A neutralizing IL-11 antibody reduces vessel hyperplasia in a mouse carotid artery wire injury model

Vascular restenosis remains a major problem in patients with coronary artery disease (CAD) and peripheral artery disease (PAD). Neointimal hyperplasia, defined by post-procedure proliferation and migration of vascular smooth muscle cells (VSMCs) is a key underlying pathology. Here we investigated the role of Interleukin 11 (IL-11) in a mouse model of injury-related plaque development. Apoe−/− mice were fed a hyperlipidaemic diet and subjected to carotid wire injury of the right carotid. Mice were injected with an anti-IL11 antibody (X203), IgG control antibody or buffer. We performed ultrasound analysis to assess vessel wall thickness and blood velocity. Using histology and immunofluorescence approaches, we determined the effects of IL-11 inhibition on VSMC and macrophages phenotypes and fibrosis. Treatment of mice with carotid wire injury using X203 significantly reduced post-endothelial injury vessel wall thickness, and injury-related plaque, when compared to control. Immunofluorescence staining of the injury-related plaque showed that X203 treatment did not reduce macrophage numbers, but reduced the number of VSMCs and lowered matrix metalloproteinase 2 (MMP2) levels and collagen content in comparison to control. X203 treatment was associated with a significant increase in smooth muscle protein 22α (SM22α) positive cells in injury-related plaque compared to control, suggesting preservation of the contractile VSMC phenotype. Interestingly, X203 also reduced the collagen content of uninjured carotid arteries as compared to IgG, showing an additional effect on hyperlipidemia-induced arterial remodeling in the absence of mechanical injury. Therapeutic inhibition of IL-11 reduced vessel wall thickness, attenuated neointimal hyperplasia, and has favorable effects on vascular remodeling following wire-induced endothelial injury. This suggests IL-11 inhibition as a potential novel therapeutic approach to reduce arterial stenosis following revascularization in CAD and PAD patients

Cysteine oxidation targets peroxiredoxins 1 and 2 for exosomal release through a novel mechanism of redox-dependent secretion

Non-classical protein secretion is of major importance as a number of cytokines and inflammatory mediators are secreted via this route. Current evidence indicates that there are several mechanistically distinct methods of non-classical secretion. We have recently shown that peroxiredoxin (Prdx) 1 and Prdx2 are released by various cells upon exposure to inflammatory stimuli such as LPS or TNF-α. The released Prdx then acts to induce production of inflammatory cytokines. However, Prdx1 and 2 do not have signal peptides and therefore must be secreted by alternative mechanisms as has been postulated for the inflammatory mediators IL-1β and HMGB1. We show here that circulating Prdx1 and 2 are present exclusively as disulphide-linked homodimers. Inflammatory stimuli also induce in vitro release of Prdx1 and 2 as disulfide-linked homodimers. Mutation of cysteines Cys51 or Cys172 (but not Cys70) in Prdx2, and Cys52 or Cys173 (but not Cys71 or Cys83) in Prdx1 prevented dimer formation and this was associated with inhibition of their TNF-α-induced release. Thus, the presence and oxidation of key cysteine residues in these proteins are a prerequisite for their secretion in response to TNF-α and this release can be induced with an oxidant. In contrast, the secretion of the nuclear-associated danger signal HMGB1 is independent of cysteine oxidation, as shown by experiments with a cysteine-free HMGB1 mutant. Release of Prdx1 and 2 is not prevented by inhibitors of the classical secretory pathway; instead, both Prdx1 and 2 are released in exosomes from both HEK cells and monocytic cells. Serum Prdx1 and 2 are also associated with the exosomes. These results describe a novel pathway of protein secretion mediated by cysteine oxidation that underlines the importance of redox-dependent signalling mechanisms in inflammation

Lymph node infarction – a rare complication associated with disseminated intra vascular coagulation in a case of dengue fever

BACKGROUND: Lymph node infarction is known to occur in association with many non-neoplastic and neoplastic conditions however its occurrence in association with DIC is not reported hitherto in the literature. CASE PRESENTATION: We describe an unusual case of lymph node infarction in a twenty seven year old male following disseminated intravascular coagulation (DIC) in a case of dengue fever. Multiple sections of the infarcted and the surrounding non-infarcted lymph nodes failed to reveal any predisposing condition. How ever the parahilar vessels showed thrombotic occlusion, which must have been responsible for the infarction. CONCLUSION: Global infarction of the lymph node may mask the underlying pathology. Any malignancy especially lymphoma may coexist or follow lymph node infarction, therefore the patient needs constant surveillance

Detection of Stance-Related Characteristics in Social Media Text

In this paper, we present a study for the identification of stance-related features in text data from social media. Based on our previous work on stance and our findings on stance patterns, we detected stance-related characteristics in a data set from Twitter and Facebook. We extracted various corpus-, quantitative- and computational-based features that proved to be significant for six stance categories (contrariety, hypotheticality, necessity, prediction, source of knowledge, and uncertainty), and we tested them in our data set. The results of a preliminary clustering method are presented and discussed as a starting point for future contributions in the field. The results of our experiments showed a strong correlation between different characteristics and stance constructions, which can lead us to a methodology for automatic stance annotation of these data

Minimally invasive scoliosis surgery: an innovative technique in patients with adolescent idiopathic scoliosis

Minimally invasive spine surgery is becoming more common in the treatment of adult lumbar degenerative disorders. Minimally invasive techniques have been utilized for multilevel pathology, including adult lumbar degenerative scoliosis. The next logical step is to apply minimally invasive surgical techniques to the treatment of adolescent idiopathic scoliosis (AIS). However, there are significant technical challenges of performing minimally invasive surgery on this patient population. For more than two years, we have been utilizing minimally invasive spine surgery techniques in patients with adolescent idiopathic scoliosis. We have developed the present technique to allow for utilization of all standard reduction maneuvers through three small midline skin incisions. Our technique allows easy passage of contoured rods, placement of pedicle screws without image guidance, and allows adequate facet osteotomy to enable fusion. There are multiple potential advantages of this technique, including: less blood loss, shorter hospital stay, earlier mobilization, and relatively less pain and need for pain medication. The operative time needed to complete this surgery is longer. We feel that a minimally invasive approach, although technically challenging, is a feasible option in patients with adolescent idiopathic scoliosis. Although there are multiple perceived benefits, long term data is needed before it can be recommended for routine use

Length of stay and associated costs of obesity related hospital admissions in Ireland

BACKGROUND: Obesity is the cause of other chronic diseases, psychological problems, obesity shortens the lifespan and puts strain on health systems. The risk associated with childhood obesity in particular, which will accelerate the development of adult morbidity and mortality, has been identified as an emerging public health problem. METHODS: To estimate the length of stay and associated hospital costs for obesity related illnesses a cost of illness study was set up. All discharges from all acute hospitals in the Republic of Ireland from 1997 to 2004 with a principal or secondary diagnostic code for obesity for all children from 6 to 18 years of age and for adults were collected.A discharge frequency was calculated by dividing obesity related discharges by the total number of diagnoses (principal and secondary) for each year. The hospital costs related to obesity was calculated based on the total number of days care. RESULTS: The discharge frequency of obesity related conditions increased from 1.14 in 1997 to 1.49 in 2004 for adults and from 0.81 to 1.37 for children. The relative length of stay (number of days in care for obesity related conditions per 1000 days of hospital care given) increased from 1.47 in 1997 to 4.16 in 2004 for children and from 3.68 in 1997 to 6.74 in 2004 for adults.Based on the 2001 figures for cost per inpatient bed day, the annual hospital cost was calculated to be 4.4 Euromillion in 1997, increasing to 13.3 Euromillion in 2004. At a 20% variable hospital cost the cost ranges from 0.9 Euromillion in 1997 to 2.7 Euromillion in 2004; a 200% increase. CONCLUSION: The annual increase in the proportion of hospital discharges related to obesity is alarming. This increase is related to a significant increase in economic costs. This paper emphasises the need for action at an early stage of life. Health promotion and primary prevention of obesity should be high on the political agenda

A new framework for sign language alphabet hand posture recognition using geometrical features through artificial neural network (part 1)

Hand pose tracking is essential in sign languages. An automatic recognition of performed hand signs facilitates a number of applications, especially for people with speech impairment to communication with normal people. This framework which is called ASLNN proposes a new hand posture recognition technique for the American sign language alphabet based on the neural network which works on the geometrical feature extraction of hands. A user’s hand is captured by a three-dimensional depth-based sensor camera; consequently, the hand is segmented according to the depth analysis features. The proposed system is called depth-based geometrical sign language recognition as named DGSLR. The DGSLR adopted in easier hand segmentation approach, which is further used in segmentation applications. The proposed geometrical feature extraction framework improves the accuracy of recognition due to unchangeable features against hand orientation compared to discrete cosine transform and moment invariant. The findings of the iterations demonstrate the combination of the extracted features resulted to improved accuracy rates. Then, an artificial neural network is used to drive desired outcomes. ASLNN is proficient to hand posture recognition and provides accuracy up to 96.78% which will be discussed on the additional paper of this authors in this journal

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Risk of high blood pressure in salt workers working near salt milling plants: A cross-sectional and interventional study

BACKGROUND: Workers working close to salt milling plants may inhale salt particles floating in the air, leading to a rise in plasma sodium, which, in turn, may increase the blood pressure and the risk of hypertension. METHODS: To test the above hypothesis, occupational health check-up camps were organized near salt manufacturing units and all workers were invited for a free health examination. The workers who worked with dry salt in the vicinity of salt milling plants were defined as "non-brine workers," while those working in brine pans located far away from milling plants were defined as "brine workers." Blood pressure (BP) was measured during each clinical examination. In all, 474 non-brine workers and 284 brine workers were studied. RESULTS: Mean systolic blood pressure of non-brine workers (122.1 ± 13.3 mm Hg) was significantly higher than that of brine workers (118.8 ± 12.8 mm Hg, p < 0.01). Mean diastolic blood pressure of non-brine workers (71.5 ± 10.4 mm Hg) was significantly higher than that of brine workers (69.7 ± 9.4 mm Hg, p = 0.02). The prevalence of hypertension was significantly higher in non-brine workers (12.2%) than in brine workers (7.0%, p = 0.02). Nineteen salt workers were monitored while they used face masks and spectacles, for six days. Systolic, as well as diastolic, blood pressure of these workers began declining on the third day and continued to decline on the fourth day, but remained stationary up to the sixth day. The concentration of salt particles in the breathing zone of these workers was 376 mg/m(3 )air. CONCLUSION: Inhalation of salt particles in non-brine workers may be an occupational cause of increased blood pressure