Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition.

BACKGROUND ErbB2-positive breast cancer is characterized by highly aggressive phenotypes and reduced responsiveness to standard therapies. Although specific ErbB2-targeted therapies have been designed, only a small percentage of patients respond to these treatments and most of them eventually relapse. The existence of this population of particularly aggressive and non-responding or relapsing patients urges the search for novel therapies. The purpose of this study was to determine whether cannabinoids might constitute a new therapeutic tool for the treatment of ErbB2-positive breast tumors. We analyzed their antitumor potential in a well established and clinically relevant model of ErbB2-driven metastatic breast cancer: the MMTV-neu mouse. We also analyzed the expression of cannabinoid targets in a series of 87 human breast tumors. RESULTS Our results show that both Delta9-tetrahydrocannabinol, the most abundant and potent cannabinoid in marijuana, and JWH-133, a non-psychotropic CB2 receptor-selective agonist, reduce tumor growth, tumor number, and the amount/severity of lung metastases in MMTV-neu mice. Histological analyses of the tumors revealed that cannabinoids inhibit cancer cell proliferation, induce cancer cell apoptosis, and impair tumor angiogenesis. Cannabinoid antitumoral action relies, at least partially, on the inhibition of the pro-tumorigenic Akt pathway. We also found that 91% of ErbB2-positive tumors express the non-psychotropic cannabinoid receptor CB2. CONCLUSIONS Taken together, these results provide a strong preclinical evidence for the use of cannabinoid-based therapies for the management of ErbB2-positive breast cancer.

Modulation of the Endocannabinoids N-Arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) on Executive Functions in Humans.

Animal studies point to an implication of the endocannabinoid system on executive functions. In humans, several studies have suggested an association between acute or chronic use of exogenous cannabinoids (Δ9-tetrahydrocannabinol) and executive impairments. However, to date, no published reports establish the relationship between endocannabinoids, as biomarkers of the cannabinoid neurotransmission system, and executive functioning in humans. The aim of the present study was to explore the association between circulating levels of plasma endocannabinoids N-arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) and executive functions (decision making, response inhibition and cognitive flexibility) in healthy subjects. One hundred and fifty seven subjects were included and assessed with the Wisconsin Card Sorting Test; Stroop Color and Word Test; and Iowa Gambling Task. All participants were female, aged between 18 and 60 years and spoke Spanish as their first language. Results showed a negative correlation between 2-AG and cognitive flexibility performance (r = -.37; p<.05). A positive correlation was found between AEA concentrations and both cognitive flexibility (r = .59; p<.05) and decision making performance (r = .23; P<.05). There was no significant correlation between either 2-AG (r = -.17) or AEA (r = -.08) concentrations and inhibition response. These results show, in humans, a relevant modulation of the endocannabinoid system on prefrontal-dependent cognitive functioning. The present study might have significant implications for the underlying executive alterations described in some psychiatric disorders currently associated with endocannabinoids deregulation (namely drug abuse/dependence, depression, obesity and eating disorders). Understanding the neurobiology of their dysexecutive profile might certainly contribute to the development of new treatments and pharmacological approaches.

Nabil: un jove d'Aghbala a Girona

Anàlisi de la realitat dels joves marroquins nouvinguts, explicada des de la perspectiva d’un dels seus protagonistes. L’ús dels espais urbans al poble d’Aghbala i a la ciutat de Girona, i l’experiència vital a partir de la transcripció del Relat de Vida, són els dos recursos que reflecteixen el procés migratori i la curta biografia d’en Nabil

Ecoepidemiology, short history and control of Chagas disease in the endemic countries and the new challenge for non-endemic countries

Chagas disease is maintained in nature through the interchange of three cycles: the wild, peridomestic and domestic cycles. The wild cycle, which is enzootic, has existed for millions of years maintained between triatomines and wild mammals. Human infection was only detected in mummies from 4,000-9,000 years ago, before the discovery of the disease by Carlos Chagas in 1909. With the beginning of deforestation in the Americas, two-three centuries ago for the expansion of agriculture and livestock rearing, wild mammals, which had been the food source for triatomines, were removed and new food sources started to appear in peridomestic areas: chicken coops, corrals and pigsties. Some accidental human cases could also have occurred prior to the triatomines in peridomestic areas. Thus, triatomines progressively penetrated households and formed the domestic cycle of Chagas disease. A new epidemiological, economic and social problem has been created through the globalisation of Chagas disease, due to legal and illegal migration of individuals infected by Trypanosoma cruzi or presenting Chagas disease in its varied clinical forms, from endemic countries in Latin America to non-endemic countries in North America, Europe, Asia and Oceania, particularly to the United States of America and Spain. The main objective of the present paper was to present a general view of the interchanges between the wild, peridomestic and domestic cycles of the disease, the development of T. cruzi among triatomine, their domiciliation and control initiatives, the characteristics of the disease in countries in the Americas and the problem of migration to non-endemic countries.

Cannabis et conduite automobile [Cannabis and automobile driving]

Cannabis use has increased considerably during the last 15 years. One of the major problems dealing with cannabis use is driving under the influence of drugs. With the exception of ethyl alcohol, the majority of the epidemiological studies have shown that cannabis is the most frequently detected substance in people suspected of driving under the influence of drugs. Experimental studies are therefore needed to assess cannabis effects on driving capability. Many studies indicate that cannabis impairs psychomotor performance. This impairment becomes obvious when high doses of cannabis are taken, when ethyl alcohol or other drugs are simultaneously ingested, or when sustained attention is needed. Moreover, cannabis effects are qualitatively different from those observed after ethyl alcohol consumption. In forensic practice, cannabis impairment of driving performance must be related to cannabinoids blood concentrations. To facilitate the interpretation of cannabinoids blood levels, several models were set up recently. These models must be further improved in order to fit in with all circumstances of cannabis use.

Malaria in gold-mining areas in Colombia

Gold-mining may play an important role in the maintenance of malaria worldwide. Gold-mining, mostly illegal, has significantly expanded in Colombia during the last decade in areas with limited health care and disease prevention. We report a descriptive study that was carried out to determine the malaria prevalence in gold-mining areas of Colombia, using data from the public health surveillance system (National Health Institute) during the period 2010-2013. Gold-mining was more prevalent in the departments of Antioquia, Córdoba, Bolívar, Chocó, Nariño, Cauca, and Valle, which contributed 89.3% (270,753 cases) of the national malaria incidence from 2010-2013 and 31.6% of malaria cases were from mining areas. Mining regions, such as El Bagre, Zaragoza, and Segovia, in Antioquia, Puerto Libertador and Montelíbano, in Córdoba, and Buenaventura, in Valle del Cauca, were the most endemic areas. The annual parasite index (API) correlated with gold production (R2 0.82, p < 0.0001); for every 100 kg of gold produced, the API increased by 0.54 cases per 1,000 inhabitants. Lack of malaria control activities, together with high migration and proliferation of mosquito breeding sites, contribute to malaria in gold-mining regions. Specific control activities must be introduced to control this significant source of malaria in Colombia.

Inferring about individual drug and schizotypy effects on cognitive functioning in polydrug using mephedrone users before and after clubbing

Objective: Mephedrone has been recently made illegal in Europe, but little empirical evidence is available on its impact on human cognitive functions. We investigated acute and chronic effects of mephedrone consumption on drug-sensitive cognitive measures, while also accounting for the influence of associated additional drug use and personality features. Method: Twenty-six volunteers from the general population performed tasks measuring verbal learning, verbal fluency and cognitive flexibility before and after a potential drug-taking situation (pre- and post-clubbing at dance clubs, respectively). Participants also provided information on chronic and recent drug use, schizotypal (O-LIFE) and depressive symptoms (Beck depression inventory), sleep pattern and premorbid IQ. Results: We found that i) mephedrone users performed worse than non-users pre-clubbing, and deteriorated from the pre-clubbing to the post-clubbing assessment, ii) pre-clubbing cannabis and amphetamine (not mephedrone) use predicted relative cognitive attenuations, iii) post-clubbing, depression scores predicted relative cognitive attenuations, and iv) schizotypy was largely unrelated to cognitive functioning, apart from a negative relationship between cognitive disorganisation and verbal fluency. Conclusion: Results suggest that polydrug use and depressive symptoms in the general population negatively affect cognition. For schizotypy, only elevated cognitive disorganisation showed potential links to a pathological cognitive profile previously reported along the psychosis dimension.

False identity documents forensic profiling: study of known-sources and cross-border seizures

A forensic intelligence process was conducted over cross-border seizures of false identity documents whose sources were partly known to be the same. Visual features of 300 counterfeit Portuguese and French identity cards seized in France and Switzerland were observed and integrated in a structured database developed to detect and analyze forensic links. Based on a few batches of documents known to come from common sources, the forensic profiling method could be validated and its performance evaluated. The method also proved efficient and complementary to conventional means of detecting connections between cases. Cross-border links were detected, highlighting the need for more collaboration. Forensic intelligence could be produced, uncovering the structure of counterfeits' illegal trade, the concentration of their sources and the evolution of their quality over time. In addition, two case examples illustrated how forensic profiling may support specific investigations. The forensic intelligence process and its results will underline the need to develop such approaches to support the fight against fraudulent documents and organized crime.

The association between cigarettes smoking, cannabis use and alcohol consumption in a population of young men: results of a population-based survey.

BACKGROUND: Cigarette smoking is often initiated at a young age as well as other risky behaviors such as alcohol drinking, cannabis and other illicit drugs use. Some studies suggest that cigarette smoking may have an influence on other risky behaviors but little is known about the chronology of occurrence of those different habits. The aim of this study was to assess, by young men, what were the other risky behaviors associated with cigarette smoking and the joint prevalence and chronology of occurrence of those risky behaviors. METHODS: Cross-sectional analyses of a population-based census of 3526 young men attending the recruitment for the Swiss army, aged between 17 and 25 years old (mean age: 19 years old), who filled a self reported questionnaire about their alcohol, cigarettes, cannabis and other illicit drugs habits. Actual smoking was defined as either regular smoking (¡Ý1 cigarette/day, on every day) or occasional smoking, binge drinking as six or more drinks at least twice a month, at risk drinking as 21 drinks or more per week, recent cannabis use as cannabis consumption at least once during the last month, and use of illicit drugs as consumption once or more of illicit drugs other than cannabis. Age at begin was defined as age at first use of cannabis or cigarette smoking. RESULTS: In this population of young men, the prevalence of actual smoking was 51.2% (36.5% regular smoking, 14.6% occasionnal smoking). Two third of participamnts (60.1%) declared that they ever used cannabis, 25.2% reported a recent use of cannabis. 53.8% of participants had a risky alcohol consumption considered as either binge or at risk drinking. Cigarette smoking was significantly associated with recent cannabis use (Odds Ratio (OR): 3.85, 95% Confidence Interval (CI): 3.10- 4.77), binge drinking (OR: 3.48, 95% CI: 3.03-4.00), at risk alcohol drinking (OR: 4.04, 95% CI: 3.12-5.24), and ever use of illicit drugs (OR: 4.34, 95% CI: 3.54-5.31). In a multivariate logistic regression, odds ratios for smoking were increased for cannabis users (OR 3.10,, 95% CI: 2.48-3.88), binge drinkers (OR: 1.77, 95% CI: 1.44-2.17), at risk alcohol drinkers (OR 2.26, 95% CI: 1.52-3.36) and ever users of illicit drugs (OR: 1.56, 95% CI: 1.20-2.03). The majority of young men (57.3%) initiated smoking before cannabis and mean age at onset was 13.4 years old, whereas only 11.1% began to use cannabis before smoking cigarettes and mean age at onset was slightly older (14.4 years old). 31.6% started both cannabis and tobacco at the same age (15 years old). About a third of participants (30.5%) did have a cluster of risky behaviours (smoking, at risk drinking, cannabis use) and 11.0% did cumulate smoking, drinking, cannabis and ever use of illegal drugs. More than half of the smokers (59.6%) did cumulate cannabis use and at risk alcohol drinking whereas only 18.5% of non-smokers did. CONCLUSIONS: The majority of young smokers initiated their risky behaviors by first smoking and then by other psychoactive drugs. Smokers have an increased risk to present other risky behaviors such as cannabis use, at risk alcohol consumtion and illicit drug use compared to nonsmokers. Prevention by young male adults should focus on smoking and also integrate interventions on other risky behaviors.

Absence of delta-9-tetrahydrocannabinol dysphoric effects in dynorphin-deficient mice

The involvement of dynorphin on Delta-9-tetrahydrocannabinol (THC) and morphine responses has been investigated by using mice with a targeted inactivation of the prodynorphin (Pdyn) gene. Dynorphin-deficient mice show specific changes in the behavioral effects of THC, including a reduction of spinal THC analgesia and the absence of THC-induced conditioned place aversion. In contrast, acute and chronic opioid effects were normal. The lack of negative motivational effects of THC in the absence of dynorphin demonstrates that this endogenous opioid peptide mediates the dysphoric effects of marijuana.

The differentiation of fibre- and drug type Cannabis seedlings by gas chromatography/mass spectrometry and chemometric tools

Cannabis cultivation in order to produce drugs is forbidden in Switzerland. Thus, law enforcement authorities regularly ask forensic laboratories to determinate cannabis plant's chemotype from seized material in order to ascertain that the plantation is legal or not. As required by the EU official analysis protocol the THC rate of cannabis is measured from the flowers at maturity. When laboratories are confronted to seedlings, they have to lead the plant to maturity, meaning a time consuming and costly procedure. This study investigated the discrimination of fibre type from drug type Cannabis seedlings by analysing the compounds found in their leaves and using chemometrics tools. 11 legal varieties allowed by the Swiss Federal Office for Agriculture and 13 illegal ones were greenhouse grown and analysed using a gas chromatograph interfaced with a mass spectrometer. Compounds that show high discrimination capabilities in the seedlings have been identified and a support vector machines (SVMs) analysis was used to classify the cannabis samples. The overall set of samples shows a classification rate above 99% with false positive rates less than 2%. This model allows then discrimination between fibre and drug type Cannabis at an early stage of growth. Therefore it is not necessary to wait plants' maturity to quantify their amount of THC in order to determine their chemotype. This procedure could be used for the control of legal (fibre type) and illegal (drug type) Cannabis production.

Sexual dysfunctions among young men: prevalence and associated factors.

PURPOSE: The purposes of this study are to measure the prevalence of premature ejaculation (PE) and erectile dysfunction (ED) among a population of Swiss young men and to assess which factors are associated with these sexual dysfunctions in this age-group. METHODS: For each condition (PE and ED), we performed separate analyses comparing young men suffering from the condition with those who were not. Groups were compared for substance use (tobacco, alcohol, cannabis, other illegal drugs, and medication without a prescription), self-reported body mass index, sexual orientation, physical activity, professional activity, sexual experience (sexual life length and age at first intercourse), depression status, mental health, and physical health in a bivariate analysis. We then used a log-linear analysis to consider all significant variables simultaneously. RESULTS: Prevalence rates for PE and ED were 11% and 30%, respectively. Poor mental health was the only variable to have a direct association with both conditions after controlling for potential confounders. In addition, PE was directly associated with tobacco, illegal drugs, professional activity, and physical activity, whereas ED was directly linked with medication without a prescription, length of sexual life, and physical health. CONCLUSIONS: In Switzerland, one-third of young men suffer from at least one sexual dysfunction. Multiple health-compromising factors are associated with these dysfunctions. These should act as red flags for health professionals to encourage them to take any opportunity to talk about sexuality with their young male patients.

The externalisation of the asylum function in the European Union

This paper aims to identify and assess the main items in the strategy followed by the EU and its member states on the externalisation of their asylum function. First, it analyses the European harmonisation of the return to safe third countries and to countries of first asylum, which is carried out by means of readmission agreements. Second, it refers to the strategies defined by the Hague and the Stockholm programs concerning the External Aspects of the European Union Asylum Policy, on the detention centres for illegal immigrants abroad, and on the proposals for delocalisation of asylum applications processing centres beyond the EU borders. Finally, this paper considers whether the strategy of externalisation of the function of asylum sometimes lacks legitimacy, and to what extent there is a fair balance between the interests of the states and the protection of the human rights of refugees and asylum seekers.

Monitoring de la problématique du cannabis en Suisse : étude sentinelle : panels 2008

A l'heure actuelle, le monitoring de la problématique du cannabis en Suisse constitue un ensemble de travaux qui permettent le suivi de la situation au niveau national et qui sont mis en oeuvre par un consortium d'instituts. Ce monitoring comprend l'étude présentée dans ce rapport, l'étude sentinelle. Elle s'intéresse à l'évolution de la situation en matière de cannabis ainsi qu'à la gestion de cette situation au niveau local. Ainsi, les observations relevées par des professionnels de terrain dans différents domaines (santé/social, école/formation professionnelle, police/justice) et dans quatre cantons suisses (St Gall, Tessin, Vaud, Zurich), dits "sentinelle", sont récoltées et analysées annuellement. [P. 5]

Elokuvien levittäminen Internetissä

Movie distribution on the Internet has become more common in recent years along with fast broadband internet connections. The problem so far has been that the greatest part of movie distribution on the Internet has been illegal. This is about to change because the major film distributors are finally starting to rent and sell movies more and more on the Internet due to their growing confidence in new copy protection methods. The importance of movie online distribution to the movie industry is still tiny but it is increasing rapidly as is investing in new business models and distribution methods in the USA and Europe. This thesis examines the basic concepts of online movie distribution, such as distribution techniques and copy protection, the main companies that rent and sell movies on the internet and their business models, the effects of movie piracy and non-commercial distribution channels. The intention was to provide the reader with an overview of different aspects of movie distribution on the Internet and its future. The conclusion was that movie distribution on the Internet will play a bigger financial part in the future although it was still too early to say just how significant that will be. We will probably see many corresponding distribution techniques, like peer-to-peer networks and streaming servers distributing and broadcasting movies to different end-user platforms like television, PC and portable media players. Internet distribution of movies will not revolutionize movie distribution in the next couple of years but it will make possible new efficient and inexpensive ways to distribute movies globally which will in turn increase the possibilities for revenue, especially for small independent movie producers and distributors.