Bilateral calf chronic compartment syndrome in an elderly male: a case report

Leg pain is a common presentation to the outpatient department. Bilateral calf chronic compartment syndrome is a rare cause of bilateral calf pain. Although this condition has been well documented in young athletes, it has rarely been reported in the elderly. We present the case of a 68-year-old male bodybuilder with bilateral calf chronic compartment syndrome, describe the presentation and evaluation of the condition, and provide a review of the literature herewith

Post-Transcriptional Dysregulation by miRNAs Is Implicated in the Pathogenesis of Gastrointestinal Stromal Tumor [GIST]

peer-reviewedIn contrast to adult mutant gastrointestinal stromal tumors [GISTs], pediatric/wild-type GISTs remain poorly understood overall, given their lack of oncogenic activating tyrosine kinase mutations. These GISTs, with a predilection for gastric origin in female patients, show limited response to therapy with tyrosine kinase inhibitors and generally pursue a more indolent course, but still may prove fatal. Defective cellular respiration appears to underpin tumor development in these wild-type cases, which as a group lack expression of succinate dehydrogenase [SDH] B, a surrogate marker for respiratory chain metabolism. Yet, only a small subset of the wild-type tumors show mutations in the genes coding for the SDH subunits [SDHx]. To explore additional pathogenetic mechanisms in these wild-type GISTs, we elected to investigate posttranscriptional regulation of these tumors by conducting microRNA (miRNA) profiling of a mixed cohort of 73 cases including 18 gastric pediatric wild-type, 25 (20 gastric, 4 small bowel and 1 retroperitoneal) adult wild-type GISTs and 30 gastric adult mutant GISTs. By this approach we have identified distinct signatures for GIST subtypes which correlate tightly with clinico-pathological parameters. A cluster of miRNAs on 14q32 show strikingly different expression patterns amongst GISTs, a finding which appears to be explained at least in part by differential allelic methylation of this imprinted region. Small bowel and retroperitoneal wild-type GISTs segregate with adult mutant GISTs and express SDHB, while adult wildtype gastric GISTs are dispersed amongst adult mutant and pediatric wild-type cases, clustering in this situation on the basis of SDHB expression. Interestingly, global methylation analysis has recently similarly demonstrated that these wild-type, SDHB-immunonegative tumors show a distinct pattern compared with KIT and PDGFRA mutant tumors, which as a rule do express SDHB. All cases with Carney triad within our cohort cluster together tightly.Funding was obtained from the Medical Research Charities Group (http://www.mrcg.ie/) and Health Research Board of Ireland (http://www.hrb.ie) (MO’S), The Children’s Medical and Research Foundation (http://www.cmrf.org) (MO’S), the GIST Cancer Awareness Foundation [GCAF] (http://www. gistawareness.org/)(MO’S), and research grants from the Life Raft Group (http://www.liferaftgroup.org/)(MD-R) and from the Fonds voor Wetenschappelijk Onderzoek Vlaanderen (http://www.fwo.be/)(grant # G.0286.05 MD-R)

Perceptual learning in a non-human primate model of artificial vision

Visual perceptual grouping, the process of forming global percepts from discrete elements, is experience-dependent. Here we show that the learning time course in an animal model of artificial vision is predicted primarily from the density of visual elements. Three naïve adult non-human primates were tasked with recognizing the letters of the Roman alphabet presented at variable size and visualized through patterns of discrete visual elements, specifically, simulated phosphenes mimicking a thalamic visual prosthesis. The animals viewed a spatially static letter using a gaze-contingent pattern and then chose, by gaze fixation, between a matching letter and a non-matching distractor. Months of learning were required for the animals to recognize letters using simulated phosphene vision. Learning rates increased in proportion to the mean density of the phosphenes in each pattern. Furthermore, skill acquisition transferred from trained to untrained patterns, not depending on the precise retinal layout of the simulated phosphenes. Taken together, the findings suggest that learning of perceptual grouping in a gaze-contingent visual prosthesis can be described simply by the density of visual activation

Chapter 15. COMET2.0-Decision Support System for Agricultural Greenhouse Gas Accounting

Improved agricultural practices have a significant potential to mitigate greenhouse gas (GHG) emissions. A key issue for implementing mitigation options is quantifying emissions practically and cost effectively. Web-based systems using process-based models provide a promising approach. COMET2.0 is a further development of the web-based COMET-VR system with an expanded set of crop management systems, inclusion of orchard and vineyards, new agroforestry options, and a nitrous oxide (N2O) emissions estimator, using the Century and DAYCENT dynamic ecosystem models. Compared to empirical emission factor models, COMET2.0 accounted for more of the between site variation in soil C changes following no-till adoption in Corn Belt and Great Plains experiment sites. Predicted N2O emission rates, as a function of application rate, timing (spring vs. fall), and use of nitrification inhibitors, were consistent with observations in the literature. Carbon dynamics for orchard and agroforestry compared well with field measurements but limited availability of data poses a challenge for a fuller validation of these systems. Advantages of a practiced-based approach, using dynamic process-based models include integration of interacting processes and local conditions for more accurate and complete GHG accounting. Web-based systems, designed for non-experts, allow land managers and others to evaluate trade-offs and select mitigation options for their particular conditions. Experimental networks such as GRACEnet will play an important role in improving decision support tools for implementation of agricultural GHG mitigation.Peer Reviewe

Histone demethylase Jumonji D3 (JMJD3) as a tumor suppressor by regulating p53 protein nuclear stabilization.

Histone methylation regulates normal stem cell fate decisions through a coordinated interplay between histone methyltransferases and demethylases at lineage specific genes. Malignant transformation is associated with aberrant accumulation of repressive histone modifications, such as polycomb mediated histone 3 lysine 27 (H3K27me3) resulting in a histone methylation mediated block to differentiation. The relevance, however, of histone demethylases in cancer remains less clear. We report that JMJD3, a H3K27me3 demethylase, is induced during differentiation of glioblastoma stem cells (GSCs), where it promotes a differentiation-like phenotype via chromatin dependent (INK4A/ARF locus activation) and chromatin independent (nuclear p53 protein stabilization) mechanisms. Our findings indicate that deregulation of JMJD3 may contribute to gliomagenesis via inhibition of the p53 pathway resulting in a block to terminal differentiation

Sustained proliferation in cancer: mechanisms and novel therapeutic targets

Proliferation is an important part of cancer development and progression. This is manifest by altered expression and/or activity of cell cycle related proteins. Constitutive activation of many signal transduction pathways also stimulates cell growth. Early steps in tumor development are associated with a fibrogenic response and the development of a hypoxic environment which favors the survival and proliferation of cancer stem cells. Part of the survival strategy of cancer stem cells may manifested by alterations in cell metabolism. Once tumors appear, growth and metastasis may be supported by overproduction of appropriate hormones (in hormonally dependent cancers), by promoting angiogenesis, by undergoing epithelial to mesenchymal transition, by triggering autophagy, and by taking cues from surrounding stromal cells. A number of natural compounds (e.g., curcumin, resveratrol, indole-3-carbinol, brassinin, sulforaphane, epigallocatechin-3-gallate, genistein, ellagitannins, lycopene and quercetin) have been found to inhibit one or more pathways that contribute to proliferation (e.g., hypoxia inducible factor 1, nuclear factor kappa B, phosphoinositide 3 kinase/Akt, insulin-like growth factor receptor 1, Wnt, cell cycle associated proteins, as well as androgen and estrogen receptor signaling). These data, in combination with bioinformatics analyses, will be very important for identifying signaling pathways and molecular targets that may provide early diagnostic markers and/or critical targets for the development of new drugs or drug combinations that block tumor formation and progression

Comprehensive Genomic Profiling of 274 Thymic Epithelial Tumors Unveils Oncogenic Pathways and Predictive Biomarkers

International audienceBACKGROUND: Thymic malignancies represent a heterogeneous group of rare thoracic cancers, which are classified according to the World Health Organization histopathologic classification, that distinguishes thymomas from thymic carcinomas. Data regarding the biology of those tumors are limited in the literature, and the vast majority have been obtained using surgical specimens from early-stage disease. Meanwhile, treatment of advanced, refractory thymic tumors currently relies on chemotherapy, with limited efficacy. Comprehensive genomic profiling (CGP) of advanced, refractory tumors would open some opportunities for innovative treatments. PATIENTS AND METHODS: A total of 90 and 174 consecutive patients with thymoma or thymic carcinoma, respectively, for whom formalin-fixed, paraffin-embedded specimens from recurrent, refractory tumor were sequenced, were included. Sequencing was performed using hybridization-captured, adaptor ligation-based libraries to a mean coverage depth of >500× for up to 315 cancer-related genes plus 37 introns from 28 genes frequently rearranged in cancer. RESULTS: Thymomas featured a low frequency of genomic alterations (average of 1.8/tumor), and low levels of TMB. The genomic alterations identified in more than 10% of cases were in the CDKN2A/B and TP53 genes. Amplification in the NTRK1 gene was found in an unresectable, stage III, type B3 thymoma. Thymic carcinomas featured a significantly higher frequency of alterations at 4.0/tumor (P < .0001). Clinically relevant genomic alterations were observed in the CDKN2A, KIT, and PTEN/PI3K/MTOR pathways. Elevated TMB in thymic carcinomas was uncommon with only 6% of cases featuring ≥10 mutations/Mb. CONCLUSIONS: Our cohort is the largest available so far, reporting on CGP of thymic epithelial tumors in the setting of advanced disease. The identification of clinically relevant genomic alterations in the KIT, PI3K, CDKN2A/B, or NTRK genes provides a strong rationale for potential precision medicine approaches using targeted agents. A subset of thymic carcinomas show high tumor mutation burden, what may be a predictor of efficacy of immune checkpoint inhibitors