Cuban scientific production in Medicine and Public Health: Scopus 2003-2011

El objetivo de este trabajo fue analizar la evolución del volumen y la visibilidad de la producción científica cubana en Salud Pública y en Medicina para determinar si siguen los mismos patrones de comunicación, y recomendar buenas prácticas de publicación. Se aplicaron indicadores bibliométricos de volumen, visibilidad y colaboración extraídos del portal SCImago Institutions Rankings a partir de datos de Scopus, para el área temática Medicine y la categoría Public Health, Environmental and Occupational Health, período 2003-2011. Cuba tiene una posición relativamente alta en los rankings de volumen de producción científica tanto en Medicina como en Salud Pública en los contextos internacionales y regionales, mientras que en impacto está entre los últimos países. La tendencia de la producción es al crecimiento, aunque en Salud Pública es más acelerado. El liderazgo es alto, pero la colaboración internacional está por debajo de lo esperado. La publicación en revistas de alto impacto (primer cuartil) y los artículos en el 10% más citado (excelencia) son escasos. Se concluye que el volumen y el impacto de la publicación no están acorde al potencial científico de salud cubana. Se recomienda incrementar la colaboración científica, la publicación de artículos en revistas de alto impacto, la preparación de los recursos humanos y seguir las recomendaciones internacionales sobre las buenas prácticas de edición y publicación científica.The aim of this study was to analyze the evolution of the quantity and visibility of Cuban scientific production in Public Health and Medicine to determine if they follow the same patterns of scientific communication and the recommended best practices for publication. Bibliometric indicators of quantity, visibility and cooperation were extracted from the SCImago Institutions Rankings website, which is based on Scopus data, in the field of Medicine and category of Public Health, Environmental and Occupational Health from 2003 to 2011.Cubahas a relatively high position in the rankings of scientific production in both Medicine and Public Health within the international and regional contexts, but its impact is ranked among the last countries. The production trend of both fields has increased, but public health is increasing faster. Leadership is high, but international collaboration is below expectations. Publication in high impact journals (first quartile) and articles in the set 10% most cited documents (excellence) are scarce. Thus, it may be concluded that the volume and impact of publication are not in accordance with the scientific potential of Cuban health. We recommend increasing scientific cooperation, publishing articles in high impact journals, training human resources and following the international recommendations for good editorial and scientific publication practices

Data mining of high density genomic variant data for prediction of Alzheimer's disease risk

<p>Abstract</p> <p>Background</p> <p>The discovery of genetic associations is an important factor in the understanding of human illness to derive disease pathways. Identifying multiple interacting genetic mutations associated with disease remains challenging in studying the etiology of complex diseases. And although recently new single nucleotide polymorphisms (SNPs) at genes implicated in immune response, cholesterol/lipid metabolism, and cell membrane processes have been confirmed by genome-wide association studies (GWAS) to be associated with late-onset Alzheimer's disease (LOAD), a percentage of AD heritability continues to be unexplained. We try to find other genetic variants that may influence LOAD risk utilizing data mining methods.</p> <p>Methods</p> <p>Two different approaches were devised to select SNPs associated with LOAD in a publicly available GWAS data set consisting of three cohorts. In both approaches, single-locus analysis (logistic regression) was conducted to filter the data with a less conservative p-value than the Bonferroni threshold; this resulted in a subset of SNPs used next in multi-locus analysis (random forest (RF)). In the second approach, we took into account prior biological knowledge, and performed sample stratification and linkage disequilibrium (LD) in addition to logistic regression analysis to preselect loci to input into the RF classifier construction step.</p> <p>Results</p> <p>The first approach gave 199 SNPs mostly associated with genes in calcium signaling, cell adhesion, endocytosis, immune response, and synaptic function. These SNPs together with <it>APOE and GAB2 </it>SNPs formed a predictive subset for LOAD status with an average error of 9.8% using 10-fold cross validation (CV) in RF modeling. Nineteen variants in LD with <it>ST5, TRPC1, ATG10, ANO3, NDUFA12, and NISCH </it>respectively, genes linked directly or indirectly with neurobiology, were identified with the second approach. These variants were part of a model that included <it>APOE </it>and <it>GAB2 </it>SNPs to predict LOAD risk which produced a 10-fold CV average error of 17.5% in the classification modeling.</p> <p>Conclusions</p> <p>With the two proposed approaches, we identified a large subset of SNPs in genes mostly clustered around specific pathways/functions and a smaller set of SNPs, within or in proximity to five genes not previously reported, that may be relevant for the prediction/understanding of AD.</p

Ih Current Is Necessary to Maintain Normal Dopamine Fluctuations and Sleep Consolidation in Drosophila

HCN channels are becoming pharmacological targets mainly in cardiac diseases. But apart from their well-known role in heart pacemaking, these channels are widely expressed in the nervous system where they contribute to the neuron firing pattern. Consequently, abolishing Ih current might have detrimental consequences in a big repertoire of behavioral traits. Several studies in mammals have identified the Ih current as an important determinant of the firing activity of dopaminergic neurons, and recent evidences link alterations in this current to various dopamine-related disorders. We used the model organism Drosophila melanogaster to investigate how lack of Ih current affects dopamine levels and the behavioral consequences in the sleep∶activity pattern. Unlike mammals, in Drosophila there is only one gene encoding HCN channels. We generated a deficiency of the DmIh core gene region and measured, by HPLC, levels of dopamine. Our data demonstrate daily variations of dopamine in wild-type fly heads. Lack of Ih current dramatically alters dopamine pattern, but different mechanisms seem to operate during light and dark conditions. Behaviorally, DmIh mutant flies display alterations in the rest∶activity pattern, and altered circadian rhythms. Our data strongly suggest that Ih current is necessary to prevent dopamine overproduction at dark, while light input allows cycling of dopamine in an Ih current dependent manner. Moreover, lack of Ih current results in behavioral defects that are consistent with altered dopamine levels

Calpain inhibition mediates autophagy-dependent protection against polyglutamine toxicity.

Over recent years, accumulated evidence suggests that autophagy induction is protective in animal models of a number of neurodegenerative diseases. Intense research in the field has elucidated different pathways through which autophagy can be upregulated and it is important to establish how modulation of these pathways impacts upon disease progression in vivo and therefore which, if any, may have further therapeutic relevance. In addition, it is important to understand how alterations in these target pathways may affect normal physiology when constitutively modulated over a long time period, as would be required for treatment of neurodegenerative diseases. Here we evaluate the potential protective effect of downregulation of calpains. We demonstrate, in Drosophila, that calpain knockdown protects against the aggregation and toxicity of proteins, like mutant huntingtin, in an autophagy-dependent fashion. Furthermore, we demonstrate that, overexpression of the calpain inhibitor, calpastatin, increases autophagosome levels and is protective in a mouse model of Huntington's disease, improving motor signs and delaying the onset of tremors. Importantly, long-term inhibition of calpains did not result in any overt deleterious phenotypes in mice. Thus, calpain inhibition, or activation of autophagy pathways downstream of calpains, may be suitable therapeutic targets for diseases like Huntington's disease.This is the published version of the manuscript. It is available online from NPG in Cell Death and Differentiaiton here: http://www.nature.com/cdd/journal/vaop/ncurrent/full/cdd2014151a.html

Tricyclic pyrazoles. Part 8. Synthesis, biological evaluation and modelling of tricyclic pyrazole carboxamides as potential CB2 receptor ligands with antagonist/inverse agonist properties.

Previous studies have investigated the relevance and structure-activity relationships (SARs) of pyrazole derivatives in relation with cannabinoid receptors, and the series of tricyclic 1,4-dihydroindeno[1,2-c] pyrazoles emerged as potent CB2 receptor ligands. In the present study, novel 1,4-dihydroindeno[1,2-c] pyrazole and 1H-benzo[g]indazole carboxamides containing a cyclopropyl or a cyclohexyl substituent were designed and synthesized to evaluate the influence of these structural modifications towards CB1 and CB2 receptor affinities. Among these derivatives, compound 15 (6-cyclopropyl-1-(2,4- dichlorophenyl)-N-(adamantan-1-yl)-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamide) showed the highest CB2 receptor affinity (Ki \ubc 4 nM) and remarkable selectivity (KiCB1/KiCB2 \ubc 2232), whereas a similar affinity, within the nM range, was seen for the fenchyl derivative (compound 10: Ki \ubc 6 nM), for the bornyl analogue (compound 14: Ki \ubc 38 nM) and, to a lesser extent, for the aminopiperidine derivative (compound 6: Ki \ubc 69 nM). Compounds 10 and 14 were also highly selective for the CB2 receptor (KiCB1/KiCB2 &gt; 1000), whereas compound 6 was relatively selective (KiCB1/KiCB2 \ubc 27). The four compounds were also subjected to GTPgS binding analysis showing antagonist/inverse agonist properties (IC50 for compound 14 \ubc 27 nM, for 15 \ubc 51 nM, for 10 \ubc 80 nM and for 6 \ubc 294 nM), and this activity was confirmed for the three more active compounds in a CB2 receptor-specific in vitro bioassay consisting in the quantification of prostaglandin E2 release by LPS-stimulated BV2 cells, in the presence and absence of WIN55,212-2 and/or the investigated compounds. Modelling studies were also conducte