Possible new ways in the pharmacological treatment of bipolar disorder and comorbid alcoholism.

Possible new ways in the pharmacological treatment of bipolar disorder and comorbid alcoholism. Azorin JM, Bowden CL, Garay RP, Perugi G, Vieta E, Young AH. Source Department of Psychiatry, CHU Sainte Marguerite, Marseilles, France. Abstract About half of all bipolar patients have an alcohol abuse problem at some point of their lifetime. However, only one randomized, controlled trial of pharmacotherapy (valproate) in this patient population was published as of 2006. Therefore, we reviewed clinical trials in this indication of the last four years (using mood stabilizers, atypical antipsychotics, and other drugs). Priority was given to randomized trials, comparing drugs with placebo or active comparator. Published studies were found through systematic database search (PubMed, Scirus, EMBASE, Cochrane Library, Science Direct). In these last four years, the only randomized, clinically relevant study in bipolar patients with comorbid alcoholism is that of Brown and colleagues (2008) showing that quetiapine therapy decreased depressive symptoms in the early weeks of use, without modifying alcohol use. Several other open-label trials have been generally positive and support the efficacy and tolerability of agents from different classes in this patient population. Valproate efficacy to reduce excessive alcohol consumption in bipolar patients was confirmed and new controlled studies revealed its therapeutic benefit to prevent relapse in newly abstinent alcoholics and to improve alcohol hallucinosis. Topiramate deserves to be investigated in bipolar patients with comorbid alcoholism since this compound effectively improves physical health and quality of life of alcohol-dependent individuals. In conclusion, randomized, controlled research is still needed to provide guidelines for possible use of valproate and other agents in patients with a dual diagnosis of bipolar disorder and substance abuse or dependence.

Influència de la música sobre l'atenció humana: especial a la metodologia d'anàlisi, tot combinant metodologia quantitavia amb qualitativa (mix method)

Projecte de recerca elaborat a partir d’una estada a la University of Calgary, Canadà, entre desembre del 2007 i febrer del 2008. El projecte ha consistit en l'anàlisi de les dades d'una recerca en el camp de la psicologia de la música, concretament en com influeix la música en l'atenció a través de les vies dels estats emocionals i enèrgics de la persona. Per a la recerca es feu ús de videu en les sessions, obtenint dades visuals i auditives per a complementar les dades de tipus quantitatiu provinents dels resultats d'uns tests d'atenció subministrats. L'anàlisi es realitzà segons mètodes i tècniques de caràcter qualitatiu, apresos durant l'estada. Així mateix també s'ha aprofundit en la comprensió del paradigma qualitatiu com a paradigma vàlid i realment complementari del paradigma qualitatiu. S'ha focalitzat especialment en l'anàlisi de la conversa des d'un punt de vista interpretatiu així com l'anàlisi de llenguatge corporal i facial a partir de l'observació de videu, tot formulant descriptors i subdescriptors de la conducta que està relacionada amb la hipòtesis. Alguns descriptors havien estat formulats prèviament a l’anàlisi, en base a altres investigacions i al background de la investigadora; altres s’han anat descobrint durant l’anàlisi. Els descriptors i subdescriptors de la conducta estan relacionats amb l'intent dels estats anímics i enèrgics dels diferents participants. L'anàlisi s'ha realitzat com un estudi de casos, fent un anàlisi exhaustiu persona per persona amb l'objectiu de trobar patrons de reacció intrapersonals i intrapersonals. Els patrons observats s'utilitzaran com a contrast amb la informació quantitativa, tot realitzant triangulació amb les dades per trobar-ne possibles recolzaments o contradiccions entre sí. Els resultats preliminars indiquen relació entre el tipus de música i el comportament, sent que la música d'emotivitat negativa està associada a un tancament de la persona, però quan la música és enèrgica els participants s'activen (conductualment observat) i somriuen si aquesta és positiva.

Distribution of events of positive selection and population differentiation in a metabolic pathway: the case of asparagine N-glycosylation

Background: Asparagine N-Glycosylation is one of the most important forms of protein post-translational modification in eukaryotes. This metabolic pathway can be subdivided into two parts: an upstream sub-pathway required for achieving proper folding for most of the proteins synthesized in the secretory pathway, and a downstream sub-pathway required to give variability to trans-membrane proteins, and involved in adaptation to the environment andinnate immunity. Here we analyze the nucleotide variability of the genes of this pathway in human populations, identifying which genes show greater population differentiation and which genes show signatures of recent positive selection. We also compare how these signals are distributed between the upstream and the downstream parts of the pathway, with the aim of exploring how forces of population differentiation and positive selection vary among genes involved in the same metabolic pathway but subject to different functional constraints. Results:Our results show that genes in the downstream part of the pathway are more likely to show a signature of population differentiation, while events of positive selection are equally distributed among the two parts of the pathway. Moreover, events of positive selection arefrequent on genes that are known to be at bifurcation points, and that are identified as beingin key position by a network-level analysis such as MGAT3 and GCS1.Conclusions: These findings indicate that the upstream part of the Asparagine N-Glycosylation pathway has lower diversity among populations, while the downstream part is freer to tolerate diversity among populations. Moreover, the distribution of signatures of population differentiation and positive selection can change between parts of a pathway, especially between parts that are exposed to different functional constraints. Our results support the hypothesis that genes involved in constitutive processes can be expected to show lower population differentiation, while genes involved in traits related to the environment should show higher variability. Taken together, this work broadens our knowledge on how events of population differentiation and of positive selection are distributed among different parts of a metabolic pathway.

The risk of divorce and household saving behavior

We analyze the impact of an increase in the risk of divorce on the savingbehaviour of married couples. From a theoretical perspective, the expected sign of theeffect is ambiguous. We take advantage of the legalization of divorce in Ireland in 1996as an exogenous increase in the likelihood of marital dissolution. We analyze the savingbehaviour over time of couples who were married before the law was passed. We proposea difference-in-differences approach where we use as comparison groups either marriedcouples in other European countries (not affected by the law change), or Irish familieswho did not experience a significant increase in the expected risk of divorce (such as veryreligious families, or single individuals). Our results suggest that the increase in the riskof divorce brought about by the law was followed by an increase in the propensity to saveof married couples, consistent with a rise in precautionary savings interpretation. Anincrease in the risk of marital dissolution of about 40 percent led to a 7 to 13 percent risein the proportion of married couples reporting positive savings.

A positive theory of geographic mobility and social insurance

This paper presents a tractable dynamic general equilibrium model thatcan explain cross-country empirical regularities in geographical mobility,unemployment and labor market institutions. Rational agents vote overunemployment insurance (UI), taking the dynamic distortionary effects ofinsurance on the performance of the labor market into consideration.Agents with higher cost of moving, i.e., more attached to their currentlocation, prefer more generous UI. The key assumption is that an agent'sattachment to a location increases the longer she has resided there. UIreduces the incentive for labor mobility and increases, therefore, thefraction of attached agents and the political support for UI. The mainresult is that this self-reinforcing mechanism can give rise to multiplesteady-states-one 'European' steady-state featuring high unemployment,low geographical mobility and high unemployment insurance, and one'American' steady-state featuring low unemployment, high mobility andlow unemployment insurance.

Hypocretins regulate the anxiogenic-like effects of nicotine and induce reinstatement of nicotine-seeking behavior

Emerging evidence suggests that the hypocretinergic system is involved in addictive behavior. In this study, we investigated the role of these hypothalamic neuropeptides in anxiety-like responses of nicotine and stress-induced reinstatement of nicotine-seeking behavior. Acute nicotine (0.8 mg/kg, s.c.) induced anxiogenic-like effects in the elevated plus-maze and activated the paraventricular nucleus of thehypothalamus (PVN) as revealed by c-Fos expression. Pretreatment with the hypocretin receptor 1 (Hcrtr-1) antagonist SB334867 orpreprohypocretin gene deletion blocked both nicotine effects. In the PVN, SB334867 also prevented the activation of corticotrophinreleasing factor (CRF) and arginine-vasopressin (AVP) neurons, which expressed Hcrtr-1. In addition, an increase of the percentage of c-Fos-positive hypocretin cells in the perifornical and dorsomedial hypothalamic (PFA/DMH) areas was found after nicotine (0.8 mg/kg,s.c.) administration. Intracerebroventricular infusion of hypocretin-1 (Hcrt-1) (0.75 nmol/1 l) or footshock stress reinstated a previouslyextinguished nicotine-seeking behavior. The effects of Hcrt-1 were blocked by SB334867, but not by the CRF1 receptor antagonistantalarmin. Moreover, SB334867 did not block CRF-dependent footshock-induced reinstatement of nicotine-seeking while antalarmin was effective in preventing this nicotine motivational response. Therefore, the Hcrt system interacts with CRF and AVP neurons in the PVN and modulates the anxiogenic-like effects of nicotine whereas Hcrt and CRF play a different role in the reinstatement of nicotineseeking.Indeed, Hcrt-1 reinstates nicotine-seeking through a mechanism independent of CRF activation whereas CRF mediates the reinstatement induced by stress.

Distribution of events of positive selection and population differentiation in a metabolic pathway: the case of asparagine N-glycosylation

Asparagine N-Glycosylation is one of the most important forms of protein post-translational modification in eukaryotes. This metabolic pathway can be subdivided into two parts: an upstream sub-pathway required for achieving proper folding for most of the proteins synthesized in the secretory pathway, and a downstream sub-pathway required to give variability to trans-membrane proteins, and involved in adaptation to the environment and innate immunity. Here we analyze the nucleotide variability of the genes of this pathway in human populations, identifying which genes show greater population differentiation and which genes show signatures of recent positive selection. We also compare how these signals are distributed between the upstream and the downstream parts of the pathway, with the aim of exploring how forces of population differentiation and positive selection vary among genes involved in the same metabolic pathway but subject to different functional constraints. Our results show that genes in the downstream part of the pathway are more likely to show a signature of population differentiation, while events of positive selection are equally distributed among the two parts of the pathway. Moreover, events of positive selection are frequent on genes that are known to be at bifurcation points, and that are identified as being in key position by a network-level analysis such as MGAT3 and GCS1. These findings indicate that the upstream part of the Asparagine N-Glycosylation pathway has lower diversity among populations, while the downstream part is freer to tolerate diversity among populations. Moreover, the distribution of signatures of population differentiation and positive selection can change between parts of a pathway, especially between parts that are exposed to different functional constraints. Our results support the hypothesis that genes involved in constitutive processes can be expected to show lower population differentiation, while genes involved in traits related to the environment should show higher variability. Taken together, this work broadens our knowledge on how events of population differentiation and of positive selection are distributed among different parts of a metabolic pathway.

Using a blog to create and support a Community of Inquiry in Secondary Education

Understanding how blogs can support collaborative learning is a vital concern for researchers and teachers. This paper explores how blogs may be used to support Secondary Education students’ collaborative interaction and how such an interaction process can promote the creation of a Community of Inquiry to enhance critical thinking and meaningful learning. We designed, implemented and evaluated a science case-based project in which fifteen secondary students participated. Students worked in the science blogging project during 4 months. We asked students to be collaboratively engaged in purposeful critical discourse and reflection in their blogs in order to solve collectively science challenges and construct meaning about topics related to Astronomy and Space Sciences. Through student comments posted in the blog, our findings showed that the blog environment afforded the construction of a Community of Inquiry and therefore the creation of an effective online collaborative learning community. In student blog comments, the three presences for collaborative learning took place: cognitive, social, and teaching presence. Moreover, our research found a positive correlation among the three presences –cognitive, social and teaching– of the Community of Inquiry model with the level of learning obtained by the students. We discuss a series of issues that instructors should consider when blogs are incorporated into teaching and learning. We claim that embedded scaffolds to help students to argue and reason their comments in the blog are required to foster blog-supported collaborative learning.