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- Wasserman, D, et al.
(författare)
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Compulsory admissions of patients with mental disorders: State of the art on ethical and legislative aspects in 40 European countries
- 2020
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Ingår i: European psychiatry : the journal of the Association of European Psychiatrists. - : Royal College of Psychiatrists. - 1778-3585. ; 63:1, s. e82-
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Tidskriftsartikel (refereegranskat)abstract
- Background.Compulsory admission procedures of patients with mental disorders vary between countries in Europe. The Ethics Committee of the European Psychiatric Association (EPA) launched a survey on involuntary admission procedures of patients with mental disorders in 40 countries to gather information from all National Psychiatric Associations that are members of the EPA to develop recommendations for improving involuntary admission processes and promote voluntary care.Methods.The survey focused on legislation of involuntary admissions and key actors involved in the admission procedure as well as most common reasons for involuntary admissions.Results.We analyzed the survey categorical data in themes, which highlight that both medical and legal actors are involved in involuntary admission procedures.Conclusions.We conclude that legal reasons for compulsory admission should be reworded in order to remove stigmatization of the patient, that raising awareness about involuntary admission procedures and patient rights with both patients and family advocacy groups is paramount, that communication about procedures should be widely available in lay-language for the general population, and that training sessions and guidance should be available for legal and medical practitioners. Finally, people working in the field need to be constantly aware about the ethical challenges surrounding compulsory admissions.
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- Kiekens, L, et al.
(författare)
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T-BET and EOMES Accelerate and Enhance Functional Differentiation of Human Natural Killer Cells
- 2021
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 12, s. 732511-
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Tidskriftsartikel (refereegranskat)abstract
- T-bet and Eomes are transcription factors that are known to be important in maturation and function of murine natural killer (NK) cells. Reduced T-BET and EOMES expression results in dysfunctional NK cells and failure to control tumor growth. In contrast to mice, the current knowledge on the role of T-BET and EOMES in human NK cells is rudimentary. Here, we ectopically expressed either T-BET or EOMES in human hematopoietic progenitor cells. Combined transcriptome, chromatin accessibility and protein expression analyses revealed that T-BET or EOMES epigenetically represses hematopoietic stem cell quiescence and non-NK lineage differentiation genes, while activating an NK cell-specific transcriptome and thereby drastically accelerating NK cell differentiation. In this model, the effects of T-BET and EOMES are largely overlapping, yet EOMES shows a superior role in early NK cell maturation and induces faster NK receptor and enhanced CD16 expression. T-BET particularly controls transcription of terminal maturation markers and epigenetically controls strong induction of KIR expression. Finally, NK cells generated upon T-BET or EOMES overexpression display improved functionality, including increased IFN-γ production and killing, and especially EOMES overexpression NK cells have enhanced antibody-dependent cellular cytotoxicity. Our findings reveal novel insights on the regulatory role of T-BET and EOMES in human NK cell maturation and function, which is essential to further understand human NK cell biology and to optimize adoptive NK cell therapies.
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- Persyn, E, et al.
(författare)
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IRF2 is required for development and functional maturation of human NK cells
- 2022
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 13, s. 1038821-
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Tidskriftsartikel (refereegranskat)abstract
- Natural killer (NK) cells are cytotoxic and cytokine-producing lymphocytes that play an important role in the first line of defense against malignant or virus-infected cells. A better understanding of the transcriptional regulation of human NK cell differentiation is crucial to improve the efficacy of NK cell-mediated immunotherapy for cancer treatment. Here, we studied the role of the transcription factor interferon regulatory factor (IRF) 2 in human NK cell differentiation by stable knockdown or overexpression in cord blood hematopoietic stem cells and investigated its effect on development and function of the NK cell progeny. IRF2 overexpression had limited effects in these processes, indicating that endogenous IRF2 expression levels are sufficient. However, IRF2 knockdown greatly reduced the cell numbers of all early differentiation stages, resulting in decimated NK cell numbers. This was not caused by increased apoptosis, but by decreased proliferation. Expression of IRF2 is also required for functional maturation of NK cells, as the remaining NK cells after silencing of IRF2 had a less mature phenotype and showed decreased cytotoxic potential, as well as a greatly reduced cytokine secretion. Thus, IRF2 plays an important role during development and functional maturation of human NK cells.
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- Taveirne, S, et al.
(författare)
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The transcription factor ETS1 is an important regulator of human NK cell development and terminal differentiation
- 2020
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 136:3, s. 288-298
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Tidskriftsartikel (refereegranskat)abstract
- Natural killer (NK) cells are important in the immune defense against tumor cells and pathogens, and regulate other immune cells by cytokine secretion. Whereas murine NK cell biology has been extensively studied, knowledge about transcriptional circuitries controlling human NK cell development and maturation is limited. By generating ETS1-deficient human embryonic stem cells (hESC) and by expressing the dominant-negative ETS1 p27 isoform in cord blood (CB) hematopoietic progenitor cells (HPCs), we show that the transcription factor ETS1 is critically required for human NK cell differentiation. Genome-wide transcriptome analysis determined by RNA-sequencing combined with chromatin immunoprecipitation-sequencing (ChIP-seq) analysis reveals that human ETS1 directly induces expression of key transcription factors that control NK cell differentiation, i.e. E4BP4, TXNIP, TBET, GATA3, HOBIT and BLIMP1. In addition, ETS1 regulates expression of genes involved in apoptosis and NK cell activation. Our study provides important molecular insights into the role of ETS1 as an important regulator of human NK cell development and terminal differentiation.
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- Van Lierde, KM, et al.
(författare)
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Impact of fixed implant prosthetics using the 'all-on-four' treatment concept on speech intelligibility, articulation and oromyofunctional behaviour
- 2012
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Ingår i: International Journal of Oral and Maxillofacial Surgery. - : Elsevier. - 0901-5027 .- 1399-0020. ; 41:12, s. 1550-1557
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this case control study is to determine the impact of screw-retained fixed cross-arch prostheses, supported by four osseointegrated implants, on articulation and oromyofunctional behaviour. Objective (acoustic analysis) and subjective assessment techniques were used to determine the overall intelligibility, phonetic characteristics and oromyofunctional behaviour at an average period of 7.3 months after placement of the fixed implant prosthesis in 15 patients and 9 age-matched controls with intact dentition and without prosthetic appliances. Overall satisfaction with the prosthesis was 87%, but 53% of the subjects mentioned an impact on speech. 87% of the subjects presented with one or more distortions of the consonants. The most common distortions were distortions of the sound /s/ (sigmatismus simplex, 40% and sigmatismus stridens, 33%), simplex /z/ (27%), insufficient frication of /f/ (20%), /[symbol in text]/ (20%), addental production of /d/ (20%), /t/ (20%) or /s/ sound (13%) and devoiced /d/ (7%). In the control group, no articulation disorders were noted. Oromyofunctional behaviour in both groups was normal. To what extent motor-oriented speech therapy (with focus on tongue function) immediately after periodontal treatment (after wound healing) would decrease the persistent phonetic distortions is a subject for further research.
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