19 research outputs found
Validation of the children's sleep habits questionnaire in a sample of Greek children with allergic rhinitis
BACKGROUND: Obstructive respiratory disorders, such as allergic rhinitis and asthma may impair sleep quality. The aim of this study is to validate the Children's Sleep Habits Questionnaire (CSHQ) for Greek children from 6 to 14 years of age. No validated tool has been developed so far to assess sleep disturbances in Greek school-aged children. METHODS: We examined the reliability and validity of the CSHQ in a sample of children with allergic rhinitis (AR) and a non-clinical population of parents of these children as a proxy measure of children's AR quality of life (QoL) as evaluated by the Pediatric Allergic Rhinitis Quality of Life (PedARQoL) questionnaire. RESULTS: The CSHQ questionnaire Child's Form (CF) had a moderate internal consistency with a Cronbach's alpha 0.671 and Guttman split-half coefficient of 0.563 when correlated with the PedARQoL (CF). There was also a moderate intraclass correlation of ICC=0.505 between the responses to both questionnaires in the two visits. The CSHQ Parent's Form (PF) had a very good internal consistency with a Cronbach's alpha of 0.928 and Guttman split-half coefficient of 0.798. There was a high intraclass correlation of 0.643 between the responses in the two visits. CONCLUSIONS: The Greek version of the CSHQ CF, but particularly the PF has proved to be a very reliable clinical instrument, which can be used in clinical trials for assessing sleep quality in school-aged children with sleep disturbances because of obstructive airway disorders, such as AR
Extramedullary leukemia relapse after allogeneic stem cell transplantation: A novel mechanism of immune escape?
Background: Relapse is a significant cause of treatment failure after allogeneic stem cell transplantation. In many cases relapse occurs when leukemic cells escape from immune surveillance. Methods &results: In the setting of haploidentical transplantation, immune escape is usually the result of the loss of the mismatched haplotype from leukemic cells, while downregulation of HLA-expression has been postulated as a significant cause of immune escape after transplantation with the use of HLA-matched donors. We observed that patients with acute leukemia who relapse at the time of active graft-versus-host-disease, usually develop extramedullary leukemia while they remain free of leukemia in peripheral blood and bone marrow. Conclusion: Our observation points toward a novel mechanism of immune escape which is microenvironment-specific. © 2020 Future Medicine Ltd
The role of skills, attitudes, and perceived behaviour control in pedestrian decision-making of adolescents aged 11-15 years
The peak age for pedestrian accidents among school pupils in the UK is between 12 and 14 years, following the transition to secondary school, and after children have apparently become relatively competent at interacting with traffic. The reason why vulnerability should increase when underlying skills have improved is unclear. A better understanding of the processes at work is therefore needed in order to determine what steps might be taken to counteract this problem. This report details two studies designed to unravel which factors contribute most to increases in unsafe pedestrian behaviour between the ages of 11 and 15 years. Study 1 focused on whether young adolescents do, in fact, have limited skills for dealing with more complex traffic environments; and whether, in spite of this, they underestimate the difficulty of road-crossing decisions, and ignore signs that their performance is less adequate than they believe. Study 2 was designed to investigate the source of young adolescents' misperceptions of difficulty, and the relative impact of these and attitudes or other perceptions on pedestrian decision-making
Effective interventions for potentially modifiable risk factors for late-onset dementia: a costs and cost-effectiveness modelling study
BACKGROUND: The potential economic value of interventions to prevent late-onset dementia is unknown. We modelled this for potentially modifiable risk factors for dementia. METHODS: For this modelling study, we searched PubMed and Web of Science from inception to March 12, 2020, and included interventions that: successfully targeted any of nine prespecified potentially modifiable risk factors (hypertension, diabetes, hearing loss, obesity, physical inactivity, social isolation, depression, cigarette smoking, and less childhood education); had robust evidence that the intervention improved risk or risk behaviour; and are feasible to enact in an adult population. We established when in the life course each intervention would be delivered. We calculated dementia incidence reduction from annual incidence of dementia in people with each risk factor, and population attributable fraction for each risk, corrected for risk factor clustering, and how effectively the intervention controls the risk factor. We calculated the discounted value of lifetime health gain and effect on cost (including NHS, social care and carer costs) per person eligible for treatment. We estimated annual total expenditure on the fully operational intervention programme in England. FINDINGS: We found effective interventions for hypertension, smoking cessation, diabetes prevention, and hearing loss. Treatments for stopping smoking and provision of hearing aids reduced cost. Treatment of hypertension was cost-effective by reference to standard UK thresholds. The three interventions when fully implemented would save £1·863 billion annually in England, reduce dementia prevalence by 8·5%, and produce quality-adjusted life-year gains. The intervention for diabetes was unlikely to be cost-effective in terms of effect on dementia alone. INTERPRETATION: There is a strong case for implementing the three effective interventions on grounds of cost-effectiveness and quality-of-life gains, as well as for improvements in general health. The interventions have the potential to remain cost-saving or cost-effective even with variations in dementia incidence and costs and effectiveness of interventions
Generation of human β-thalassemia induced pluripotent cell lines by reprogramming of bone marrow-derived mesenchymal stromal cells using modified mRNA
Synthetic modified mRNA molecules encoding pluripotency transcription factors have been used successfully in reprogramming human fibroblasts to induced pluripotent stem cells (iPSCs). We have applied this method on bone marrow-derived mesenchymal stromal cells (BM-MSCs) obtained from a patient with β-thalassemia (β-thal) with the aim to generate trangene-free β-thal-iPSCs. Transfection of 104 BM-MSCs by lipofection with mRNA encoding the reprogramming factors Oct4, Klf4, Sox2, cMyc, and Lin28 resulted in formation of five iPSC colonies, from which three were picked up and expanded in β-thal-iPSC lines. After 10 serial passages in vitro, β-thal-iPSCs maintain genetic stability as shown by array comparative genomic hybridization (aCGH) and are capable of forming embryoid bodies in vitro and teratomas in vivo. Their gene expression profile compared to human embryonic stem cells (ESCs) and BM-MSCs seems to be similar to that of ESCs, whereas it differs from the profile of the parental BM-MSCs. Differentiation cultures toward a hematopoietic lineage showed the generation of CD34+ progenitors up to 10%, but with a decreased hematopoietic colony-forming capability. In conclusion, we report herein the generation of transgene-free β-thal-iPSCs that could be widely used for disease modeling and gene therapy applications. Moreover, it was demonstrated that the mRNA-based reprogramming method, used mainly in fibroblasts, is also suitable for reprogramming of human BM-MSCs. © Mary Ann Liebert, Inc. 2014
Mesenchymal derivatives of genetically unstable human embryonic stem cells are maintained unstable but undergo senescence in culture as do bone marrow-derived mesenchymal stem cells
Recurrent chromosomal alterations have been repeatedly reported in cultured human embryonic stem cells (hESCs). The effects of these alterations on the capability of pluripotent cells to differentiate and on growth potential of their specific differentiated derivatives remain unclear. Here, we report that the hESC lines HUES-7 and -9 carrying multiple chromosomal alterations produce in vitro mesenchymal stem cells (MSCs) that show progressive growth arrest and enter senescence after 15 and 16 passages, respectively. There was no difference in their proliferative potential when compared with bone marrow-derived MSCs. Array comparative genomic hybridization analysis (aCGH) of hESCs and their mesenchymal derivatives revealed no significant differences in chromosomal alterations, suggesting that genetically altered hESCs are not selected out during differentiation. Our findings indicate that genetically unstable hESCs maintain their capacity to differentiate in vitro into MSCs, which exhibit an in vitro growth pattern of normal MSCs and not that of transformed cells. © Mary Ann Liebert, Inc
Therapeutic Effects of Mesenchymal Stem Cells Derived From Bone Marrow, Umbilical Cord Blood, and Pluripotent Stem Cells in a Mouse Model of Chemically Induced Inflammatory Bowel Disease
Acute inflammatory bowel disease (AIBD) is a wide clinical entity including severe gastrointestinal pathologies with common histopathological basis. Epidemiologically increasing diseases, such as necrotizing enterocolitis (NEC), gastrointestinal graft versus host disease (GVHD), and the primary acute phase of chronic inflammatory bowel disease (CIBD), exhibit a high necessity for new therapeutic strategies. Mesenchymal stem cell (MSC) cellular therapy represents a promising option for the treatment of these diseases. In our study, we comparatively assess the efficacy of human MSCs derived from bone marrow (BM), umbilical cord blood (UCB), human embryonic stem cells (ESCs), or human-induced pluripotent stem cells (iPSCs) in a mouse model of chemically induced acute enterocolitis. The laboratory animals were provided ad libitum potable dextrane sulfate sodium solution (DSS) in order to reproduce an AIBD model and then individually exposed intraperitoneally to MSCs derived from BM (BM-MSCs), UCB (UCB-MSCs), ESCs (ESC-MSCs), or iPSCs (iPSC-MSCs). The parameters used to evaluate the cellular treatment efficacy were the animal survival prolongation and the histopathological-macroscopic picture of bowel sections. Although all categories of mesenchymal stem cells led to statistically significant survival prolongation compared to the control group, significant clinical and histopathological improvement was observed only in mice receiving BM-MSCs and UCB-MSCs. Our results demonstrated that the in vivo anti-inflammatory effect of ESC-MSCs and iPSC-MSCs was inferior to that of UCB-MSCs and BM-MSCs. Further investigation will clarify the potential of ESCs and iPSC-derived MSCs in AIBD treatment. © 2019, Springer Science+Business Media, LLC, part of Springer Nature