A three-miRNA signature as promising non-invasive diagnostic marker for gastric cancer

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Surgical care for the direct and indirect victims of violence in the eastern Democratic Republic of Congo

ABSTRACT: BACKGROUND: The provision of surgical assistance in conflict is often associated with care for victims of violence. However, there is an increasing appreciation that surgical care is needed for non-traumatic morbidities. In this paper we report on surgical interventions carried out by Medecins sans Frontieres in Masisi, North Kivu, Democratic Republic of Congo to contribute to the scarce evidence base on surgical needs in conflict. METHODS: We analysed data on all surgical interventions done at Masisi district hospital between September 2007 to December 2009. Types of interventions are described, and logistic regression used to model associations with violence-related injury. RESULTS: 2869 operations were performed on 2441 patients. Obstetric emergencies accounted for over half (675, 57%) of all surgical pathology and infections for another quarter (160, 14%). Trauma-related injuries accounted for only one quarter (681, 24%) of all interventions; among these, 363 (13%) were violence-related. Male gender (adjusted odds ratio (AOR)=20.0, p<0.001), military status (AOR=4.1, p<0.001), and age less than 20 years (AOR=2.1, p<0.001) were associated with violence-related injury. Immediate peri-operative mortality was 0.2%. CONCLUSIONS: In this study, most surgical interventions were unrelated to violent trauma and rather reflected the general surgical needs of a low-income tropical country. Programs in conflict zones in low-income countries need to be prepared to treat both the war-wounded and non-trauma related life-threatening surgical needs of the general population. Given the limited surgical workforce in these areas, training of local staff and task shifting is recommended to support broad availability of essential surgical care. Further studies into the surgical needs of the population are warranted, including population-based surveys to improve program planning and resource allocation and the effectiveness of the humanitarian response

Modeling performance of Hadoop applications: A journey from queueing networks to stochastic well formed nets

Nowadays, many enterprises commit to the extraction of actionable knowledge from huge datasets as part of their core business activities. Applications belong to very different domains such as fraud detection or one-to-one marketing, and encompass business analytics and support to decision making in both private and public sectors. In these scenarios, a central place is held by the MapReduce framework and in particular its open source implementation, Apache Hadoop. In such environments, new challenges arise in the area of jobs performance prediction, with the needs to provide Service Level Agreement guarantees to the enduser and to avoid waste of computational resources. In this paper we provide performance analysis models to estimate MapReduce job execution times in Hadoop clusters governed by the YARN Capacity Scheduler. We propose models of increasing complexity and accuracy, ranging from queueing networks to stochastic well formed nets, able to estimate job performance under a number of scenarios of interest, including also unreliable resources. The accuracy of our models is evaluated by considering the TPC-DS industry benchmark running experiments on Amazon EC2 and the CINECA Italian supercomputing center. The results have shown that the average accuracy we can achieve is in the range 9–14%

Mycolactone-dependent depletion of endothelial cell thrombomodulin is strongly associated with fibrin deposition in Buruli ulcer lesions

A well-known histopathological feature of diseased skin in Buruli ulcer (BU) is coagulative necrosis caused by the Mycobacterium ulcerans macrolide exotoxin mycolactone. Since the underlying mechanism is not known, we have investigated the effect of mycolactone on endothelial cells, focussing on the expression of surface anticoagulant molecules involved in the protein C anticoagulant pathway. Congenital deficiencies in this natural anticoagulant pathway are known to induce thrombotic complications such as purpura fulimans and spontaneous necrosis. Mycolactone profoundly decreased thrombomodulin (TM) expression on the surface of human dermal microvascular endothelial cells (HDMVEC) at doses as low as 2ng/ml and as early as 8hrs after exposure. TM activates protein C by altering thrombin's substrate specificity, and exposure of HDMVEC to mycolactone for 24 hours resulted in an almost complete loss of the cells' ability to produce activated protein C. Loss of TM was shown to be due to a previously described mechanism involving mycolactone-dependent blockade of Sec61 translocation that results in proteasome-dependent degradation of newly synthesised ER-transiting proteins. Indeed, depletion from cells determined by live-cell imaging of cells stably expressing a recombinant TM-GFP fusion protein occurred at the known turnover rate. In order to determine the relevance of these findings to BU disease, immunohistochemistry of punch biopsies from 40 BU lesions (31 ulcers, nine plaques) was performed. TM abundance was profoundly reduced in the subcutis of 78% of biopsies. Furthermore, it was confirmed that fibrin deposition is a common feature of BU lesions, particularly in the necrotic areas. These findings indicate that there is decreased ability to control thrombin generation in BU skin. Mycolactone's effects on normal endothelial cell function, including its ability to activate the protein C anticoagulant pathway are strongly associated with this. Fibrin-driven tisischemia could contribute to the development of the tissue necrosis seen in BU lesions

High motor variability in DYT1 dystonia is associated with impaired visuomotor adaptation.

For the healthy motor control system, an essential regulatory role is maintaining the equilibrium between keeping unwanted motor variability in check whilst allowing informative elements of motor variability. Kinematic studies in children with generalised dystonia (due to mixed aetiologies) show that movements are characterised by increased motor variability. In this study, the mechanisms by which high motor variability may influence movement generation in dystonia were investigated. Reaching movements in the symptomatic arm of 10 patients with DYT1 dystonia and 12 age-matched controls were captured using a robotic manipulandum and features of motor variability were extracted. Given that task-relevant variability and sensorimotor adaptation are related in health, markers of variability were then examined for any co-variance with performance indicators during an error-based learning visuomotor adaptation task. First, we confirmed that motor variability on a trial-by-trial basis was selectively increased in the homogenous and prototypical dystonic disorder DYT1 dystonia. Second, high baseline variability predicted poor performance in the subsequent visuomotor adaptation task offering insight into the rules which appear to govern dystonic motor control. The potential mechanisms behind increased motor variability and its corresponding implications for the rehabilitation of patients with DYT1 dystonia are highlighted

Family History and Breast Cancer Hormone Receptor Status in a Spanish Cohort

Breast cancer is a heterogenous disease that impacts racial/ethnic groups differently. Differences in genetic composition, lifestyles, reproductive factors, or environmental exposures may contribute to the differential presentation of breast cancer among Hispanic women.A population-based study was conducted in the city of Santiago de Compostela, Spain. A total of 645 women diagnosed with operable invasive breast cancer between 1992 and 2005 participated in the study. Data on demographics, breast cancer risk factors, and clinico-pathological characteristics of the tumors were collected. Hormone receptor negative tumors were compared with hormone receptor postive tumors on their clinico-pathological characteristics as well as risk factor profiles.Among the 645 breast cancer patients, 78% were estrogen receptor-positive (ER+) or progesterone receptor-positive (PR+), and 22% were ER−&PR−. Women with a family history of breast cancer were more likely to have ER−&PR− tumors than women without a family history (Odds ratio, 1.43; 95% confidence interval, 0.91–2.26). This association was limited to cancers diagnosed before age 50 (Odds ratio, 2.79; 95% confidence interval, 1.34–5.81).An increased proportion of ER−&PR− breast cancer was observed among younger Spanish women with a family history of the disease

Anti-inflammatory effect of rosiglitazone is not reflected in expression of NFκB-related genes in peripheral blood mononuclear cells of patients with type 2 diabetes mellitus

<p>Abstract</p> <p>Background</p> <p>Rosiglitazone not only improves insulin-sensitivity, but also exerts anti-inflammatory effects. We have now examined in type 2 diabetic patients if these effects are reflected by changes in mRNA expression in peripheral blood mononuclear cells (PBMCs) to see if these cells can be used to study these anti-inflammatory effects at the molecular level <it>in vivo</it>.</p> <p>Method</p> <p>Eleven obese type 2 diabetic patients received rosiglitazone (2 × 4 mg/d) for 8 weeks. Fasting blood samples were obtained before and after treatment. Ten obese control subjects served as reference group. The expression of NFκB-related genes and PPARγ target genes in PBMCs, plasma TNFα, IL6, MCP1 and hsCRP concentrations were measured. In addition, blood samples were obtained after a hyperinsulinemic-euglycemic clamp.</p> <p>Results</p> <p>Rosiglitazone reduced plasma MCP1 and hsCRP concentrations in diabetic patients (-9.5 ± 5.3 pg/mL, <it>p </it> = 0.043 and -1.1 ± 0.3 mg/L <it>p </it> = 0.003), respectively). For hsCRP, the concentration became comparable with the non-diabetic reference group. However, of the 84 NFκB-related genes that were measured in PBMCs from type 2 diabetic subjects, only RELA, SLC20A1, INFγ and IL1R1 changed significantly (<it>p </it> < 0.05). In addition, PPARγ and its target genes (CD36 and LPL) did not change. During the clamp, insulin reduced plasma MCP1 concentration in the diabetic and reference groups (-9.1 ± 1.8%, <it>p </it> = 0.001 and -11.1 ± 4.1%, <it>p </it> = 0.023, respectively) and increased IL6 concentration in the reference group only (23.5 ± 9.0%, <it>p </it> = 0.028).</p> <p>Conclusion</p> <p>In type 2 diabetic patients, the anti-inflammatory effect of rosiglitazone is not reflected by changes in NFκB and PPARγ target genes in PBMCs <it>in vivo</it>. Furthermore, our results do not support that high insulin concentrations contribute to the pro-inflammatory profile in type 2 diabetic patients.</p