Investigation of memory, executive functions, and anatomic correlates in asymptomatic FMR1 premutation carriers

AbstractFragile X–associated tremor/ataxia syndrome (FXTAS) is a late-onset movement disorder associated with FMR1 premutation alleles. Asymptomatic premutation (aPM) carriers have preserved cognitive functions, but they present subtle executive deficits. Current efforts are focusing on the identification of specific cognitive markers that can detect aPM carriers at higher risk of developing FXTAS. This study aims at evaluating verbal memory and executive functions as early markers of disease progression while exploring associated brain structure changes using diffusion tensor imaging. We assessed 30 aPM men and 38 intrafamilial controls. The groups perform similarly in the executive domain except for decreased performance in motor planning in aPM carriers. In the memory domain, aPM carriers present a significant decrease in verbal encoding and retrieval. Retrieval is associated with microstructural changes of the white matter (WM) of the left hippocampal fimbria. Encoding is associated with changes in the WM under the right dorsolateral prefrontal cortex, a region implicated in relational memory encoding. These associations were found in the aPM group only and did not show age-related decline. This may be interpreted as a neurodevelopmental effect of the premutation, and longitudinal studies are required to better understand these mechanisms

Rational use of antioxidants in solid oral pharmaceutical preparations

Antioxidants are currently used as efficient excipients that delay or inhibit the oxidation process of molecules. Excipients are often associated with adverse reactions. Stability studies can guide the search for solutions that minimize or delay the processes of degradation. The ability to predict oxidation reactions in different drugs is important. Methods: This study was conducted to assess the rational use of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sodium metabisulfite (SMB), propyl gallate (PG) and cysteine (CYS) in tablet formulations of simvastatin and ketoconazole. These antioxidants were evaluated according to stability parameters and the relationship between efficiency of the antioxidant and chemical structure of the drugs. Results were compared with DPPH tests and computational simulations. BHT was most efficient regarding simvastatin stability, and the most effective BHT concentrations for maintaining stability were 0.5 and 0.1%. In relation to ketoconazole, SMB was most efficient for maintaining content and dissolution profile. The evaluation by DPPH showed that the largest percentage of absorbance reduction was observed for PG, while SMB proved most efficient and had lower consumption of DPPH. The same pattern was observed, albeit with lower efficiency, for the other lipophilic antioxidants such as BHT and BHA. The results of the molecular modeling study demonstrated that electronic properties obtained were correlated with antioxidant activity in solution, being useful for the rational development of liquid pharmaceutical formulations but not for solid oral formulations. This study demonstrated the importance of considering stability parameters and molecular modeling to elucidate the chemical phenomena involved in antioxidant activity, being useful for the rational use of antioxidants in the development of pharmaceutical formulations.Atualmente, antioxidantes são usados como excipientes eficientes, que retardam ou inibem o processo de oxidação de moléculas. Excipientes são frequentemente associados a efeitos adversos. Estudos de estabilidade podem ajudar na busca por possíveis soluções para minimizar ou retardar os processos de degradação. A habilidade de prever as reações de oxidação em diferentes fármacos é importante. O estudo foi conduzido com o objetivo de avaliar o uso racional de hidroxianisol butilado (BHA), hidroxitolueno butilado (BHT), metabissulfito sódico (SMB), galato de propila (PG) e cisteína (CYS) em formulações de comprimidos de sinvastatina e cetoconazol. Eles foram avaliados por parâmetros de estabilidade e pela relação entre a eficiência dos antioxidantes e a estrutura química do fármaco. Os resultados foram comparados com testes de DPPH e simulações em computador. BHT foi mais eficiente com relação a estabilidade da sinvastatina e às concentrações mais eficientes para manutenção de estabilidade foram 0,5 e 0,1%. Com relação ao cetoconazol, SMB foi mais eficiente em manter o conteúdo e o perfil de dissolução. A avaliação por DPPH mostrou que o maior percentual de redução de absorção foi observado para PG, enquanto que SMB mostrou ser mais eficiente e consumir menos DPPH. A mesma tendência foi observada com menos eficiência em todos os outros antioxidantes lipofílicos como o BHT e BHA. Os resultados do estudo de modelagem molecular demonstraram que as propriedades eletrônicas obtidas podem ser correlacionadas com a atividade antioxidante em solução, sendo útil para o desenvolvimento racional de formulações farmacêuticas líquidas, mas não para formulações sólidas orais. Este estudo demonstrou a importância de considerar parâmetros de estabilidade e modelagem molecular para elucidar os fenômenos químicos envolvidos na atividade antioxidante, sendo úteis para o uso racional de antioxidantes no desenvolvimento de formulações farmacêuticas

A consensus protocol for functional connectivity analysis in the rat brain

Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows for comparisons with data modalities collected under invasive or terminal procedures. Currently, animal acquisitions are performed with varying protocols and analyses that hamper result comparison and integration. Here we introduce StandardRat, a consensus rat functional magnetic resonance imaging acquisition protocol tested across 20 centers. To develop this protocol with optimized acquisition and processing parameters, we initially aggregated 65 functional imaging datasets acquired from rats across 46 centers. We developed a reproducible pipeline for analyzing rat data acquired with diverse protocols and determined experimental and processing parameters associated with the robust detection of functional connectivity across centers. We show that the standardized protocol enhances biologically plausible functional connectivity patterns relative to previous acquisitions. The protocol and processing pipeline described here is openly shared with the neuroimaging community to promote interoperability and cooperation toward tackling the most important challenges in neuroscience

Rational Design of W-Doped Ag3PO4 as an Efficient Antibacterial Agent and Photocatalyst for Organic Pollutant Degradation

International audienceBacterial and organic pollutants are major problems with potential adverse impacts on human health and the environment. A promising strategy to alleviate these impacts consists in designing innovative photocatalysts with a wider spectrum of application. In this paper, we report the improved photocatalytic and antibacterial activities of chemically precipitated Ag3PO4 microcrystals by the incorporation of W at doping levels 0.5, 1, and 2 mol %. The presence of W directly influences the crystallization of Ag3PO4, affecting the morphology, particle size, and surface area of the microcrystals. Also, the characterization via experimental and theoretical approaches evidenced a high density of disordered [AgO4], [PO4], and [WO4] structural clusters due to the substitution of P5+ by W6+ into the Ag3PO4 lattice. This leads to new defect-related energy states, which decreases the band gap energy of the materials (from 2.27 to 2.04 eV) and delays the recombination of e'-h(center dot) pairs, leading to an enhanced degradation process. As a result of such behaviors, W-doped Ag3PO4 (Ag3PO4:W) is a better visible-light photocatalyst than Ag3PO4, demonstrated here by the photodegradation of potential environmental pollutants. The degradation of rhodamine B dye was 100% in 4 min for Ag3PO4:W 1%, and for Ag3PO4, the obtained result was 90% of degradation in 15 min of reaction. Ag3PO4:W 1% allowed the total degradation of cephalexin antibiotic in only 4 min, whereas pure Ag3PO4 took 20 min to achieve the same result. For the degradation of imidacloprid insecticide, Ag3PO4:W 1% allowed 90% of degradation, whereas Ag3PO4 allowed 40%, both in 20 min of reaction. Moreover, the presence of W-dopant results in a 16-fold improvement of bactericidal performance against methicillin-resistant Staphylococcus aureus. The outstanding results using the Ag3PO4:W material demonstrated its potential multifunctionality for the control of organic pollutants and bacteria in environmental applications

A consensus protocol for functional connectivity analysis in the rat brain

International audienc