La pandémie a besoin d'une stratégie cantonale et supracantonale : changement de perspective après deux ans de gestion du Covid-19 = Zeit für eine kantonale und überkantonale Corona-Strategie : Perspektivenwechsel nach zwei Jahren Corona-Politik

Das Ende der Corona-Pandemie für die Schweiz zeichnet sich ab. Damit wird sich die Gesundheitspolitik wieder auf ihre Regelstrukturen abstützen und sich statt nur auf die Kapazität der Intensivpflegestationen wieder auf umfassendere Ziele ausrichten können. Eine besondere Bedeutung werden dabei kantonale und überkantonale Corona-Strategien erlangen. = La fin de la pandémie de coronavirus se dessine en Suisse. Ainsi, la politique de la santé pourra s’appuyer à nouveau sur ses structures ordinaires et se recentrer sur des objectifs plus larges que la seule capacité des unités de soins intensifs. Les stratégies cantonales et supracantonales en matière de coronavirus revêtiront une importance particulière

Development of a battery of instruments for detailed measurement of health status in patients with COPD in routine care: the Nijmegen Clinical Screening Instrument

Contains fulltext : 80284.pdf (publisher's version ) (Closed access)PURPOSE: To compose a battery of instruments that provides a detailed assessment of health status (HS) in COPD but that is applicable and clinically meaningful in routine care. METHODS: In a previous study, we developed the Nijmegen Integral Assessment Framework (NIAF) that organizes existing tests and instruments by the sub-domains of HS they measure. Based on clinical and statistical criteria (correlation coefficients and Cronbach alpha's) we selected for each sub-domain instruments from the NIAF. A COPD-study group was used to determine c-scores, and two control groups were used to determine the score ranges indicating normal functioning versus clinically relevant problems for each sub-domain. Existing questionnaire completion software (TestOrganiser) was adapted to enhance clinical applicability. RESULTS: The NCSI measures eleven sub-domains of physiological functioning, symptoms, functional impairment, and quality of life. The TestOrganiser automatically processes the data and produces the graphical PatientProfileChart, which helps to easily interpret results. This envisages the problem areas and discrepancies between the different sub-domains. CONCLUSION: The NCSI provides a valid and detailed picture of a patient's HS within 15-25 min. In combination with the PatientProfileChart, the NCSI can be used perfectly in routine care as screening instrument and as a guide in patient-tailored treatment

Molecular approaches for in vitro expansion of human haematopoietic stem and progenitor cells

In vitro expansion of haematopoietic stem and progenitor cells (HSPCs) is a challenging task since these cells tend to differentiate under culture conditions resulting in loss of their stem cell character. Possibilities to enhance HSPC self-renewal involve intrinsic regulators such as transcription factors or microRNAs (miRNAs) but also extrinsic stimulation by signalling molecules. Most attempts for intrinsic stimulation of HSPC proliferation utilise stable gene modification such as viral vectors that are still controversial in clinical settings as they harbour the risk of insertional mutagenesis. Therefore, our study aimed to investigate new approaches to modify HSPC gene expression at the post-transcriptional level by using novel and established RNA-based molecules. First, various transfection methods were tested to deliver non-integrating RNA molecules into HSPCs. Standard chemical transfection methods including lipofection for delivery of siRNAs targeting surface markers did not lead to protein knockdown although more than 90% of fluorescent cells were detected using a fluorescently labelled control siRNA. By means of confocal microscopy, we showed that the siRNA-reagent complexes stuck to or inside the cell membrane after transfection, thereby mimicking a transfection event. In contrast, efficient siRNA-mediated protein knockdown was achieved using electroporation, proving that this is the method of choice for HSPC transfection. For RNA-mediated HSPC expansion, the function of selected candidate miRNAs was modulated by electroporation of specific inhibitors or mimics. Enhancement of miRNA 125b and miRNA-99a function or inhibition of miRNA 142 3p slightly increased the expansion of HSPCs compared to a scrambled negative control. Serum taken from patients after chemotherapy has previously been shown to stimulate HSPC expansion. In this study, microarray analysis of miRNAs circulating in serum indicated that miRNAs are differentially expressed in serum before and after therapy. However, a combination of different soluble factors rather than a single miRNA probably is responsible for the observed growth-promoting effect. Overexpression of regulatory proteins such as HOXB4 using mRNAs was efficient but presumably too short-lived to significantly impact on HSPC behaviour. Novel, self-replicating RNAs resulted in prolonged protein expression, offering new opportunities for DNA-free gene modulation in HSPCs. Preliminary data suggest that overexpression of the epigenetic modifier BMI1 by self-replicating RNAs could prevent stem cell loss in vitro, but its effect on HSPC expansion has to be investigated more in detail in future studies.As an extrinsic approach for HSPC expansion, the Notch ligand Delta like 4 (Dll4) was coupled to beads and added to long-term cultures. This system promoted the expansion of primitive HSPC subpopulations in a stromal cell- and serum-free culture system. In conclusion, non-integrating intrinsic HSPC modulation in combination with extrinsic stimulation might be the key to successful in vitro expansion of HSPCs

RNA-based, transient modulation of gene expression in human haematopoietic stem and progenitor cells

Modulation of gene expression is a useful tool to study the biology of haematopoietic stem and progenitor cells (HSPCs) and might also be instrumental to expand these cells for therapeutic approaches. Most of the studies so far have employed stable gene modification by viral vectors that are burdensome when translating protocols into clinical settings. Our study aimed at exploring new ways to transiently modify HSPC gene expression using non-integrating, RNA-based molecules. First, we tested different methods to deliver these molecules into HSPCs. The delivery of siRNAs with chemical transfection methods such as lipofection or cationic polymers did not lead to target knockdown, although we observed more than 90% fluorescent cells using a fluorochrome-coupled siRNA. Confocal microscopic analysis revealed that despite extensive washing, siRNA stuck to or in the cell surface, thereby mimicking a transfection event. In contrast, electroporation resulted in efficient, siRNA-mediated protein knockdown. For transient overexpression of proteins, we used optimised mRNA molecules with modified 5'- and 3'-UTRs. Electroporation of mRNA encoding GFP resulted in fast, efficient and persistent protein expression for at least seven days. Our data provide a broad-ranging comparison of transfection methods for hard-to-transfect cells and offer new opportunities for DNA-free, non-integrating gene modulation in HSPCs

MicroRNA expression profiles of serum from patients before and after chemotherapy

AbstractRecovery of the blood and immune system after chemotherapy requires proliferation of hematopoietic stem and progenitor cells (HPSCs). It has been shown that systemically released factors in serum after chemotherapy stimulate HSPC expansion in vitro. We wondered if microRNAs (miRNAs) circulating in serum could account for this effect. Therefore, we compared the miRNA expression profiles of serum from patients with hematologic malignancies before and after chemotherapy. In addition to a general decrease in miRNA expression after chemotherapy, we found 23 miRNAs to be significantly differentially expressed in serum before versus after chemotherapy. The miRNA microarray data are available at NCBI's Gene Expression Omnibus (GEO) Series accession number GSE57570. Here, we provide a detailed protocol of the miRNA microarray and data analysis

Proteolysis of ribulose-1,5-bisphosphate carboxylase oxygenase in citrus leaf extracts

Peer reviewe

What Kind of Self-Care Strategies Do People Report Using and is There an Association with Well-Being?

mental health, self-care,