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BACKGROUND: Somali Red Crescent Society (SRCS), supported by Norwegian Red Cross, has implemented community-based surveillance (CBS) in Somaliland. This methodology aims to reduce the high risk of epidemics by strengthening early warning and response from and at community level, particularly where there is a weak public health surveillance system. CBS is implemented through SRCS community volunteers, who report signals from the community via SMS to the software platform Nyss. This paper presents key findings from the CBS programme evaluation. METHODS: A retrospective observational mixed-methods approach to evaluate the CBS programme was conducted, using routine CBS data from 2021 for Awdal and Togdheer regions and qualitative interviews with stakeholders' representatives. RESULTS: The usefulness of the CBS programme in preventing, detecting, and responding to disease outbreaks was acknowledged by the stakeholders' representatives. 83% of the signals in Awdal region matched a Community Case Definition (CCD) and were escalated to the Ministry of Health and Development (MoHD)). For Togdheer region, 97% were escalated. Verification of signals by supervisors and escalation to the authorities was done timely.Alert outcome and response action was not well recorded, therefore there is limited evidence on sensitivity. The programme was shown to be simple and can be flexibly adjusted for new diseases and changing CCDs.Stakeholders appreciated being engaged, the good collaboration, their participation throughout the implementation and expressed high acceptance of the programme. CONCLUSION: CBS can support early warning and response for a variety of public health risks. Improved documentation for alert outcomes could help to better evaluate the sensitivity of CBS. A participatory approach is vital to achieve successful community volunteer engagement. Software tools, such as the Nyss platform, can be useful to support effective and efficient CBS implementation.
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Background: Cardiac arrhythmias have markedly increased in recent decades, highlighting the urgent need for appropriate test systems to evaluate the efficacy and safety of new pharmaceuticals and the potential side effects of established drugs. Methods: The Microelectrode Array (MEA) system may be a suitable option, as it provides both real-time and non-invasive monitoring of cellular networks of spontaneously active cells. However, there is currently no commercially available cell source to apply this technology in the context of the cardiac conduction system (CCS). In response to this problem, our group has previously developed a protocol for the generation of pure functional cardiac pacemaker cells from mouse embryonic stem cells (ESCs). In addition, we compared the hanging drop method, which was previously utilized, with spherical plate-derived embryoid bodies (EBs) and the pacemaker cells that are differentiated from these. Results: We described the application of these pacemaker cells on the MEA platform, which required a number of crucial optimization steps in terms of coating, dissociation, and cell density. As a result, we were able to generate a monolayer of pure pacemaker cells on an MEA surface that is viable and electromechanically active for weeks. Furthermore, we introduced spherical plates as a convenient and scalable method to be applied for the production of induced sinoatrial bodies. Conclusion: We provide a tool to transfer modeling and analysis of cardiac rhythm diseases to the cell culture dish. Our system allows answering CCS-related queries within a cellular network, both under baseline conditions and post-drug exposure in a reliable and affordable manner. Ultimately, our approach may provide valuable guidance not only for cardiac pacemaker cells but also for the generation of an MEA test platform using other sensitive non-proliferating cell types.
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INTRODUCTION: Public health surveillance traditionally occurs at a health facility; however, there is growing concern that this provides only partial and untimely health information. Community-based surveillance (CBS) enables early warning and the mobilization of early intervention and response to disease outbreaks. CBS is a method of surveillance that can monitor a wide range of information directly from community members. CBS can be done using short message service, phone calls, paper forms, or a specialized software tool. No scoping review of the available software tools with the capability for CBS exists in the literature. This review aims to map software tools that can be used for CBS in both community health programs and emergency settings and demonstrate their use cases. METHODS: We conducted a scoping review of academic literature and supplemental resources and conducted qualitative interviews with stakeholders working with digital community health and surveillance tools. RESULTS: All of the tools reviewed have features necessary to support the reporting process of CBS; only 3 (CommCare, Community Health Toolkit, and DHIS2 Tracker) provided all 10 attributes included in the mapping. AVADAR and Nyss were the only tools designed specifically for CBS and for use by volunteers, while the other tools were designed for community health workers and have a broader use case. CONCLUSION: The findings demonstrate that several software tools are available to facilitate public health surveillance at the community level. In the future, emphasis should be put on contextualizing these tools to meet a country's public health needs and promoting institutionalization and ownership by the national health system. There is also an opportunity to explore improvements in event-based surveillance at the community level.
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Saúde Pública , Software , Humanos , Surtos de Doenças/prevenção & controle , Instalações de SaúdeRESUMO
BACKGROUND: Unlike atrial fibrillation (AF), atrial flutter (AFl) is thought to be relatively refractory to pharmacological cardioversion (PC), but the evidence is scarce. The aim of this study was to evaluate the clinical characteristics and efficacy of the PC of AFl with amiodarone in comparison to AF. MATERIALS AND METHODS: This retrospective study covered 727 patients with urgent consult for AF/AFl in a high-volume emergency department between 2015 and 2018. AFl was diagnosed in 222 (30.5%; median age: 68 (62; 75) years; 65.3% men). In a nested case-control study, 59 control patients with AF, matched in terms of age and sex with 60 AFl patients, were subject to PC with amiodarone. The primary endpoint was return of sinus rhythm confirmed using a 12-lead ECG. RESULTS: The AFl population had a median CHA2DS2-VASc score of 3 (2; 4) and episode duration of 72 h (16; 120). In the AFl cohort, 36% of patients were initially subject to PC, 33.3% to electrical cardioversion (EC) and 40.5% to catheter ablation. In comparison to the AF group, the AFl patients required a longer hospitalization time, had a higher rate of EC (p < 0.001) and less frequent use of PC (p < 0.001) and, lower left ventricular ejection fraction (p < 0.001) and more pronounced cardiovascular risk factors. The efficacy of PC with amiodarone was significantly lower in AFl than AF group (39% vs. 65%, relative risk (RR) 0.60, p = 0.007). CONCLUSIONS: AFl patients shared a greater burden of comorbidities than AF patients, while the efficacy of PC in AFl was low. Patients should be initially managed with primary electrical cardioversion.
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IntroductionTransgender and gender diverse (TGD) populations with hereditary cancer syndromes face unique barriers to care and thus may not be accessing appropriate cancer screening or risk-reducing procedures. Our objective was to evaluate health care utilization of TGD patients with hereditary cancer syndromes. This includes counseling received, cancer screenings conducted, and risk-reducing procedures performed. MethodsA case series of TGD patients (N = 11) with hereditary breast and ovarian cancer (n = 9) or Lynch syndrome (n = 2) who received care within Kaiser Permanente Northern California between 2009 and 2019. ResultsAll patients received counseling and prophylactic options. Three patients (27%) completed all recommended screening, 6 (54%) had partial screening, 1 (9%) received no screening, and 1 (9%) did not require any screening. Six (55%) underwent a risk-reducing procedure. DiscussionThis case series highlights that despite all the study participants being appropriately counseled by practitioners about their risk of cancer, screening, and prophylactic options, in many cases, the screening received was partial or absent. Relatively few completed all the recommended screenings based on their clinical risk factors. ConclusionMany of the TGD patients with hereditary cancer syndromes in this cohort did not complete all the recommended cancer screening. This can be an area of focus in order to improve the quality of care provided to this vulnerable population.
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Neoplasias Colorretais Hereditárias sem Polipose , Síndromes Neoplásicas Hereditárias , Neoplasias Ovarianas , Pessoas Transgênero , Carcinoma Epitelial do Ovário , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Detecção Precoce de Câncer , Feminino , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/prevenção & controle , Fatores de Risco , Pessoas Transgênero/psicologiaRESUMO
The natural substance class of terpenoids covers an extremely wide range of different structures, although their building block repertoire is limited to the C5 compounds DMAPP and IPP. This study aims at the characterization of methyltransferases (MTases) that modify these terpene precursors and the demonstration of their suitability for biotechnological purposes. All seven enzymes tested accepted IPP as substrate and altogether five C6 compounds and six C7 compounds were formed within the reactions. A high selectivity for the deprotonation site as well as high stereoselectivity could be observed for most of the biocatalysts. Only the enzyme from Micromonospora humi also accepted DMAPP as substrate, converting it into (2R)-2-methyl-IPP inâ vitro. In vivo studies demonstrated the production of a C8 compound and a hydride shift step within the MTase-catalyzed reaction. Our study presents IPP/DMAPP MTases with very different catalytic properties, which provide biosynthetic access to many novel terpene-derived structures.
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Metiltransferases , Terpenos , Hemiterpenos , Compostos OrganofosforadosRESUMO
BACKGROUND/AIMS: The availability of truly maturated cardiomyocytic subtypes is a major prerequisite for cardiovascular cell replacement therapies. Pluripotent stem cells provide a suitable source for the development of new strategies to overcome enormous hurdles such as yield, purity and safety of in vitro generated cells. METHODS: To address these issues, we have refined existing forward programming protocols by combining forced exogenous overexpression of the early cardiovascular transcription factor Nkx2.5 with a αMHC-promoter-based antibiotic selection step. Additionally, we applied small molecules such as ascorbic acid to enhance cardiomyogenic differentiation efficiency. Subsequently, we evaluated the cell fate of the resulting cardiomyocytes on the mRNA as well as protein levels. The latter was performed using high-resolution confocal microscopy. Furthermore, we examined the response of the cells` beating activities to pharmacological substance administration. RESULTS: Our results reveal an apparent influence of Nkx2.5 on the cell fate of ESC-derived cardiomyocytes. Resulting single cells exhibit characteristics of early ventricular cardiomyocytes, such as sarcomeric marker expression, spontaneous beating frequency, and distinct L-type calcium channel occurrence. CONCLUSION: Therefore, we demonstrate cardiovascular subtype forward programming of ESCs using a combination of transcription factors along with small molecule administration. However, our findings also underline current assumptions, that a terminal maturation of PSC derived cardiomyocytes in vitro is still an unsolved problem which urgently needs to be addressed in the field.
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Reprogramação Celular , Células-Tronco Embrionárias/metabolismo , Proteína Homeobox Nkx-2.5/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Ácido Ascórbico/farmacologia , Diferenciação Celular/efeitos dos fármacos , Células-Tronco Embrionárias/citologia , Proteína Homeobox Nkx-2.5/antagonistas & inibidores , Proteína Homeobox Nkx-2.5/genética , Camundongos , Microscopia Confocal , Miócitos Cardíacos/citologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Verapamil/farmacologiaRESUMO
Many disorders are manifested by dysfunction of key cell types or their disturbed integration in complex organs. Thereby, adult organ systems often bear restricted self-renewal potential and are incapable of achieving functional regeneration. This underlies the need for novel strategies in the field of cell (re-)programming-based regenerative medicine as well as for drug development in vitro. The regenerative field has been hampered by restricted availability of adult stem cells and the potentially hazardous features of pluripotent embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Moreover, ethical concerns and legal restrictions regarding the generation and use of ESCs still exist. The establishment of direct reprogramming protocols for various therapeutically valuable somatic cell types has overcome some of these limitations. Meanwhile, new perspectives for safe and efficient generation of different specified somatic cell types have emerged from numerous approaches relying on exogenous expression of lineage-specific transcription factors, coding and noncoding RNAs, and chemical compounds.It should be of highest priority to develop protocols for the production of mature and physiologically functional cells with properties ideally matching those of their endogenous counterparts. Their availability can bring together basic research, drug screening, safety testing, and ultimately clinical trials. Here, we highlight the remarkable successes in cellular (re-)programming, which have greatly advanced the field of regenerative medicine in recent years. In particular, we review recent progress on the generation of cardiomyocyte subtypes, with a focus on cardiac pacemaker cells. Graphical Abstract.
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Técnicas de Reprogramação Celular/métodos , Reprogramação Celular , Células-Tronco Embrionárias Humanas/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Animais , Células-Tronco Embrionárias Humanas/citologia , Humanos , Células-Tronco Pluripotentes Induzidas/citologiaRESUMO
AMPK is a conserved serine/threonine kinase whose activity maintains cellular energy homeostasis. Eukaryotic AMPK exists as αßγ complexes, whose regulatory γ subunit confers energy sensor function by binding adenine nucleotides. Humans bearing activating mutations in the γ2 subunit exhibit a phenotype including unexplained slowing of heart rate (bradycardia). Here, we show that γ2 AMPK activation downregulates fundamental sinoatrial cell pacemaker mechanisms to lower heart rate, including sarcolemmal hyperpolarization-activated current (I f) and ryanodine receptor-derived diastolic local subsarcolemmal Ca2+ release. In contrast, loss of γ2 AMPK induces a reciprocal phenotype of increased heart rate, and prevents the adaptive intrinsic bradycardia of endurance training. Our results reveal that in mammals, for which heart rate is a key determinant of cardiac energy demand, AMPK functions in an organ-specific manner to maintain cardiac energy homeostasis and determines cardiac physiological adaptation to exercise by modulating intrinsic sinoatrial cell behavior.
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Proteínas Quinases Ativadas por AMP/genética , Bradicardia/genética , Cálcio/metabolismo , Frequência Cardíaca/genética , Sarcolema/metabolismo , Nó Sinoatrial/metabolismo , Adulto , Animais , Bradicardia/metabolismo , Eletrocardiografia Ambulatorial , Exercício Físico , Coração/diagnóstico por imagem , Humanos , Imagem Cinética por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Camundongos , Microscopia Eletrônica de Transmissão , Mutação , Miocárdio/metabolismo , Miocárdio/patologia , Miocárdio/ultraestrutura , Condicionamento Físico Animal , Resistência Física , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Nó Sinoatrial/patologiaRESUMO
Adult cardiomyocytes (CMs) possess a highly restricted intrinsic regenerative potential - a major barrier to the effective treatment of a range of chronic degenerative cardiac disorders characterized by cellular loss and/or irreversible dysfunction and which underlies the majority of deaths in developed countries. Both stem cell programming and direct cell reprogramming hold promise as novel, potentially curative approaches to address this therapeutic challenge. The advent of induced pluripotent stem cells (iPSCs) has introduced a second pluripotent stem cell source besides embryonic stem cells (ESCs), enabling even autologous cardiomyocyte production. In addition, the recent achievement of directly reprogramming somatic cells into cardiomyocytes is likely to become of great importance. In either case, different clinical scenarios will require the generation of highly pure, specific cardiac cellular-subtypes. In this review, we discuss these themes as related to the cardiovascular stem cell and programming field, including a focus on the emergent topic of pacemaker cell generation for the development of biological pacemakers and in vitro drug testing.
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Reprogramação Celular/fisiologia , Miócitos Cardíacos/fisiologia , Animais , Doenças Cardiovasculares/terapia , Regeneração Tecidual Guiada , Humanos , Células-Tronco Pluripotentes Induzidas/fisiologiaRESUMO
In cancer care, where patients and their families experience significant emotional distress and patients have to deal with complex medical information, patient centeredness is an important aspect of quality of care. The aim of this study is to examine the impact of patients' trust in their oncologists and patients' enablement on changes in health-related quality of life of colon cancer patients during follow-up care. We conducted a prospective study in a representative sample of private practices of German oncologists (N = 44). Patients (N = 131) filled out a standardized questionnaire prior to their first consultation (T0), directly after the first consultation (T1) and after two months (T2). Data were analyzed by structural equation modeling. Significant associations were found between trust in physician and changes in physical functioning between T1 and T2, and between trust in physician and patient enablement. Patient enablement is significantly associated with changes in physical functioning between T1 and T2. The results underline the importance of building a close and trustful patient-physician relationship in the oncology encounter. A central mechanism of the association between the quality of the relationship and health outcomes seems to be patient enablement. To enable patients to cope with their situation by making them understand their diagnosis, treatments, and side effects can impact health-related quality of life in physical domains.
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Neoplasias do Colo/terapia , Oncologistas/estatística & dados numéricos , Relações Médico-Paciente , Qualidade de Vida , Confiança , Adaptação Psicológica , Feminino , Alemanha , Humanos , Masculino , Oncologia , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Technical advances in Next Generation Sequencing (NGS) provide a means to acquire deeper insights into cellular functions. The lack of standardized and automated methodologies poses a challenge for the analysis and interpretation of RNA sequencing data. We critically compare and evaluate state-of-the-art bioinformatics approaches and present a workflow that integrates the best performing data analysis, data evaluation and annotation methods in a Transparent, Reproducible and Automated PipeLINE (TRAPLINE) for RNA sequencing data processing (suitable for Illumina, SOLiD and Solexa). RESULTS: Comparative transcriptomics analyses with TRAPLINE result in a set of differentially expressed genes, their corresponding protein-protein interactions, splice variants, promoter activity, predicted miRNA-target interactions and files for single nucleotide polymorphism (SNP) calling. The obtained results are combined into a single file for downstream analysis such as network construction. We demonstrate the value of the proposed pipeline by characterizing the transcriptome of our recently described stem cell derived antibiotic selected cardiac bodies ('aCaBs'). CONCLUSION: TRAPLINE supports NGS-based research by providing a workflow that requires no bioinformatics skills, decreases the processing time of the analysis and works in the cloud. The pipeline is implemented in the biomedical research platform Galaxy and is freely accessible via www.sbi.uni-rostock.de/RNAseqTRAPLINE or the specific Galaxy manual page (https://usegalaxy.org/u/mwolfien/p/trapline---manual).
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Biologia Computacional/normas , Sequenciamento de Nucleotídeos em Larga Escala/normas , Análise de Sequência de RNA/normas , Biologia Computacional/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , MicroRNAs/genética , MicroRNAs/metabolismo , Anotação de Sequência Molecular , Polimorfismo de Nucleotídeo Único , Domínios e Motivos de Interação entre Proteínas , Alinhamento de Sequência , Análise de Sequência de RNA/métodos , TranscriptomaRESUMO
Treatment of the "sick sinus syndrome" is based on artificial pacemakers. These bear hazards such as battery failure and infections. Moreover, they lack hormone responsiveness and the overall procedure is cost-intensive. "Biological pacemakers" generated from PSCs may become an alternative, yet the typical content of pacemaker cells in Embryoid Bodies (EBs) is extremely low. The described protocol combines "forward programming" of murine PSCs via the sinus node inducer TBX3 with Myh6-promoter based antibiotic selection. This yields cardiomyocyte aggregates consistent of >80% physiologically functional pacemaker cells. These "induced-sinoatrial-bodies" ("iSABs") are spontaneously contracting at yet unreached frequencies (400-500 bpm) corresponding to nodal cells isolated from mouse hearts and are able to pace murine myocardium ex vivo. Using the described protocol highly pure sinus nodal single cells can be generated which e.g. can be used for in vitro drug testing. Furthermore, the iSABs generated according to this protocol may become a crucial step towards heart tissue engineering.
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Células-Tronco Pluripotentes/fisiologia , Nó Sinoatrial/fisiologia , Proteínas com Domínio T/genética , Animais , Agregação Celular/fisiologia , Diferenciação Celular/fisiologia , Camundongos , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/fisiologia , Cadeias Pesadas de Miosina/biossíntese , Cadeias Pesadas de Miosina/genética , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/metabolismo , Regiões Promotoras Genéticas , Nó Sinoatrial/citologia , Nó Sinoatrial/metabolismo , Transplante de Células-Tronco/métodos , Proteínas com Domínio T/biossíntese , TransfecçãoRESUMO
Therapeutic approaches for "sick sinus syndrome" rely on electrical pacemakers, which lack hormone responsiveness and bear hazards such as infection and battery failure. These issues may be overcome via "biological pacemakers" derived from pluripotent stem cells (PSCs). Here, we show that forward programming of PSCs with the nodal cell inducer TBX3 plus an additional Myh6-promoter-based antibiotic selection leads to cardiomyocyte aggregates consisting of >80% physiologically and pharmacologically functional pacemaker cells. These induced sinoatrial bodies (iSABs) exhibited highly increased beating rates (300-400 bpm), coming close to those found in mouse hearts, and were able to robustly pace myocardium ex vivo. Our study introduces iSABs as highly pure, functional nodal tissue that is derived from PSCs and may be important for future cell therapies and drug testing in vitro.
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Reprogramação Celular , Células-Tronco Pluripotentes/citologia , Nó Sinoatrial/fisiologia , Animais , Relógios Biológicos , Cálcio/metabolismo , Diferenciação Celular , Linhagem Celular , Técnicas de Cocultura , Técnicas In Vitro , Camundongos , Modelos Biológicos , Miócitos Cardíacos/metabolismo , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo , Técnicas de Patch-Clamp , Células-Tronco Pluripotentes/metabolismo , Síndrome do Nó Sinusal/metabolismo , Síndrome do Nó Sinusal/patologia , Síndrome do Nó Sinusal/veterinária , Nó Sinoatrial/citologia , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismoRESUMO
OBJECTIVE: The purpose of this paper is to describe the theoretical development and initial validation of the newly developed Work-Life Balance Culture Scale (WLBCS), an instrument for measuring an organizational culture that promotes the work-life balance of employees. METHODS: In Study 1 (N=498), the scale was developed and its factorial validity tested through exploratory factor analyses. In Study 2 (N=513), confirmatory factor analysis (CFA) was performed to examine model fit and retest the dimensional structure of the instrument. To assess construct validity, a priori hypotheses were formulated and subsequently tested using correlation analyses. RESULTS: Exploratory and confirmatory factor analyses revealed a one-factor model. Results of the bivariate correlation analyses may be interpreted as preliminary evidence of the scale's construct validity. CONCLUSION: The five-item WLBCS is a new and efficient instrument with good overall quality. Its conciseness makes it particularly suitable for use in employee surveys to gain initial insight into a company's perceived work-life balance culture.
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Satisfação no Emprego , Saúde Ocupacional , Cultura Organizacional , Satisfação Pessoal , Qualidade de Vida , Inquéritos e Questionários , Trabalho/psicologia , Adulto , Estudos Transversais , Análise Fatorial , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: The aim of this study was to investigate the impact of a transformational leadership style on employee well-being. METHODS: Data for the study were taken from an on-line survey of all employees from six German companies in the information and communication technology sector. The data obtained were analyzed using multiple logistic regressions. RESULTS: Analysis of data from a total of 318 employees (response rate 58.4%) revealed a significant relationship between transformational leadership and employee well-being (P = 0.00; OR = 1.13; 95% CI = 1.05 to 1.22). A higher degree of perceived transformational leadership is associated with greater well-being. CONCLUSIONS: The results of this study suggest that a transformational leadership style, which both conveys a sense of trust and meaningfulness and individually challenges and develops employees, also has a positive effect on employee well-being.
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Ciência da Informação/organização & administração , Liderança , Saúde Mental/estatística & dados numéricos , Saúde Ocupacional/estatística & dados numéricos , Gestão de Recursos Humanos/métodos , Tecnologia/organização & administração , Adulto , Estudos Transversais , Feminino , Alemanha , Inquéritos Epidemiológicos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise MultivariadaRESUMO
OBJECTIVE: Little is known about how organizational factors influence the patient-physician interaction. This study investigates the relationship between physician workload in hospitals and breast cancer patients' perceptions of the support provided by physicians. METHODS: Data from 1844 newly diagnosed breast cancer patients treated in 35 breast cancer center hospitals in the German state of North Rhine-Westphalia in 2010 were combined with data from 348 physicians from the same hospitals. Multilevel logistic regression models were calculated using 31 hospitals with complete patient and physician data. Patients' perceptions of physician support were studied in relation to physician workload in hospitals. RESULTS: Breast cancer patients perceived themselves as receiving less support from physicians when treated in hospitals where physicians reported working more overtime hours and having less time for patient care. CONCLUSION: This study provides preliminary evidence of the association between the hospital work environment and physicians' ability to support patients. Future studies should investigate the extent to which physicians' interaction performance can be modified through hospital-level interventions aimed at managing workload. PRACTICE IMPLICATIONS: By approaching the problem of physician staffing in hospitals and investing in the hospitals' working conditions, health policy and hospital management could create conditions conducive to better patient-physician interaction.
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Neoplasias da Mama/psicologia , Neoplasias da Mama/terapia , Satisfação do Paciente , Relações Médico-Paciente , Carga de Trabalho/estatística & dados numéricos , Estudos Transversais , Feminino , Alemanha , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários , Fatores de TempoRESUMO
Post-translational modifications (PTMs) of histones exert fundamental roles in regulating gene expression. During development, groups of PTMs are constrained by unknown mechanisms into combinatorial patterns, which facilitate transitions from uncommitted embryonic cells into differentiated somatic cell lineages. Repressive histone modifications such as H3K9me3 or H3K27me3 have been investigated in detail, but the role of H4K20me3 in development is currently unknown. Here we show that Xenopus laevis Suv4-20h1 and h2 histone methyltransferases (HMTases) are essential for induction and differentiation of the neuroectoderm. Morpholino-mediated knockdown of the two HMTases leads to a selective and specific downregulation of genes controlling neural induction, thereby effectively blocking differentiation of the neuroectoderm. Global transcriptome analysis supports the notion that these effects arise from the transcriptional deregulation of specific genes rather than widespread, pleiotropic effects. Interestingly, morphant embryos fail to repress the Oct4-related Xenopus gene Oct-25. We validate Oct-25 as a direct target of xSu4-20h enzyme mediated gene repression, showing by chromatin immunoprecipitaton that it is decorated with the H4K20me3 mark downstream of the promoter in normal, but not in double-morphant, embryos. Since knockdown of Oct-25 protein significantly rescues the neural differentiation defect in xSuv4-20h double-morphant embryos, we conclude that the epistatic relationship between Suv4-20h enzymes and Oct-25 controls the transit from pluripotent to differentiation-competent neural cells. Consistent with these results in Xenopus, murine Suv4-20h1/h2 double-knockout embryonic stem (DKO ES) cells exhibit increased Oct4 protein levels before and during EB formation, and reveal a compromised and biased capacity for in vitro differentiation, when compared to normal ES cells. Together, these results suggest a regulatory mechanism, conserved between amphibians and mammals, in which H4K20me3-dependent restriction of specific POU-V genes directs cell fate decisions, when embryonic cells exit the pluripotent state.
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Diferenciação Celular , Histona-Lisina N-Metiltransferase/genética , Placa Neural , Fatores do Domínio POU , Proteínas de Xenopus/genética , Xenopus laevis , Animais , Técnicas de Cultura de Células , Linhagem da Célula , Cromatina/genética , Metilação de DNA , Embrião não Mamífero , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Silenciamento de Genes , Histona-Lisina N-Metiltransferase/metabolismo , Placa Neural/crescimento & desenvolvimento , Placa Neural/metabolismo , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo , Fatores do Domínio POU/genética , Fatores do Domínio POU/metabolismo , Sequências Reguladoras de Ácido Nucleico , Proteínas de Xenopus/metabolismo , Xenopus laevis/genética , Xenopus laevis/crescimento & desenvolvimentoRESUMO
BACKGROUND: Depression is the leading cause of disability and high costs worldwide. One possibility for preventing depression in the workplace, which has received little consideration so far, is the promotion of a successful balance between work and personal life. The aim of this study was to investigate employees' negative and positive work-home interaction and their association with depressive symptoms. METHODS: A cross-sectional study was conducted in the micro- and nanotechnology sector in Germany. A stepwise multivariate logistic regression analysis was performed using data from N = 213 employees. RESULTS: The results suggest that while negative work-home interaction is associated with an increased risk for depressive symptoms, positive work-home interaction is correlated with a lower risk. Neither positive nor negative interaction in the home-to-work direction demonstrated a significant association with depressive symptoms. CONCLUSION: When attempting to prevent mental illnesses, such as depression, it is important to develop strategies aimed at reducing conflict between work and personal life and promoting a positive exchange between these two domains.
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Atitude , Depressão/epidemiologia , Estilo de Vida , Microtecnologia , Nanotecnologia , Saúde Ocupacional , Adulto , Estudos Transversais , Feminino , Alemanha , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise de RegressãoRESUMO
OBJECTIVE: To examine the relationships among employees' emotional exhaustion, positive and negative work-home interaction, and perceived work-life balance culture in companies. METHODS: Data for this study were collected through online surveys of employees from companies in the micro- and nanotechnology sectors (N = 509). A structural equation modeling analysis was performed. RESULTS: A company culture perceived by employees as supportive of their work-life balance was found to have both a direct negative effect on emotional exhaustion and an indirect negative effect meditated by negative work-home interaction. In addition, whereas negative work-home interaction associated positively with emotional exhaustion, positive work-home interaction had no significant effect. CONCLUSIONS: The direct and indirect relationship between work-life balance culture and emotional exhaustion has practical implications for health promotion in companies.