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1.
Z Evid Fortbild Qual Gesundhwes ; 185: 35-44, 2024 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-38388280

RESUMEN

In Germany, there are 1.8 million people currently living with dementia, and the trend is rising. In particular, the health system at the transition from hospital to outpatient care is facing major challenges given the high increase in a difficult patient clientele. Legal efforts have been undertaken (sect. 39a of the Fifth Social Code Book [SGB V]) to close the care gaps in the discharge and transfer process. This article aims to provide an overview of the documentation process of the discharge and transfer management for people with cognitive impairments in everyday clinical practice according to SGB V sect. 39 para. 1a after the Discharge Management Act came into force. Furthermore, the manuscript answers the research question "How is the statutory discharge management of people with cognitive impairments (MmkB) aged 65 and over documented" and highlights further characteristics of the discharge documentation for MmkB starting with the transition from the inpatient setting to other care settings. In order to answer the research question(s), a qualitative content analysis of all discharge documents available at the time of discharge was carried out as part of the intervention study on cross-sector care management to support cognitively impaired people during and after a hospital stay [intersec-CM], which was funded by the Federal Ministry of Education and Research. The results of the analysis show that, despite legal efforts, there are currently no standardized, unified processes of discharge management for people with cognitive impairments that can be traced in writing. However, departments with a large proportion of vulnerable patient groups were able to offer valuable insights: for example, their discharge documents included a short social history. Further evidence-based research and development in the domain of discharge management for people with cognitive impairments remains essential.


Asunto(s)
Disfunción Cognitiva , Demencia , Humanos , Alta del Paciente , Alemania , Hospitalización , Demencia/terapia , Disfunción Cognitiva/terapia
2.
J Adv Nurs ; 80(3): 1043-1057, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37775954

RESUMEN

AIMS: To investigate factors that influence the willingness of inactive nurses to return to nursing in a crisis situation and to identify aspects that need to be considered with regard to a possible deployment. DESIGN: A deductive and inductive qualitative content analysis of semi-structured focus group interviews. METHODS: Semi-structured focus group interviews with inactive or marginally employed nurses, nurses who have been inactive for some time and nursing home managers in October and November 2021. The participating inactive nurses had declared their willingness for a deployment during the COVID-19 pandemic or not. Data were analysed using qualitative content analysis. RESULTS: Communication was seen as essential by the participants for an informed decision for or against a temporary return to nursing and to potential or actual deployments. To make them feel safe, inactive nurses need to know what to expect and what is expected of them, for example, regarding required training and responsibilities. Considering their current employment status, some flexibility in terms of deployment conditions is needed. A remaining attachment to care can trigger a sense of duty. Knowledge of (regular) working conditions in nursing can lead to both a desire to support former colleagues and a refusal to be exposed to these conditions again. CONCLUSION: Past working experiences and the current employment situation play a major role in the willingness of inactive nurses to return to nursing in a crisis situation. Unbureaucratic arrangements must be provided for those who are willing to return. SUMMARY STATEMENT: What already is known - In crisis situations, not every inactive nurse is willing or able to return to nursing and therefore, the 'silent reserve' may not be as large as suspected. What this paper adds - Inactive nurses need to know what to expect and what is expected of them for their decision regarding a return to active patient care during a crisis situation. Implications for practice/policy - Inactive nurses need to be informed and should be offered free training and refresher courses to ensure patient safety. IMPACT: This research shows that the group of inactive nurses are not a silent workforce which can be activated anytime. Those who are able and willing to return to direct patient care in crisis situations need the best possible support - during and between crises. REPORTING METHOD: This study adhered to COREQ guidelines. NO PATIENT OR PUBLIC CONTRIBUTION: The involvement of patients or members of the public did not apply for the study, as the aim was to gain insight into the motivations and attitudes of the group of inactive nurses.


Asunto(s)
COVID-19 , Enfermeras y Enfermeros , Humanos , Pandemias , Investigación Cualitativa , Casas de Salud
3.
J Clin Med ; 12(12)2023 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-37373660

RESUMEN

Post-COVID-19 syndrome (PCS) has been described as 'the pandemic after the pandemic' with more than 65 million people worldwide being affected. The enormous range of symptoms makes both diagnosis complex and treatment difficult. In a post-COVID rehabilitation outpatient clinic, 184 patients, mostly non-hospitalized, received a comprehensive, interdisciplinary diagnostic assessment with fixed follow-up appointments. At baseline, three in four patients reported more than 10 symptoms, the most frequent symptoms were fatigue (84.9%), decreased physical capacity (83.0%), tiredness (81.1%), poor concentration (73.6%), sleeping problems (66.7%) and shortness of breath (67.3%). Abnormalities were found in the mean values of scores for fatigue (FAS = 34.3), cognition (MoCA = 25.5), psychological alterations (anxiety, depression, post-traumatic stress disorder), limitation of lung function (CAT) and severity scores for PCS (PCFS, MCRS). Clinical abnormalities were found in elevated values of heart rate, breathing rate at rest, blood pressure and NT-proBNP levels. As the frequency of the described symptoms decreases only slowly but most often significantly over the course, it is important to monitor the patients over a longer period of time. Many of them suffer from an immense symptom burden, often without pre-existing clinical correlates. Our results show a clear association with objectifiable assessments and tests as well as pronounced symptoms.

4.
Artículo en Inglés | MEDLINE | ID: mdl-36498196

RESUMEN

Teaching is amongst the six professions with the highest stress levels and lowest job satisfaction, leading to a high turnover rate and teacher shortages. During the pandemic, teachers and school principals were confronted with new regulations and teaching methods. This study aims to examine post-pandemic stress levels, as well as resilience factors to proactively cope with stress and thoughts of leaving the profession among teachers and school principals. We used a cross-sectional online survey. The validated instruments Perceived Stress Scale (PSS-10) and Proactive Coping Subscale (PCI) were used. We included 471 teachers and 113 school principals in the analysis. Overall, respondents had a moderate stress level. During the pandemic, every fourth teacher (27.2%) and every third principal (32.7%) had serious thoughts of leaving the profession. More perceived helplessness (OR = 1.2, p < 0.001), less self-efficacy (OR = 0.8, p = 0.002), and poorer coping skills (OR = 0.96, p = 0.044) were associated with a higher likelihood of thoughts of leaving the profession for teachers, whereas for school principals, only higher perceived helplessness (OR = 1.2, p = 0.008) contributed significantly. To prevent further teacher attrition, teachers and school principals need support to decrease stress and increase their ability to cope.


Asunto(s)
Personal Docente , Instituciones Académicas , Humanos , Estudios Transversales , Encuestas y Cuestionarios , Adaptación Psicológica , Maestros
5.
Front Public Health ; 10: 1003876, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36438295

RESUMEN

Background: Over the course of the COVID-19 pandemic, previous studies have shown that the physical as well as the mental health of children and adolescents significantly deteriorated. Future anxiety caused by the COVID-19 pandemic and its associations with quality of life has not previously been examined in school children. Methods: As part of a cross-sectional web-based survey at schools in Mecklenburg-Western Pomerania, Germany, two years after the outbreak of the pandemic, school children were asked about COVID-19-related future anxiety using the German epidemic-related Dark Future Scale for children (eDFS-K). Health-related quality of life (HRQoL) was assessed using the self-reported KIDSCREEN-10. The eDFS-K was psychometrically analyzed (internal consistency and confirmatory factor analysis) and thereafter examined as a predictor of HRQoL in a general linear regression model. Results: A total of N = 840 8-18-year-old children and adolescents were included in the analysis. The eDFS-K demonstrated adequate internal consistency reliability (Cronbach's α = 0.77), and the confirmatory factor analysis further supported the one-factor structure of the four-item scale with an acceptable model fit. Over 43% of students were found to have low HRQoL. In addition, 47% of the students sometimes to often reported COVID-19-related fears about the future. Children with COVID-19-related future anxiety had significantly lower HRQoL (B = - 0.94, p < 0.001). Other predictors of lower HRQoL were older age (B = - 0.63, p < 0.001), and female (B = - 3.12, p < 0.001) and diverse (B = - 6.82, p < 0.001) gender. Conclusion: Two years after the outbreak of the pandemic, school-aged children continue to exhibit low HRQoL, which is further exacerbated in the presence of COVID-19-related future anxiety. Intervention programs with an increased focus on mental health also addressing future anxiety should be provided.


Asunto(s)
COVID-19 , Calidad de Vida , Niño , Humanos , Adolescente , Femenino , Calidad de Vida/psicología , Estudios Transversales , COVID-19/epidemiología , Encuestas y Cuestionarios , Reproducibilidad de los Resultados , Pandemias , Ansiedad/epidemiología
6.
PLoS One ; 17(9): e0274545, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36099277

RESUMEN

BACKGROUND: Since the onset of the COVID-19 pandemic, children have been mentally and physically burdened, particularly due to school closures, with an associated loss of learning. Therefore, efficient testing strategies with high sensitivity are necessary to keep schools open. Apart from individual rapid antigen testing, various methods have been investigated, such as PCR-based pool-testing of nasopharyngeal swabs, gargle, or saliva samples. To date, previous validation studies have found the PCR-based saliva swab pool testing method to be an effective screening method, however, the acceptability and feasibility of a widespread implementation in the school-setting among stakeholders has not been comprehensively evaluated. METHODS: In this pilot study, SARS-CoV-2 saliva swab pool testing of up to 15 swabs per pool was conducted in ten primary and special schools in Mecklenburg-Western Pomerania, Germany, over a period of one month. Thereafter, parents, teachers and school principals of the participating schools as well as the participating laboratories were surveyed about the feasibility and acceptability of this method, its large-scale implementation and challenges. Data were analyzed quantitatively and qualitatively. RESULTS: During the study period, 1,630 saliva swab pools were analyzed, of which 22 tested SARS-CoV-2 positive (1.3%). A total of N = 315 participants took part in the survey. Across all groups, the saliva swab pool testing method was perceived as more child-friendly (>87%), convenient (>82%), and easier (>81%) compared to rapid antigen testing by an anterior nasal swab. Over 80% of all participants favored widespread, regular use of the saliva swab method. CONCLUSION: In school settings in particular, a high acceptability of the test method is crucial for a successful SARS-CoV-2 surveillance strategy. All respondents clearly preferred the saliva swab method, which can be used safely without complications in children six years of age and older. Hurdles and suggestions for improvement of an area-wide implementation were outlined.


Asunto(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , COVID-19/epidemiología , Estudios de Factibilidad , Humanos , Pandemias , Proyectos Piloto , Reacción en Cadena en Tiempo Real de la Polimerasa , SARS-CoV-2/genética , Saliva
7.
J Adv Nurs ; 78(11): 3687-3695, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35441728

RESUMEN

AIMS: To examine whether inactive nurses are willing to return to nursing during the COVID-19 pandemic, the reasons for or against their decision and further, possibly relevant factors. DESIGN: Cross-sectional online survey. METHODS: We developed a questionnaire, addressing registration, professional experiences, anticipations, and internal and external factors that might affect the decision of inactive nurses to return to nursing during the pandemic. Between 27 April and 15 June 2020, we recruited participants in Germany via social networks, organizations and institutions and asked them to forward the link to wherever other inactive nurses might be reached. RESULTS: Three hundred and thirty-two participants (73% female) could be included in the analysis. The majority of the participants (n = 262, 79%) were general nurses. The main reason for registering was 'want to do my bit to manage the crisis' (n = 73, 22.8%). More than two thirds of the participants (n = 230, 69%) were not or not yet registered. One hundred and twelve (49%) out of 220 participants, who gave reasons why they did not register, selected they 'could not see a necessity at that time'. The few inactive nurses who were deployed reported a variety of experiences. CONCLUSIONS: Different factors influence the nurses' decision to register or not. A critical factor for their decision was previous experiences that had made them leave the job and prevented a return-even for a limited time in a special situation. IMPACT: From the responses of the participants in this study, it can be deduced that: negative experiences made while working in nursing influence the willingness to volunteer for a deployment; only one-third of the inactive nurses would be willing to return to the nursing profession to help manage the Corona pandemic; policymakers and nursing leaders should not rely on the availability of inactive nurses in a crisis.


Asunto(s)
COVID-19 , Enfermeras y Enfermeros , COVID-19/epidemiología , Estudios Transversales , Empleo , Femenino , Humanos , Masculino , Pandemias , Encuestas y Cuestionarios
8.
Z Evid Fortbild Qual Gesundhwes ; 169: 59-66, 2022 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-35339414

RESUMEN

BACKGROUND: For many years, the redistribution of tasks and thus a transfer of medical activities to nursing professionals with extended competencies has been discussed in Germany and is currently being regulated by the federal government. OBJECTIVES: The aim of this study was to record the opinions of GPs and nurses on the qualification requirements for possible delegable and substitutable medical activities to nurses using the example of outpatient dementia care. METHOD: In the context of a quantitative survey, the qualification requirements for the delegation of 30 different activities to nurses were collected from primary care physicians and nurses. A total of 1,634 questionnaires was distributed. The response rate was 28.0 % (primary care physicians: n=225, and nursing specialists: n=232). The analyses were carried out descriptively using SPSS software (version 25, IBM Corp., 2017). RESULTS: 45.1% of the respondents said they needed additional qualification prior to such a task transfer. This need primarily relates to further training (37.3%). Those seeking a university education (36.2%), will either pursue a Bachelor's (15.6%) or a Master's degree (20.6%) to obtain the necessary qualification. CONCLUSION: The results of this study can help define the activity profiles of academically qualified nursing professionals and inform the development of curricula for their university education. Furthermore, they will support the further development of the legal framework.


Asunto(s)
Actitud , Curriculum , Alemania , Humanos , Encuestas y Cuestionarios
9.
Gesundheitswesen ; 84(5): 438-447, 2022 May.
Artículo en Alemán | MEDLINE | ID: mdl-35318624

RESUMEN

THE AIM OF THE STUDY: A transfer of medical activities to nurses and thus the redistribution of tasks has been discussed for almost 15 years. A legal base for model projects has been enacted. However, clearly defined tasks for substitution are still lacking. The aim of this study was to solicit opinions of general practitioners, nurses, people with dementia (PwD) and their relatives about the possibility of a large number of specific General practitioner (GP) tasks being performed by nurses in outpatient dementia care. METHODS: A mixed-methods study with a sequential in-depth design was conducted. The analysis presented here refers to the quantitative survey of the four participant groups. 865 participants were asked about the acceptance of substitution of assessments, primary and follow-up prescriptions, health monitoring measures and other activities currently performed by physicians. RESULTS: Across all groups of subjects, the highest level of approval for substitution was achieved for the assessment of mobility restrictions, everyday competencies, nutritional abnormalities, prescription of transportation, nursing aids, home nursing services and drawing of blood samples. Among PwD and relatives, the level of acceptance for substitution was very high. 88% of the PwD and relatives indicated that many activities can be substituted while the general practitioner remained their first point of contact. More GPs (63.2%) than nurses (56.7%) would accept the substitution. CONCLUSION: The results indicate that a large number of GPs, nurses, patients and their relatives welcome substitution. However, PwD and relatives have a significantly more positive attitude towards substitution.


Asunto(s)
Demencia , Médicos Generales , Actitud , Demencia/epidemiología , Alemania/epidemiología , Humanos , Encuestas y Cuestionarios
10.
Pflege ; 35(4): 215-222, 2022 Aug.
Artículo en Alemán | MEDLINE | ID: mdl-34814707

RESUMEN

Task sharing in outpatient dementia care - Focus groups with GPs and nurses Abstract. Background: Caring for people with dementia (PWD) is challenging for the health system and family carers and can only be managed through interprofessional medical and nursing care. AIM: The AHeaD study investigated attitudes of general practitioners (GPs) and nurses towards the transfer of activities previously performed by GPs to advanced nurses in the outpatient care of PWDs. METHODS: In four focus group discussions with 10 GPs and 13 nurses, qualitative content analysis was used to investigate attitudes towards the transfer of certain tasks and to identify opportunities and barriers to their introduction. RESULTS: GPs primarily preferred the transfer of nursing activities such as blood sampling, assessments, their monitoring or follow-up prescriptions for nursing aids. "Classical" medical tasks (e. g. diagnosis of diseases, initial prescription of medication) are still seen in the hands of GPs. Nurses demanded more appreciation and recognition for the relationship between GPs and nurse and criticised the lack of trust and insufficient communication. Both sides pointed to tight time budgets that were hardly oriented towards the actual needs of the PWD. CONCLUSIONS: The implementation of a redistribution of tasks requires the creation of legal and financial framework conditions, time resources, concrete task descriptions as well as a stronger cooperation between the professional groups involved. Innovative concepts could contribute to the sensible use of the resources GP and nurses and strengthen the care of PWDs.


Asunto(s)
Demencia , Médicos Generales , Atención Ambulatoria , Actitud del Personal de Salud , Grupos Focales , Humanos , Pacientes Ambulatorios
11.
Gesundheitswesen ; 83(11): 890-893, 2021 Nov.
Artículo en Alemán | MEDLINE | ID: mdl-34571553

RESUMEN

BACKGROUND: The current risk of infection with SARS-CoV-2 in schools continues to be a subject of controversy. METHODOLOGY: "schugi-MV" collects data on the incidence of infection, hygiene management and other factors in structured inspections of schools in Mecklenburg-Western Pomerania. Recommendations for safe teaching are to be derived from the results. This article presents information on the first 10 schools visited between 18.12.2020 and 20.01.2021. RESULTS: At the schools visited, the ratio of the number of index cases among adults and children was 1:1.25. The inspections showed a great heterogeneity of schools and school buildings and the resulting possibilities for implementing infection control measures. CONCLUSION: Based on the present preliminary results, hygiene and infection control measures at schools in Mecklenburg-Western Pomerania cannot be standardised, but should leave room for design.


Asunto(s)
COVID-19 , Adulto , Niño , Alemania/epidemiología , Humanos , Pandemias/prevención & control , SARS-CoV-2 , Instituciones Académicas
12.
Z Gerontol Geriatr ; 54(4): 359-364, 2021 Jul.
Artículo en Alemán | MEDLINE | ID: mdl-33856530

RESUMEN

BACKGROUND: As older people are at increased risk of severe and fatal courses of SARS-CoV­2 infection, they receive special attention, which, however, often refers one-sidedly to their need for protection. What is needed is a discussion that considers the subjective reality and resources as well as risks. OBJECTIVE: The study focused on the perspectives of older people. The aim was to shed light on their subjective experience of the corona pandemic. The questions were how they experienced the pandemic, the risks, consequences and protective measures, to what extent these affected their everyday life and how they dealt with it. MATERIAL AND METHODS: A total of 12 guideline-based telephone interviews were conducted in May and June 2020 with 9 women and 3 men between 77 and 91 years of age, who lived in their own homes, had impaired health and needed help and care. The data were evaluated by structuring content analysis. RESULTS: The respondents were generally concerned about the corona pandemic but considered their own risk to be low. They saw themselves as hardly affected by the immediate consequences of the crisis or severely restricted in their everyday lives. They experienced insecurity in social life and fear of loneliness was central. Overall, they considered the protective measures to be appropriate but criticized early cancelling, family contact restrictions and dealing with the dying. CONCLUSION: A moderate degree of direct personal involvement, acceptance and adaptability characterized the experience and handling of the corona pandemic. Resources and skills in dealing with the crisis become visible.


Asunto(s)
COVID-19 , Pandemias , Anciano , Femenino , Humanos , Soledad , Masculino , Pandemias/prevención & control , SARS-CoV-2
13.
Front Public Health ; 9: 780039, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34988054

RESUMEN

Introduction: With the increased emergence of SARS-CoV-2 variants, the impact on schools and preschools remains a matter of debate. To ensure that schools and preschools are kept open safely, the identification of factors influencing the extent of outbreaks is of importance. Aim: To monitor dynamics of COVID-19 infections in schools and preschools and identify factors influencing the extent of outbreaks. Methods: In this prospective observational study we analyzed routine surveillance data of Mecklenburg-Western Pomerania, Germany, from calendar week (CW) 32, 2020 to CW19, 2021 regarding SARS-CoV-2 infection events in schools and preschools considering changes in infection control measures over time. A multivariate linear regression model was fitted to evaluate factors influencing the number of students, teachers and staff tested positive following index cases in schools and preschools. Due to an existing multicollinearity in the common multivariate regression model between the variables "face mask obligation for children" and "face mask obligation for adults", two further separate regression models were set up (Multivariate Model Adults and Multivariate Model Children). Results: We observed a significant increase in secondary cases in preschools in the first quarter of 2021 (CW8 to CW15, 2021), and simultaneously a decrease in secondary cases in schools. In multivariate regression analysis, the strongest predictor of the extent of the outbreaks was the teacher/ caregiver mask obligation (B = -1.9; 95% CI: -2.9 to -1.0; p < 0.001). Furthermore, adult index cases (adult only or child+adult combinations) increased the likelihood of secondary cases (B = 1.3; 95% CI: 0.9 to 1.8; p < 0.001). The face mask obligation for children also showed a significant reduction in the number of secondary cases (B = -0.6; 95% CI: -0.9 to -0.2; p = 0.004. Conclusion: The present study indicates that outbreak events at schools and preschools are effectively contained by an obligation for adults and children to wear face masks.


Asunto(s)
COVID-19 , Control de Enfermedades Transmisibles/métodos , Instituciones Académicas , Adulto , COVID-19/prevención & control , Niño , Preescolar , Brotes de Enfermedades/prevención & control , Alemania , Humanos , Máscaras , Estudios Prospectivos , SARS-CoV-2
14.
Biotechnol Bioeng ; 111(12): 2537-48, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24889796

RESUMEN

Grooved substrates are commonly used to guide cell alignment and produce in vitro tissues that mimic certain aspects of in vivo cellular organization. These more sophisticated tissues provide valuable in vitro models for testing drugs and for dissecting out molecular mechanisms that direct tissue organization. To increase the accessibility of these tissue models we describe a simple and yet reproducible strategy to produce 1 µm-spaced grooved well plates suitable for conducting automated analysis of cellular responses. We characterize the alignment of four human cell types: retinal epithelial cells, umbilical vein endothelial cells, foreskin fibroblasts, and human pluripotent stem-cell-derived cardiac cells on grooves. We find all cells align along the grooves to differing extents at both sparse and confluent densities. To increase the sophistication of in vitro tissue organization possible, we also created hybrid substrates with controlled patterns of microgrooved and flat regions that can be identified in real-time using optical microscopy. Using our hybrid patterned surfaces we explore: (i) the ability of neighboring cells to provide a template to organize surrounding cells that are not directly exposed to grooved topographic cues, and (ii) the distance over which this template effect can operate in confluent cell sheets. We find that in fibroblast sheets, but not epithelial sheets, cells aligned on grooves can direct alignment of neighboring cells in flat regions over a limited distance of approximately 200 µm. Our hybrid surface plate provides a novel tool for studying the collective response of groups of cells exposed to differential topographical cues.


Asunto(s)
Comunicación Celular/fisiología , Ensayos Analíticos de Alto Rendimiento/instrumentación , Ingeniería de Tejidos/instrumentación , Línea Celular , Células Cultivadas , Diseño de Equipo , Humanos , Propiedades de Superficie
15.
Methods Mol Biol ; 1202: 37-55, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24687428

RESUMEN

In many tissues, cells must be aligned for proper function. This alignment can occur at the cellular and/or subcellular (protein/molecular) level. The alignment of cytoskeletal components, in fact, precedes whole cell alignment. A variety of methods exist to manipulate cytoskeletal and whole cell alignment; one of the simplest and most predictable involves seeding adherent cells onto defined substrate topography. We present here two methods to create grooved multiwell plates: one involving microfabrication, which allows for custom design of substrate topography, and a simpler, inexpensive method using commercially available diffraction gratings. We also include methods for manual and automatic quantification of cell alignment.


Asunto(s)
Técnicas de Cultivo de Célula/instrumentación , Células/citología , Línea Celular , Citoesqueleto/metabolismo , Humanos , Microtecnología , Programas Informáticos
16.
Proc Natl Acad Sci U S A ; 111(5): 1807-12, 2014 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-24449852

RESUMEN

Directed migration of groups of cells is a critical aspect of tissue morphogenesis that ensures proper tissue organization and, consequently, function. Cells moving in groups, unlike single cells, must coordinate their migratory behavior to maintain tissue integrity. During directed migration, cells are guided by a combination of mechanical and chemical cues presented by neighboring cells and the surrounding extracellular matrix. One important class of signals that guide cell migration includes topographic cues. Although the contact guidance response of individual cells to topographic cues has been extensively characterized, little is known about the response of groups of cells to topographic cues, the impact of such cues on cell-cell coordination within groups, and the transmission of nonautonomous contact guidance information between neighboring cells. Here, we explore these phenomena by quantifying the migratory response of confluent monolayers of epithelial and fibroblast cells to contact guidance cues provided by grooved topography. We show that, in both sparse clusters and confluent sheets, individual cells are contact-guided by grooves and show more coordinated behavior on grooved versus flat substrates. Furthermore, we demonstrate both in vitro and in silico that the guidance signal provided by a groove can propagate between neighboring cells in a confluent monolayer, and that the distance over which signal propagation occurs is not significantly influenced by the strength of cell-cell junctions but is an emergent property, similar to cellular streaming, triggered by mechanical exclusion interactions within the collective system.


Asunto(s)
Comunicación Celular , Movimiento Celular , Células Epiteliales/citología , Fibroblastos/citología , Transducción de Señal , Recuento de Células , Línea Celular , Células Epiteliales/metabolismo , Fibroblastos/metabolismo , Humanos , Uniones Intercelulares/metabolismo , Masculino , Modelos Biológicos
17.
Nat Methods ; 10(12): 1225-31, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24141495

RESUMEN

Populations of cells create local environments that lead to emergent heterogeneity. This is particularly evident with human pluripotent stem cells (hPSCs): microenvironmental heterogeneity limits hPSC cell fate control. We developed a high-throughput platform to screen hPSCs in configurable microenvironments in which we optimized colony size, cell density and other parameters to achieve rapid and robust cell fate responses to exogenous cues. We used this platform to perform single-cell protein expression profiling, revealing that Oct4 and Sox2 costaining discriminates pluripotent, neuroectoderm, primitive streak and extraembryonic cell fates. We applied this Oct4-Sox2 code to analyze dose responses of 27 developmental factors to obtain lineage-specific concentration optima and to quantify cell line-specific endogenous signaling pathway activation and differentiation bias. We demonstrated that short-term responses predict definitive endoderm induction efficiency and can be used to rescue differentiation of cell lines reticent to cardiac induction. This platform will facilitate high-throughput hPSC-based screening and quantification of lineage-induction bias.


Asunto(s)
Técnicas de Cultivo de Célula , Endodermo/metabolismo , Células Madre Pluripotentes/citología , Animales , Diferenciación Celular , Línea Celular , Linaje de la Célula , Medios de Cultivo Condicionados/química , Células Madre Embrionarias/citología , Perfilación de la Expresión Génica , Humanos , Ratones , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Fenotipo , Factores de Transcripción SOXB1/metabolismo , Transducción de Señal , Factores de Tiempo
18.
Toxicol Appl Pharmacol ; 262(1): 1-10, 2012 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-22676972

RESUMEN

Anthracycline-based regimens are a mainstay of early breast cancer therapy, however their use is limited by cardiac toxicity. The potential for cardiotoxicity is a major consideration in the design and development of combinatorial therapies incorporating anthracyclines and agents that target the HER2-mediated signaling pathway, such as trastuzumab. In this regard, HER2-targeted liposomal doxorubicin was developed to provide clinical benefit by both reducing the cardiotoxicity observed with anthracyclines and enhancing the therapeutic potential of HER2-based therapies that are currently available for HER2-overexpressing cancers. While documenting the enhanced therapeutic potential of HER2-targeted liposomal doxorubicin can be done with existing models, there has been no validated human cardiac cell-based assay system to rigorously assess the cardiotoxicity of anthracyclines. To understand if HER2-targeting of liposomal doxorubicin is possible with a favorable cardiac safety profile, we applied a human stem cell-derived cardiomyocyte platform to evaluate the doxorubicin exposure of human cardiac cells to HER2-targeted liposomal doxorubicin. To the best of our knowledge, this is the first known application of a stem cell-derived system for evaluating preclinical cardiotoxicity of an investigational agent. We demonstrate that HER2-targeted liposomal doxorubicin has little or no uptake into human cardiomyocytes, does not inhibit HER2-mediated signaling, results in little or no evidence of cardiomyocyte cell death or dysfunction, and retains the low penetration into heart tissue of liposomal doxorubicin. Taken together, this data ultimately led to the clinical decision to advance this drug to Phase I clinical testing, which is now ongoing as a single agent in HER2-expressing cancers.


Asunto(s)
Antibióticos Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos , Miocitos Cardíacos/efectos de los fármacos , Animales , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/toxicidad , Neoplasias de la Mama/patología , Doxorrubicina/administración & dosificación , Doxorrubicina/toxicidad , Femenino , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Ratones , Ratones Desnudos , Miocitos Cardíacos/metabolismo , Receptor ErbB-2/metabolismo , Transducción de Señal/efectos de los fármacos
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