An Automated Telephone Nutrition Support System for Spanish-Speaking Patients With Diabetes

In the United States, Spanish-speaking patients with diabetes often receive inadequate dietary counseling. Providing language and culture-concordant dietary counseling on an ongoing basis is critical to diabetes self-care. To determine if automated telephone nutrition support (ATNS) counseling could help patients improve glycemic control by duplicating a successful pilot in Mexico in a Spanish-speaking population in Oakland, California. A prospective randomized open-label trial with blinded endpoint assessment (PROBE) was performed. The participants were seventy-five adult patients with diabetes receiving care at a federally qualified health center in Oakland, California. ATNS, a computerized system that dialed patients on their phones, prompted them in Spanish to enter (via keypad) portions consumed in the prior 24 hours of various cultural-specific dietary items, and then provided dietary feedback based on proportion of high versus low glycemic index foods consumed. The control group received the same ATNS phone calls 14 weeks after enrollment. The primary outcome was hemoglobin A1c % (A1c) 12 weeks following enrollment. Participants had no significant improvement in A1c (–0.3% in the control arm, –0.1% in the intervention arm, P = .41 for any difference) or any secondary parameters. In our study, an ATNS system did not improve diabetes control in a Spanish-speaking population in Oakland.     

Muramyl dipeptide: Not just another brick in the wall

The robust expression of microbial pattern recognition receptors such as TLR4 and Nod2 in intestinal stem cells reflects an active communication dynamic between the host and the gut microbiota. A new study reveals that muramyl dipeptide, the bacterial cell wall peptidoglycan motif, activates Nod2 within crypt base columnar Lgr5-positive stem cells and promotes their survival. Apart from the immediate relevance to the growth of organoids for in vitro experiments, the study raises new questions about the molecular mechanisms whereby gut microbes influence intestinal physiology.     

“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.