Retinoid acid receptors in human colorectal cancer: An unexpected link with patient outcome.

International audienceThe status of the three retinoic acid receptors (RARs) α, β and γ in human colorectal cancer (CRC) has not as yet been examined. RARs are in part responsible for the actions of the retinoids (vitamin A and its derivatives), which are essential for human health and survival due to their extensive involvement in numerous cellular processes, in particular in epithelial morphology. The present study examined the expression of the three RARs in CRC using immunohistochemical analysis of paraffin-embedded tissue sections. RAR expression in tumor (T) and adjacent non-tumor (NT) specimens from stage I (n=6), stage II (n=34), stage III (n=26) and stage IV (n=14) CRC patients was compared with that in normal mucous membranes (n=10) from control individuals. The findings were correlated with tumor grade, treatment response (progression during treatment, remission, chemoresistance) and survival as clinicopathological parameters. RARα and γ expression was decreased with CRC stage in the T tissues (P=0.016 and P=0.052, respectively), suggesting that they may be used as predictive markers. RARβ expression in the NT tissues was associated with a more favorable prognosis (P=0.04). These results provide important information on the tumor microenvironment (the area adjacent to tumor cells)

A review on gamma greenhouse as a chronic gamma irradiation facility for plant breeding and improvement program

The research on radiation induced mutation has been conducted as one of the promising method of plant breeding in Malaysia since 1980s. Nuclear Malaysia is leading research institute in Malaysia conducting plant mutation breeding research. Gamma Greenhouse facility located in Nuclear Malaysia is one of the irradiation facilities to serve as a chronic irradiation facility for inducing mutation in various organisms including plants, fungi and microbes. Chronic irradiation refers to the exposure of materials at a lower dose rate over a long period of time. Previous studies have shown that this type of irradiation can minimize radiation damages to living materials and produces a wider mutation spectrum, therefore is very useful for trait improvements in irradiated organisms. Experiments on induce mutation using Gamma Greenhouse facility for crop improvement program have been conducted since its first operation in 2009. Various plant species including ornamental and herbal plants, food crops and industrial crops have been irradiated to improve their traits such as higher yield and biomass, pest and disease tolerance, higher bioactive compounds, longer bloom time and many others. Most of these crop improvement programs were done through collaborations with other agencies in Malaysia such as universities, research institutes and government departments. A number of publications on crop improvement using Gamma Greenhouse have been published in local and international journals as well as seminar presentations at national and international levels. The outputs from induced mutation via chronic radiation using Gamma Greenhouse could be of great interest for plant breeders dealing with improvement and development of new cultivars. This paper discusses the activities and achievement in plant breeding and improvement using Gamma Greenhouse Facility in Malaysia

Use of high-plex data provides novel insights into the temporal artery processes of giant cell arteritis

ObjectiveTo identify the key coding genes underlying the biomarkers and pathways associated with giant cell arteritis (GCA), we performed an in situ spatial profiling of molecules involved in the temporal arteries of GCA patients and controls. Furthermore, we performed pharmacogenomic network analysis to identify potential treatment targets.MethodsUsing human formalin-fixed paraffin-embedded temporal artery biopsy samples (GCA, n = 9; controls, n = 7), we performed a whole transcriptome analysis using the NanoString GeoMx Digital Spatial Profiler. In total, 59 regions of interest were selected in the intima, media, adventitia, and perivascular adipose tissue (PVAT). Differentially expressed genes (DEGs) (fold-change > 2 or < −2, p-adjusted < 0.01) were compared across each layer to build a spatial and pharmacogenomic network and to explore the pathophysiological mechanisms of GCA.ResultsMost of the transcriptome (12,076 genes) was upregulated in GCA arteries, compared to control arteries. Among the screened genes, 282, 227, 40, and 5 DEGs were identified in the intima, media, adventitia, and PVAT, respectively. Genes involved in the immune process and vascular remodeling were upregulated within GCA temporal arteries but differed across the arterial layers. The immune-related functions and vascular remodeling were limited to the intima and media.ConclusionThis study is the first to perform an in situ spatial profiling characterization of the molecules involved in GCA. The pharmacogenomic network analysis identified potential target genes for approved and novel immunotherapies

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Fine-Tuning Roles of Endogenous Brain-Derived Neurotrophic Factor, TrkB and Sortilin in Colorectal Cancer Cell Survival

International audienceBACKGROUND: Neurotrophin receptors were initially identified in neural cells. They were recently detected in some cancers in association with invasiveness, but the function of these tyrosine kinase receptors was not previously investigated in colorectal cancer (CRC) cells. METHODS AND FINDINGS: We report herein that human CRC cell lines synthesize the neural growth factor Brain-derived neurotrophic factor (BDNF) under stress conditions (serum starvation). In parallel, CRC cells expressed high- (TrkB) and low-affinity (p75(NTR)) receptors at the plasma membrane, whereas TrkA and TrkC, two other high affinity receptors for NGF and NT-3, respectively, were undetectable. We demonstrate that BDNF induced cell proliferation and had an anti-apoptotic effect mediated through TrkB, as assessed by K252a, a Trk pharmacologic inhibitor. It suppressed both cell proliferation and survival of CRC cells that do not express TrkA nor TrkC. In parallel to the increase of BDNF secretion, sortilin, a protein acting as a neurotrophin transporter as well as a co-receptor for p75(NTR), was increased in the cytoplasm of primary and metastatic CRC cells, which suggests that sortilin could regulate neurotrophin transport in these cells. However, pro-BDNF, also detected in CRC cells, was co-expressed with p75(NTR) at the cell membrane and co-localized with sortilin. In contrast to BDNF, exogenous pro-BDNF induced CRC apoptosis, which suggests that a counterbalance mechanism is involved in the control of CRC cell survival, through sortilin as the co-receptor for p75(NTR), the high affinity receptor for pro-neurotrophins. Likewise, we show that BDNF and TrkB transcripts (and not p75(NTR)) are overexpressed in the patients' tumors by comparison with their adjacent normal tissues, notably in advanced stages of CRC. CONCLUSION: Taken together, these results highlight that BDNF and TrkB are essential for CRC cell growth and survival in vitro and in tumors. This autocrine loop could be of major importance to define new targeted therapies

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Proposal and development of a research program on the effectiveness of communication registers in the fight against climate change : the case of low carbon consumption

Cette recherche s’intéresse à l’efficacité des registres communicationnels actuels dans une perspective de mobilisation des consommateurs dans la sobriété carbone. Afin d’examiner l’efficacité de ces registres, quatre études ont été menées, i.e. une « méthode-Q » et trois expérimentations. Les deux premières études visent à explorer le rôle des représentations visuelles (i.e. images) et linguistiques (i.e. contenus sémantiques) utilisées pour désigner le changement climatique dans la transmission des préoccupations, des perceptions et des intentions envers la décarbonisation. La troisième étude cherche à expliquer l’effet de l’exploitation de la saillance de mortalité dans ces registres (i.e., anxiogènes vs. informatives) sur les choix de consommation pro-environnementaux (vs. pro-matérialistes). La dernière étude cherche à confirmer qu’une saillance de mortalité, quel que soit son origine (e.g. le changement climatique ou les attaques terroristes) est générateur en majorité des choix de consommation pro-matérialistes (vs. pro-environnementaux). En s’appuyant sur les résultats des ces études, nous mettons en lumière, tout d’abord, la nécessité de modifier ces registres afin de réduire leurs effets négatifs et/ou contreproductifs. Ensuite, la nécessité d’adopter une stratégie de segmentation de la communication selon la vision culturelle du monde dominante des individus pour les engager dans une lutte effective contre le changement climatique.This research focuses on the effectiveness of climate change communications in order to engage the consumer behaviour in carbon sobriety. To examine this effectiveness, four studies were carried out, i.e., a “Q-method” research and three experiments. The first two studies aim to explore the role of visual representation of climate change and semantic expressions, used to describe this phenomenon in conveying perceptions and attitudes towards decarbonisation. The third study aims to explain the impact of the type of communication (anxiety induced vs. informative) on consumption choices (pro-materialistic vs. pro-environmental). The last study seeks to confirm that mortality salience, whatever its origin is (e.g., climate change or terrorist attacks), generates mostly pro-materialistic consumption choices (vs. pro-environmental). Based on the results of these studies, we highlight, firstly, the necessity to modify these registers in order to reduce their negative and/or counterproductive effects. Secondly, the necessity to adopt a segmentation strategy of communication according to the cultural worldviews of individuals to engage them in an effective fight against the climate changes

Étude de facteurs apoptiques et neurotrophiques dans le cancer colorectal

Le but de cette étude était de rechercher des marqueurs cellulaires et tissulaires prédictifs de gravité dans le cancer colorectal (CCR). A l'aide d'une cohorte de 82 patients, nous avons étudié l'expression de diverses protéines impliquées dans la signalisation apoptique. Seules les expressions de le DR5 ont été significativement corrélées aux stades avancés (article 1). De plus, les expressions de l'AIF et de la caspase-3 clivée sont corrélées à l'âge des patients (article 2). Dans une autre partie, l'expression des neurotrophines (NTs) a été étudiée dans les CCR. En condition basale, notre étude a mis en évidence la présence des NTs (NGF, BDNF et NT3) et leurs récepteurs (TrkB et p75ntr) au sein d'un panel de lignées cellulaires de CCR. La privation sérique induit la sélection du BDNF conjointement à l'expresion membranaire de ses deux récepteurs. A l'aide d'anticorps neutralisants, le rôle du BDNF comme facteur autocrine de survie a été démontré. Nous avons également mis en évidence l'effet anti-apoptique et prolifératif du BDNF qui passe par son récepteur TrkB via l'activation de la voie PI3K/Akt. En revanche, le BDNF immature induit l'apoptose dans ces lignées. Enfin, l'expression du BDNF et de ses récepteurs a été confirmée avec des tissus issus de patients atteints de CCR à différents stades. En effet, nous avons montré une présence plus importante des transcrits de BDNF et de TrkB dans les tissus tumoraux que dans les tissus non tumoraux. En conclusion, nos résultats montrent pour la première fois le rôle de l'axe BDNF/TrkB comme une voie autocrine de survie dans les cellules du CCR (article3).LIMOGES-BU Médecine pharmacie (870852108) / SudocSudocFranceF

Global warming', ' climatic change' or 'climate imbalance' ? An experimental study on the effectiveness of climate change semantic expressions and imagery

Prix de la meilleure communicationInternational audienceThis paper is intended to explain the impact of visual and linguistic communications related to climate change, as employed in the media, on perceptions and attitudes towards decarbonisation. An experimental study based on approaches using collage and linguistic semantics is conducted in order to assess the effectiveness of climate change communication on French behaviour (sample size N = 126). Our findings show that only a small percentage of consumers are actually focused on alternative imaginaries of consumption. Climate change communication serves to activate concerns and perceptions about the causes and consequences of climate change more than the specific solutions and intentions to decarbonise. Broad differences are also found in individuals' responses with regard to their perception, self-efficacy and sensitivity specific to this issue. Mitigating the effects of climate change implies a new communication strategy. The stakeholders (governments, NGOs, corporations, etc.) would need to address this phenomenon optimistically, by promoting solution discourses for disaster scenarios and segmenting their communications. In contrast however, apathetic behaviour continues to spread despite multiple warnings pointing to its tragic consequences. The literature lacks substantial knowledge of the causes and consequences due to the failure of climate change communication campaigns to influence consumer behaviour. This study demonstrates that climate change is not just a political or socio-economic issue, but also a marketing problem that generates consumer barriers to decarbonisation