“Not Just Right Experiences” in Adolescents: Phenomenology and Associated Characteristics

Efforts to understand the nature of “Not Just Right Experiences” (NJREs) have expanded the scientific understanding of obsessive–compulsive (OC) behavior. Approximately 80 % of unselected adults report experiencing NJREs and these experiences have been found to highly correlate with OC behavior. The purpose of this study was to assess NJREs in an unselected sample of adolescents (ages 14–17; N = 152), to compare their experience with adults (N = 237), and to assess the relation between NJREs and OC symptoms. Findings from questionnaires completed on the Internet were consistent with previous findings in adults, 81 % of adolescents endorsed recently having an NJRE. Some reactions differed according to age: adults reported NJREs as more frequent and adolescents endorsed feeling more compelled to respond. Surprisingly, OC symptoms were not significantly related to NJREs in the adolescents. Implications, limitations, and future directions for the study of NJREs in youth are discussed.     

Withania somnifera reverses Alzheimer's disease pathology by enhancing low-density lipoprotein receptor-related protein in liver

A 30-d course of oral administration of a semipurified extract of the root of Withania somnifera consisting predominantly of withanolides and withanosides reversed behavioral deficits, plaque pathology, accumulation of β-amyloid peptides (Aβ) and oligomers in the brains of middle-aged and old APP/PS1 Alzheimer's disease transgenic mice. It was similarly effective in reversing behavioral deficits and plaque load in APPSwInd mice (line J20). The temporal sequence involved an increase in plasma Aβ and a decrease in brain Aβ monomer after 7 d, indicating increased transport of Aβ from the brain to the periphery. Enhanced expression of low-density lipoprotein receptor-related protein (LRP) in brain microvessels and the Aβ-degrading protease neprilysin (NEP) occurred 14-21 d after a substantial decrease in brain Aβ levels. However, significant increase in liver LRP and NEP occurred much earlier, at 7 d, and were accompanied by a rise in plasma sLRP, a peripheral sink for brain Aβ. In WT mice, the extract induced liver, but not brain, LRP and NEP and decreased plasma and brain Aβ, indicating that increase in liver LRP and sLRP occurring independent of Aβ concentration could result in clearance of Aβ. Selective down-regulation of liver LRP, but not NEP, abrogated the therapeutic effects of the extract. The remarkable therapeutic effect of W. somnifera mediated through up-regulation of liver LRP indicates that targeting the periphery offers a unique mechanism for Aβ clearance and reverses the behavioral deficits and pathology seen in Alzheimer's disease models.     

Autophagy mediates transporter associated with antigen processing-independent presentation of viral epitopes through MHC class I pathway

The endogenous presentation of the majority of viral epitopes through MHC class I pathway is strictly dependent on the transporter associated with antigen processing (TAP) complex, which transfers the peptide products of proteasomal degradation into the endoplasmic reticulum. A small number of epitopes can be presented through the TAP-independent pathway, the precise mechanism for which remains largely unresolved. Here we show that TAP-independent presentation can be mediated by autophagy and that this process uses the vacuolar pathway and not the conventional secretory pathway. After macroautophagy, the antigen is processed through a proteasome-independent pathway, and the peptide epitopes are loaded within the autophagolysosomal compartment in a process facilitated by the relative acid stability of the peptide-MHC interaction. Despite bypassing much of the conventional MHC class I pathway, the autophagy-mediated pathway generates the same epitope as that generated through the conventional pathway and thus may have a role in circumventing viral immune evasion strategies that primarily target the conventional pathway.     

Transcatheter Retrieval of Embolized AMPLATZER Septal Occluder

In selected patients, transcatheter closure of atrial septal defects with the AMPLATZER Septal Occluder has yielded excellent results. However, there is a slight risk of device embolization after deployment. We report the case of a 26-year-old woman in whom an embolized AMPLATZER device was retrieved percutaneously from the right pulmonary artery. We also discuss important technical principles for managing this uncommon but potentially severe complication.Key words: Device removal/methods, embolization, therapeutic/instrumentation, heart catheterization/instrumentation, heart septal defects, atrial/ultrasonography, patient selection, prosthesis implantation/adverse effects, prostheses and implants, septal occluder device/adverse effects, treatment outcomeTranscatheter closure of atrial septal defects (ASDs) with use of the AMPLATZER® Septal Occluder (St. Jude Medical, Inc.; St. Paul, Minn) has yielded excellent results in properly selected patients.^1,2 The major advantage of the AMPLATZER occluder is its easy retrieval at all stages of deployment before its final release from the delivery cable. Although embolization of AMPLATZER ASD occluders is rare, it can occur even when interventional cardiologists are experienced. Despite an earlier belief that the transcatheter retrieval of embolized AMPLATZER devices would be difficult, success rates from 50% to 75% have been reported.^3,4 We describe the retrieval of an embolized AMPLATZER device in a young woman. In addition, we present some technical principles with which operators practicing device closure should be familiar.     

Discovery of Lacosamide Affinity Bait Agents That Exhibit Potent Voltage-Gated Sodium Channel Blocking Properties

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