MiR-219a-5p Enriched Extracellular Vesicles Induce OPC Differentiation and EAE Improvement More Efficiently Than Liposomes and Polymeric Nanoparticles.

Remyelination is a key aspect in multiple sclerosis pathology and a special effort is being made to promote it. However, there is still no available treatment to regenerate myelin and several strategies are being scrutinized. Myelination is naturally performed by oligodendrocytes and microRNAs have been postulated as a promising tool to induce oligodendrocyte precursor cell differentiation and therefore remyelination. Herein, DSPC liposomes and PLGA nanoparticles were studied for miR-219a-5p encapsulation, release and remyelination promotion. In parallel, they were compared with biologically engineered extracellular vesicles overexpressing miR-219a-5p. Interestingly, extracellular vesicles showed the highest oligodendrocyte precursor cell differentiation levels and were more effective than liposomes and polymeric nanoparticles crossing the blood-brain barrier. Finally, extracellular vesicles were able to improve EAE animal model clinical evolution. Our results indicate that the use of extracellular vesicles as miR-219a-5p delivery system can be a feasible and promising strategy to induce remyelination in multiple sclerosis patients.

Models for Studying Myelination, Demyelination and Remyelination.

One of the most widely studied demyelinating diseases is multiple sclerosis, which is characterised by the appearance of demyelinating plaques, followed by myelin regeneration. Nevertheless, with disease progression, remyelination tends to fail, increasing the characteristic neurodegeneration of the disease. It is essential to understand the mechanisms that operate in the processes of myelination, demyelination and remyelination to develop treatments that promote the production of new myelin, thereby protecting the central nervous system. A huge variety of models have been developed to help improve our understanding of these processes. Nevertheless, no single model allows us to study all the processes involved in remyelination and usually more than one is needed to provide a full picture of related mechanisms. In this review, we summarise the most commonly used models for studying myelination, demyelination and remyelination and we analyse them critically to outline the most suitable ways of using them.

Adaptation and validation of the Spanish version of the Mood Disorder Questionnaire for the detection of bipolar disorder.

OBJECTIVE: The Mood Disorder Questionnaire (MDQ) is an instrument for the detection of patients with bipolar disorder (BD). The original English version is validated in both the psychiatric and the general population, but a validated Spanish version is not yet available. Psychometric properties of the Spanish adaptation of the MDQ in psychiatry are described. METHODS: The MDQ is a self-administered questionnaire comprising a list of 13 hypomanic symptoms and two questions about concurrence of symptoms and functional impairment caused by the symptoms. We selected patients from 15 psychiatric outpatient departments, diagnosed with BD type I and II (BDI and BDII) and major depression (MD) according to DSM-IV-TR criteria (concurrent validity instrument). A control group of healthy subjects (HS) was selected. The patient-selection criteria included stability of the disorder and pharmacological treatment. The MDQ was administered to 236 subjects, distributed among the four groups, on two occasions, four weeks apart. We analysed the internal consistency, test-retest reliability, and discriminative capacity of the MDQ for the detection of patients with BD. RESULTS: Concurrent validity based on diagnosis according to DSM-IV-TR was 0.83. The internal consistency, evaluated by Cronbach's alpha, was 0.90. The mean (SD) number of affirmative responses by group was: 9.8 (2.4) for BDI, 8.5 (2.8) for BDII, 2.7 (2.2) for MD, and 1.02 (1.9) for HS. Statistically significant differences between all the groups were found (Kruskal-Wallis test, p < 0.001). Concurrent validity using the diagnostic variable was 0.83. Test-retest reliability was 0.92. We analysed the scale's discriminative capacity, revealing a sensitivity value of 0.60 [95% confidence interval (CI) = 0.51-0.69] and a specificity value of 0.98 (95% CI = 0.94-0.99) in the detection of BD. The positive and negative probability ratios were 35.5 and 2.4, respectively. If we consider only seven positive responses as the discriminative criterion, sensitivity increases to 0.81 (95% CI = 0.73-0.88), the specificity value is 0.95 (95% CI = 0.89-0.98) and the positive and negative probability quotients are 16 and 5.3. CONCLUSIONS: The psychometric characteristics of the Spanish version are similar to those of the original version. In the Spanish adaptation of the MDQ, seven positive responses to hypomanic symptoms show a good discriminative capacity for BD in patients attending psychiatric outpatient facilities; therefore, this cut-off score is proposed for the detection of BD in psychiatric outpatients.

A naturalistic multicenter study of intramuscular olanzapine in the treatment of acutely agitated manic or schizophrenic patients.

BACKGROUND: We conducted a naturalistic, multicenter, 24-hour, nonrandomized, observational study describing for the first time the effectiveness and safety of intramuscular (IM) olanzapine to control agitation and aggression in "real world" patients with psychosis. The data thus obtained was compared with that reported from randomized double-blind clinical trials. METHOD: 92 patients attending psychiatric emergency settings were enrolled. The study subjects were 44 male and 48 female patients with a mean age of 36.5+/-12 years and DSM-IV-TR diagnoses of schizophrenia (48.9%), psychotic disorder not specified (23.9%) or bipolar disorder (27.2%). 10 mg IM olanzapine was administered to all patients. An optional second injection was permitted> or =2 hours later in line with hospital policy. Evaluations (PANSS-EC and CGI-S) were performed at baseline and 2 and 24 hours following the IM injection. RESULTS: Two hours after IM olanzapine was administered, a mean decrease of -9.6 in the PANSS-EC from a baseline score of 26.5 was recorded. At the 24-hour endpoint a statistically and clinically significant reduction in the PANSS-EC scores (11.6+/-5.3) was observed as compared with values at study entry (26.5+/-5.9) and at 2 hours endpoint (16.9+/-9.3), which represent a mean decrease of -14.9 and -5.3, respectively. CONCLUSION: The present naturalistic study provides naturalistic data on the effectiveness of IM olanzapine in the treatment of acute agitation in patients with schizophrenia or bipolar mania that is in line the data obtained in randomized double-blind clinical trials.

Eficacia del consejo médico para la reducción del consumo excesivo de alcohol. Metaanálisis de estudios españoles en atención primaria / Effectiveness of medical advice for reducing excessive alcohol conssumption. Meta-analysis of Spanish studies in primary care

Introducción: Revisiones sistemáticas previas han apoyado la eficacia del consejo médico, como intervención breve, en el abordaje de bebedores excesivos detectados en la asistencia primaria. Sin embargo, estos resultados no pueden extrapolarse directamente a poblaciones que, como las mediterráneas, no están representadas en dichas revisiones. El objetivo de este estudio fue actualizar la evidencia sobre la eficacia de la intervención breve en consumidores excesivos de alcohol según estudios españoles. Métodos: Búsqueda de estudios en bases bibliográficas y consultas a expertos para localizar estudios no publicados. Se calcularon las estimaciones combinadas para dos variables de resultado, la reducción del consumo de alcohol y la disminución de la frecuencia de bebedores excesivos. Resultados: Dos de los 5 estudios localizados no estaban incluidos en una revisión previa. La eficacia de la intervención breve fue moderada para la disminución del consumo de alcohol (d = -0,46; intervalo de confianza (IC) del 95 por ciento, -0,29 a -0,63; p < 0,0005; el grupo tratado mejoró un 22 por ciento más que el control) y pequeña para la disminución de la frecuencia de bebedores excesivos (OR = 1,55; IC del 95 por ciento, 1,06 a 2,26; p = 0,02; el grupo tratado mejoró un 11 por ciento más que el control).El análisis basado en el cumplimiento del protocolo sobrestimó 1,5 veces el tamaño del efecto respecto del análisis basado en la intención de tratamiento. Conclusiones: Los resultados del estudio señalan que, en nuestro país, la intervención breve en atención primaria sobre bebedores a riesgo es eficaz, aunque su efecto sea sólo moderado (AU)

Introduction: Former systematic reviews have backed the efficacy of medical counselling, a form of brief intervention, on the treatment of excessive drinkers detected in primary care settings. Nevertheless, these results cannot be applied without criticism to Mediterranean populations which, so far, have not been represented in the aforementioned studies. The aim of the present study was to update the results on the efficacy of brief interventions in primary care by pooling Spanish studies. Methods: Studies were searched for by using appropriate databases and also by consulting to experts in the field to retrieve grey literature. Pooled estimations of effect sizes were calculated for two outcomes, the reduction in the amount of alcohol consumption and the decrease in the number of excessive drinkers. Results: Two over the 5 retrieved studies were not included in a former review. The effect size regarding the decrease of alcohol consumption was medium (d = - 0.46; 95% CI, - 0.29 to - 0.63; p < 0.0005; the intervention group outperformed the control by a 22%) and small for the decrease in the frequency of excessive drinkers (OR = 1.55; 95% CI, 1.06 to 2.26; p = 0.02; the intervention group outperformed the control by a 11%). The analysis by complimented protocols at the end of the study showed an effect size 1.5 times larger than the analysis performed on intention-to-treat basis. Conclusions: The results of this meta-analysis support the efficacy of brief intervention for excessive drinkers in primary care settings in Spain (AU)

Attempted and completed suicide in older subjects: results from the WHO/EURO Multicentre Study of Suicidal Behaviour.

OBJECTIVE: The authors present an analysis of findings for the 65 years and over age group from the WHO/EURO Multicentre Study of Suicidal Behaviour (1989-93). METHODS: Multinational data on non-fatal suicidal behaviour is derived from 1518 subjects in 16 European centres. Local district data on suicide were available from 10 of the collaborating centres. RESULTS: Stockholm (Sweden), Pontoise (France) and Oxford (UK) had the highest suicide attempts rates. In most centres, the majority of elderly who attempted suicide were widow(er)s, often living alone, who used predominantly voluntary drug ingestion. Non-fatal suicidal behaviour decreased with increasing age, whereas suicide rates rose. The ratio between fatal and non-fatal behaviours was 1:2, that for males/females almost 1:1. In the years considered, substantial stability in suicide and attempted suicide rates was observed. As their age increased, suicidal subjects displayed only a limited tendency to repeat self-destructive acts. Moreover, there was little correlation between attempted suicide and suicide rates, which carries different clinical implications for non-fatal suicidal behaviour in the elderly compared with younger subjects in the same WHO/EURO study.

Recommended care for young people (15-19 years) after suicide attempts in certain European countries.

Data on recommended care for young people aged 15-19 years after attempted suicide from nine European research centres during the period 1989-1992 were analysed in terms of gender, history of previous suicide attempt and methods used. Altogether 438 suicide attempts made by 353 boys and 1,102 suicide attempts made by 941 girls were included. Analyses of the total data from all centres showed that young people with a history of previous suicide attempt and those using violent methods had significantly higher chance of being recommended aftercare than first-time attempters or those choosing self-poisoning. There were no significant differences of being recommended care between genders. Logistic regression analyses of the material were performed and the results were similar. Both having previous attempted suicide (odds ratio 2.0, 95% CI 1.53-2.61) and using "hard" methods (odds ratio 1.71, 95% CI 1.49-1.96) were significantly associated with increased possibility of being recommended aftercare. When individual centres were analysed, large disparities of recommended care after suicide attempts were found and there were no uniform criteria of recommending care for young suicide attempters in Europe.

Methods used for parasuicide: results of the WHO/EURO Multicentre Study on Parasuicide.

BACKGROUND: National suicide statistics show remarkable differences in the frequencies of various methods used for completed suicide. The WHO/EURO Multicentre Study on Parasuicide makes possible for the first time an international comparison of the frequencies of methods used in attempted suicide, because the data are based on geographical catchment areas of medical institutions. METHOD: Ongoing standardized monitoring of attempted suicide in all medical institutions serving the catchment areas was performed in 14 centres in 12 European countries. The data analysis is based on 20,649 events involving 15,530 persons, recorded between 1989 and 1993. RESULTS: The comparison of rates per 100,000 shows striking differences between the centres. The highest rates for drug overdoses were found for female attempters in Oxford (347/100,000), Helsinki (238/100,000) and Stockholm (221/100,000). Guipuzcoa had the lowest rates (61/100,000). The differences were most prominent in the age group 15-24, with outstanding rates for women in Oxford (653/100,000), which was mainly due to the frequent use of analgesics. Szeged had outstandingly high rates for pesticides and solvents. In some centres the use of multiple methods was frequent. CONCLUSIONS: There is a need, especially for areas with high frequencies for certain methods, to understand the factors involved and to develop new and specific prevention projects and to monitor their effects. The WHO/EURO Multicentre Study on Parasuicide has proved to be a useful and reliable instrument for continuous monitoring of trends in parasuicide.

Relation between attempted suicide and suicide rates among young people in Europe.

STUDY OBJECTIVE: To determine if there are associations between rates of suicide and attempted suicide in 15-24 year olds in different countries in Europe. DESIGN: Attempted suicide rates were based on data collected in centres in Europe between 1989 and 1992 as part of the WHO/EURO Multicentre Study of Parasuicide. Comparison was made with both national suicide rates and local suicide rates for the areas in which the attempted suicide monitoring centres are based. SETTING: 15 centres in 13 European countries. PATIENTS: Young people aged 15-24 years who had taken overdoses or deliberately injured themselves and been identified in health care facilities. MAIN RESULTS: There were positive correlations (Spearman rank order) between rates of attempted suicide and suicide rates in both sexes. The correlations only reached statistical significance for male subjects: regional suicide rates, r = 0.65, p < 0.02; national suicide rates, r = 0.55, p < 0.02. CONCLUSIONS: Rates of attempted suicide and suicide in the young covary. The recent increase in attempted suicide rates in young male subjects in several European countries could herald a further increase in suicide rates.

Attempted suicide in Europe: rates, trends and sociodemographic characteristics of suicide attempters during the period 1989-1992. Results of the WHO/EURO Multicentre Study on Parasuicide.

The World Health Organization/EURO Multicentre Project on Parasuicide is part of the action to implement target 12 of the WHO programme, "Health for All by the Year 2000', for the European region. Sixteen centres in 13 European countries are participating in the monitoring aspect of the project, in which trends in the epidemiology of suicide attempts are assessed. The highest average male age-standardized rate of suicide attempts was found for Helsinki, Finland (314/100,000), and the lowest rate (45/100,000) was for Guipuzcoa, Spain, representing a sevenfold difference. The highest average female age-standardized rate was found for Cergy-Pontoise, France (462/100,000), and the lowest (69/100,000) again for Guipuzcoa, Spain. With only one exception (Helsinki), the person-based suicide attempt rates were higher among women than among men. In the majority of centres, the highest person-based rates were found in the younger age groups. The rates among people aged 55 years or over were generally the lowest. For the majority of the centres, the rates for individuals aged 15 years or over decreased between 1989 and 1992. The methods used were primarily "soft' (poisoning) or cutting. More than 50% of the suicide attempters made more than one attempt, and nearly 20% of the second attempts were made within 12 months after the first attempt. Compared with the general population, suicide attempters more often belong to the social categories associated with social destabilization and poverty.

The WHO-EURO Multicentre Study: risk of parasuicide and the comparability of the areas under study.

The 15 areas under study in the WHO/Euro Multicentre Study on Parasuicide vary considerably with regard to socio-economic factors, culture, life-styles, etc. In this paper, the authors discuss whether the traditional high risk factors for suicidal behavior (such as unemployment, abuse, divorce, etc.) take on different weights depending on local societal and cultural settings. Results from analyzing covariations between various background factors characteristic of the different areas under study and the frequency of attempted suicide showed weak or insignificant correlations, indicating that high-risk factors can only be identified from international pooled data with great care.

Depression in three populations in the Basque country--a comparison with Britain.

A psychiatric survey in three regions of the Basque Autonomous Community aimed to replicate two British surveys, in London and a rural area of Scotland, investigating both prevalence of psychiatric disorder and its relationship with certain key psychosocial factors. The Spanish rural-urban differences in rates of depression and anxiety closely paralleled the earlier British results. As in Britain, Spanish rural rates of depression were lower among those most integrated into the traditional family ways of life, but in contrast to Britain the urban rates did not vary with social class or the presence of children at home. As in Britain, severe life event and major difficulties were associated with onset of depression, and varied in prevalence and type with degree of integration with the traditional lifestyle. The protective role of intimate confiding with a partner against depressive onset was confirmed among non-churchgoers in Bilbao, but not among churchgoers, while in the rural samples there was only a nonsignificant trend.