-threatening cytokine release syndrome. Although TGN1412 was designed as IgG4, known for weak Fc:Fcγ receptor (FcγR) interactions, these interactions contributed to TGN1412-induced T-cell activation. Using cell lines (TFs) expressing human FcγRI, -IIa, -IIb, or -III, we show that TGN1412 and TGN1412 as IgG1 and IgG2 are bound by FcγRs as it can be deduced from literature. However, upon coculture of TGN1412-decorated T cells with TFs or human primary blood cells, we observed that binding capacities by FcγRs do not correlate with the strength of the mediated effector function. FcγRIIa and FcγRIIb, showing no or very minor binding to TGN1412, mediated strongest T cell proliferation, while high-affinity FcγRI, exhibiting strong TGN1412 binding, mediated hardly any T-cell proliferation. These findings are of biological relevance because we show that FcγRI binds TGN1412, thus prevents binding to FcγRIIa or FcγRIIb, and consequently disables T-cell proliferation. In line with this, FcγRI- FcγRII+ but not FcγRI+ FcγRII+ monocytes mediate TGN1412-induced T-cell proliferation. Collectively, by using TGN1412 as example, our results indicate that binding of monomeric IgG subclasses does not predict the FcγR-mediated effector function, which has major implications for the design of therapeutic mAbs.
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Anticuerpos Monoclonales Humanizados/metabolismo , Síndrome de Liberación de Citoquinas/inmunología , Inmunoglobulina G/metabolismo , Inmunoterapia/efectos adversos , Monocitos/inmunología , Receptores de IgG/metabolismo , Linfocitos T/inmunología , Animales , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antígenos CD28/antagonistas & inhibidores , Línea Celular , Proliferación Celular , Síndrome de Liberación de Citoquinas/etiología , Humanos , Activación de Linfocitos , Ratones , Unión Proteica , Receptores de IgG/genéticaRESUMEN
BACKGROUND: Individualization and patient-specific optimization of treatment is a major goal of modern health care. One way to achieve this goal is the application of high-resolution diagnostics together with the application of targeted therapies. However, the rising number of different treatment modalities also induces new challenges: Whereas randomized clinical trials focus on proving average treatment effects in specific groups of patients, direct conclusions at the individual patient level are problematic. Thus, the identification of the best patient-specific treatment options remains an open question. Systems medicine, specifically mechanistic mathematical models, can substantially support individual treatment optimization. In addition to providing a better general understanding of disease mechanisms and treatment effects, these models allow for an identification of patient-specific parameterizations and, therefore, provide individualized predictions for the effect of different treatment modalities. RESULTS: In the following we describe a software framework that facilitates the integration of mathematical models and computer simulations into routine clinical processes to support decision-making. This is achieved by combining standard data management and data exploration tools, with the generation and visualization of mathematical model predictions for treatment options at an individual patient level. CONCLUSIONS: By integrating model results in an audit trail compatible manner into established clinical workflows, our framework has the potential to foster the use of systems-medical approaches in clinical practice. We illustrate the framework application by two use cases from the field of haematological oncology.
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Toma de Decisiones Clínicas/métodos , Simulación por Computador , Sistemas de Apoyo a Decisiones Clínicas , Enfermedades Hematológicas , Modelos Teóricos , Programas Informáticos , Flujo de Trabajo , Humanos , Prueba de Estudio ConceptualRESUMEN
The integration of artificial intelligence (AI) algorithms into clinical practice holds immense potential to improve patient care, but widespread adoption still faces significant challenges, including interoperability issues. We propose a concept for the agile development of an IT platform to integrate AI-based applications into clinical workflows for a use case in ophthalmology.
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Inteligencia Artificial , Integración de Sistemas , Oftalmología , Sistemas de Apoyo a Decisiones Clínicas/organización & administración , Humanos , Registros Electrónicos de Salud , Algoritmos , Flujo de TrabajoRESUMEN
This study advances the utility of synthetic study data in hematology, particularly for Acute Myeloid Leukemia (AML), by facilitating its integration into healthcare systems and research platforms through standardization into the Observational Medical Outcomes Partnership (OMOP) and Fast Healthcare Interoperability Resources (FHIR) formats. In our previous work, we addressed the need for high-quality patient data and used CTAB-GAN+ and Normalizing Flow (NFlow) to synthesize data from 1606 patients across four multicenter AML clinical trials. We published the generated synthetic cohorts, that accurately replicate the distributions of key demographic, laboratory, molecular, and cytogenetic variables, alongside patient outcomes, demonstrating high fidelity and usability. The conversion to the OMOP format opens avenues for comparative observational multi-center research by enabling seamless combination with related OMOP datasets, thereby broadening the scope of AML research. Similarly, standardization into FHIR facilitates further developments of applications, e.g. via the SMART-on-FHIR platform, offering realistic test data. This effort aims to foster a more collaborative research environment and facilitate the development of innovative tools and applications in AML care and research.
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Leucemia Mieloide Aguda , Humanos , Hematología , Interoperabilidad de la Información en Salud , Registros Electrónicos de Salud , Evaluación de Resultado en la Atención de SaludRESUMEN
Introduction: Obtaining real-world data from routine clinical care is of growing interest for scientific research and personalized medicine. Despite the abundance of medical data across various facilities - including hospitals, outpatient clinics, and physician practices - the intersectoral exchange of information remains largely hindered due to differences in data structure, content, and adherence to data protection regulations. In response to this challenge, the Medical Informatics Initiative (MII) was launched in Germany, focusing initially on university hospitals to foster the exchange and utilization of real-world data through the development of standardized methods and tools, including the creation of a common core dataset. Our aim, as part of the Medical Informatics Research Hub in Saxony (MiHUBx), is to extend the MII concepts to non-university healthcare providers in a more seamless manner to enable the exchange of real-world data among intersectoral medical sites. Methods: We investigated what services are needed to facilitate the provision of harmonized real-world data for cross-site research. On this basis, we designed a Service Platform Prototype that hosts services for data harmonization, adhering to the globally recognized Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR) international standard communication format and the Observational Medical Outcomes Partnership (OMOP) common data model (CDM). Leveraging these standards, we implemented additional services facilitating data utilization, exchange and analysis. Throughout the development phase, we collaborated with an interdisciplinary team of experts from the fields of system administration, software engineering and technology acceptance to ensure that the solution is sustainable and reusable in the long term. Results: We have developed the pre-built packages "ResearchData-to-FHIR," "FHIR-to-OMOP," and "Addons," which provide the services for data harmonization and provision of project-related real-world data in both the FHIR MII Core dataset format (CDS) and the OMOP CDM format as well as utilization and a Service Platform Prototype to streamline data management and use. Conclusion: Our development shows a possible approach to extend the MII concepts to non-university healthcare providers to enable cross-site research on real-world data. Our Service Platform Prototype can thus pave the way for intersectoral data sharing, federated analysis, and provision of SMART-on-FHIR applications to support clinical decision making.
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Human cytomegalovirus (HCMV) encodes four viral Fc-gamma receptors (vFcγRs) that counteract antibody-mediated activation in vitro , but their role in infection and pathogenesis is unknown. To examine the in vivo function of vFcγRs in animal hosts closely related to humans, we identified and characterized vFcγRs encoded by rhesus CMV (RhCMV). We demonstrate that Rh05, Rh152/151 and Rh173 represent the complete set of RhCMV vFcγRs, each displaying functional similarities to their respective HCMV orthologs with respect to antagonizing host FcγR activation in vitro . When RhCMV-naïve rhesus macaques were infected with vFcγR-deleted RhCMV, peak plasma viremia levels and anti-RhCMV antibody responses were comparable to wildtype infections. However, the duration of plasma viremia was significantly shortened in immunocompetent, but not in CD4+ T cell-depleted animals. Since vFcγRs were not required for superinfection, we conclude that vFcγRs delay control by virus-specific adaptive immune responses, particularly antibodies, during primary infection.
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Immune cell phenotyping frequently detects lineage-unrelated receptors. Here, we report that surface receptors can be transferred from primary macrophages to CD4 T cells and identify the Fcγ receptor CD32 as driver and cargo of this trogocytotic transfer. Filamentous CD32+ nanoprotrusions deposit distinct plasma membrane patches onto target T cells. Transferred receptors confer cell migration and adhesion properties, and macrophage-derived membrane patches render resting CD4 T cells susceptible to infection by serving as hotspots for HIV-1 binding. Antibodies that recognize T cell epitopes enhance CD32-mediated trogocytosis. Such autoreactive anti-HIV-1 envelope antibodies can be found in the blood of HIV-1 patients and, consistently, the percentage of CD32+ CD4 T cells is increased in their blood. This CD32-mediated, antigen-independent cell communication mode transiently expands the receptor repertoire and functionality of immune cells. HIV-1 hijacks this mechanism by triggering the generation of trogocytosis-promoting autoantibodies to gain access to immune cells critical to its persistence.
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Infecciones por VIH , Seropositividad para VIH , VIH-1 , Humanos , Linfocitos T CD4-Positivos , Receptores de IgG/metabolismo , Autoanticuerpos/metabolismo , TrogocitosisRESUMEN
The transfer of new insights from basic or clinical research into clinical routine is usually a lengthy and time-consuming process. Conversely, there are still many barriers to directly provide and use routine data in the context of basic and clinical research. In particular, no coherent software solution is available that allows a convenient and immediate bidirectional transfer of data between concrete treatment contexts and research settings. Here, we present a generic framework that integrates health data (e.g., clinical, molecular) and computational analytics (e.g., model predictions, statistical evaluations, visualizations) into a clinical software solution which simultaneously supports both patient-specific healthcare decisions and research efforts, while also adhering to the requirements for data protection and data quality. Specifically, our work is based on a recently established generic data management concept, for which we designed and implemented a web-based software framework that integrates data analysis, visualization as well as computer simulation and model prediction with audit trail functionality and a regulation-compliant pseudonymization service. Within the front-end application, we established two tailored views: a clinical (i.e., treatment context) perspective focusing on patient-specific data visualization, analysis and outcome prediction and a research perspective focusing on the exploration of pseudonymized data. We illustrate the application of our generic framework by two use-cases from the field of haematology/oncology. Our implementation demonstrates the feasibility of an integrated generation and backward propagation of data analysis results and model predictions at an individual patient level into clinical decision-making processes while enabling seamless integration into a clinical information system or an electronic health record.
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Human cytomegalovirus (HCMV) frequently causes congenital infections, resulting in birth defects and developmental disorders. A vaccine is needed, but unavailable. We analyzed the potential of CMV mutants, lacking their STAT2 antagonists to serve as live attenuated vaccine viruses in mice. Infections with attenuated viruses elicited strong ELISA-reactive binding IgG responses and induced neutralizing antibodies as well as antibodies stimulating cellular Fcγ receptors, including the antibody-dependent cellular cytotoxicity (ADCC)-eliciting receptors FcγRIII/CD16 and FcγRIV. Accordingly, vaccinated mice were fully protected against challenge infections. Female mice vaccinated prior to gestation transmitted CMV-specific IgG to their offspring, which protected the progeny from perinatal infections in a mouse model for congenital CMV disease. To define the role of maternal antibodies, female mice either capable or incapable of producing antibodies were vaccinated and subsequently bred to males of the opposite genotype. Challenge infections of the genotypically identical F1 generation revealed the indispensability of maternal antibodies for vaccine-induced protection against cytomegaloviruses.
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Human cytomegalovirus (HCMV) is endowed with multiple highly sophisticated immune evasion strategies. This includes the evasion from antibody mediated immune control by counteracting host Fc-gamma receptor (FcγR) mediated immune control mechanisms such as antibody-dependent cellular cytotoxicity (ADCC). We have previously shown that HCMV avoids FcγR activation by concomitant expression of the viral Fc-gamma-binding glycoproteins (vFcγRs) gp34 and gp68. We now show that gp34 and gp68 bind IgG simultaneously at topologically different Fcγ sites and achieve efficient antagonization of host FcγR activation by distinct but synergizing mechanisms. While gp34 enhances immune complex internalization, gp68 acts as inhibitor of host FcγR binding to immune complexes. In doing so, gp68 induces Fcγ accessibility to gp34 and simultaneously limits host FcγR recognition. The synergy of gp34 and gp68 is compelled by the interfering influence of excessive non-immune IgG ligands and highlights conformational changes within the IgG globular chains critical for antibody effector function.
Human cytomegalovirus is a type of herpes virus that rarely causes symptoms in healthy people but can cause serious complications in unborn babies and in people with compromised immune systems, such as transplant recipients. The virus has found ways to successfully evade the immune system, and once infected, the body retains the virus for life. It deploys an arsenal of proteins that bind to antibodies, specialized proteins the immune system uses to flag virus-infected cells for destruction. This prevents certain cells of the immune system, the natural killer cells, from recognizing and destroying virus-infected cells. These immune-evading proteins are called viral Fc-gamma receptors, or vFcγRs. While it has been previously shown that these receptors are able to evade the immune system, it remained unknown how exactly they prevent natural killer cells from recognizing infected cells. Now, Kolb et al. show that the cytomegalovirus deploys two vFcγRs called gp34 and gp68, which work together to block natural killer cells. The latter reduces the ability of natural killer cells to bind to antibodies on cytomegalovirus-infected cells. This paves the way for gp34 to pull virus proteins from the surface of the infected cell, making them inaccessible to the immune system. Neither protein fully protects virus-infected cells on its own, but together they are highly effective. The experiments reveal further details about how cytomegalovirus uses two defense mechanisms simultaneously to outmaneuver the immune system. Understanding this two-part viral evasion system may help scientists to develop vaccines or new treatments that can protect vulnerable people from diseases caused by the cytomegalovirus.
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Citomegalovirus/inmunología , Inmunoglobulina G/metabolismo , Receptores de IgG/antagonistas & inhibidores , Citotoxicidad Celular Dependiente de Anticuerpos , Proteínas Portadoras/metabolismo , Línea Celular , Citomegalovirus/metabolismo , Glicoproteínas/metabolismo , Humanos , Evasión Inmune , Células Asesinas Naturales/metabolismo , Glicoproteínas de Membrana/metabolismo , Unión Proteica , Receptores de IgG/inmunología , Receptores de IgG/metabolismo , Proteínas Virales/metabolismoRESUMEN
Viral infections are a global disease burden with only a limited number of antiviral agents available. Due to newly emerging viral pathogens and increasing occurrence of drug resistance, there is a continuous need for additional therapeutic options, preferably with extended target range. In the present study, we describe a novel antiviral peptide with broad activity against several double-stranded DNA viruses. The 22-mer peptide TAT-I24 potently neutralized viruses such as herpes simplex viruses, adenovirus type 5, cytomegalovirus, vaccinia virus, and simian virus 40 in cell culture models, while being less active against RNA viruses. The peptide TAT-I24 therefore represents a novel and promising drug candidate for use against double-stranded DNA viruses.
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OBJECTIVE: To describe the lymphatic vessel density and to determine the functional and prognostic significance of tumoral lymphatic vessels in upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: The study included 65 patients who had a radical nephroureterectomy (RNU) for UTUC between 1997 and 2004. All pathological slides were re-evaluated by one reference pathologist and clinical data were reviewed. Lymphatic endothelial cells (LECs) were stained immunohistochemically using D2-40. The lymphatic vessel density (LVD) was described in representative intratumoral (ITLVD), peritumoral (PTLVD) and non-tumoral (NTLVD) areas. Random samples were selected for double-immunostaining with D2-40 and CD-34 (to distinguish blood and lymphatic vessels) and the proliferation marker Ki-67 to detect lymphangiogenesis. The primary outcome measures were disease-specific survival (DSS) and disease recurrence (urothelial and/or distant). RESULTS: The median (interquartile range) PTLVD was 4.0 (3.0-6.3), and significantly higher than that for ITLVD, of 0.3 (0-1.7) (P < 0.001), and NTLVD, of 3 (2.0-3.7) (P < 0.001). Both a higher ITLVD and PTLVD, the presence of lymphovascular invasion (LVI) (each P < 0.001) and a high tumour grade (P = 0.004) were associated with reduced DSS on univariate analysis. A higher PTLVD (P = 0.028) and the presence of LVI (P = 0.020) independently predicted reduced DSS on multivariate analysis. IT and PT lymphatic vessels showed proliferating LECs in all analysed samples. CONCLUSION: Lymphangiogenesis is present in UTUC, as shown by a significantly increased PTLVD and proliferating LECs. Our findings suggest functional relevance of PT lymphatic vessels during lymphatic tumour spread. PTLVD is a potential novel prognostic factor for DSS in UTUC, and further prospective studies will be needed to determine the effect of its routine evaluation on clinical outcomes of this malignancy.
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Carcinoma de Células Transicionales/patología , Linfangiogénesis , Vasos Linfáticos/patología , Nefrectomía/métodos , Neoplasias Urológicas/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/cirugía , Femenino , Humanos , Inmunohistoquímica , Metástasis Linfática , Masculino , Glicoproteínas de Membrana/metabolismo , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Pronóstico , Resultado del Tratamiento , Neoplasias Urológicas/cirugíaRESUMEN
Lower respiratory tract infections, such as infections caused by influenza A viruses, are a constant threat for public health. Antivirals are indispensable to control disease caused by epidemic as well as pandemic influenza A. We developed a novel anti-influenza A virus approach based on an engineered single-domain antibody (VHH) construct that can selectively recruit innate immune cells to the sites of virus replication. This protective construct comprises two VHHs. One VHH binds with nanomolar affinity to the conserved influenza A matrix protein 2 (M2) ectodomain (M2e). Co-crystal structure analysis revealed that the complementarity determining regions 2 and 3 of this VHH embrace M2e. The second selected VHH specifically binds to the mouse Fcγ Receptor IV (FcγRIV) and was genetically fused to the M2e-specific VHH, which resulted in a bi-specific VHH-based construct that could be efficiently expressed in Pichia pastoris. In the presence of M2 expressing or influenza A virus-infected target cells, this single domain antibody construct selectively activated the mouse FcγRIV. Moreover, intranasal delivery of this bispecific FcγRIV-engaging VHH construct protected wild type but not FcγRIV-/- mice against challenge with an H3N2 influenza virus. These results provide proof of concept that VHHs directed against a surface exposed viral antigen can be readily armed with effector functions that trigger protective antiviral activity beyond direct virus neutralization.
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Anticuerpos Antivirales/inmunología , Virus de la Influenza A/inmunología , Gripe Humana/inmunología , Gripe Humana/metabolismo , Gripe Humana/virología , Receptores de IgG/metabolismo , Anticuerpos de Dominio Único/inmunología , Proteínas de la Matriz Viral/inmunología , Secuencia de Aminoácidos , Animales , Anticuerpos Biespecíficos/química , Anticuerpos Biespecíficos/inmunología , Anticuerpos Antivirales/química , Línea Celular , Humanos , Ratones , Modelos Moleculares , Péptidos/química , Péptidos/inmunología , Conformación Proteica , Receptores de IgG/química , Anticuerpos de Dominio Único/química , Relación Estructura-Actividad , Proteínas de la Matriz Viral/químicaRESUMEN
Procrastination is a form of self-regulation failure characterized by the irrational delay of tasks despite potentially negative consequences. Previous research on procrastination was mainly conducted in academic settings, oftentimes combined with a focus on individual differences. As a consequence, scholarly knowledge about how situational factors affect procrastination in work settings is still scarce. Drawing on job stress literature, we assumed that work characteristics go along with cognitive appraisals of the work situation as a challenge and/or hindrance, that these cognitive appraisals affect employees' self-regulation effort to overcome inner resistances, and that self-regulation effort should in turn be related to workplace procrastination. In our study, we focused on three specific work characteristics that we expected to trigger both challenge and hindrance appraisal simultaneously: time pressure, problem solving, and planning and decision-making. We hypothesized serial indirect effects of these work characteristics on workplace procrastination via cognitive appraisal and self-regulation processes that unfold within individuals over short periods of time. Consequently, we conducted a diary study with three measurement occasions per workday over a period of 12 days. Overall, 762 day-level datasets from 110 employees were included in Bayesian multilevel structural equation modeling (MSEM; controlled for sleep quality and occupational self-efficacy). Our results revealed negative serial indirect effects of all three work characteristics on workplace procrastination via increased challenge appraisal and subsequently reduced self-regulation effort. Further, our results showed a positive serial indirect effect of time pressure (but not of problem solving or planning and decision making) on workplace procrastination via increased hindrance appraisal and subsequently increased self-regulation effort. Overall, our study showed that work characteristics are linked to workplace procrastination via within-person processes of cognitive appraisal and self-regulation. Because not all work characteristics triggered hindrance appraisal, we argue that it may make sense to further differentiate challenge stressors in the future. Moreover, cognitive appraisals affected self-regulation effort only on the within-person level. On the between-person level self-regulation effort was strongly negatively related with occupational self-efficacy. Thus, we conclude that depending the perspective on procrastination (e.g., differential psychology perspective vs. situational perspective) different variables will be considered relevant to explain the emergence of procrastination.
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INTRODUCTION: Following the recent amendment to the Medical Education Act in Germany (Approbationsordnung 2002) and the abolition of the preliminary approbation for early residency (AiP), the discussion increasingly focuses on the restructuring of German post-graduate medical training. The training should include well-defined learning objectives and an educational concept with a central emphasis on communication skills training. In the German-speaking countries there has as yet been no publication of a structured training course for the improvement of communication skills in the context of post-graduate education. METHODS: Jointly designed by the University of Heidelberg's Clinic of Internal Medicine and Clinic of Paediatrics, this study aimed to measure the effect of a training programme for handling problems and difficult situations arising in the communication with parents and patients. 28 paediatric residents took part in a randomised controlled trial using standardized patients and video-feedback (intervention group: N = 14; control group: N = 14). Upon completion of the study, the control group also received training and was subsequently evaluated. The training course consisted of four units, lasting 90 minutes each. Both the acceptance of the training units and the self-evaluation of communication skills in dealing with parents were subject to assessment. RESULTS: The participating residents acknowledged the training course to be an extremely useful tool for improving their communication skills and confidence in dealing with the parents of ill children. A pre-post comparison of self-assessed communication skills revealed a significant increase in the intervention group, but not in the control group. DISCUSSION: The structured training course presented in the current study proved highly effective and should serve as a model for a compulsory component of a post-graduate training.
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Educación Basada en Competencias/métodos , Curriculum/normas , Educación Médica Continua , Relaciones Médico-Paciente , Comunicación , Educación Basada en Competencias/organización & administración , Educación Basada en Competencias/normas , Alemania , Humanos , Enseñanza/métodosRESUMEN
In a laboratory experiment, we compare the relative impact of two possible determinants of intuitive evaluative judgments: ease of recognition and total value of prior encounters with a target. Participants encode daily return values of shares on the stock market while watching videotaped ads on the computer screen. This dual-task procedure ensures that participants subsequently lack relevant event memories and thus have to rely on their intuition when evaluating the targets. In the presentation, the share appearing least frequently produced the highest sum of returns. In contrast, the share appearing most frequently produced the lowest sum of returns. Evaluative judgments reveal a preference for the share with the highest sum of returns, although, as evident from recognition latencies, it was the one that was more difficult to recognize. The results provide evidence for the value-account model of implicit attitude formation (Betsch, Plessner, Schwieren, & Gütig, 2001), which predicts that intuitive evaluative judgments reflect the total value of prior encounters.
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Intuición , Reconocimiento en Psicología , Adulto , Femenino , Humanos , MasculinoRESUMEN
The constant region of IgG antibodies mediates antiviral activities upon engaging host Fcγ receptors (FcγRs) expressed by a variety of immune cells, such as antibody-dependent cellullar cytotoxcity (ADCC) executed by natural killer (NK)cells. Human cytomegalovirus (HCMV) is unique among viruses by encoding also an array of several Fcγ-binding glycoproteins with cell surface disposition and concomitant incorporation into the virion. Evidence is increasing that the virus-encoded Fcγ receptors differ in their Fcγ binding mode but effectively operate as adversaries of host FcγRs since they are able to prevent IgG-mediated triggering of activating host FcγRs, i.e., FcγRI, FcγRIIA, and FcγRIIIA. Here we discuss virus-encoded FcγRs as the first known HCMV inhibitors of IgG-mediated immunity which could account for the limited efficacy of HCMV hyperimmune globulin in clinical settings. A better understanding of their molecular mode of action opens up new perspectives for improving IgG therapies against HCMV disease.
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Infecciones por Citomegalovirus/inmunología , Citomegalovirus/genética , Citomegalovirus/inmunología , Receptores de IgG/genética , Proteínas Virales/genética , Inmunidad Adaptativa , Animales , Anticuerpos Antivirales/inmunología , Proteínas Portadoras/metabolismo , Infecciones por Citomegalovirus/genética , Infecciones por Citomegalovirus/metabolismo , Infecciones por Citomegalovirus/terapia , Humanos , Inmunidad Innata , Inmunoglobulina G/inmunología , Inmunomodulación , Inmunoterapia , Ligandos , Unión Proteica , Receptores de IgG/química , Receptores de IgG/metabolismo , Proteínas Virales/metabolismoRESUMEN
BACKGROUND: Peer-assisted learning (PAL) has become a well-accepted teaching method within medical education. However, descriptions of on-ward PAL programs are rare. A focus group analysis of a newly established PAL program on an internal medicine ward was conducted to provide insights into PAL teaching from a student perspective. PURPOSE: To provide insights into students' experiences regarding their on-ward training with and without accompanying PAL tutors. METHODS: A total of N=168 medical students in their sixth semester participated in the investigation (intervention group: N=88; control group: N=80). The intervention group took part in the PAL program, while the control group received standard on-ward training. There were seven focus groups with N=43 participants (intervention group: four focus groups, N=28 participants; control group: three focus groups, N=15 participants). The discussions were analyzed using content analysis. RESULTS: The intervention group emphasized the role of the tutors as competent and well-trained teachers, most beneficial in supervising clinical skills. Tutors motivate students, help them to integrate into the ward team, and provide a non-fear-based working relationship whereby students' anxiety regarding working on ward decreases. The control group had to rely on autodidactic learning strategies when neither supervising physicians nor final-year students were available. CONCLUSION: On-ward PAL programs represent a particularly valuable tool for students' support in training clinical competencies on ward. The tutor-student working alliance acts through its flat hierarchy. Nevertheless, tutors cannot represent an adequate substitute for experienced physicians.
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BACKGROUND: Learning on the ward as a practice-oriented preparation for the future workplace plays a crucial role in the medical education of future physicians. However, students' ward internship is partially problematic due to condensed workflows on the ward and the high workload of supervising physicians. For the first time in a German-speaking setting, students' expectations and concerns about their internship on the ward are examined in a qualitative analysis regarding their internal medicine rotation within clinical medical education. METHODS: Of a total of 168 medical students in their 6th semester at the Medical Faculty of Heidelberg, 28 students (m=8, f=20, Ø 23.6 years) took part in focus group interviews 3 to 5 days prior to their internship on the internal medicine ward within their clinical internal medicine rotation. Students were divided into four different focus groups. The protocols were transcribed and a content analysis was conducted based on grounded theory. RESULTS: We gathered a total of 489 relevant individual statements. The students hope for a successful integration within the ward team, reliable and supportive supervisors and supervision in small groups. They expect to face the most common diseases, to train the most important medical skills, to assume full responsibility for their own patients and to acquire their own medical identity. The students fear an insufficient time frame to achieve their aims. They are also concerned they will have too little contact with patients and inadequate supervision. CONCLUSION: For the development and standardization of effective student internships, the greatest relevance should be attributed to guidance and supervision by professionally trained and well-prepared medical teachers, entailing a significant increase in staff and costs. A structural framework is required in order to transfer the responsibility for the treatment of patients to the students at an early stage in medical education and in a longitudinal manner. The data suggest that the development and establishment of guidelines for medical teachers associated with clearly defined learning objectives for the students' internships are urgently needed. Based on our findings, we provide first recommendations and suggest possible solutions.