Topiramato en el tratamiento de la dependencia etílica: un metaanálisis

Introduction. Several controlled clinical trials have studied the efficacy of topiramate in the treatment of alcoholism. In this paper, we have performed a meta-analysis of those trials in which topiramate was compared with placebo and then we reviewed its efficacy in trials in which it was compared with other drugs. Method. A quantitative synthesis of data was performed using inverse variance weighting in a random effects model. Results. Based on three placebo-controlled trials, topiramate is more efficacious than placebo in reducing the percentage of heavy drinking days (23.2%, 95% confidence interval [CI]: 15.7 to 34.4), increasing the number of days of abstinence (mean difference: 2.9 days, 95% CI: 2.5 to 3.3), and lowering the logarithm of γ-GT levels (mean difference: 0.075 95% CI: 0.048 to 0.118). Two trials suggested that topiramate is also more efficacious than naltrexone, and one open-label study reported better results for disulfiram than for topiramate. Conclusion. Topiramate can be used in alcohol dependence. Adverse effects such as paresthesia or insomnia should be taken into account when prescribing topiramate. Its optimal dosage requires further research.Introducción. Algunos ensayos clínicos controlados han estudiado la eficacia del topiramato para el tratamiento del alcoholismo. En este artículo, primero realizamos un metaanálisis de los ensayos donde el topiramato era comparado con el placebo, y después revisamos la eficacia en los ensayos donde era comparado con otros fármacos. Método. Una síntesis cuantitativa de los datos se llevó a cabo ponderando por el inverso de la varianza en un modelo de efectos aleatorios. Resultados. En base a tres ensayos clínicos controlados, el topiramato es más eficaz que el placebo en: reducción del porcentaje de los días de consumo elevado (23,2%, intervalo de confianza [IC] del 95%: 15,7 a 34,4), incremento del número de días de abstinencia (diferencia media: 2,9 días, IC del 95%: 2,5 a 3,3) y descenso del logaritmo de los niveles de γ-GT (diferencia media: 0,075, IC del 95%: 0,048 a 0,118). Dos ensayos sugirieron que el topiramato es también más eficaz que la naltrexona y un estudio abierto refirió mejores resultados para el disulfirán que para el topiramato. Conclusiones. el topiramato puede ser utilizado para el tratamiento en la dependencia etílica; los efectos adversos tales como las parestesias o el insomnio deben ser tenidos en cuenta cuando se prescribe topiramato. La dosis óptima precisa investigación adiciona

Semantic Verbal Fluency Pattern, Dementia Rating Scores and Adaptive Behavior Correlate With Plasma Aβ Concentrations in Down Syndrome Young Adults

Down syndrome (DS) is an intellectual disability (ID) disorder in which language and specifically, verbal fluency are strongly impaired domains; nearly all adults show neuropathology of Alzheimer's disease (AD), including amyloid deposition by their fifth decade of life. In the general population, verbal fluency deficits are considered a strong AD predictor being the semantic verbal fluency task (SVFT) a useful tool for enhancing early diagnostic. However, there is a lack of information about the association between the semantic verbal fluency pattern (SVFP) and the biological amyloidosis markers in DS. In the current study, we used the SVFT in young adults with DS to characterize their SVFP, assessing total generated words, clustering, and switching. We then explored its association with early indicators of dementia, adaptive behavior and amyloidosis biomarkers, using the Dementia Questionnaire for Persons with Intellectual Disability (DMR), the Adaptive Behavior Assessment System-Second Edition (ABAS-II), and plasma levels of Aβ peptides (Aβ and Aβ), as a potent biomarker of AD. In DS, worse performance in SVFT and poorer communication skills were associated with higher plasma Aβ concentrations, a higher DMR score and impaired communication skills (ABAS-II). The total word production and switching ability in SVFT were good indicators of plasma Aβ concentration. In conclusion, we propose the SVFT as a good screening test for early detection of dementia and amyloidosis in young adults with DS

QWIP: A Quantitative Metric for Quality Control of Aquatic Reflectance Spectral Shape Using the Apparent Visible Wavelength

The colors of the ocean and inland waters span clear blue to turbid brown, and the corresponding spectral shapes of the water-leaving signal are diverse depending on the various types and concentrations of phytoplankton, sediment, detritus and colored dissolved organic matter. Here we present a simple metric developed from a global dataset spanning blue, green and brown water types to assess the quality of a measured or derived aquatic spectrum. The Quality Water Index Polynomial (QWIP) is founded on the Apparent Visible Wavelength (AVW), a one-dimensional geophysical metric of color that is inherently correlated to spectral shape calculated as a weighted harmonic mean across visible wavelengths. The QWIP represents a polynomial relationship between the hyperspectral AVW and a Normalized Difference Index (NDI) using red and green wavelengths. The QWIP score represents the difference between a spectrum’s AVW and NDI and the QWIP polynomial. The approach is tested extensively with both raw and quality controlled field data to identify spectra that fall outside the general trends observed in aquatic optics. For example, QWIP scores less than or greater than 0.2 would fail an initial screening and be subject to additional quality control. Common outliers tend to have spectral features related to: 1) incorrect removal of surface reflected skylight or 2) optically shallow water. The approach was applied to hyperspectral imagery from the Hyperspectral Imager for the Coastal Ocean (HICO), as well as to multispectral imagery from the Visual Infrared Imaging Radiometer Suite (VIIRS) using sensor-specific extrapolations to approximate AVW. This simple approach can be rapidly implemented in ocean color processing chains to provide a level of uncertainty about a measured or retrieved spectrum and flag questionable or unusual spectra for further analysis

E-cadherin transcriptional downregulation by promoter methylation but not mutation is related to epithelial-to-mesenchymal transition in breast cancer cell lines

Using genome-wide expression profiling of a panel of 27 human mammary cell lines with different mechanisms of E-cadherin inactivation, we evaluated the relationship between E-cadherin status and gene expression levels. Expression profiles of cell lines with E-cadherin (CDH1) promoter methylation were significantly different from those with CDH1 expression or, surprisingly, those with CDH1 truncating mutations. Furthermore, we found no significant differentially expressed genes between cell lines with wild-type and mutated CDH1. The expression profile complied with the fibroblastic morphology of the cell lines with promoter methylation, suggestive of epithelial-mesenchymal transition (EMT). All other lines, also the cases with CDH1 mutations, had epithelial features. Three non-tumorigenic mammary cell lines derived from normal breast epithelium also showed CDH1 promoter methylation, a fibroblastic phenotype and expression profile. We suggest that CDH1 promoter methylation, but not mutational inactivation, is part of an entire programme, resulting in EMT and increased invasiveness in breast cancer. The molecular events that are part of this programme can be inferred from the differentially expressed genes and include genes from the TGFbeta pathway, transcription factors involved in CDH1 regulation (i.e. ZFHX1B, SNAI2, but not SNAI1, TWIST), annexins, AP1/2 transcription factors and members of the actin and intermediate filament cytoskeleton organisation.Toxicolog

Alteration of inhibitory circuits in the somatosensory cortex of Ts65Dn mice, a model for Down's syndrome

Down's syndrome (DS), with an incidence of one in 800 live births, is the most common genetic disorder associated with mental retardation. This trisomy on chromosome 21 induces a variable phenotype in which the only common feature is the presence of mental retardation. The neural mechanisms underlying mental retardation might include defects in the formation of neuronal networks and neural plasticity. DS patients have alterations in the morphology, the density and the distribution of dendritic spines in the pyramidal neurons of the cortex. Our hypothesis is that the deficits in dendritic arborization observed in the principal neurons of DS patients and Ts65Dn mice (a model for DS that mimics most of the structural alterations observed in humans) may be mediated to some extent by changes in their inhibitory inputs. Different types of interneurons control different types of inhibition. Therefore, to understand well the changes in inhibition in DS, it is necessary to study the different types of interneurons separately. We have studied the expression of synaptophysin, Glutamic acid decarboxylase-67 (GAD-67) and calcium-binding protein-expressing cells in the primary somatosensory cortex of 4¿5 month old Ts65Dn mice. We have observed an increment of GAD67 immunoreactivity that is related mainly to an increment of calretinin-immunoreactive cells and among them the ones with bipolar morphology. Since there is a propensity for epilepsy in DS patients, this increase in interneurons might reflect an attempt by the system to block overexcitation rather than an increment in total inhibition and could explain the deficit in interneurons and principal cells observed in elderly DS patients

Retrieving Aerosol Characteristics From the PACE Mission, Part 1: Ocean Color Instrument

NASA’s Plankton, Aerosol, Clouds, ocean Ecosystem (PACE) satellite mission is scheduled to launch in 2022, with the Ocean Color Instrument (OCI) on board. For the first time reflected sunlight from the Earth across a broad spectrum from the ultraviolet (UV: 350 nm) to the short wave infrared (SWIR: 2260 nm) will be measured from a single instrument at 1 km spatial resolution. While seven discrete bands will represent the SWIR, the spectrum from 350 to 890 nm will be continuously covered with a spectral resolution of 5 nm. OCI will thus combine in a single instrument (and at an enhanced spatial resolution for the UV) the heritage capabilities of the Moderate resolution Imaging Spectroradiometer (MODIS) and the Ozone Monitoring Instrument (OMI), while covering the oxygen A-band (O2A). Designed for ocean color and ocean biology retrievals, OCI also enables continuation of heritage satellite aerosol products and the development of new aerosol characterization from space. In particular the combination of MODIS and OMI characteristics allows deriving aerosol height, absorption and optical depth along with a measure of particle size distribution. This is achieved by using the traditional MODIS visible-to-SWIR wavelengths to constrain spectral aerosol optical depth and particle size. Extrapolating this information to the UV channels allows retrieval of aerosol absorption and layer height. A more direct method to derive aerosol layer height makes use of O2A absorption methods, despite the relative coarseness of the nominal 5 nm spectral resolution of OCI. Altogether the PACE mission with OCI will be an unprecedented opportunity for aerosol characterization that will continue climate data records from the past decades and propel aerosol science forward toward new opportunities

Climatically sensitive transfer of iron to maritime Antarctic ecosystems by surface runoff

Iron supplied by glacial weathering results in pronounced hotspots of biological production in an otherwise iron-limited Southern Ocean Ecosystem. However, glacial iron inputs are thought to be dominated by icebergs. Here we show that surface runoff from three island groups of the maritime Antarctic exports more filterable (<0.45 μm) iron (6–81 kg km−2 a−1) than icebergs (0.0–1.2 kg km−2 a−1). Glacier-fed streams also export more acid-soluble iron (27.0–18,500 kg km−2 a−1) associated with suspended sediment than icebergs (0–241 kg km−2 a−1). Significant fluxes of filterable and sediment-derived iron (1–10 Gg a−1 and 100–1,000 Gg a−1, respectively) are therefore likely to be delivered by runoff from the Antarctic continent. Although estuarine removal processes will greatly reduce their availability to coastal ecosystems, our results clearly indicate that riverine iron fluxes need to be accounted for as the volume of Antarctic melt increases in response to 21st century climate change

Regional to global assessments of phytoplankton dynamics from the SeaWiFS mission

Photosynthetic production of organic matter by microscopic oceanic phytoplankton fuels ocean ecosystems and contributes roughly half of the Earth\u27s net primary production. For 13. years, the Sea-viewing Wide Field-of-view Sensor (SeaWiFS) mission provided the first consistent, synoptic observations of global ocean ecosystems. Changes in the surface chlorophyll concentration, the primary biological property retrieved from SeaWiFS, have traditionally been used as a metric for phytoplankton abundance and its distribution largely reflects patterns in vertical nutrient transport. On regional to global scales, chlorophyll concentrations covary with sea surface temperature (SST) because SST changes reflect light and nutrient conditions. However, the ocean may be too complex to be well characterized using a single index such as the chlorophyll concentration. A semi-analytical bio-optical algorithm is used to help interpret regional to global SeaWiFS chlorophyll observations from using three independent, well-validated ocean color data products; the chlorophyll a concentration, absorption by CDM and particulate backscattering. First, we show that observed long-term, global-scale trends in standard chlorophyll retrievals are likely compromised by coincident changes in CDM. Second, we partition the chlorophyll signal into a component due to phytoplankton biomass changes and a component caused by physiological adjustments in intracellular chlorophyll concentrations to changes in mixed layer light levels. We show that biomass changes dominate chlorophyll signals for the high latitude seas and where persistent vertical upwelling is known to occur, while physiological processes dominate chlorophyll variability over much of the tropical and subtropical oceans. The SeaWiFS data set demonstrates complexity in the interpretation of changes in regional to global phytoplankton distributions and illustrates limitations for the assessment of phytoplankton dynamics using chlorophyll retrievals alone

Clinical impact of HLA class I expression in rectal cancer

Contains fulltext : 69499.pdf (publisher's version ) (Open Access)PURPOSE: To determine the clinical impact of human leukocyte antigen (HLA) class I expression in irradiated and non-irradiated rectal carcinomas. EXPERIMENTAL DESIGN: Tumor samples in tissue micro array format were collected from 1,135 patients. HLA class I expression was assessed after immunohistochemical staining with two antibodies (HCA2 and HC10). RESULTS: Tumors were split into two groups: (1) tumors with >50% of tumor cells expressing HLA class I (high) and (2) tumors with < or =50% of tumor cells expressing HLA class I (low). No difference in distribution or prognosis of HLA class I expression was found between irradiated and non-irradiated patients. Patients with low expression of HLA class I (15% of all patients) showed an independent significantly worse prognosis with regard to overall survival and disease-free survival. HLA class I expression had no effect on cancer-specific survival or recurrence-free survival. CONCLUSIONS: Down-regulation of HLA class I in rectal cancer is associated with poor prognosis. In contrast to our results, previous reports on HLA class I expression in colorectal cancer described a large population of patients with HLA class I negative tumors, having a good prognosis. This difference might be explained by the fact that a large proportion of HLA negative colon tumors are microsatellite instable (MSI). MSI tumors are associated with a better prognosis than microsatellite stable (MSS). As rectal tumors are mainly MSS, our results suggest that it is both, oncogenic pathway and HLA class I expression, that dictates patient's prognosis in colorectal cancer. Therefore, to prevent confounding in future prognostic analysis on the impact of HLA expression in colorectal tumors, separate analysis of MSI and MSS tumors should be performed

Changing Paradigms in Down Syndrome: The First International Conference of the Trisomy 21 Research Society

Down syndrome (DS) is the most common genetic cause of intellectual disability (ID) in humans with an incidence of ∼1:1,000 live births worldwide. It is caused by the presence of an extra copy of all or a segment of the long arm of human chromosome 21 (trisomy 21). People with DS present with a constellation of phenotypic alterations involving most organs and organ systems. ID is present in all people with DS, albeit with variable severity. DS is also the most frequent genetic cause of Alzheimer's disease (AD), and ∼50% of those with DS will develop AD-related dementia. In the last few years, significant progress has been made in understanding the crucial genotype-phenotype relationships in DS, in identifying the alterations in molecular pathways leading to the various clinical conditions present in DS, and in preclinical evaluations of potential therapies to improve the overall health and well-being of individuals with DS. In June 2015, 230 scientists, advocates, patients, and family members met in Paris for the 1st International Conference of the Trisomy 21 Research Society. Here, we report some of the most relevant presentations that took place during the meeting