69 research outputs found

    Does methylphenidate improve inhibition and other cognitive abilities in adults with childhood-onset ADHD?

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    Contains fulltext : 48908.pdf (publisher's version ) (Closed access)We examined the effect of methylphenidate (Mph) on inhibition and several other cognitive abilities in 43 adults with Attention Deficit Hyperactivity Disorder (ADHD) by use of Conners' Continuous Performance Test (CPT) and the Change Task (ChT), an extension of the Stop Signal Test (SST). In a double blind, cross-over, placebo controlled study with Mph, tests were administered during the third week of individually titrated treatment with Mph (maximum dose 1 mg / kg / day) and during the third week of treatment with placebo. We established large medication effects for commission errors, standard error of mean reaction time, and attentiveness on the CPT, as well as moderate medication effects for mean reaction time on the CPT and response re-engagement speed on the ChT. For Stop Signal Reaction Time (SSRT) on the ChT, we also established large effects of Mph, but only in a group of participants who showed slow SSRTs on placebo. Mph indeed ameliorates inhibition, which is the core problem of ADHD, and certain other cognitive abilities in adults with ADHD

    Advances in understanding and treating ADHD

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    Attention deficit hyperactivity disorder (ADHD) is a neurocognitive behavioral developmental disorder most commonly seen in childhood and adolescence, which often extends to the adult years. Relative to a decade ago, there has been extensive research into understanding the factors underlying ADHD, leading to far more treatment options available for both adolescents and adults with this disorder. Novel stimulant formulations have made it possible to tailor treatment to the duration of efficacy required by patients, and to help mitigate the potential for abuse, misuse and diversion. Several new non-stimulant options have also emerged in the past few years. Among these, cognitive behavioral interventions have proven popular in the treatment of adult ADHD, especially within the adult population who cannot or will not use medications, along with the many medication-treated patients who continue to show residual disability

    One for All, All for One: A Close Look at In-Resin Fluorescence Protocols for CLEM

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    Sample preparation is the novel bottleneck for high throughput correlative light and electron microscopy (CLEM). Protocols suitable for both imaging methods must therefore balance the requirements of each technique. For fluorescence light microscopy, a structure of interest can be targeted using: 1) staining, which is often structure or tissue specific rather than protein specific, 2) dye-coupled proteins or antibodies, or 3) genetically encoded fluorescent proteins. Each of these three methods has its own advantages. For ultrastructural investigation by electron microscopy (EM) resin embedding remains a significant sample preparation approach, as it stabilizes the sample such that it withstands the vacuum conditions of the EM, and enables long-term storage. Traditionally, samples are treated with heavy metal salts prior to resin embedding, in order to increase imaging contrast for EM. This is particularly important for volume EM (vEM) techniques. Yet, commonly used contrasting agents (e.g., osmium tetroxide, uranyl acetate) tend to impair fluorescence. The discovery that fluorescence can be preserved in resin-embedded specimens after mild heavy metal staining was a game changer for CLEM. These so-called in-resin fluorescence protocols present a significant leap forward for CLEM approaches towards high precision localization of a fluorescent signal in (volume) EM data. Integrated microscopy approaches, combining LM and EM detection into a single instrument certainly require such an "all in one" sample preparation. Preserving, or adding, dedicated fluorescence prior to resin embedding requires a compromise, which often comes at the expense of EM imaging contrast and membrane visibility. Especially vEM can be strongly hampered by a lack of heavy metal contrasting. This review critically reflects upon the fundamental aspects of resin embedding with regard to 1) specimen fixation and the physics and chemistry underlying the preservation of protein structure with respect to fluorescence and antigenicity, 2) optimization of EM contrast for transmission or scanning EM, and 3) the choice of embedding resin. On this basis, various existing workflows employing in-resin fluorescence are described, highlighting their common features, discussing advantages and disadvantages of the respective approach, and finally concluding with promising future developments for in-resin CLEM.ISSN:2296-634
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