The canonical NF-κB pathway differentially protects normal and human tumor cells from ROS-induced DNA damage

DNA damage responses (DDR) invoke senescence or apoptosis depending on stimulus intensity and the degree of activation of the p53-p21(Cip1/Waf1) axis; but the functional impact of NF-κB signaling on these different outcomes in normal vs. human cancer cells remains poorly understood. We investigated the NF-κB-dependent effects and mechanism underlying reactive oxygen species (ROS)-mediated DDR outcomes of normal human lung fibroblasts (HDFs) and A549 human lung cancer epithelial cells. To activate DDR, ROS accumulation was induced by different doses of H(2)O(2). The effect of ROS induction caused a G2 or G2-M phase cell cycle arrest of both human cell types. However, ROS-mediated DDR eventually culminated in different end points with HDFs undergoing premature senescence and A549 cancer cells succumbing to apoptosis. NF-κB p65/RelA nuclear translocation and Ser536 phosphorylation were induced in response to H(2)O(2)-mediated ROS accumulation. Importantly, blocking the activities of canonical NF-κB subunits with an IκBα super-repressor or suppressing canonical NF-κB signaling by IKKβ knock-down accelerated HDF premature senescence by up-regulating the p53-p21(Cip1/Waf1) axis; but inhibiting the canonical NF-κB pathway exacerbated H(2)O(2)-induced A549 cell apoptosis. HDF premature aging occurred in conjunction with γ-H2AX chromatin deposition, senescence-associated heterochromatic foci and beta-galactosidase staining. p53 knock-down abrogated H(2)O(2)-induced premature senescence of vector control- and IκBαSR-expressing HDFs functionally linking canonical NF-κB-dependent control of p53 levels to ROS-induced HDF senescence. We conclude that IKKβ-driven canonical NF-κB signaling has different functional roles for the outcome of ROS responses in the contexts of normal vs. human tumor cells by respectively protecting them against DDR-dependent premature senescence and apoptosis.     

Fish models in prion biology: Underwater issues

Transmissible spongiform encephalopathies (TSEs), otherwise known as prion disorders, are fatal diseases causing neurodegeneration in a wide range of mammalian hosts, including humans. The causative agents - prions - are thought to be composed of a rogue isoform of the endogenous prion protein (PrP). Beyond these and other basic concepts, fundamental questions in prion biology remain unanswered, such as the physiological function of PrP, the molecular mechanisms underlying prion pathogenesis, and the origin of prions. To date, the occurrence of TSEs in lower vertebrates like fish and birds has received only limited attention, despite the fact that these animals possess bona fide PrPs. Recent findings, however, have brought fish before the footlights of prion research. Fish models are beginning to provide useful insights into the roles of PrP in health and disease, as well as the potential risk of prion transmission between fish and mammals. Although still in its infancy, the use of fish models in TSE research could significantly improve our basic understanding of prion diseases, and also help anticipate risks to public health. This article is part of a Special Issue entitled Zebrafish Models of Neurological Diseases.     

The effect of acute taurine ingestion on 3-km running performance in trained middle-distance runners

Limited research examining the effect of taurine (TA) ingestion on human exercise performance exists. The aim of this study was to investigate the effect of acute ingestion of 1,000 mg of TA on maximal 3-km time trial (3KTT) performance in trained middle-distance runners (MDR). Eight male MDR (mean ± SD: age 19.9 ± 1.2 years, body mass 69.4 ± 6.6 kg, height 180.5 ± 7.5 cm, 800 m personal best time 121.0 ± 5.3 s) completed TA and placebo (PL) trials 1 week apart in a double-blind, randomised, crossover designed study. Participants consumed TA or PL in capsule form on arrival at the laboratory followed by a 2-h ingestion period. At the end of the ingestion period, participants commenced a maximal simulated 3KTT on a treadmill. Capillary blood lactate was measured pre- and post-3KTT. Expired gas, heart rate (HR), ratings of perceived exertion (RPE), and split times were measured at 500-m intervals during the 3KTT. Ingestion of TA significantly improved 3KTT performance (TA 646.6 ± 52.8 s and PL 658.5 ± 58.2 s) (p = 0.013) equating to a 1.7 % improvement (range 0.34–4.24 %). Relative oxygen uptake, HR, RPE and blood lactate did not differ between conditions (p = 0.803, 0.364, 0.760 and 0.302, respectively). Magnitude-based inference results assessing the likeliness of a beneficial influence of TA were 99.3 %. However, the mechanism responsible for this improved performance is unclear. TA’s potential influence on exercise metabolism may involve interaction with the muscle membrane, the coordination or the force production capability of involved muscles. Further research employing more invasive techniques may elucidate TA’s role in improving maximal endurance performance.     

Schistosoma japonicum: monoclonal antibodies to the Mr 26,000 schistosome glutathione S-transferase (Sj26) in an assay for circulating antigen in infected individuals

Two monoclonal antibodies have been produced that bind to separate epitopes on the Mr 26,000 glutathione S-transferase (GST) of Schistosoma japonicum worms (Sj26). Both antibodies have been used in an enzyme immunoassay (EIA) with sera from infected individuals from the Philippines. Relatively high signals were obtained with sera from some, but not all, individuals who are positive for fecal eggs. Evidence was obtained that the material detected by the monoclonal antibodies was present in minute amounts and in some sera was bound in a complex with phosphorylcholine-containing molecules. It could not be absorbed by reaction with glutathione-agarose columns. There was no detectable immunoglobulin in the complex. The possibility exists that the complexes are composed of schistosome GST, or fragments, and damaged tegumental lipids shed as a result of surface immune attack. However, the presence of the native Sj26 molecule has not been proven. More detailed longitudinal studies in endemic areas are required to determine whether the assay can be used as an indicator of acquired resistance ("concomitant immunity") and whether it will be useful in the search for immunological correlates of this resistance in humans.     

Prevalence of comorbidities in systemic sclerosis versus rheumatoid arthritis: a comparative,multicenter, matched-cohort study

Background

Comorbidities are common in chronic systemic connective tissue diseases and are associated with adverse outcomes, increased morbidity and mortality. Although the prevalence of comorbidities has been well-studied in isolated diseases, comparative studies between different autoimmune diseases are limited. In this study, we compared the prevalence of common comorbidities between patients with systemic sclerosis (SSc) and patients with rheumatoid arthritis (RA).

Methods

Between 2016 and 2017, 408 consecutive patients with SSc, aged 59?±?13?years (87% women), were matched 1:1 for age and gender with 408 patients with RA; mean disease duration was 10?±?8 and 9?±?8?years, respectively. Rates of cardiovascular risk factors, coronary artery disease, stroke, chronic obstructive pulmonary disease (COPD), osteoporosis, neoplasms and depression were compared between the two cohorts.

Results

The prevalence of dyslipidemia (18.4% vs 30.1%, p?=?0.001) and diabetes mellitus (5.6% vs 11.8%, p?=?0.007) and body mass index (p?=?0.001) were lower in SSc compared to RA, while there was no difference in arterial hypertension or smoking. While there was a trend for lower prevalence of ischemic stroke in SSc than in RA (1.1% vs 3.2%, p?=?0.085), coronary artery disease was comparable (2.7% vs 3.7%). No differences were found between patients with SSc and patients with RA in the prevalence of COPD (5.2% vs 3.7%), osteoporosis (24% vs 22%) or neoplasms overall (1.1% vs 1.7%); however lung cancer was the most prevalent cancer in SSc (7/17, 41%), whereas hematologic malignancies (7/19, 36%) and breast cancer (7/19, 36%) predominated in RA. Depression was more prevalent in SSc (22% vs 12%, p?=?0.001), especially in diffuse SSc.

Conclusions

Despite the prevalence of dyslipidemia and diabetes mellitus in SSc being almost half that in RA, the cardiovascular comorbidity burden appears to be similar in both. The overall prevalence of neoplasms is no higher in SSc than in RA, but SSc has a more negative impact on quality of life, as clearly, more SSc patients develop depression compared to patients with RA.

     

Improved indices of insulin resistance and insulin secretion for use in genetic and population studies of type 2 diabetes mellitus.

Homeostasis model assessment (HOMA) provides indices of insulin secretion (beta) and insulin resistance (R) derived from fasting plasma glucose (FPG) and fasting plasma insulin (FPI) levels. However, these indices could not account for a significant heritability of fasting plasma glucose (FPG) (h2 = 0.75, P<0.01) in a group of 214 female twins. This result is consistent with a misclassification between effects due to insulin secretion and resistance in the HOMA indices. We report here evidence of such misclassification in the HOMA indices and describe a minor modification to the model which corrects it. Direct measures of insulin resistance (euglycaemic clamp) and secretion (i.v. glucose bolus) were obtained in 43 non-diabetic subjects. Heritability was estimated by statistical modelling of genetic and environmental influences in data from 214 non-diabetic female subjects. Modified HOMA (HOMA') indices were obtained from beta' = (Ln(FPI) - c)/FPG and R' = (Ln(FPI) - c)*FPG where c is a constant derived from regression analysis of Ln(FPI) vs FPG. Indices from both models correlated with the direct measures similarly (r = 0.63 (R), 0.49 (R'), 0.45 (beta), 0.39 (beta'), all P< 0.01). Directly measured insulin resistance and secretion were not significantly correlated (r = 0.13, P = 0.21). However, unmodified HOMA-beta and R were strongly related (r = 0.78, P<0.0001 vs. 0.13) demonstrating substantial misclassification. The relationship between beta' and R' (r = 0.13) was not different from that between the two direct measures and significant heritability of beta' (h2 = 0.68, P<0.01) and R' (h2 = 0.59, P<0.05) was evident in the twin data. The proposed modification to HOMA significantly reduces misclassification and reveals separate components of insulin resistance and insulin secretion in the heritability of FPG.     

Spatial and temporal RF electromagnetic field exposure of children and adults in indoor micro environments in Belgium and Greece

Personal radio frequency electromagnetic field (RF-EMF) exposure, or exposimetry, is gaining importance in the bioelectromagnetics community but only limited data on personal exposure is available in indoor areas, namely schools, crèches, homes, and offices. Most studies are focused on adult exposure, whereas indoor microenvironments, where children are exposed, are usually not considered. A method to assess spatial and temporal indoor exposure of children and adults is proposed without involving the subjects themselves. Moreover, maximal possible daily exposure is estimated by combining instantaneous spatial and temporal exposure. In Belgium and Greece, the exposure is measured at 153 positions spread over 55 indoor microenvironments with spectral equipment. In addition, personal exposimeters (measuring EMFs of people during their daily activities) captured the temporal exposure variations during several days up to one week at 98 positions. The data were analyzed using the robust regression on order statistics (ROS) method to account for data below the detection limit. All instantaneous and maximal exposures satisfied international exposure limits and were of the same order of magnitude in Greece and Belgium. Mobile telecommunications and radio broadcasting (FM) were most present. In Belgium, digital cordless phone (DECT) exposure was present for at least 75% in the indoor microenvironments except for schools. Temporal variations of the exposure were mainly due to variations of mobile telecommunication signals. The exposure was higher during daytime than at night due to the increased voice and data traffic on the networks. Total exposure varied the most in Belgian crèches (39.3%) and Greek homes (58.2%).     

The direct cost of "Thriasio" school screening program

Background

Adolescent girls treated with a brace for scoliosis are submitted to prolonged stress related to both the disease and the therapy. Currently proposed quality of life questionnaires are focused on the outcome of therapy. Bad Sobernheim Stress Questionnaire (BSSQ) enables monitoring of patients being under treatment with a brace or exercises. The aim of the study was to assess the stress level in conservatively managed scoliotic girls using BSSQ.

Materials and methods

111 girls, aged 14,2 ± 2,2 years, mean Cobb angle of the primary curve 42,8° ± 17,0° and mean Bunnell angle of 11,4° ± 4,5° were examined with two versions of BSSQ (Deformity and Brace). The analysis considered the type of treatment, curve location, correlation of the total score with age, Cobb angle and Bunnell rotation angle.

Results

The BSSQ Deformity revealed the median of 17 points in patients managed with exercises (from 4 to 24 points), 18 in patients managed with a brace (from 8 to 24 points) and 12 in patients before surgery (from 3 to 21 points). Braced patients who completed both questionnaires (n = 50) revealed significantly higher score with BSSQ Deformity (median = 18) comparing to BSSQ Brace (median = 9). There was a correlation between the total score of BSSQ Deformity and the Cobb angle (r = -0,34), Bunnell primary curve rotation (r = -0,34) and Bunnell sum of rotation (r = -0,33) but not with the age of patients.

Conclusion

Scoliotic adolescents managed with exercises and brace suffered little stress from the deformity. The brace increased the level of stress over the stress induced by the deformity. The stress level correlated with clinical deformity (Bunnell angle), radiological deformity (Cobb angle) and the type of treatment (exercises, bracing, surgery). Bad Sobernheim Stress Questionnaires are simple and helpful in the management of girls treated conservatively for idiopathic scoliosis.     

SOSORT consensus paper: school screening for scoliosis. Where are we today?

This report is the SOSORT Consensus Paper on School Screening for Scoliosis discussed at the 4^th International Conference on Conservative Management of Spinal Deformities, presented by SOSORT, on May 2007. The objectives were numerous, 1) the inclusion of the existing information on the issue, 2) the analysis and discussion of the responses by the meeting attendees to the twenty six questions of the questionnaire, 3) the impact of screening on frequency of surgical treatment and of its discontinuation, 4) the reasons why these programs must be continued, 5) the evolving aim of School Screening for Scoliosis and 6) recommendations for improvement of the procedure.