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OBJECTIVES: To conduct an intrapatient comparison of ultra-low-dose computed tomography (ULDCT) and standard-of-care-dose CT (SDCT) of the chest in terms of the diagnostic accuracy of ULDCT and intrareader agreement in patients with post-COVID conditions. METHODS: We prospectively included 153 consecutive patients with post-COVID-19 conditions. All participants received an SDCT and an additional ULDCT scan of the chest. SDCTs were performed with standard imaging parameters and ULDCTs at a fixed tube voltage of 100 kVp (with tin filtration), 50 ref. mAs (dose modulation active), and iterative reconstruction algorithm level 5 of 5. All CT scans were separately evaluated by four radiologists for the presence of lung changes and their consistency with post-COVID lung abnormalities. Radiation dose parameters and the sensitivity, specificity, and accuracy of ULDCT were calculated. RESULTS: Of the 153 included patients (mean age 47.4 ± 15.3 years; 48.4% women), 45 (29.4%) showed post-COVID lung abnormalities. In those 45 patients, the most frequently detected CT patterns were ground-glass opacities (100.0%), reticulations (43.5%), and parenchymal bands (37.0%). The accuracy, sensitivity, and specificity of ULDCT compared to SDCT for the detection of post-COVID lung abnormalities were 92.6, 87.2, and 94.9%, respectively. The median total dose length product (DLP) of ULDCTs was less than one-tenth of the radiation dose of our SDCTs (12.6 mGy*cm [9.9; 15.5] vs. 132.1 mGy*cm [103.9; 160.2]; p < 0.001). CONCLUSION: ULDCT of the chest offers high accuracy in the detection of post-COVID lung abnormalities compared to an SDCT scan at less than one-tenth the radiation dose, corresponding to only twice the dose of a standard chest radiograph in two views. CLINICAL RELEVANCE STATEMENT: Ultra-low-dose CT of the chest may provide a favorable, radiation-saving alternative to standard-dose CT in the long-term follow-up of the large patient cohort of post-COVID-19 patients.
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This paper consists of an analysis of the concept of empowerment-which is often defined as a key issue in health care-at the macro, meso, and micro levels by focusing on health care reform in Belgium. Three research teams collected data and combined them in an inductive secondary analysis. Our preliminary results demonstrate that patient empowerment does not always encompass the same scientific reality. At the macro level, this concept is linked to the authorities' wish to support at-home care for chronic patients. At the meso level, the role of caregivers in maintaining patients' autonomy, but also the social conditions of their lives, is a salient component of empowerment. At the micro level, individual and personal features such as identity can influence patient empowerment and behavior in the health care system. This cross-level research suggests that patient empowerment is not sufficiently clearly defined at each level of the care production chain, which could impede the reform of health care. This paper underlines the polysemy of a concept viewed as a milestone in European health care policy and the necessity of a clear, collective definition to operationalize and implement it.
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Aging results in a decline of physiological functions and in reduced repair capacities, in part due to impaired regenerative power of stem cells, influenced by the systemic environment. In particular osteogenic differentiation capacity (ODC) of mesenchymal stem cells (MSCs) has been shown to decrease with age, thereby contributing to reduced bone formation and an increased fracture risk. Searching for systemic factors that might contribute to this age related decline of regenerative capacity led us to investigate plasma-derived extracellular vesicles (EVs). EVs of the elderly were found to inhibit osteogenesis compared to those of young individuals. By analyzing the differences in the vesicular content Galectin-3 was shown to be reduced in elderly-derived vesicles. While overexpression of Galectin-3 resulted in an enhanced ODC of MSCs, siRNA against Galectin-3 reduced osteogenesis. Modulation of intravesicular Galectin-3 levels correlated with an altered osteo-inductive potential indicating that vesicular Galectin-3 contributes to the biological response of MSCs to EVs. By site-directed mutagenesis we identified a phosphorylation-site on Galectin-3 mediating this effect. Finally, we showed that cell penetrating peptides comprising this phosphorylation-site are sufficient to increase ODC in MSCs. Therefore, we suggest that decrease of Galectin-3 in the plasma of elderly contributes to the age-related loss of ODC.
Assuntos
Envelhecimento/metabolismo , Senescência Celular , Vesículas Extracelulares/metabolismo , Galectina 3/metabolismo , Células-Tronco Mesenquimais/metabolismo , Osteogênese , Adulto , Fatores Etários , Envelhecimento/sangue , Proteínas Sanguíneas , Peptídeos Penetradores de Células/metabolismo , Peptídeos Penetradores de Células/farmacologia , Células Cultivadas , Regulação para Baixo , Vesículas Extracelulares/efeitos dos fármacos , Feminino , Galectina 3/sangue , Galectina 3/genética , Galectinas , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Pessoa de Meia-Idade , Mutagênese Sítio-Dirigida , Mutação , Osteogênese/efeitos dos fármacos , Fosforilação , Interferência de RNA , Transdução de Sinais , Fatores de Tempo , Transfecção , Adulto JovemRESUMO
OBJECTIVE: Information and communication technologies (ICT) have become an integral part of people's lives. Trends suggest that the age when technology is used for the first time is rapidly decreasing and that children are exposed to ICT daily. However, the focus of the existing research has been on adolescents, and there is a dearth of knowledge about the use of ICT amongst children in middle childhood in South Africa. The objective of this study was to address this issue. METHOD: The research participants included 12 children aged between 6 and 12 years old from two private schools (a boys' school and a girls' school) in the Gauteng region. A phenomenological approach was used to explore the use and trends of ICT among this age group. A semi-structured interview approach was employed for the data collection and each interview was tape-recorded and transcribed by the researcher. The Interpretative Phenomenological Analysis was used to analyse and interpret the data collected. RESULTS: Various themes were identified. While all the participants had been exposed to and used ICT, a clear developmental trend was observed: not only were younger children less sophisticated users of ICT, but they were also less informed about the dangers of ICT usage. The participants were generally not supervised but some rules were implemented by the parents. Although the children did not experience cyber bullying, they did report exposure to pornography. CONCLUSION: The results suggest various implications for developmental trends and protection of children.
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The tumour suppressor HIPK2 is an important regulator of cell death induced by DNA damage, but how its activity is regulated remains largely unclear. Here we demonstrate that HIPK2 is an unstable protein that colocalizes and interacts with the E3 ubiquitin ligase Siah-1 in unstressed cells. Siah-1 knockdown increases HIPK2 stability and steady-state levels, whereas Siah-1 expression facilitates HIPK2 polyubiquitination, degradation and thereby inactivation. During recovery from sublethal DNA damage, HIPK2, which is stabilized on DNA damage, is degraded through a Siah-1-dependent, p53-controlled pathway. Downregulation of Siah-1 inhibits HIPK2 degradation and recovery from damage, driving the cells into apoptosis. We have also demonstrated that DNA damage triggers disruption of the HIPK2-Siah-1 complex, resulting in HIPK2 stabilization and activation. Disruption of the HIPK2-Siah-1 complex is mediated by the ATM/ATR pathway and involves ATM/ATR-dependent phosphorylation of Siah-1 at Ser 19. Our results provide a molecular framework for HIPK2 regulation in unstressed and damaged cells.