Multiple courses of stereotactic re-irradiation in recurrent oligodendroglioma: a case report

INTRODUCTION: High grade gliomas are an insidious disease associated with an extremely poor prognosis. The role of re-irradiation for recurrent gliomas is unclear but several retrospective studies have indicated mild toxicity and modest outcomes with this regimen. With subsequent progression, it is unclear what options remain and more radiotherapy is rarely offered for fear of surpassing normal central nervous system tissue tolerance and causing significant side effects without significant benefit. CASE PRESENTATION: In this report, we describe a 37-year-old Caucasian male initially diagnosed with a grade IV oligodendroglioma, who received multiple courses of re-irradiation and experienced a survival of 10 years with minimal cognitive or neurologic deficits. CONCLUSION: Significant toxicity with multiple courses of radiation does not always occur. Re-irradiation should be considered in a salvage setting

Basic and clinical significance of IGF-I-induced signatures in cancer

The insulin-like growth factor (IGF) system mediates growth, differentiation and developmental processes; it is also involved in various metabolic activities. Deregulation of IGF system expression and action is linked to diverse pathologies, ranging from growth deficits to cancer development. Targeting of the IGF axis emerged in recent years as a promising therapeutic approach in cancer and other medical conditions. Rational use of IGF-I-induced gene signatures may help to identify patients who might benefit from IGF axis-directed therapeutic modalities. In the accompanying research article in BMC Medicine, Rajski et al. show that IGF-I-induced gene expression in primary breast and lung fibroblasts accurately predict outcomes in breast and lung cancer patients

Does bariatric surgery prior to total hip or knee arthroplasty reduce post-operative complications and improve clinical outcomes for obese patients? Systematic review and meta-analysis.

AIMS: Our aim was to determine whether, based on the current literature, bariatric surgery prior to total hip (THA) or total knee arthroplasty (TKA) reduces the complication rates and improves the outcome following arthroplasty in obese patients. METHODS: A systematic literature search was undertaken of published and unpublished databases on the 5 November 2015. All papers reporting studies comparing obese patients who had undergone bariatric surgery prior to arthroplasty, or not, were included. Each study was assessed using the Downs and Black appraisal tool. A meta-analysis of risk ratios (RR) and 95% confidence intervals (CI) was performed to determine the incidence of complications including wound infection, deep vein thrombosis (DVT), pulmonary embolism (PE), revision surgery and mortality. RESULTS: From 156 potential studies, five were considered to be eligible for inclusion in the study. A total of 23 348 patients (657 who had undergone bariatric surgery, 22 691 who had not) were analysed. The evidence-base was moderate in quality. There was no statistically significant difference in outcomes such as superficial wound infection (relative risk (RR) 1.88; 95% confidence interval (CI) 0.95 to 0.37), deep wound infection (RR 1.04; 95% CI 0.65 to 1.66), DVT (RR 0.57; 95% CI 0.13 to 2.44), PE (RR 0.51; 95% CI 0.03 to 8.26), revision surgery (RR 1.24; 95% CI 0.75 to 2.05) or mortality (RR 1.25; 95% CI 0.16 to 9.89) between the two groups. CONCLUSION: For most peri-operative outcomes, bariatric surgery prior to THA or TKA does not significantly reduce the complication rates or improve the clinical outcome. This study questions the previous belief that bariatric surgery prior to arthroplasty may improve the clinical outcomes for patients who are obese or morbidly obese. This finding is based on moderate quality evidence. Cite this article: Bone Joint J 2016;98-B:1160-6

Efimov physics beyond three particles

Efimov physics originally refers to a system of three particles. Here we review recent theoretical progress seeking for manifestations of Efimov physics in systems composed of more than three particles. Clusters of more than three bosons are tied to each Efimov trimer, but no independent Efimov physics exists there beyond three bosons. The case of a few heavy fermions interacting with a lighter atom is also considered, where the mass ratio of the constituent particles plays a significant role. Following Efimov's study of the (2+1) system, the (3+1) system was shown to have its own critical mass ratio to become Efimovian. We show that the (4+1) system becomes Efimovian at a mass ratio which is smaller than its sub-systems thresholds, giving a pure five-body Efimov effect. The (5+1) and (6+1) systems are also discussed, and we show the absence of 6- and 7-body Efimov physics there

Recovery from Posttraumatic Stress Symptoms: A Qualitative Study of Attributions in Survivors of War

This study was funded by a grant from the European Commission, contract number INCO-CT-2004-50917

Discovery of Sexual Dimorphisms in Metabolic and Genetic Biomarkers

Metabolomic profiling and the integration of whole-genome genetic association data has proven to be a powerful tool to comprehensively explore gene regulatory networks and to investigate the effects of genetic variation at the molecular level. Serum metabolite concentrations allow a direct readout of biological processes, and association of specific metabolomic signatures with complex diseases such as Alzheimer's disease and cardiovascular and metabolic disorders has been shown. There are well-known correlations between sex and the incidence, prevalence, age of onset, symptoms, and severity of a disease, as well as the reaction to drugs. However, most of the studies published so far did not consider the role of sexual dimorphism and did not analyse their data stratified by gender. This study investigated sex-specific differences of serum metabolite concentrations and their underlying genetic determination. For discovery and replication we used more than 3,300 independent individuals from KORA F3 and F4 with metabolite measurements of 131 metabolites, including amino acids, phosphatidylcholines, sphingomyelins, acylcarnitines, and C6-sugars. A linear regression approach revealed significant concentration differences between males and females for 102 out of 131 metabolites (p-values<3.8 x 10(-4); Bonferroni-corrected threshold). Sex-specific genome-wide association studies (GWAS) showed genome-wide significant differences in beta-estimates for SNPs in the CPS1 locus (carbamoyl-phosphate synthase 1, significance level: p<3.8 x 10(-10); Bonferroni-corrected threshold) for glycine. We showed that the metabolite profiles of males and females are significantly different and, furthermore, that specific genetic variants in metabolism-related genes depict sexual dimorphism. Our study provides new important insights into sex-specific differences of cell regulatory processes and underscores that studies should consider sex-specific effects in design and interpretation

Dectin-1 isoforms contribute to distinct Th1/Th17 cell activation in mucosal candidiasis

We thank Dr. Cristina Massi Benedetti for digital art and editingRecognition of β-glucans by dectin-1 has been shown to mediate cell activation, cytokine production and a variety of antifungal responses. Here, we report that the functional activity of dectin-1 in mucosal immunity to Candida albicans is influenced by the genetic background of the host. Dectin-1 was required for the proper control of gastrointestinal and vaginal candidiasis in C57BL/6 but not BALB/c mice, the latter actually showing increased resistance in the absence of dectin-1. Susceptibility of dectin-1-deficient C57BL/6 mice to infection was associated with defective IL-17A, aryl hydrocarbon receptor-dependent IL-22 production as well as adaptive Th1 responses. In contrast, resistance of dectin-1-deficient BALB/c mice was associated with increased IL-17A and IL-22 production, and the skewing towards Th1/Treg immune responses that provide immunological memory. Disparate canonical/noncanonical NF-κB signaling pathways downstream dectin-1were activated in the two different mouse strains. Thus, the net activity of dectin-1 in antifungal mucosal immunity is dependent on the host’s genetic background that affects both the innate cytokine production as well as the adaptive Th1/Th17 cell activation upon dectin-1 signaling.The studies were supported by the Specific Targeted Research Project “ALLFUN” (FP7−HEALTH−2009 contract number 260338 to LR) and the Italian Project AIDS 2010 by ISS (Istituto Superiore di Sanità - contract number 40H40 to LR) and Fondazione Cassa di Risparmio di Perugia Project n. 2011.0124.021. AC and CC were financially supported by fellowships from Fundação para a Ciência e Tecnologia, Portugal (contracts SFRH/BPD/46292/2008 and SFRH/BD/65962/2009, respectively)

Expression of Matrix Metalloproteinases and Their Inhibitors in Squamous Cell Carcinoma of the Tonsil and Their Clinical Significance

ObjectivesTo investigate expressions of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in squamous cell carcinoma of the tonsil and to correlate expression profiles with clinicopathological characteristics.MethodsParaffin blocks were obtained from 45 tonsil squamous cell carcinoma (SCC) patients, who underwent surgery as an initial treatment between 1994 and 2004, and from 20 normal controls. Expressions of MMP-2, MMP-9, MMP-13, TIMP-1, and TIMP-2 were investigated immunohistochemically.ResultsThe expressions of MMPs (except MMP-2) and TIMPs were found to be significantly different in tonsil SCC and normal control tissues. Furthermore, MMP-13 expression was found to be correlated with tumor invasion (P=0.05), and the expressions of MMP-9 and TIMP-1 with nodal metastasis (P=0.048, 0.031). No relation was found between MMP or TIMP expression and recurrence. However, MMP-9 expression was found to be significantly associated with 5-year survival in tonsil SCC patients by multivariate analysis (hazard ratio, 3.853; P=0.013).ConclusionSignificant overexpressions of multiple MMPs and TIMPs were found in tonsil SCC tissues. Furthermore, our findings suggest that MMP-9 expression might be a useful prognostic factor

Multilevel Deconstruction of the In Vivo Behavior of Looped DNA-Protein Complexes

Protein-DNA complexes with loops play a fundamental role in a wide variety of cellular processes, ranging from the regulation of DNA transcription to telomere maintenance. As ubiquitous as they are, their precise in vivo properties and their integration into the cellular function still remain largely unexplored. Here, we present a multilevel approach that efficiently connects in both directions molecular properties with cell physiology and use it to characterize the molecular properties of the looped DNA-lac repressor complex while functioning in vivo. The properties we uncover include the presence of two representative conformations of the complex, the stabilization of one conformation by DNA architectural proteins, and precise values of the underlying twisting elastic constants and bending free energies. Incorporation of all this molecular information into gene-regulation models reveals an unprecedented versatility of looped DNA-protein complexes at shaping the properties of gene expression.Comment: Open Access article available at http://www.plosone.org/article/fetchArticle.action?articleURI=info%3Adoi%2F10.1371%2Fjournal.pone.000035

Evaluation of the performance of different atmospheric chemical transport models and inter-comparison of nitrogen and sulphur deposition estimates for the UK

An evaluation has been made of a number of contrasting atmospheric chemical transport models, of varying complexity, applied to estimate sulphur and nitrogen deposition in the UK. The models were evaluated by comparison with annually averaged measurements of gas, aerosol and precipitation concentrations from the national monitoring networks. The models were evaluated in relation to performance criteria. They were generally able to satisfy a criterion of ‘fitness for purpose’ that at least 50% of modelled concentrations should be within a factor of two of measured values. The second criterion, that the magnitude of the normalised mean bias should be less than 20%, was not always satisfied. Considering known uncertainties in measurement techniques, this criterion may be too strict. Overall, simpler models were able to give a good representation of measured gas concentrations whilst the use of dynamic meteorology, and complex photo-chemical reactions resulted in a generally better representation of measured aerosol and precipitation concentrations by more complex models. The models were compared graphically by plotting maps and cross-country transects of wet and dry deposition as well as calculating budgets of total wet and dry deposition to the UK for sulphur, oxidised nitrogen and reduced nitrogen. The total deposition to the UK varied by ±22–36% amongst the different models depending on the deposition component. At a local scale estimates of both dry and wet deposition for individual 5 km × 5 km model grid squares were found to vary between the different models by up to a factor of 4.This work was funded by the Department for the Environment, Food and Rural Affairs. Additional support was provided by the Joint Environmental Program, the Natural Environment Research Council and the Environment Agency.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.atmosenv.2015.08.00