A Ten-microRNA Expression Signature Predicts Survival in Glioblastoma

Glioblastoma (GBM) is the most common and aggressive primary brain tumor with very poor patient median survival. To identify a microRNA (miRNA) expression signature that can predict GBM patient survival, we analyzed the miRNA expression data of GBM patients (n = 222) derived from The Cancer Genome Atlas (TCGA) dataset. We divided the patients randomly into training and testing sets with equal number in each group. We identified 10 significant miRNAs using Cox regression analysis on the training set and formulated a risk score based on the expression signature of these miRNAs that segregated the patients into high and low risk groups with significantly different survival times (hazard ratio HR] = 2.4; 95% CI = 1.4-3.8; p < 0.0001). Of these 10 miRNAs, 7 were found to be risky miRNAs and 3 were found to be protective. This signature was independently validated in the testing set (HR = 1.7; 95% CI = 1.1-2.8; p = 0.002). GBM patients with high risk scores had overall poor survival compared to the patients with low risk scores. Overall survival among the entire patient set was 35.0% at 2 years, 21.5% at 3 years, 18.5% at 4 years and 11.8% at 5 years in the low risk group, versus 11.0%, 5.5%, 0.0 and 0.0% respectively in the high risk group (HR = 2.0; 95% CI = 1.4-2.8; p < 0.0001). Cox multivariate analysis with patient age as a covariate on the entire patient set identified risk score based on the 10 miRNA expression signature to be an independent predictor of patient survival (HR = 1.120; 95% CI = 1.04-1.20; p = 0.003). Thus we have identified a miRNA expression signature that can predict GBM patient survival. These findings may have implications in the understanding of gliomagenesis, development of targeted therapy and selection of high risk cancer patients for adjuvant therapy.

Factors associated with 2009 pandemic influenza A (H1N1) vaccination acceptance among university students from India during the post-pandemic phase

Background: There was a low adherence to influenza A (H1N1) vaccination program among university students and health care workers during the pandemic influenza in many parts of the world. Vaccination of high risk individuals is one of the recommendations of World Health Organization during the post-pandemic period. It is not documented about the student's knowledge, attitude and willingness to accept H1N1 vaccination during the post-pandemic period. We aimed to analyze the student's knowledge, attitude and willingness to accept H1N1 vaccination during the post-pandemic period in India. Methods: Vaccine against H1N1 was made available to the students of Vellore Institute of Technology, India from September 2010. The data are based on a cross-sectional study conducted during October 2010 to January 2011 using a self-administered questionnaire with a representative sample of the student population (N = 802). Results: Of the 802 respondents, only 102/802 (12.7%) had been vaccinated and 105/802 (13%) planned to do so in the future, while 595/802 (74%) would probably or definitely not get vaccinated in the future. The highest coverage was among the female (65/102, 63.7%) and non-compliance was higher among men in the group (384/595; 64.5%) (p < 0.0001). The representation of students from school of Bio-sciences and Bio-technology among vaccinees is significantly higher than that of other schools. Majority of the study population from the three groups perceived vaccine against H1N1 as the effective preventive measure when compared to other preventive measures. 250/595 (42%) of the responders argued of not being in the risk group. The risk perception was significantly higher among female (p < 0.0001). With in the study group, 453/802 (56.4%) said that they got the information, mostly from media. Conclusions: Our study shows that the vaccination coverage among university students remains very low in the post-pandemic period and doubts about the safety and effectiveness of the vaccine are key elements in their rejection. Our results indicate a need to provide accessible information about the vaccine safety by scientific authorities and fill gaps and confusions in this regard.

Long-Term Environmental Correlates of Invasion by Lantana camara (Verbenaceae) in a Seasonally Dry Tropical Forest

Invasive species, local plant communities and invaded ecosystems change over space and time. Quantifying this change may lead to a better understanding of the ecology and the effective management of invasive species. We used data on density of the highly invasive shrub Lantana camara (lantana) for the period 1990-2008 from a 50 ha permanent plot in a seasonally dry tropical forest of Mudumalai in southern India. We used a cumulative link mixed-effects regression approach to model the transition of lantana from one qualitative density state to another as a function of biotic factors such as indicators of competition from local species (lantana itself, perennial grasses, invasive Chromolaena odorata, the native shrub Helicteres isora and basal area of native trees) and abiotic factors such as fire frequency, inter-annual variability of rainfall and relative soil moisture. The density of lantana increased substantially during the study period. Lantana density was negatively associated with the density of H. isora, positively associated with basal area of native trees, but not affected by the presence of grasses or other invasive species. In the absence of fire, lantana density increased with increasing rainfall. When fires occurred, transitions to higher densities occurred at low rainfall values. In drier regions, lantana changed from low to high density as rainfall increased while in wetter regions of the plot, lantana persisted in the dense category irrespective of rainfall. Lantana seems to effectively utilize resources distributed in space and time to its advantage, thus outcompeting local species and maintaining a population that is not yet self-limiting. High-risk areas and years could potentially be identified based on inferences from this study for facilitating management of lantana in tropical dry forests.

A DNA methylation prognostic signature of glioblastoma: identification of NPTX2-PTEN-NF-kappa B nexus

Glioblastoma (GBM) is the most common, malignant adult primary tumor with dismal patient survival, yet the molecular determinants of patient survival are poorly characterized. Global methylation profile of GBM samples (our cohort; n = 44) using high-resolution methylation microarrays was carried out. Cox regression analysis identified a 9-gene methylation signature that predicted survival in GBM patients. A risk-score derived from methylation signature predicted survival in univariate analysis in our and The Cancer Genome Atlas (TCGA) cohort. Multivariate analysis identified methylation risk score as an independent survival predictor in TCGA cohort. Methylation risk score stratified the patients into low-risk and high-risk groups with significant survival difference. Network analysis revealed an activated NF-kappa B pathway association with high-risk group. NF-kappa B inhibition reversed glioma chemoresistance, and RNA interference studies identified interleukin-6 and intercellular adhesion molecule-1 as key NF-kappa B targets in imparting chemoresistance. Promoter hypermethylation of neuronal pentraxin II (NPTX2), a risky methylated gene, was confirmed by bisulfite sequencing in GBMs. GBMs and glioma cell lines had low levels of NPTX2 transcripts, which could be reversed upon methylation inhibitor treatment. NPTX2 overexpression induced apoptosis, inhibited proliferation and anchorage-independent growth, and rendered glioma cells chemosensitive. Furthermore, NPTX2 repressed NF-kappa B activity by inhibiting AKT through a p53-PTEN-dependent pathway, thus explaining the hypermethylation and downregulation of NPTX2 in NF-kappa B-activated high-risk GBMs. Taken together, a 9-gene methylation signature was identified as an independent GBM prognosticator and could be used for GBM risk stratification. Prosurvival NF-kappa B pathway activation characterized high-risk patients with poor prognosis, indicating it to be a therapeutic target. (C) 2013 AACR.

Qualitative toxicity assessment of silver nanoparticles on the fresh water bacterial isolates and consortium at low level of exposure concentration

Silver nanoparticles (AgNPs) pose a high risk of exposure to the natural environment owing to their extensive usage in various consumer products. In the present study we attempted to understand the harmful effect of AgNPs at environmentally relevant low concentration levels (<= 1 ppm) towards two different freshwater bacterial isolates and their consortium. The standard plate count assay suggested that the AgNPs were toxic towards the fresh water bacterial isolates as well as the consortium, though toxicity was significantly reduced for the cells in the consortium. The oxidative stress assessment and membrane permeability studies corroborated with the toxicity data. The detailed electron microscopic studies suggested the cell degrading potential of the AgNPs, and the FT-IR studies confirmed the involvement of the surface groups in the toxic effects. No significant ion leaching from the AgNPs was observed at the applied concentration levels signifying the dominant role of the particle size, and size distribution in bacterial toxicity. The reduced toxicity for the cells in the consortium than the individual isolates has major significance in further studies on the ecotoxicity of the AgNPs. (C) 2014 Elsevier Inc. All rights reserved.

Groups constrain the use of risky habitat by individuals: a new cost to sociality?

Predation risk can strongly constrain how individuals use time and space. Grouping is known to reduce an individual's time investment in costly antipredator behaviours. Whether grouping might similarly provide a spatial release from antipredator behaviour and allow individuals to use risky habitat more and, thus, improve their access to resources is poorly known. We used mosquito larvae, Aedes aegypti, to test the hypothesis that grouping facilitates the use of high-risk habitat. We provided two habitats, one darker, low-risk and one lighter, high-risk, and measured the relative time spent in the latter by solitary larvae versus larvae in small groups. We tested larvae reared under different resource levels, and thus presumed to vary in body condition, because condition is known to influence risk taking. We also varied the degree of contrast in habitat structure. We predicted that individuals in groups should use high-risk habitat more than solitary individuals allowing for influences of body condition and contrast in habitat structure. Grouping strongly influenced the time spent in the high-risk habitat, but, contrary to our expectation, individuals in groups spent less time in the high-risk habitat than solitary individuals. Furthermore, solitary individuals considerably increased the proportion of time spent in the high-risk habitat over time, whereas individuals in groups did not. Both solitary individuals and those in groups showed a small increase over time in their use of riskier locations within each habitat. The differences between solitary individuals and those in groups held across all resource and contrast conditions. Grouping may, thus, carry a poorly understood cost of constraining habitat use. This cost may arise because movement traits important for maintaining group cohesion (a result of strong selection on grouping) can act to exaggerate an individual preference for low-risk habitat. Further research is needed to examine the interplay between grouping, individual movement and habitat use traits in environments heterogeneous in risk and resources. (C) 2015 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

Number of prior episodes and the presence of depressive symptoms are associated with longer length of stay for patients with acute manic episodes

Background: Few studies have analyzed predictors of length of stay (LOS) in patients admitted due to acute bipolar manic episodes. The purpose of the present study was to estimate LOS and to determine the potential sociodemographic and clinical risk factors associated with a longer hospitalization. Such information could be useful to identify those patients at high risk for long LOS and to allocate them to special treatments, with the aim of optimizing their hospital management. Methods: This was a cross-sectional study recruiting adult patients with a diagnosis of bipolar disorder (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) criteria) who had been hospitalized due to an acute manic episode with a Young Mania Rating Scale total score greater than 20. Bivariate correlational and multiple linear regression analyses were performed to identify independent predictors of LOS. Results: A total of 235 patients from 44 centers were included in the study. The only factors that were significantly associated to LOS in the regression model were the number of previous episodes and the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at admission (P < 0.05). Conclusions: Patients with a high number of previous episodes and those with depressive symptoms during mania are more likely to stay longer in hospital. Patients with severe depressive symptoms may have a more severe or treatment-resistant course of the acute bipolar manic episode.

Una imagen vale más que mil palabras: efectos de las advertencias sanitarias visuales en el descenso del consumo de tabaco: un estudio desde la perspectiva del marketing social

[ES] El tabaco está reconocido hoy día como un factor de riesgo muy importante en multitud de enfermedades, representando un grave riesgo para la salud pública. Entre las medidas previstas por la Organización Mundial de la Salud y por la Comisión Europea está la utilización de advertencias sanitarias sobre los efectos del tabaco en las personas. En España actualmente esas advertencias contienen solo texto.

Deportividad y violencia en el fútbol base: un programa de evaluación y de prevención de partidos de riesgo

Este trabajo ha recibido el “Primer Premio Delegación del Gobierno en Aragón a las buenas prácticas contra la delincuencia juvenil” (Convocatoria 2007).

Chemical contaminants, pathogen exposure and general health status of live and beach-cast Washington sea otters (Enhydra lutris kenyoni)

Analyses of blood and liver samples from live captured sea otters and liver samples from beachcast sea otter carcasses off the remote Washington coast indicate relatively low exposure to contaminants, but suggest that even at the low levels measured, exposure may be indicated by biomarker response. Evidence of pathogen exposure is noteworthy - infectious disease presents a potential risk to Washington sea otters, particularly due to their small population size and limited distribution. During 2001 and 2002, 32 sea otters were captured, of which 28 were implanted with transmitters to track their movements and liver and blood samples were collected to evaluate contaminant and pathogen exposure. In addition, liver samples from fifteen beachcast animals that washed ashore between 1991 and 2002 were analyzed to provide historical information and a basis of reference for values obtained from live otters. The results indicate low levels of metals, butyltins, and organochlorine compounds in the blood samples, with many of the organochlorines not detected except polychlorinated biphenyls (PCBs), and a few aromatic hydrocarbons detected in the liver of the live captured animals. Aliphatic hydrocarbons were measurable in the liver from the live captured animals; however, some of these are likely from biogenic sources. A significant reduction of vitamin A storage in the liver was observed in relation to PCB, dibutyltin and octacosane concentration. A significant and strong positive correlation in vitamin A storage in the liver was observed for cadmium and several of the aliphatic hydrocarbons. Peripheral blood mononuclear cell (PBMC) cytochrome P450 induction was elevated in two of 16 animals and may be potentially related to aliphatic and aromatic hydrocarbon exposure. Mean concentration of total butyltin in the liver of the Washington beach-cast otters was more than 15 times lower than the mean concentration reported by Kannan et al. (1998) for Southern sea otters in California. Organochlorine compounds were evident in the liver of beach-cast animals, despite the lack of large human population centers and development along the Washington coast. Concentrations of PCBs and chlordanes (e.g., transchlordane, cis-chlordane, trans-nonachlor, cis-nonachlor and oxychlordane) in liver of Washington beach-cast sea otters were similar to those measured in Aleutian and California sea otters, excluding those from Monterey Bay, which were higher. Mean concentrations of 1,1,1,- trichloro-2,2-bis(p-chlorophyenyl)ethanes (DDTs) were lower, and mean concentrations of cyclohexanes (HCH, e.g., alpha BHC, beta BHC, delta BHC and gamma BHC) were slightly higher in Washington beach-cast otters versus those from California and the Aleutians. Epidemiologically, blood tests revealed that 80 percent of the otters tested positive for morbillivirus and 60 percent for Toxoplasma, the latter of which has been a significant cause of mortality in Southern sea otters in California. This is the first finding of positive morbillivirus titers in sea otters from the Northeast Pacific. Individual deaths may occur from these diseases, perhaps more so when animals are otherwise immuno-compromised or infected with multiple diseases, but a population-threatening die-off from these diseases singly is unlikely while population immunity remains high. The high frequency of detection of morbillivirus and Toxoplasma in the live otters corresponds well with the cause of death of stranded Washington sea otters reported herein, which has generally been attributable to infectious disease. Washington’s sea otter population continues to grow, with over 1100 animals currently inhabiting Washington waters; however, the rate of growth has slowed over recent years. The population has a limited distribution and has not yet reached its carrying capacity and as such, is still considered at high risk to catastrophic events. (PDF contains 189 pages)

New Oncogenic Drivers in Hepatocellular Carcinoma: Role of the RNA Binding Protein Hu antigen R

156 p. : graf.

Diagnosis of invasive candidiasis by enzyme-linked immunosorbent assay using the N-terminal fragment of Candida albicans hyphal wall protein I

Background: The diagnosis of invasive candidiasis is difficult because there are no specific clinical manifestations of the disease and colonization and infection are difficult to distinguish. In the last decade, much effort has been made to develop reliable tests for rapid diagnosis of invasive candidiasis, but none of them have found widespread clinical use. Results: Antibodies against a recombinant N-terminal fragment of the Candida albicans germ tube-specific antigen hyphal wall protein 1 (Hwp1) generated in Escherichia coli were detected by both immunoblotting and ELISA tests in a group of 36 hematological or Intensive Care Unit patients with invasive candidiasis and in a group of 45 control patients at high risk for the mycosis who did not have clinical or microbiological data to document invasive candidiasis. Results were compared with an immunofluorescence test to detect antibodies to C. albicans germ tubes (CAGT). The sensitivity, specificity, positive and negative predictive values of a diagnostic test based on the detection of antibodies against the N-terminal fragment of Hwp1 by immunoblotting were 27.8 %, 95.6 %, 83.3 % and 62.3 %, respectively. Detection of antibodies to the N-terminal fragment of Hwp1 by ELISA increased the sensitivity (88.9 %) and the negative predictive value (90.2 %) but slightly decreased the specificity (82.6 %) and positive predictive values (80 %). The kinetics of antibody response to the N-terminal fragment of Hwp1 by ELISA was very similar to that observed by detecting antibodies to CAGT. Conclusion: An ELISA test to detect antibodies against a recombinant N-terminal fragment of the C. albicans germ tube cell wall antigen Hwp1 allows the diagnosis of invasive candidiasis with similar results to those obtained by detecting antibodies to CAGT but without the need of treating the sera to adsorb the antibodies against the cell wall surface of the blastospore.

Climate change adaptation and planning: An example from Kailua Beach, Oahu, Hawaii

The University of Hawaii Sea Grant College Program (UHSG) in partnership with the Hawaii Department of Land and Natural Resources (DLNR), Office of Conservation and Coastal Lands (OCCL) is developing a beach and dune management plan for Kailua Beach on the eastern shoreline of Oahu. The objective of the plan is to develop a comprehensive beach management and land use development plan for Kailua Beach that reflects the state of scientific understanding of beach processes in Kailua Bay and abutting shoreline areas and is intended to provide long-term recommendations to adapting to climate change including potential coastal hazards such as sea level rise. The development of the plan has lead to wider recognition of the significance of projected sea level rise to the region and provides the rational behind some of the land use conservation strategies. The plan takes on a critical light given global predictions for continued, possibly accelerated, sea-level rise and the ongoing focus of intense development along the Hawaiian shoreline. Hawaii’s coastal resource managers are faced with the daunting prospect of managing the effects of erosion while simultaneously monitoring and regulating high-risk coastal development that often impacts the shoreline. The beach and dune preservation plan is the first step in a more comprehensive effort prepare for and adapt to sea level rise and ensure the preservation of the beach and dune ecosystem for the benefit of present and future generations. The Kailua Beach and Dune Management plan is intended to be the first in a series of regional plans in Hawaii to address climate change adaptation through land use planning. (PDF contains 3 pages)

Reforming state-level coastal management and development policies: strategic retreat as an innovative, proactive and equitable coastal environmental management strategy

Atlantic and Gulf Coast shorelines include some of the most unique and biologically rich ecosystems in the United States that provide immeasurable aesthetic, habitat and economic benefits. Natural coastal ecosystems, however, are under increasing threat from rampant and irresponsible growth and development. Once a boon to local economies, complex natural forces – enhanced by global climate change and sea level rise - are now considered hazards and eroding the very foundation upon which coastal development is based. For nearly a century, beach restoration and erosion control structures have been used to artificially stabilize shorelines in an effort to protect structures and infrastructure. Beach restoration, the import and emplacement of sand on an eroding beach, is expensive, unpredictable, inefficient and may result in long-term environmental impacts. The detrimental environmental impacts of erosion control structures such as sea walls, groins, bulkheads and revetments include sediment deficits, accelerated erosion and beach loss. These and other traditional responses to coastal erosion and storm impacts- along with archaic federal and state policies, subsidies and development incentives - are costly, encourage risky development, artificially increase property values of high-risk or environmentally sensitive properties, reduce the post-storm resilience of shorelines, damage coastal ecosystems and are becoming increasingly unsustainable. Although communities, coastal managers and property owners face increasingly complex and difficult challenges, there is an emerging public, social and political awareness that, without meaningful policy reforms, coastal ecosystems and economies are in jeopardy. Strategic retreat is a sustainable, interdisciplinary management strategy that supports the proactive, planned removal of vulnerable coastal development; reduces risk; increases shoreline resiliency and ensures long term protection of coastal systems. Public policies and management strategies that can overcome common economic misperceptions and promote the removal of vulnerable development will provide state and local policy makers and coastal managers with an effective management tool that concomitantly addresses the economic, environmental, legal and political issues along developed shorelines. (PDF contains 4 pages)

Reforming state-level coastal management and development policies: strategic retreat as an innovative, proactive and equitable coastal environmental management strategy

Atlantic and Gulf Coast shorelines include some of the most unique and biologically rich ecosystems in the United States that provide immeasurable aesthetic, habitat and economic benefits. Natural coastal ecosystems, however, are under increasing threat from rampant and irresponsible growth and development. Once a boon to local economies, complex natural forces – enhanced by global climate change and sea level rise - are now considered hazards and eroding the very foundation upon which coastal development is based. For nearly a century, beach restoration and erosion control structures have been used to artificially stabilize shorelines in an effort to protect structures and infrastructure. Beach restoration, the import and emplacement of sand on an eroding beach, is expensive, unpredictable, inefficient and may result in long-term environmental impacts. The detrimental environmental impacts of erosion control structures such as sea walls, groins, bulkheads and revetments include sediment deficits, accelerated erosion and beach loss. These and other traditional responses to coastal erosion and storm impacts- along with archaic federal and state policies, subsidies and development incentives - are costly, encourage risky development, artificially increase property values of high-risk or environmentally sensitive properties, reduce the post-storm resilience of shorelines, damage coastal ecosystems and are becoming increasingly unsustainable. Although communities, coastal managers and property owners face increasingly complex and difficult challenges, there is an emerging public, social and political awareness that, without meaningful policy reforms, coastal ecosystems and economies are in jeopardy. Strategic retreat is a sustainable, interdisciplinary management strategy that supports the proactive, planned removal of vulnerable coastal development; reduces risk; increases shoreline resiliency and ensures long term protection of coastal systems. Public policies and management strategies that can overcome common economic misperceptions and promote the removal of vulnerable development will provide state and local policy makers and coastal managers with an effective management tool that concomitantly addresses the economic, environmental, legal and political issues along developed shorelines. (PDF contains 4 pages)