Pharmacogenomic insights into treatment and management of statin-induced myopathy

Although statins are generally well tolerated, the most common adverse drug reaction from statin therapy is myopathy. This article reviews the current pharmacogenomic knowledge of statin-induced myopathy. Furthermore, we will discuss the importance of recent pharmacogenetic advances for the treatment and management of statin-induced myopathy. Variation in the SLCO1B1 gene is associated with increased incidence of statin-induced myopathy, particularly with simvastatin and less so with other statins. If different pharmacokinetic enzymes and transporters are responsible for susceptibility to myopathy, this may explain differences in the occurrence of statin-induced myopathy in individual patients. Genotyping in patients suffering from statin-induced myopathy may help to personalize the choice of statin for the lowest chance of developing myopathy

Doping Engineering Enables Highly Conductive and Thermally Stable n-Type Organic Thermoelectrics with High Power Factor

This work exploits the scope of doping engineering as an enabler for better-performing and thermally stable n-type organic thermoelectrics. A fullerene derivative with polar triethylene glycol type side chain (PTEG-1) is doped either by "coprocessing doping" with n-type dopants such as n-DMBI and TBAF or by "sequential doping" through thermal deposition of Cs2CO3. Solid-state diffusion of Cs2CO3 appears to dope PTEG-1 in the strongest manner, leading to the highest electrical conductivity of similar to 17.5 S/cm and power factor of 32 mu W/(m K-2). Moreover, the behavior of differently doped PTEG-1 films under thermal stress is examined by electric and spectroscopic means. Cs2CO3-doped films are most stable, likely due to a coordinating interaction between the polar side chain and Cs+-based species, which immobilizes the dopant. The high power factor and good thermal stability of Cs2CO3-doped PTEG-1 make it very promising for tangible thermoelectric applications

Molecular Doping Directed by a Neutral Radical

[Image: see text] Molecular doping makes possible tunable electronic properties of organic semiconductors, yet a lack of control of the doping process narrows its scope for advancing organic electronics. Here, we demonstrate that the molecular doping process can be improved by introducing a neutral radical molecule, namely nitroxyl radical (2,2,6,6-teramethylpiperidin-i-yl) oxyl (TEMPO). Fullerene derivatives are used as the host and 1,3-dimethyl-2-phenyl-2,3-dihydro-1H-benzo[d]imidazoles (DMBI-H) as the n-type dopant. TEMPO can abstract a hydrogen atom from DMBI-H and transform the latter into a much stronger reducing agent DMBI(•), which efficiently dopes the fullerene derivative to yield an electrical conductivity of 4.4 S cm(–1). However, without TEMPO, the fullerene derivative is only weakly doped likely by a hydride transfer following by an inefficient electron transfer. This work unambiguously identifies the doping pathway in fullerene derivative/DMBI-H systems in the presence of TEMPO as the transfer of a hydrogen atom accompanied by electron transfer. In the absence of TEMPO, the doping process inevitably leads to the formation of less symmetrical hydrogenated fullerene derivative anions or radicals, which adversely affect the molecular packing. By adding TEMPO we can exclude the formation of such species and, thus, improve charge transport. In addition, a lower temperature is sufficient to meet an efficient doping process in the presence of TEMPO. Thereby, we provide an extra control of the doping process, enabling enhanced thermoelectric performance at a low processing temperature

N-type organic thermoelectrics : demonstration of ZT > 0.3

The 'phonon-glass electron-crystal' concept has triggered most of the progress that has been achieved in inorganic thermoelectrics in the past two decades. Organic thermoelectric materials, unlike their inorganic counterparts, exhibit molecular diversity, flexible mechanical properties and easy fabrication, and are mostly 'phonon glasses'. However, the thermoelectric performances of these organic materials are largely limited by low molecular order and they are therefore far from being 'electron crystals'. Here, we report a molecularly n-doped fullerene derivative with meticulous design of the side chain that approaches an organic 'PGEC' thermoelectric material. This thermoelectric material exhibits an excellent electrical conductivity of >10Scm(-1) and an ultralow thermal conductivity of 0.3 for organic thermoelectrics

Graft dilatation and Barrett's esophagus in adults after gastric pull-up and jejunal interposition for long-gap esophageal atresia

BACKGROUND: Esophageal replacement (ER) with gastric pull-up (GPU) or jejunal interposition (JI) used to be the standard treatment for long-gap esophageal atresia (LGEA). Changes of the ER grafts on a macro- and microscopic level however, are unknown. AIM: To evaluate long-term clinical symptoms and anatomical and mucosal changes in adolescents and adults after ER for LGEA. METHODS: A cohort study was conducted including all LGEA patients ≥ 16 years who had undergone GPU or JI between 1985-2003 at two tertiary referral centers in the Netherlands. Patients underwent clinical assessment, contrast study and endoscopy with biopsy. Data was collected prospectively. Group differences between JI and GPU patients, and associations between different outcome measures were assessed using the Fisher's exact test for bivariate variables and the Mann-Whitney U-test for continuous variables. Differences with a P-value < 0.05 were considered statistically significant. RESULTS: Nine GPU patients and eleven JI patients were included. Median age at follow-up was 21.5 years and 24.4 years, respectively. Reflux was reported in six GPU patients (67%) vs four JI patients (36%) ( P = 0.37). Dysphagia symptoms were reported in 64% of JI patients, compared to 22% of GPU patients ( P = 0.09). Contrast studies showed dilatation of the jejunal graft in six patients (55%) and graft lengthening in four of these six patients. Endoscopy revealed columnar-lined esophagus in three GPU patients (33%) and intestinal metaplasia was histologically confirmed in two patients (22%). No association was found between reflux symptoms and macroscopic anomalies or intestinal metaplasia. Three GPU patients (33%) experienced severe feeding problems vs none in the JI group. The median body mass index of JI patients was 20.9 kg/m 2 vs 19.5 kg/m 2 in GPU patients ( P = 0.08). CONCLUSION: The majority of GPU patients had reflux and intestinal metaplasia in 22%. The majority of JI patients had dysphagia and a dilated graft. Follow-up after ER for LGEA is essential

Evaluating retrieval practice in a MOOC how writing and reading summaries of videos affects student learning

Videos are often the core content in open online education, such as in Massive Open Online Courses (MOOCs). Students spend most of their time in a MOOC on watching educational videos. However, merely watching a video i s a relatively passive learning activity. To increase the educational benefits of online videos, students could benefit from more actively interacting with the to-be-learned material. In this paper two studies (n = 13k) are presented which examined the educational benefits of two more active learning strategies: 1) Retrieval Practice tasks which asked students to shortly summarize the content of videos, and 2) Given Summary tasks in which the students were asked to read pre-written summaries of videos. Writing, as well as reading summaries of videos were positively related to quiz grades. Both interventions seemed to help students to perform better, but there was no apparent difference between the efficacy of these interventions. These studies show how the quality of online education can be improved by adapting course design to established approaches from the learning sciences