German translation and external validation of the Radboud Skills Questionnaire in patients suffering from Complex Regional Pain Syndrome 1

BACKGROUND: Patients suffering from Complex Regional Pain Syndrome commonly complain of substantial limitations in their activities of daily living. The Radboud Skills Questionnaire measures alterations in the level of disability of patients with Complex Regional Pain Syndrome, but this instrument is currently not available in German. The goals of our study were to translate the Dutch Radboud Skills Questionnaire into German and to assess its external criterion validity with the German version of the Disabilities of the Arm, Shoulder and Hand Questionnaire. METHODS: We translated the Radboud Skills Questionnaire according to published guidelines. Demographic data and validity were assessed in 57 consecutive patients with Complex Regional Pain Syndrome 1 of the upper extremity. Information on age, duration of symptoms, type of Complex Regional Pain Syndrome 1 and type of initiating event was obtained. We assessed the external criterion validity by comparing the German Radboud Skills Questionnaire and the German Disabilities of the Arm, Shoulder and Hand Questionnaire and calculated the prediction intervals. RESULTS: Score values ranged from 55.4 +/- 22.0 for the Disabilities of the Arm, Shoulder and Hand Questionnaire score and 140.1 +/- 39.2 for the Radboud Skills Questionnaire. We found a high correlation between the Radboud Skills Questionnaire and the Disabilities of the Arm, Shoulder and Hand Questionnaire (R2 = 0.83). CONCLUSION: This validation of the Radboud Skills Questionnaire demonstrates that this German version is a simple and accurate instrument to assess and quantify disabilities of patients suffering from Complex Regional Pain Syndrome 1 of the upper extremity for clinical and research purposes

Epigenetic control of the ubiquitin carboxyl terminal hydrolase 1 in renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>The ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) gene involved in the regulation of cellular ubiquitin levels plays an important role in different cellular processes including cell growth and differentiation. Aberrant expression of UCHL1 has been found in a number of human solid tumors including renal cell carcinoma (RCC). In RCC, UCHL1 overexpression is associated with tumor progression and an altered von Hippel Lindau gene expression.</p> <p>Methods</p> <p>To determine the underlying mechanisms for the heterogeneous UCHL1 expression pattern in RCC the UCHL1 promoter DNA methylation status was determined in 17 RCC cell lines as well as in 32 RCC lesions and corresponding tumor adjacent kidney epithelium using combined bisulfite restriction analysis as well as bisulfite DNA sequencing.</p> <p>Results</p> <p>UCHL1 expression was found in all 32 tumor adjacent kidney epithelium samples. However, the lack of or reduced UCHL1 mRNA and/or protein expression was detected in 13/32 RCC biopsies and 7/17 RCC cell lines and due to either a total or partial methylation of the UCHL1 promoter DNA. Upon 2'-deoxy-5-azacytidine treatment an induction of UCHL1 mRNA and protein expression was found in 9/17 RCC cell lines, which was linked to the demethylation degree of the UCHL1 promoter DNA.</p> <p>Conclusion</p> <p>Promoter hypermethylation represents a mechanism for the silencing of the UCHL1 gene expression in RCC and supports the concept of an epigenetic control for the expression of UCHL1 during disease progression.</p

How Similar Are the Mice to Men? Between-Species Comparison of Left Ventricular Mechanics Using Strain Imaging

BACKGROUND: While mammalian heart size maintains constant proportion to whole body size, scaling of left ventricular (LV) function parameters shows a more complex scaling pattern. We used 2-D speckle tracking strain imaging to determine whether LV myocardial strains and strain rates scale to heart size. METHODS: We studied 18 mice, 15 rats, 6 rabbits, 12 dogs and 20 human volunteers by 2-D echocardiography. Relationship between longitudinal or circumferential strains/strain rates (S(Long)/SR(Long), S(Circ)/SR(Circ)), and LV end-diastolic volume (EDV) or mass were assessed by the allometric (power-law) equation Y = kM(β). RESULTS: Mean LV mass in individual species varied from 0.038 to 134 g, LV EDV varied from 0.015 to 102 ml, while RR interval varied from 81 to 1090 ms. While S(Long) increased with increasing LV EDV or mass (β values 0.047±0.006 and 0.051±0.005, p<0.0001 vs. 0 for both) S(Circ) was unchanged (p = NS for both LV EDV or mass). Systolic and diastolic SR(Long) and SR(Circ) showed inverse correlations to LV EDV or mass (p<0.0001 vs. 0 for all comparisons). The ratio between S(Long) and S(Circ) increased with increasing values of LV EDV or mass (β values 0.039±0.010 and 0.040±0.011, p>0.0003 for both). CONCLUSIONS: While S(Circ) is unchanged, S(Long) increases with increasing heart size, indicating that large mammals rely more on long axis contribution to systolic function. SR(Long) and SR(Circ), both diastolic and systolic, show an expected decrease with increasing heart size

The oxysterol 27-hydroxycholesterol increases β-amyloid and oxidative stress in retinal pigment epithelial cells

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease (AD) and age-related macular degeneration (AMD) share several pathological features including β-amyloid (Aβ) peptide accumulation, oxidative damage, and cell death. The causes of AD and AMD are not known but several studies suggest disturbances in cholesterol metabolism as a culprit of these diseases. We have recently shown that the cholesterol oxidation metabolite 27-hydroxycholesterol (27-OHC) causes AD-like pathology in human neuroblastoma SH-SY5Y cells and in organotypic hippocampal slices. However, the extent to which and the mechanisms by which 27-OHC may also cause pathological hallmarks related to AMD are ill-defined. In this study, the effects of 27-OHC on AMD-related pathology were determined in ARPE-19 cells. These cells have structural and functional properties relevant to retinal pigmented epithelial cells, a target in the course of AMD.</p> <p>Methods</p> <p>ARPE-19 cells were treated with 0, 10 or 25 μM 27-OHC for 24 hours. Levels of Aβ peptide, mitochondrial and endoplasmic reticulum (ER) stress markers, Ca²⁺homeostasis, glutathione depletion, reactive oxygen species (ROS) generation, inflammation and cell death were assessed using ELISA, Western blot, immunocytochemistry, and specific assays.</p> <p>Results</p> <p>27-OHC dose-dependently increased Aβ peptide production, increased levels of ER stress specific markers caspase 12 and gadd153 (also called CHOP), reduced mitochondrial membrane potential, triggered Ca²⁺dyshomeostasis, increased levels of the nuclear factor κB (NFκB) and heme-oxygenase 1 (HO-1), two proteins activated by oxidative stress. Additionally, 27-OHC caused glutathione depletion, ROS generation, inflammation and apoptotic-mediated cell death.</p> <p>Conclusions</p> <p>The cholesterol metabolite 27-OHC is toxic to RPE cells. The deleterious effects of this oxysterol ranged from Aβ accumulation to oxidative cell damage. Our results suggest that high levels of 27-OHC may represent a common pathogenic factor for both AMD and AD.</p

Short-term outcomes of community-based adolescent weight management: The Loozit® Study

<p>Abstract</p> <p>Background</p> <p>The Loozit^®Study is a randomised controlled trial investigating extended support in a 24 month community-based weight management program for overweight to moderately obese, but otherwise healthy, 13 to 16 year olds.</p> <p>Methods</p> <p>This pre-post study examines the two month outcomes of the initial Loozit^®group intervention received by both study arms. Adolescents (n = 151; 48% male) and their parents separately attended seven weekly group sessions focused on lifestyle modification. At baseline and two months, adolescents' anthropometry, blood pressure, and fasted blood sample were assessed. Primary outcomes were two month changes in body mass index (BMI) z-score and waist-to-height-ratio (WHtR). Secondary outcomes included changes in metabolic profile, self-reported dietary intake/patterns, physical and sedentary activities, psychological characteristics and social status. Changes in outcome measures were assessed using paired samples t-tests for continuous variables or McNemar's test for dichotomous categorical variables.</p> <p>Results</p> <p>Of the 151 adolescents who enrolled, 130 (86%) completed the two month program. Among these 130 adolescents (47% male), there was a statistically significant (P < 0.01) reduction in mean [95% CI] BMI (0.27 kg/m²[0.41, 0.13]), BMI z-score (0.05 [0.06, 0.03]), WHtR (0.02 [0.03, 0.01]), total cholesterol (0.14 mmol/L [0.24, 0.05]) and low-density lipoprotein cholesterol (0.12 mmol/L [0.21, 0.04]). There were improvements in all psychological measures, the majority of the dietary intake measures, and some physical activities (P < 0.05). Time spent watching TV and participating in non-screen sedentary activities decreased (P < 0.05).</p> <p>Conclusions</p> <p>The Loozit^®program may be a promising option for stabilizing overweight and improving various metabolic factors, psychological functioning and lifestyle behaviors in overweight adolescents in a community setting.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry</p> <p><a href="http://www.anzctr.org.au/trial_view.aspx?ID=1277">ACTRNO12606000175572</a></p

Inhibition of radiation induced migration of human head and neck squamous cell carcinoma cells by blocking of EGF receptor pathways

<p>Abstract</p> <p>Background</p> <p>Recently it has been shown that radiation induces migration of glioma cells and facilitates a further spread of tumor cells locally and systemically. The aim of this study was to evaluate whether radiotherapy induces migration in head and neck squamous cell carcinoma (HNSCC). A further aim was to investigate the effects of blocking the epidermal growth factor receptor (EGFR) and its downstream pathways (Raf/MEK/ERK, PI3K/Akt) on tumor cell migration in vitro.</p> <p>Methods</p> <p>Migration of tumor cells was assessed via a wound healing assay and proliferation by a MTT colorimeritric assay using 3 HNSCC cell lines (BHY, CAL-27, HN). The cells were treated with increasing doses of irradiation (2 Gy, 5 Gy, 8 Gy) in the presence or absence of EGF, EGFR-antagonist (AG1478) or inhibitors of the downstream pathways PI3K (LY294002), mTOR (rapamycin) and MEK1 (PD98059). Biochemical activation of EGFR and the downstream markers Akt and ERK were examined by Western blot analysis.</p> <p>Results</p> <p>In absence of stimulation or inhibition, increasing doses of irradiation induced a dose-dependent enhancement of migrating cells (p < 0.05 for the 3 HNSCC cell lines) and a decrease of cell proliferation (p < 0.05 for the 3 HNSCC cell lines). The inhibition of EGFR or the downstream pathways reduced cell migration significantly (almost all p < 0.05 for the 3 HNSCC cell lines). Stimulation of HNSCC cells with EGF caused a significant increase in migration (p < 0.05 for the 3 HNSCC cell lines). After irradiation alone a pronounced activation of EGFR was observed by Western blot analysis.</p> <p>Conclusion</p> <p>Our results demonstrate that the EGFR is involved in radiation induced migration of HNSCC cells. Therefore EGFR or the downstream pathways might be a target for the treatment of HNSCC to improve the efficacy of radiotherapy.</p

Non-Invasive In Vivo Imaging of Calcium Signaling in Mice

Rapid and transient elevations of Ca2+ within cellular microdomains play a critical role in the regulation of many signal transduction pathways. Described here is a genetic approach for non-invasive detection of localized Ca2+ concentration ([Ca2+]) rises in live animals using bioluminescence imaging (BLI). Transgenic mice conditionally expressing the Ca2+-sensitive bioluminescent reporter GFP-aequorin targeted to the mitochondrial matrix were studied in several experimental paradigms. Rapid [Ca2+] rises inside the mitochondrial matrix could be readily detected during single-twitch muscle contractions. Whole body patterns of [Ca2+] were monitored in freely moving mice and during epileptic seizures. Furthermore, variations in mitochondrial [Ca2+] correlated to behavioral components of the sleep/wake cycle were observed during prolonged whole body recordings of newborn mice. This non-invasive imaging technique opens new avenues for the analysis of Ca2+ signaling whenever whole body information in freely moving animals is desired, in particular during behavioral and developmental studies

Animal models of cardiorenal syndrome: a review

The incidence of heart failure and renal failure is increasing and is associated with poor prognosis. Moreover, these conditions do often coexist and this coexistence results in worsened outcome. Various mechanisms have been proposed as an explanation of this interrelation, including changes in hemodynamics, endothelial dysfunction, inflammation, activation of renin-angiotensin-aldosterone system, and/or sympathetic nervous system. However, the exact mechanisms initializing and maintaining this interaction are still unknown. In many experimental studies on cardiac or renal dysfunction, the function of the other organ was either not addressed or the authors failed to show any decline in its function despite histological changes. There are few studies in which the dysfunction of both heart and kidney function has been described. In this review, we discuss animal models of combined cardiorenal dysfunction. We show that translation of the results from animal studies is limited, and there is a need for new and better models of the cardiorenal interaction to improve our understanding of this syndrome. Finally, we propose several requirements that a new animal model should meet to serve as a tool for studies on the cardiorenal syndrome

A pilot randomised controlled trial to reduce colorectal cancer risk markers associated with B-vitamin deficiency, insulin resistance and colonic inflammation

Colorectal cancer risk is associated with biochemical markers for B-vitamin deficiency, insulin resistance and colonic inflammation, suggesting that these three conditions are each involved in colon carcinogenesis. We expected that dietary supplements of folic acid, n-3 fatty acids and calcium would reduce the markers and thus possibly cancer risk. We therefore randomised 98 participants, with previous colonic polyps or intramucosal carcinomas, to a combined treatment of supplementary folic acid, fish oil and calcium carbonate, or placebos for 28 days. Blood and faecal samples were obtained prior to and at the conclusion of the intervention and analysed for plasma folate, homocysteine, insulin, free fatty acids, triglycerides and faecal calprotectin. In addition, plasma vitamin B12, thiamin, glucose and C-reactive protein were assessed. Our supplemental strategy modestly affected some of the biomarkers associated with folate metabolism and insulin resistance, but had no effect on those associated with colonic inflammation. This pilot study demonstrates the feasibility and practicality of clinical trials aimed at reducing diet-related biochemical risk markers for colon cancer. We suggest that long-term intervention studies with tumour-related end points should be undertaken when the intervention agents used are found effective in short-term biochemical risk marker trials