Clinical management and burden of bipolar disorder: a multinational longitudinal study (WAVE-bd Study)

BACKGROUND: Studies in bipolar disorder (BD) to date are limited in their ability to provide a whole-disease perspective--their scope has generally been confined to a single disease phase and/or a specific treatment. Moreover, most clinical trials have focused on the manic phase of disease, and not on depression, which is associated with the greatest disease burden. There are few longitudinal studies covering both types of patients with BD (I and II) and the whole course of the disease, regardless of patients' symptomatology. Therefore, the Wide AmbispectiVE study of the clinical management and burden of Bipolar Disorder (WAVE-bd) (NCT01062607) aims to provide reliable information on the management of patients with BD in daily clinical practice. It also seeks to determine factors influencing clinical outcomes and resource use in relation to the management of BD. METHODS: WAVE-bd is a multinational, multicentre, non-interventional, longitudinal study. Approximately 3000 patients diagnosed with BD type I or II with at least one mood event in the preceding 12 months were recruited at centres in Austria, Belgium, Brazil, France, Germany, Portugal, Romania, Turkey, Ukraine and Venezuela. Site selection methodology aimed to provide a balanced cross-section of patients cared for by different types of providers of medical aid (e.g. academic hospitals, private practices) in each country. Target recruitment percentages were derived either from scientific publications or from expert panels in each participating country. The minimum follow-up period will be 12 months, with a maximum of 27 months, taking into account the retrospective and the prospective parts of the study. Data on demographics, diagnosis, medical history, clinical management, clinical and functional outcomes (CGI-BP and FAST scales), adherence to treatment (DAI-10 scale and Medication Possession Ratio), quality of life (EQ-5D scale), healthcare resources, and caregiver burden (BAS scale) will be collected. Descriptive analysis with common statistics will be performed. DISCUSSION: This study will provide detailed descriptions of the management of BD in different countries, particularly in terms of clinical outcomes and resources used. Thus, it should provide psychiatrists with reliable and up-to-date information about those factors associated with different management patterns of BD. TRIAL REGISTRATION NO: ClinicalTrials.gov: NCT01062607.

Easy introduction of maleimides at different positions of oligonucleotide chains for conjugation purposes

[2,5-Dimethylfuran]-protected maleimides were placed at both internal positions and the 3'-end of oligonucleotides making use of solid-phase synthesis procedures. A new phosphoramidite derivative and a new solid support incorporating the protected maleimide moiety were prepared for this purpose. In all cases maleimide deprotection (retro-Diels-Alder reaction) followed by reaction with thiol-containing compounds afforded the target conjugate.

The role of counterions in the membrane-disruptive properties of pH-sensitive lysine-based surfactants

Surfactants are among the most versatile and widely used excipients in pharmaceuticals. This versatility, together with their pH-responsive membrane-disruptive activity and low toxicity, could also enable their potential application in drug delivery systems. Five anionic lysine-based surfactants which differ in the nature of their counterion were studied. Their capacity to disrupt the cell membrane was examined under a range of pH values, concentrations and incubation times, using a standard hemolysis assay as a model for endosomal membranes. The surfactants showed pH-sensitive hemolytic activity and improved kinetics at the endosomal pH range. Low concentrations resulted in negligible hemolysis at physiological pH and high membrane lytic activity at pH 5.4, which is in the range characteristic of late endosomes. With increasing concentration, the surfactants showed an enhanced capacity to lyse cell membranes, and also caused significant membrane disruption at physiological pH. This observation indicates that, at high concentrations, surfactant behavior is independent of pH. The mechanism of surfactant-mediated membrane destabilization was addressed, and scanning electron microscopy studies were also performed to evaluate the effects of the compounds on erythrocyte morphology as a function of pH. The in vitro cytotoxicity of the surfactants was assessed by MTT and NRU assays with the 3T3 cell line. The influence of different types of counterion on hemolytic activity and the potential applications of these surfactants in drug delivery are discussed. The possibility of using pH-sensitive surfactants for endosome disruption could hold great promise for intracellular drug delivery systems in future therapeutic applications.

Sciatic and femoral nerve sensory neurones occupy different regions of the L4 dorsal root ganglion in the adult rat.

The topographical distribution of sciatic and femoral nerve sensory neuronal somata in the L4 dorsal root ganglion of the adult rat was mapped after retrograde tracing with one or two of the dyes Fast Blue, Fluoro-Gold, or Diamidino Yellow. The tracers were applied to the proximal transected end of either nerve alone, or from both nerves in the same animal using separate tracers. Three-dimensional reconstructions of the distribution of labelled neurones were made from serial sections of the L4 dorsal root ganglion which is the only ganglion that these two nerves share. The results showed that with little overlap, femoral nerve neurones distribute dorsally and rostrally whereas sciatic nerve neurones distribute medially and ventrally. This finding indicates the existence of a somatotopical organisation for the representation of different peripheral nerves in dorsal root ganglia of adult animals.

On the existence and function of galanin receptor heteromers in the central nervous system

Galanin receptor (GalR) subtypes 1-3 linked to central galanin neurons may form heteromers with each other and other types of G protein-coupled receptors in the central nervous system (CNS). These heteromers may be one molecular mechanism for galanin peptides and their N-terminal fragments (gal 1-15) to modulate the function of different types of glia-neuronal networks in the CNS, especially the emotional and the cardiovascular networks. GalR-5-HT1A heteromers likely exist with antagonistic GalR-5-HT1A receptor-receptor interactions in the ascending midbrain raphe 5-HT neuron systems and their target regions. They represent a novel target for antidepressant drugs. Evidence is given for the existence of GalR1-5-HT1A heteromers in cellular models with trans-inhibition of the protomer signaling. A GalR1-GalR2 heteromer is proposed to be a galanin N-terminal fragment preferring receptor (1-15) in the CNS. Furthermore, a GalR1-GalR2-5-HT1A heterotrimer is postulated to explain why only galanin (1-15) but not galanin (1-29) can antagonistically modulate the 5-HT1A receptors in the dorsal hippocampus rich in gal fragment binding sites. The results underline a putative role of different types of GalR-5-HT1A heteroreceptor complexes in depression. GalR antagonists may also have therapeutic actions in depression by blocking the antagonistic GalR-NPYY1 receptor interactions in putative GalR-NPYY1 receptor heteromers in the CNS resulting in increases in NPYY1 transmission and antidepressant effects. In contrast the galanin fragment receptor (a postulated GalR1-GalR2 heteromer) appears to be linked to the NPYY2 receptor enhancing the affinity of the NPYY2 binding sites in a putative GalR1-GalR2-NPYY2 heterotrimer. Finally, putative GalR-α2-adrenoreceptor heteromers with antagonistic receptor-receptor interactions may be a widespread mechanism in the CNS for integration of galanin and noradrenaline signals also of likely relevance for depression

Analysis of the antibiotic prophylaxis prescribed by Spanish oral surgeons

Aim: To identify prophylactic antibiotic prescription practices among Spanish dentists with preferential dedication to Oral Surgery in different types of tooth extraction surgeries. Method: Members of the Spanish Oral Surgery Society were surveyed on antibiotic prophylaxis use in 4 different tooth extraction modalities scaled according to their surgical invasiveness. Results: Sixty-nine of the 105 distributed questionnaires were returned completed. Thirteen percent of the surveyed surgeons would prescribe antibiotics to prevent postoperative wound infection when confronted with conventional tooth extraction lasting less than 5 minutes. In the case of surgery lasting more than 5 minutes, the percentage of participants that would prescribe antibiotics increased to 39%. When a mucoperiosteal flap was elevated or an ostectomy was performed, 87% and 100%, respectively, would prescribe antibiotic prophylaxis. Amoxicillin and its combination with clavulanic acid were the most commonly prescribed antibiotics. All participants would prescribe the antibiotic orally, starting after surgery and with a duration that ranged from 2-8 days. Conclusions: The results obtained suggest that antibiotic prophylaxis for preventing local odontogenic infection is not being correctly implemented in Spain. This can generate new bacterial resistances, facilitate adverse drug reactions and favor opportunistic infections. Better designed studies are needed in order to clarify the role of antibiotics in the prevention of postsurgical wound infection

Use of amitriptyline for the treatment of chronic tension-type headache. Review of the literature

Amitriptyline is a tricyclic antidepressant, considered the treatment of choice for different types of chronic pain, including chronic myofascial pain. Its antinociceptive property is independent of its antidepressant effect. Although its analgesic mechanism is not precisely known, it is believed that the serotonin reuptake inhibition in the central nervous system plays a fundamental role in pain control. Although this medication is widely used in the prevention of chronic tension-type headache, few studies have investigated the efficacy of this treatment and the published results are contradictory. The objective of this article was to review the literature published on the use of amitriptyline in the prophylactic treatment of chronic tension-type headache, considering the level of scientific evidence of the different studies using the SORT criteria. From this review, 5 articles of evidence level 1, and another 5 articles of evidence level 2 were selected. Following analysis of the 10 studies, and in function of their scientific quality, a level A recommendation was made in favor of using amitriptyline in the treatment of chronic tension-type headache.

Determinants of Broadband Access: Is Platform Competition always the Key Variable to Success?

Previous studies have identified the rivalry among technological platforms as one of the main driving forces of broadband services penetration. This paper draws on data from the Spanish market between 2005 and 2011 to estimate the main determinants of broadband prices. Controlling for broadband tariffs features and network variables, we examine the impact of the different modes of competition on prices. We find that inter-platform competition has no significant effects over prices, while intra-platform competition is a key driver of the prices charged in the broadband market. Our analysis suggests that the impact of different types of competition on prices is critically affected by the levels of development of the broadband market achieved by the considered country

The FaceUOC Project : An Open Social Learning experience by the Open University of Catalonia

The possibilities and expansion of the use of Web 2.0 has opened up a world of possibilities in online learning. In spite of the integration of these tools in education major changes are required in the educational design of instructional processes.This paper presents an educational experience conducted by the Open University of Catalonia using the social network Facebook for the purpose of testing a learning model that uses a participation and collaboration methodology among users based on the use of open educational resources.- The aim of the experience is to test an Open Social Learning (OSL) model, understood to be a virtual learning environment open to the Internet community, based on the use of open resources and on a methodology focused on the participation and collaboration of users in the construction of knowledge.- The topic chosen for this experience in Facebook was 2.0 Journeys: online tools and resources. The objective of this 5 weeks course was to provide students with resources for managing the various textual, photographic, audiovisual and multimedia materials resulting from a journey.- The most important changes in the design and development of a course based on OSL are the role of the teacher, the role of the student, the type of content and the methodology:- The teacher mixes with the participants, guiding them and offering the benefit of his/her experience and knowledge.- Students learn through their participation and collaboration with a mixed group of users.- The content is open and editable under different types of license that specify the level of accessibility.- The methodology of the course was based on the creation of a learning community able to self-manage its learning process. For this a facilitator was needed and also a central activity was established for people to participate and contribute in the community.- We used an ethnographic methodology and also questionnaires to students in order to acquire results regarding the quality of this type of learning experience.- Some of the data obtained raised questions to consider for future designs of educational situations based on OSL:- Difficulties in breaking the facilitator-centred structure- Change in the time required to adapt to the system and to achieve the objectives- Lack of commitment with free courses- The trend to return to traditional ways of learning- Accreditation- This experience has taught all of us that education can happen any time and in any place but not in any way.

The Role of Canyons in Strata Formation

This paper provides a spatial and temporal multi-scale approach of European submarine canyons. We fi rst present the long-term geologic view of European margins as related to controls on submarine canyon development. Then we discuss the extent to which submarine canyon systems resemble river systems because both essentially form drainage networks. Finally, we deal with the hortest-term, highestresolution scale to get a fl avor of the current functioning and health of modern submarine canyons in the northwestern Mediterranean Sea. Submarine canyons are unique features of the seafl oor whose existence was known by European fi shermen centuries ago, especially for those canyons that have their heads at short distance from shoreline. Popular names given to specifi c canyons in the different languages spoken in European coastal communities refer to the concepts of a"deep" or"trench." In the old times it was also common thinking that submarine canyons where so deep that nobody could measure their depth or even that they had no bottom. Submarine canyons are just one of the seven different types of seafl oor valleys identifi ed by Shepard (1973) in his pioneering morphogenetic classifi cation. Shepard (1973) defined submarine canyons as"steep-walled, sinuous valleys, with V-shaped cross sections, and relief comparable even to the largest of land canyons; tributaries are found in most of the canyons and rock outcrops abound on their walls." Canyons are features typical of continental slopes with their upper reaches and heads cut into the continental shelf.

Early adversity and 5-HTT-BDNF genes: New evidences of Gene-Environment interactions on depressive symptoms in a general population

Background Adverse childhood experiences have been described as one of the major environmental risk factors for depressive disorder. Similarly, the deleterious impact of early traumatic experiences on depression seems to be moderated by individual genetic variability. Serotonin transporter (5-HTT) and brain-derived neurotrophic factor (BDNF) modulate the effect of childhood adversity on adult depression, although inconsistencies across studies have been found. Moreover, the gene×environment (G×E) interaction concerning the different types of childhood adversity remains poorly understood. The aim of this study was to analyse the putative interaction between the 5-HTT gene (5-HTTLPR polymorphism), the BDNF gene (Val66Met polymorphism) and childhood adversity in accounting for adult depressive symptoms. Method A sample of 534 healthy individuals filled in self-report questionnaires of depressive symptomatology [the Symptom Check List 90 Revised (SCL-90-R)] and different types of childhood adversities [the Childhood Trauma Questionnaire (CTQ)]. The 5-HTTLPR polymorphism (5-HTT gene) and the Val66Met polymorphism (BDNF gene) were genotyped in the whole sample. Results Total childhood adversity (β=0.27, p<0.001), childhood sexual abuse (CSA; β=0.17, p<0.001), childhood emotional abuse (β=0.27, p<0.001) and childhood emotional neglect (β=0.22, p<0.001) had an impact on adult depressive symptoms. CSA had a greater impact on depressive symptoms in Met allele carriers of the BDNF gene than in the Val/Val group (F=5.87, p<0.0001), and in S carriers of the 5-HTTLPR polymorphism (5-HTT gene) (F=5.80, p<0.0001). Conclusions Childhood adversity per se predicted higher levels of adult depressive symptoms. In addition, BDNF Val66Met and 5-HTTLPR polymorphisms seemed to moderate the effect of CSA on adult depressive symptoms.

Prevalence of Problematic Mobile Phone Use in British Adolescents

The problematic use of mobile phones among adolescents has not been widely studied. There are very few instruments for assessing potential technological addiction to mobile phones, or for categorizing different types of users or uses. The most widely used scale is the Mobile Phone Problem Use Scale (MPPUS), which is used to study adult populations, and has been applied in various forms in international contexts. The aims of this study were to adapt the Spanish version of this scale (MPPUSA) to British adolescents, and then to estimate the prevalence of possible problematic users. A questionnaire was administered to a sample of 1,529 secondary school pupils aged between 11 and 18 years, with 1,026 completed questionnaires being collected. The analysis showed that the factor and construct validity and reliability were comparable to those obtained in previous studies. The prevalence of problematic users among the students was 10%, and the typical problematic user tended to be an adolescent between 11 and 14 years old, studying in a public school, who considered themselves to be an expert user of this technology, who made extensive use of his/her mobile phone, and who attributed the same problem of use among their peers. These users presented notable scores in all the symptoms covered by the scale used to assess problematic use. In conclusion, the adaptation of the MPPUSA as a screening scale for British adolescents presents good sensitivity and specificity for detecting the main addictive symptoms proposed in this validated version.

Cytoplasmic accumulation of NCoR in malignant melanoma: Consequences of altered gene repression and prognostic significance

Invasive malignant melanoma (MM) is an aggressive tumor with no curative therapy available in advanced stages. Nuclear corepressor (NCoR) is an essential regulator of gene transcription, and its function has been found deregulated in different types of cancer. In colorectal cancer cells, loss of nuclear NCoR is induced by Inhibitor of kappa B kinase (IKK) through the phosphorylation of specific serine residues. We here investigate whether NCoR function impacts in MM, which might have important diagnostic and prognostic significance. By IHC, we here determined the subcellular distribution of NCoR in a cohort of 63 primary invasive MM samples, and analyzed its possible correlation with specific clinical parameters. We therefore used a microarray-based strategy to determine global gene expression differences in samples with similar tumor stage, which differ in the presence of cytoplasmic or nuclear NCoR. We found that loss of nuclear NCoR results in upregulation of a specific cancer-related genetic signature, and is significantly associated with MM progression. Inhibition of IKK activity in melanoma cells reverts NCoR nuclear distribution and specific NCoR-regulated gene transcription. Analysis of public database demonstrated that inactivating NCoR mutations are highly prevalent in MM, showing features of driver oncogene.

Lo que no es nuevo puede ser actual: hacia distintos puntos de mira de la didáctica del arte What is not new can be current - towards different approaches of the didactics of art

With this article we want to present a state of affairs of the didactics of art in our context, and at the same time we want todiscuss on its pluri- and interdisciplinary construction. We check the different disciplines that configure it and we analysethe paradigm of artistic education as a discipline (DBAE) and its passage to post-modernity. This example focuses thediscussion about the opportunity of adapting holistic educative models and the transition of the current educativeinnovation towards skill models