Preserving Creativity in Medicine

Imagination and creativity are essential traits that medicine, and medical insurers, must again learn to recognize and rewar

Effect of Atomoxetine Treatment on Reading and Phonological Skills in Children with Dyslexia or Attention-Deficit/Hyperactivity Disorder and Comorbid Dyslexia in a Randomized, Placebo-Controlled Trial

OBJECTIVES: Evaluated the effects of atomoxetine on the reading abilities of children with dyslexia only or attention-deficit/hyperactivity disorder (ADHD) and comorbid dyslexia. METHODS: Children aged 10-16 years (N = 209) met Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria for dyslexia only (n = 58), ADHD and comorbid dyslexia (n = 124), or ADHD only (n = 27) and were of normal intelligence. Patients were treated with atomoxetine (1.0-1.4 mg/kg/day) or placebo in a 16-week, randomized, placebo-controlled, double-blind trial. The dyslexia-only and ADHD and comorbid dyslexia groups were randomized 1:1; the ADHD-only group received atomoxetine in a blinded manner. Reading abilities were measured with the Woodcock Johnson III (WJIII), Comprehensive Test of Phonological Processing (CTOPP), Gray Oral Reading Tests-4, and Test of Word Reading Efficiency. RESULTS: Atomoxetine-treated dyslexia-only patients compared with placebo patients had significantly greater improvement (p < 0.02) with moderate to approaching high effect sizes (ES) on WJIII Word Attack (ES = 0.72), Basic Reading Skills (ES = 0.48), and Reading Vocabulary (ES = 0.73). In the atomoxetine-treated ADHD and comorbid dyslexia group, improvement on the CTOPP Elision measure (ES = 0.50) was significantly greater compared with placebo (p < 0.02). Total, inattentive, and hyperactive/impulsive ADHD symptom reductions were significant in the atomoxetine-treated ADHD and comorbid dyslexia group compared with placebo, and from baseline in the ADHD-only group (p ≤ 0.02). ADHD symptom improvements in the ADHD and comorbid dyslexia group were not correlated with improvements in reading. CONCLUSIONS: Atomoxetine treatment improved reading scores in patients with dyslexia only and ADHD and comorbid dyslexia. Improvements for patients with dyslexia only were in critical components of reading, including decoding and reading vocabulary. For patients with ADHD and comorbid dyslexia, improvements in reading scores were distinct from improvement in ADHD inattention symptoms alone. These data represent the first report of improvements in reading measures following pharmacotherapy treatment in patients with dyslexia only evaluated in a randomized, double-blind trial

Towards an understanding of the role of COPII subunits in vesicle coat assembly

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 1997.Includes bibliographical references.by David A. Shaywitz.Ph.D

Editorial: on the road towards treatment of gastroparesis—accelerating, but do we get closer? Authors' reply

LINKED CONTENTThis article is linked to Kuo et al and Wuestenberghs & Gourcerol papers. To view these articles, visit https://doi.org/10.1111/apt.16344 and https://doi.org/10.1111/apt.1637

Prospective isolation and global gene expression analysis of definitive and visceral endoderm

AbstractIn spite of the therapeutic importance of endoderm derivatives such as the pancreas, liver, lung, and intestine, there are few molecular markers specific for early endoderm. In order to identify endoderm-specific genes as well as to define transcriptional differences between definitive and visceral endoderm, we performed microarray analysis on E8.25 definitive and visceral endoderm. We have developed an early endoderm gene expression signature, and clarified the transcriptional similarities and differences between definitive and visceral endoderm. Additionally, we have developed methods for flow cytometric isolation of definitive and visceral endoderm. These results shed light on the mechanism of endoderm formation and should facilitate investigation of endoderm formation from embryonic stem cells

Developmental dyslexia in Chinese and English populations: dissociating the effect of dyslexia from language differences

Previous neuroimaging studies have suggested that developmental dyslexia has a different neural basis in Chinese and English populations because of known differences in the processing demands of the Chinese and English writing systems. Here, using functional magnetic resonance imaging, we provide the first direct statistically based investigation into how the effect of dyslexia on brain activation is influenced by the Chinese and English writing systems. Brain activation for semantic decisions on written words was compared in English dyslexics, Chinese dyslexics, English normal readers and Chinese normal readers, while controlling for all other experimental parameters. By investigating the effects of dyslexia and language in one study, we show common activation in Chinese and English dyslexics despite different activation in Chinese versus English normal readers. The effect of dyslexia in both languages was observed as less than normal activation in the left angular gyrus and in left middle frontal, posterior temporal and occipitotemporal regions. Differences in Chinese and English normal reading were observed as increased activation for Chinese relative to English in the left inferior frontal sulcus; and increased activation for English relative to Chinese in the left posterior superior temporal sulcus. These cultural differences were not observed in dyslexics who activated both left inferior frontal sulcus and left posterior superior temporal sulcus, consistent with the use of culturally independent strategies when reading is less efficient. By dissociating the effect of dyslexia from differences in Chinese and English normal reading, our results reconcile brain activation results with a substantial body of behavioural studies showing commonalities in the cognitive manifestation of dyslexia in Chinese and English populations. They also demonstrate the influence of cognitive ability and learning environment on a common neural system for reading

Atomoxetine for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children with ADHD and dyslexia

<p>Abstract</p> <p>Background</p> <p>The objective of this study was to assess the effects of atomoxetine on treating attention-deficit/hyperactivity disorder (ADHD), on reading performance, and on neurocognitive function in youth with ADHD and dyslexia (ADHD+D).</p> <p>Methods</p> <p>Patients with ADHD (n = 20) or ADHD+D (n = 36), aged 10-16 years, received open-label atomoxetine for 16 weeks. Data from the ADHD Rating Scale-IV (ADHDRS-IV), Kaufman Test of Educational Achievement (K-TEA), Working Memory Test Battery for Children (WMTB-C), and Life Participation Scale for ADHD-Child Version (LPS-C) were assessed.</p> <p>Results</p> <p>Atomoxetine demonstrated significant improvement for both groups on the ADHDRS-IV, LPS-C, and K-TEA reading comprehension standard and composite scores. K-TEA spelling subtest improvement was significant for the ADHD group, whereas the ADHD+D group showed significant reading decoding improvements. Substantial K-TEA reading and spelling subtest age equivalence gains (in months) were achieved for both groups. The WMTB-C central executive score change was significantly greater for the ADHD group. Conversely, the ADHD+D group showed significant phonological loop score enhancement by visit over the ADHD group. Atomoxetine was well tolerated, and commonly reported adverse events were similar to those previously reported.</p> <p>Conclusions</p> <p>Atomoxetine reduced ADHD symptoms and improved reading scores in both groups. Conversely, different patterns and magnitude of improvement in working memory component scores existed between ADHD and ADHD+D patients. Though limited by small sample size, group differences in relation to the comparable changes in improvement in ADHD symptoms could suggest that brain systems related to the therapeutic benefit of atomoxetine in reducing ADHD symptoms may be different in individuals with ADHD+D and ADHD without dyslexia.</p> <p>Trial Registration</p> <p>Clinical Trial Registry: ClinicalTrials.gov: NCT00191048</p

Sec16 Defines Endoplasmic Reticulum Exit Sites and is Required for Secretory Cargo Export in Mammalian Cells

The selective export of proteins and lipids from the endoplasmic reticulum (ER) is mediated by the coat protein complex II (COPII) that assembles onto the ER membrane. In higher eukaryotes, COPII proteins assemble at discrete sites on the membrane known as ER exit sites (ERES). Here, we identify Sec16 as the protein that defines ERES in mammalian cells. Sec16 localizes to ERES independent of Sec23/24 and Sec13/31. Overexpression, and to a lesser extent, small interfering RNA depletion of Sec16, both inhibit ER-to-Golgi transport suggesting that Sec16 is required in stoichiometric amounts. Sar1 activity is required to maintain the localization of Sec16 at discrete locations on the ER membrane, probably through preventing its dissociation. Our data suggest that Sar1-GTP-dependent assembly of Sec16 on the ER membrane forms an organized scaffold defining an ERES