682 research outputs found

    Psychometric properties of the Chinese version of the fatigue scale-adolescent

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    © 2015 Ho et al. Background: The availability of a valid and reliable instrument that accurately assesses the level of fatigue among adolescent cancer survivors is crucial before any appropriate interventions to reduce their fatigue can be appropriately planned and evaluated. The study aimed to test the psychometric properties of the Chinese version of the Fatigue Scale for Adolescents. In particular, confirmatory factor analysis was conducted to examine its factorial structure. Methods: A cross-sectional study was employed. Adolescents (13- to 18-year-olds) who had survived cancer and attended medical follow-up at the outpatient clinic in Hong Kong were invited to participate. The internal consistency, content validity and construct validity and test-retest reliability of the Chinese version of the Fatigue Scale for Adolescents were assessed. Results: The content validity index was 0.92. There was a strong positive correlation between adolescents' levels of fatigue and depressive symptoms (r=0.53) and a strong negative correlation between adolescents' levels of fatigue and quality of life (r=-0.58). The mean levels of fatigue of the survivors group was significantly lower than that of those still receiving treatment in hospital, but significantly higher than that of their healthy counterparts. Confirmatory factor analysis indicated that there were 4 factors underlying the Chinese version of the Cancer Module. Conclusions: The findings of the study add further evidence that the Chinese version of the Fatigue Scale for Adolescents (12-item) can be used as a reliable and valid tool in assessing cancer-related fatigue among Hong Kong Chinese adolescents who have survived cancer.published_or_final_versio

    Prolonged exposure to bacterial toxins downregulated expression of toll-like receptors in mesenchymal stromal cell-derived osteoprogenitors

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    <p>Abstract</p> <p>Background</p> <p>Human mesenchymal stromal cells (MSCs, also known as mesenchymal stem cells) are multipotent cells with potential therapeutic value. Owing to their osteogenic capability, MSCs may be clinically applied for facilitating osseointegration in dental implants or orthopedic repair of bony defect. However, whether wound infection or oral microflora may interfere with the growth and osteogenic differentiation of human MSCs remains unknown. This study investigated whether proliferation and osteogenic differentiation of MSCs would be affected by potent gram-positive and gram-negative derived bacterial toxins commonly found in human settings.</p> <p>Results</p> <p>We selected lipopolysaccharide (LPS) from <it>Escherichia coli </it>and lipoteichoic acid (LTA) from <it>Streptococcus pyogenes </it>as our toxins of choice. Our findings showed both LPS and LTA did not affect MSC proliferation, but prolonged LPS challenge upregulated the osteogenic differentiation of MSCs, as assessed by alkaline phosphatase activity and calcium deposition. Because toll-like receptors (TLRs), in particularly TLR4 and TLR2, are important for the cellular responsiveness to LPS and LTA respectively, we evaluated their expression profiles serially from MSCs to osteoblasts by quantitative PCR. We found that during osteogenic differentiation, MSC-derived osteoprogenitors gradually expressed TLR2 and TLR4 by Day 12. But under prolonged incubation with LPS, MSC-derived osteoprogenitors had reduced TLR2 and TLR4 gene expression. This peculiar response to LPS suggests a possible adaptive mechanism when MSCs are subjected to continuous exposure with bacteria.</p> <p>Conclusion</p> <p>In conclusion, our findings support the potential of using human MSCs as a biological graft, even under a bacterial toxin-rich environment.</p

    Glucose-induced down regulation of thiamine transporters in the kidney proximal tubular epithelium produces thiamine insufficiency in diabetes

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    Increased renal clearance of thiamine (vitamin B1) occurs in experimental and clinical diabetes producing thiamine insufficiency mediated by impaired tubular re-uptake and linked to the development of diabetic nephropathy. We studied the mechanism of impaired renal re-uptake of thiamine in diabetes. Expression of thiamine transporter proteins THTR-1 and THTR-2 in normal human kidney sections examined by immunohistochemistry showed intense polarised staining of the apical, luminal membranes in proximal tubules for THTR-1 and THTR-2 of the cortex and uniform, diffuse staining throughout cells of the collecting duct for THTR-1 and THTR-2 of the medulla. Human primary proximal tubule epithelial cells were incubated with low and high glucose concentration, 5 and 26 mmol/l, respectively. In high glucose concentration there was decreased expression of THTR-1 and THTR-2 (transporter mRNA: −76% and −53% respectively, p<0.001; transporter protein −77% and −83% respectively, p<0.05), concomitant with decreased expression of transcription factor specificity protein-1. High glucose concentration also produced a 37% decrease in apical to basolateral transport of thiamine transport across cell monolayers. Intensification of glycemic control corrected increased fractional excretion of thiamine in experimental diabetes. We conclude that glucose-induced decreased expression of thiamine transporters in the tubular epithelium may mediate renal mishandling of thiamine in diabetes. This is a novel mechanism of thiamine insufficiency linked to diabetic nephropathy

    Subcellular heterogeneity of ryanodine receptor properties in ventricular myocytes with low T-tubule density

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    Rationale: In ventricular myocytes of large mammals, not all ryanodine receptor (RyR) clusters are associated with T-tubules (TTs); this fraction increases with cellular remodeling after myocardial infarction (MI). Objective: To characterize RyR functional properties in relation to TT proximity, at baseline and after MI. Methods: Myocytes were isolated from left ventricle of healthy pigs (CTRL) or from the area adjacent to a myocardial infarction (MI). Ca2+ transients were measured under whole-cell voltage clamp during confocal linescan imaging (fluo-3) and segmented according to proximity of TTs (sites of early Ca2+ release, F&gt;F50 within 20 ms) or their absence (delayed areas). Spontaneous Ca2+ release events during diastole, Ca2+ sparks, reflecting RyR activity and properties, were subsequently assigned to either category. Results: In CTRL, spark frequency was higher in proximity of TTs, but spark duration was significantly shorter. Block of Na+/Ca2+ exchanger (NCX) prolonged spark duration selectively near TTs, while block of Ca2+ influx via Ca2+ channels did not affect sparks properties. In MI, total spark mass was increased in line with higher SR Ca2+ content. Extremely long sparks (&gt;47.6 ms) occurred more frequently. The fraction of near-TT sparks was reduced; frequency increased mainly in delayed sites. Increased duration was seen in near-TT sparks only; Ca2+ removal by NCX at the membrane was significantly lower in MI. Conclusion: TT proximity modulates RyR cluster properties resulting in intracellular heterogeneity of diastolic spark activity. Remodeling in the area adjacent to MI differentially affects these RyR subpopulations. Reduction of the number of sparks near TTs and reduced local NCX removal limit cellular Ca2+ loss and raise SR Ca2+ content, but may promote Ca2+ waves

    Reproducibility of the airway response to an exercise protocol standardized for intensity, duration, and inspired air conditions, in subjects with symptoms suggestive of asthma

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    <p>Abstract</p> <p>Background</p> <p>Exercise testing to aid diagnosis of exercise-induced bronchoconstriction (EIB) is commonly performed. Reproducibility of the airway response to a standardized exercise protocol has not been reported in subjects being evaluated with mild symptoms suggestive of asthma but without a definite diagnosis. This study examined reproducibility of % fall in FEV<sub>1 </sub>and area under the FEV<sub>1 </sub>time curve for 30 minutes in response to two exercise tests performed with the same intensity and duration of exercise, and inspired air conditions.</p> <p>Methods</p> <p>Subjects with mild symptoms of asthma exercised twice within approximately 4 days by running for 8 minutes on a motorized treadmill breathing dry air at an intensity to induce a heart rate between 80-90% predicted maximum; reproducibility of the airway response was expressed as the 95% probability interval.</p> <p>Results</p> <p>Of 373 subjects challenged twice 161 were positive (≥10% fall FEV<sub>1 </sub>on at least one challenge). The EIB was mild and 77% of subjects had <15% fall on both challenges. Agreement between results was 76.1% with 56.8% (212) negative (< 10% fall FEV<sub>1</sub>) and 19.3% (72) positive on both challenges. The remaining 23.9% of subjects had only one positive test. The 95% probability interval for reproducibility of the % fall in FEV<sub>1 </sub>and AUC<sub>0-30 </sub>min was ± 9.7% and ± 251% for all 278 adults and ± 13.4% and ± 279% for all 95 children. The 95% probability interval for reproducibility of % fall in FEV<sub>1 </sub>and AUC<sub>0-30 min </sub>for the 72 subjects with two tests ≥10% fall FEV<sub>1 </sub>was ± 14.6% and ± 373% and for the 34 subjects with two tests ≥15% fall FEV<sub>1 </sub>it was ± 12.2% and ± 411%. Heart rate and estimated ventilation achieved were not significantly different either on the two test days or when one test result was positive and one was negative.</p> <p>Conclusions</p> <p>Under standardized, well controlled conditions for exercise challenge, the majority of subjects with mild symptoms of asthma demonstrated agreement in test results. Performing two tests may need to be considered when using exercise to exclude or diagnose EIB, when prescribing prophylactic treatment to prevent EIB and when designing protocols for clinical trials.</p

    The photometric observation of the quasi-simultaneous mutual eclipse and occultation between Europa and Ganymede on 22 August 2021

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    Mutual events (MEs) are eclipses and occultations among planetary natural satellites. Most of the time, eclipses and occultations occur separately. However, the same satellite pair will exhibit an eclipse and an occultation quasi-simultaneously under particular orbital configurations. This kind of rare event is termed as a quasi-simultaneous mutual event (QSME). During the 2021 campaign of mutual events of jovian satellites, we observed a QSME between Europa and Ganymede. The present study aims to describe and study the event in detail. We observed the QSME with a CCD camera attached to a 300-mm telescope at the Hong Kong Space Museum Sai Kung iObservatory. We obtained the combined flux of Europa and Ganymede from aperture photometry. A geometric model was developed to explain the light curve observed. Our results are compared with theoretical predictions (O-C). We found that our simple geometric model can explain the QSME fairly accurately, and the QSME light curve is a superposition of the light curves of an eclipse and an occultation. Notably, the observed flux drops are within 2.6% of the theoretical predictions. The size of the event central time O-Cs ranges from -14.4 to 43.2 s. Both O-Cs of flux drop and timing are comparable to other studies adopting more complicated models. Given the event rarity, model simplicity and accuracy, we encourage more observations and analysis on QSMEs to improve Solar System ephemerides.Comment: 23 pages, 5 appendixes, 16 figures, 7 table

    Negative Feedback Regulation of T Cells via Interleukin-2 and FOXP3 Reciprocity

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    As interleukin-2 (IL2) is central to the clonal expansion of antigen-selected T cells, we investigated the relationship between IL2 and the negative regulatory transcription factor FOXP3. We found IL2 to be responsible for T cell antigen receptor (TCR)-activated FOXP3 expression by both CD4+ and CD8+ human T cells, and as anticipated, FOXP3 expression restricted TCR-stimulated IL2 expression. However, no evidence could be found that FOXP3+ cells actively suppress IL2 expression by FOXP3- cells. These data are consistent with an IL2/FOXP3-dependent negative feedback loop that normally regulates the T cell immune response. It follows that a defect in this negative feedback loop as a result of a deficiency of either IL2 or FOXP3 will lead to a hyperproliferative autoimmune syndrome, without the necessity of invoking an active suppressive function for FOXP3+ T cells

    A longitudinal study on BIO14.6 hamsters with dilated cardiomyopathy: micro-echocardiographic evaluation

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    <p>Abstract</p> <p>Background</p> <p>In recent years, several new technologies for small-animal imaging have been developed. In particular, the use of ultrasound in animal imaging has focused on the investigation of accessible biological structures such as the heart, of which it provides a morphological and functional assessment. The purpose of this study was to investigate the role of micro-ultrasonography (μ-US) in a longitudinal study on BIO14.6 cardiomyopathic hamsters treated with gene therapy.</p> <p>Methods</p> <p>Thirty hamsters were divided into three groups (n = 10): Group I, untreated BIO 14.6 hamsters; Group II, BIO 14.6 hamsters treated with gene therapy; Group III, untreated wild type (WT) hamsters. All hamsters underwent serial μ-US sessions and were sacrificed at predetermined time points.</p> <p>Results</p> <p>μ-US revealed: in Group I, progressive dilation of the left ventricle with a change in heart morphology from an elliptical to a more spherical shape, altered configuration of the mitral valve and subvalvular apparatus, and severe reduction in ejection fraction; in Group II, mild decrease in contractile function and ejection fraction; in Group III, normal cardiac chamber morphology and function. There was a negative correlation between the percentage of fibrosis observed at histology and the ejection fraction obtained on μ-echocardiography (Spearman r: -0.839; p < 0.001).</p> <p>Conclusions</p> <p>Although histological examination remains indispensable for a conclusive diagnosis, high-frequency μ-echocardiography, thanks to the high spatial and contrast resolution, can be considered sufficient for monitoring therapeutic efficacy and/or the progression of dilated cardiomyopathy, providing an alternative tool for repeatable and noninvasive evaluation.</p
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