Global transcriptional programs in peripheral nerve endoneurium and DRG are resistant to the onset of type 1 diabetic neuropathy in Ins2 mice.

While the morphological and electrophysiological changes underlying diabetic peripheral neuropathy (DPN) are relatively well described, the involved molecular mechanisms remain poorly understood. In this study, we investigated whether phenotypic changes associated with early DPN are correlated with transcriptional alterations in the neuronal (dorsal root ganglia [DRG]) or the glial (endoneurium) compartments of the peripheral nerve. We used Ins2(Akita/+) mice to study transcriptional changes underlying the onset of DPN in type 1 diabetes mellitus (DM). Weight, blood glucose and motor nerve conduction velocity (MNCV) were measured in Ins2(Akita/+) and control mice during the first three months of life in order to determine the onset of DPN. Based on this phenotypic characterization, we performed gene expression profiling using sciatic nerve endoneurium and DRG isolated from pre-symptomatic and early symptomatic Ins2(Akita/+) mice and sex-matched littermate controls. Our phenotypic analysis of Ins2(Akita/+) mice revealed that DPN, as measured by reduced MNCV, is detectable in affected animals already one week after the onset of hyperglycemia. Surprisingly, the onset of DPN was not associated with any major persistent changes in gene expression profiles in either sciatic nerve endoneurium or DRG. Our data thus demonstrated that the transcriptional programs in both endoneurial and neuronal compartments of the peripheral nerve are relatively resistant to the onset of hyperglycemia and hypoinsulinemia suggesting that either minor transcriptional alterations or changes on the proteomic level are responsible for the functional deficits associated with the onset of DPN in type 1 DM.

Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons.

BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection. METHODS: In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort. RESULTS: A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9 × 10(-4)). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05-2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06-1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16-1.96), diabetes (OR = 1.66; 95% CI, 1.10-2.49), ≥ 1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06-1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17-2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD. CONCLUSIONS: In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD.

Simultaneous use of alcohol, tobacco and cannabis in relation to severity of substance dependence: a study among young Swiss men

Objective: This study investigated patterns of the simultaneous use of alcohol, tobacco and cannabis among young polydrug users, and whether use of one substance might be a cue for use of another and associations with the severity of substance dependence. Methods: The study focused on 3 subsamples from the ongoing Swiss Cohort Study on Substance Use Risk Factors (C-SURF, N=5,990). It used 12 months of data on alcohol/tobacco co-users, alcohol/cannabis co-users and tobacco/cannabis co-users (N=2,660, 1,755 and 1,460 respectively. Simultaneous use, numbers of symptoms of substance dependence, and hazardous use of alcohol, tobacco and cannabis were assessed. The effect of simultaneous polydrug use (SPU) on the numbers of symptoms of substance dependence was tested using analysis of variance. Results: Polydrug use was most common as SPU, and less common as non/occasional SPU. Moreover, when participants started to use one substance while using another, the severity of substance dependence was more strongly associated with the triggered substance than with cue. Conclusions: This study highlights the necessity to take SPU into account. First, SPU rather than separate drug use was the most common pattern for polydrug users. Second, frequent SPU was associated with increased numbers of symptoms of substance dependence compared to non/occasional SPU. Furthermore, SPU may reveal the severity of substance use dependence, when substance use is triggered by a cue substance. For these reasons, SPU should be a serious cause for concern for prevention and intervention purposes.

Disruption of embryonic blood-CSF barrier in chick embryos reveals the actual importance of this barrier to control E-CSF composition and homeostasis in early brain development

In vertebrates, early brain development takes place at the expanded anterior end of the neural tube. After closure of the anterior neuropore, the brain wall forms a physiologically sealed cavity that encloses embryonic cerebrospinal fluid (E-CSF), a complex and protein-rich fluid that is initially composed of trapped amniotic fluid. E-CSF has several crucial roles in brain anlagen development. Recently, we reported the presence of transient blood-CSF barrier located in the brain stem lateral to the ventral midline, at the mesencephalon and prosencephalon level, in chick and rat embryos by transporting proteins, water, ions and glucose in a selective manner via transcellular routes. To test the actual relevance of the control of E-CSF composition and homeostasis on early brain development by this embryonic blood-CSF barrier, we block the activity of this barrier by treating the embryos with 6-aminonicotinamide gliotoxin (6-AN). We demonstrate that 6-AN treatment in chick embryos blocks protein transport across the embryonic blood-CSF barrier, and that the disruption of the barrier properties is due to the cease transcellular caveolae transport, as detected by CAV-1 expression cease. We also show that the lack of protein transport across the embryonic blood-CSF barrier influences neuroepithelial cell survival, proliferation and neurogenesis, as monitored by neurepithelial progenitor cells survival, proliferation and neurogenesis. The blockage of embryonic blood-CSF transport also disrupts water influx to the E-CSF, as revealed by an abnormal increase in brain anlagen volume. These experiments contribute to delineate the actual extent of this blood-CSF embryonic barrier controlling E-CSF composition and homeostasis and the actual important of this control for early brain development, as well as to elucidate the mechanism by which proteins and water are transported thought transcellular routes across the neuroectoderm, reinforcing the crucial role of E-CSF for brain development.

Neurology and psychiatry: waking up to opportunities of sleep. : State of the art and clinical/research priorities for the next decade.

In recent years, evidence has emerged for a bidirectional relationship between sleep and neurological and psychiatric disorders. First, sleep-wake disorders (SWDs) are very common and may be the first/main manifestation of underlying neurological and psychiatric disorders. Secondly, SWDs may represent an independent risk factor for neuropsychiatric morbidities. Thirdly, sleep-wake function (SWF) may influence the course and outcome of neurological and psychiatric disorders. This review summarizes the most important research and clinical findings in the fields of neuropsychiatric sleep and circadian research and medicine, and discusses the promise they bear for the next decade. The findings herein summarize discussions conducted in a workshop with 26 European experts in these fields, and formulate specific future priorities for clinical practice and translational research. More generally, the conclusion emerging from this workshop is the recognition of a tremendous opportunity offered by our knowledge of SWF and SWDs that has unfortunately not yet entered as an important key factor in clinical practice, particularly in Europe. Strengthening pre-graduate and postgraduate teaching, creating academic multidisciplinary sleep-wake centres and simplifying diagnostic approaches of SWDs coupled with targeted treatment strategies yield enormous clinical benefits for these diseases.

Waddlia: An emerging pathogen and a model organism to study the biology of chlamydiae.

Waddlia chondrophila is an emerging pathogen associated with abortion in cattle. In humans, a growing body of evidence supports its pathogenic role in miscarriage and in respiratory tract infection. The human pathogenicity of W. chondrophila is further supported by the presence of several virulence factors including a catalase, a functional T3SS and several adhesins. Despite this medical importance, no commercial tests are available and diagnostic of this strict intracellular bacterium mainly relies on serology, PCR and immunohistochemistry. So far, the epidemiology of W. chondrophila remains largely unexplored and zoonotic, waterborne or interhuman transmission has been considered. Apart from its pathogenic role, chlamydiologists are also interested in W. chondrophila in order to better understand biological mechanisms conserved and shared with Chlamydia spp. Indeed, W. chondrophila proved to be a useful model organism to study the pathobiology of chlamydiae thanks to its rapid replication, its large size allowing precise subcellular protein localization, as well as its growth in Dictyostelium amoebae.

Combining Generic Programming and Service-Oriented Architectures for the Effective and Timely Development of Complex e-Learning Systems

Peer-reviewed

An empirical study on faculty perceptions and teaching practices of Wikipedia

Peer-reviewed

Conflicto, colaboración y consenso en la enseñanza de las ciencias sociales = Conflict, collaboration and consensus in the teaching of the Social sciences

This article suggests the study of the key concept of conflict as a means of implementing a critical and communicativecurriculum based on the study of relevant social themes. To this end we put forward the principal characteristics of thecritical/communicative curriculum. We offer a didactic proposal about conflict and explain the results of its application intwo Secondary Education classrooms

Una visión actualizada de la didáctica de la matemática en educación infantil = An up-to-date vision of pre-school mathematics teaching

This article aims to investigate pre-school mathematics teaching from an uptodate perspective. To pursue this contemporary vision we focus on four key questions: what kind of maths is being worked on, who is doing it, how it is being done, and why it is being done

El juego y su estructura interna en relación con el trabajo de la condición física en primaria = Games and their internal structure in relation to the work of physical condition in Primary Education

One of the methodological resources that teachers use in a generalised way in Physical Education classes is the game. Inthis article we define the concept of game and analyse the characteristics of their internal structure. On the other hand welook at the concepts of physical condition and conditional skills and describe the objectives of its work in Primary Education.Finally, we relate these concepts and propose two practical examples of modifying the internal structure of the game so asto produce variations in the implied conditional skills

Integrating environmental education in primary school education in Tanzania : teachers’ perceptions and teaching practices

The study focuses on primary school teachers’ perceptions of environmental education, its integration into primary school education and teachers’ teaching practices in Tanzania. The thesis is based on empirical research. The theoretical underpinnings of the study are based on Palmer’s (1998) model of environmental education. According to the model, meaningful environmental education should include education about, in or through and for the environment. The study is supported by national and international literature from research done on environmental education and education for sustainable development and policy statements. The study is qualitative in nature, adopting phenomenography and phenomenology as points of departure. The empirical data was collected from four primary schools in Morogoro region in Tanzania. The study sample consisted of 31 primary school teachers. Data was collected through interviews and lesson observations. According to the results of the study, primary school teachers expressed variations in their perceptions of environmental education and education for sustainable development. Most of the teachers focused on the aspect of knowledge acquisition. According to Tanzanian education and training policy, environmental education has to be integrated into all subjects. Although there is environmental education in the primary school curriculum, it is not integrated on an equal footing in all subjects. Some subjects like science, social studies and geography have more environmental content than other subjects. Teachers claim that the approach used to integrate environmental education into the school curriculum was not favoured because many claimed that what is to be taught as environmental education in the various subjects is not shown clearly. As a result, many teachers suggested that to ensure that it is taught properly it should be included in the curriculum as an independent subject or as specific topics. The study revealed that teachers’ teaching practices in integrating environmental education varied from one subject to another. Although most of the teachers said that they used participatory methods, lesson observations showed that they limited themselves to question and answer and group discussion. However, the teachers faced a number of barriers in the teaching of environmental education, some of which include lack of teaching and learning resources, time and large class size. The role of teachers in the implementation of environmental education in developing an environmentally literate citizenry is of great significance. The responsibility of the government in developing a curriculum with clear goals and content, developing teachers’ capacity in the teaching of environmental education and provision of teaching and learning materials needs to be taken seriously by the government in educational plans and programs.

Learning through role-playing games: an approach for active learning and teaching

This study evaluates the use of role-playing games (RPGs) as a methodological approach for teaching cellular biology, assessing student satisfaction, learning outcomes, and retention of acquired knowledge. First-year undergraduate medical students at two Brazilian public universities attended either an RPG-based class (RPG group) or a lecture (lecture-based group) on topics related to cellular biology. Pre- and post-RPG-based class questionnaires were compared to scores in regular exams and in an unannounced test one year later to assess students' attitudes and learning. From the 230 students that attended the RPG classes, 78.4% responded that the RPG-based classes were an effective tool for learning; 55.4% thought that such classes were better than lectures but did not replace them; and 81% responded that they would use this method. The lecture-based group achieved a higher grade in 1 of 14 regular exam questions. In the medium-term evaluation (one year later), the RPG group scored higher in 2 of 12 questions. RPG classes are thus quantitatively as effective as formal lectures, are well accepted by students, and may serve as educational tools, giving students the chance to learn actively and potentially retain the acquired knowledge more efficiently.