Attention deficit hyperactivity disorder (ADHD) is a complex condition with a heterogeneous presentation. Current diagnosis is primarily based on subjective experience and observer reports of ...behavioral symptoms – an approach that has significant limitations. Many studies show that individuals with ADHD exhibit poorer performance on cognitive tasks than neurotypical controls, and at least seven main functional domains appear to be implicated in ADHD. We discuss the underlying neural mechanisms of cognitive functions associated with ADHD, with emphasis on the neural basis of selective attention, demonstrating the feasibility of basic research approaches for further understanding cognitive behavioral processes as they relate to human psychopathology. The study of circuit-level mechanisms underlying executive functions in nonhuman primates holds promise for advancing our understanding, and ultimately the treatment, of ADHD.
Deficits in many different cognitive domains are associated with ADHD. Cognitive batteries that assess the performance of individuals within these different cognitive domains show that the disorder is very heterogeneous.
ADHD medication that improves performance in one cognitive measure does not necessarily improve it in others.
Studies in human and nonhuman primates have revealed much about the underlying mechanisms of endogenous, exogenous, and spatial- and feature-based selective attention.
The regions of the brain and the neuromodulators that influence selective attention and other cognitive domains implicated in ADHD are non-overlapping.
We evaluated the effect of the CYP2C19 genotype on the pharmacokinetics and pharmacodynamcis of clopidogrel. Twenty‐four subjects were divided into three groups on the basis of their CYP2C19 ...genotype: homozygous extensive metabolizers (homoEMs, n = 8), heterozygous EMs (heteroEMs, n = 8), and poor metabolizers (PMs, n = 8). After a single 300‐mg loading dose of clopidogrel on day 1, followed by a 75‐mg daily maintenance dose from days 2 to 7, we measured the plasma levels of clopidogrel and assessed the antiplatelet effect as pharmacodynamics. The mean clopidogrel area under the curve (AUC) for PMs was 1.8‐ and 2.9‐fold higher than that for heteroEMs and homoEMs, respectively (P = 0.013). The mean peak plasma concentration in PMs was 1.8‐ and 4.7‐fold higher than that of heteroEMs and homoEMs, respectively (P = 0.008). PMs exhibited a significantly lower antiplatelet effect than heteroEMs or homoEMs (P < 0.001). From these findings it is clear that the CYP2C19 genotype affects the plasma levels of clopidogrel and modulates the antiplatelet effect of clopidogrel.
Clinical Pharmacology & Therapeutics (2008); 84, 2, 236–242 doi:10.1038/clpt.2008.20
Intestinal tuberculosis and Crohn's disease are chronic inflammatory bowel disorders that are difficult to differentiate from one another. This study aimed to evaluate the diagnostic value of various ...colonoscopic findings in the differential diagnosis between intestinal tuberculosis and Crohn's disease.
Colonoscopic findings on initial work-up were prospectively recorded in patients with an initial diagnosis of either intestinal tuberculosis or Crohn's disease. These findings were analyzed after a final diagnosis of intestinal tuberculosis (n = 44) or Crohn's disease (n = 44) had been made after follow-up.
Four parameters (anorectal lesions, longitudinal ulcers, aphthous ulcers, and cobblestone appearance) were significantly more common in patients with Crohn's disease than in patients with intestinal tuberculosis. Four other parameters (involvement of fewer than four segments, a patulous ileocecal valve, transverse ulcers, and scars or pseudopolyps) were observed more frequently in patients with intestinal tuberculosis than in patients with Crohn's disease. We hypothesized that a diagnosis of Crohn's disease could be made when the number of parameters characteristic of Crohn's disease was higher than the number of parameters characteristic of intestinal tuberculosis, and vice versa. Making these assumptions, we calculated that the diagnosis of either intestinal tuberculosis or Crohn's disease would have been made made correctly in 77 of our 88 patients (87.5 %), incorrectly in seven patients (8.0 %), and would not have been made in four patients (4.5 %).
A systematic analysis of colonoscopic findings is very useful in the differential diagnosis between intestinal tuberculosis and Crohn's disease.
Students with disabilities are increasingly enrolling in colleges and universities. However, many institutions are still unprepared to support them beyond the basic federal mandate of equal access ...and reasonable accommodations. This qualitative study utilized a nontraditional media of reflective journaling to capture the anecdotal experiences of 16 college students with disabilities for a 10-week period. Four major themes emerged concerning barriers and frustrations these students encountered on a daily basis: (a) faculty perception, (b) fit of advisors, (c) college stressors, and (d) quality of support services. Recommendations for higher education administrators and disability personnel to become more vigilant in improving support for this population are discussed.
Differences in global levels of histone acetylation occur in normal and cancer cells, although the reason why cells regulate these levels has been unclear. Here we demonstrate a role for histone ...acetylation in regulating intracellular pH (pHi). As pHi decreases, histones are globally deacetylated by histone deacetylases (HDACs), and the released acetate anions are coexported with protons out of the cell by monocarboxylate transporters (MCTs), preventing further reductions in pHi. Conversely, global histone acetylation increases as pHi rises, such as when resting cells are induced to proliferate. Inhibition of HDACs or MCTs decreases acetate export and lowers pHi, particularly compromising pHi maintenance in acidic environments. Global deacetylation at low pH is reflected at a genomic level by decreased abundance and extensive redistribution of acetylation throughout the genome. Thus, acetylation of chromatin functions as a rheostat to regulate pHi with important implications for mechanism of action and therapeutic use of HDAC inhibitors.
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► Global levels of histone acetylation change in response to pHi alterations ► Histone deacetylation and acetate transport through H+-coupled MCTs regulates pHi ► Proliferation of T cells results in increases in pHi and global histone acetylation ► HDAC and MCT inhibitors decrease pHi
The feasibility of using a low-cost super hydrophobic powder as water-resisting admixture or water-repellent surface coating for concrete has been investigated. The powder was produced from paper ...sludge ash (PSA), a by-product from the manufacture of recycled paper. The effect of hydrophobic PSA on workability, strength and transport properties, including sorptivity, water absorption, diffusivity, permeability and electrical conductivity is reported. Samples were prepared at water/cement ratio of 0.38, cured up to 28days and conditioned at 50°C to constant mass prior to testing. It was found that replacing Portland cement with 12% hydrophobic PSA reduced water absorption, sorptivity and conductivity by 84%, 86% and 85% respectively, with no major detrimental effects on hydration, strength and density. When used as a surface coating, the hydrophobic PSA reduced both absorption and sorptivity by 85–99% depending on the adhesive used. Samples surface coated with hydrophobic PSA showed excellent water repelling and self-cleaning characteristics.
Highlights • Substantial development in creating and validating RNA therapeutics has been made. • There are more than 100 cancer clinical trials reported, so far. • Challenges related with delivery, ...targeting and off-target effects are being optimized. • The success of these strategies in the treatment of cancer is still to come.
The use of organic–inorganic metal oxide products in biomedical applications has emerged as the most expanding field. To have long-lasting stability and improved reliability, a biomaterial must be ...specially chosen and have bioactivity and mechanical properties from the application's point of view. Rambutan (Nephelium lappaceum L.) fruit is considered as one of the bioactive components. In this study, ZrO2 is prepared by hydrothermal route using a green rambutan extract as a reducing agent and it used for biomedical applications. It was found that ZrO2 nanorods hamper the growth of cancerous cells in a dose-dependent manner at a half-maximum inhibitory concentration of 55.32 μg mL−1. Phase-contrast microscopic studies confirm that ZrO2 nanorods disrupt the cell membrane and induce cell death. Keeping this in mind, ZrO2 nanorods can be a promising agent in biomedical applications.
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