Exposure to the taste of alcohol elicits activation of the mesocorticolimbic neurocircuitry

A growing number of imaging studies suggest that alcohol cues, mainly visual, elicit activation in mesocorticolimbic structures. Such findings are consistent with the growing recognition that these structures play an important role in the attribution of incentive salience and the pathophysiology of addiction. The present study investigated whether the presentation of alcohol taste cues can activate brain regions putatively involved in the acquisition and expression of incentive salience. Using functional magnetic resonance imaging, we recorded BOLD activity while delivering alcoholic tastes to 37 heavy drinking but otherwise healthy volunteers. The results yielded a pattern of BOLD activity in mesocorticolimbic structures (ie prefrontal cortex, striatum, ventral tegmental area/substantia nigra) relative to an appetitive control. Further analyses suggested strong connectivity between these structures during cue-elicited urge and demonstrated significant positive correlations with a measure of alcohol use problems (ie the Alcohol Use Disorders Identification Test). Thus, repeated exposure to the taste alcohol in the scanner elicits activation in mesocorticolimbic structures, and this activation is related to measures of urge and severity of alcohol problems

Specific Binding and Mineralization of Calcified Surfaces by Small Peptides

Several small (<25aa) peptides have been designed based on the sequence of the dentin phosphoprotein, one of the major noncollagenous proteins thought to be involved in the mineralization of the dentin extracellular matrix during tooth development. These peptides, consisting of multiple repeats of the tripeptide aspartate-serine-serine (DSS), bind with high affinity to calcium phosphate compounds and, when immobilized, can recruit calcium phosphate to peptide-derivatized polystyrene beads or to demineralized human dentin surfaces. The affinity of binding to hydroxyapatite surfaces increases with the number of (DSS)n repeats, and though similar repeated sequences—(NTT)n, (DTT)n, (ETT)n, (NSS)n, (ESS)n, (DAA)n, (ASS)n, and (NAA)n—also showed HA binding activity, it was generally not at the same level as the natural sequence. Binding of the (DSS)n peptides to sectioned human teeth was shown to be tissue-specific, with high levels of binding to the mantle dentin, lower levels of binding to the circumpulpal dentin, and little or no binding to healthy enamel. Phosphorylation of the serines of these peptides was found to affect the avidity, but not the affinity, of binding. The potential utility of these peptides in the detection of carious lesions, the delivery of therapeutic compounds to mineralized tissues, and the modulation of remineralization is discussed

Safety in home care: A research protocol for studying medication management

<p>Abstract</p> <p>Background</p> <p>Patient safety is an ongoing global priority, with medication safety considered a prevalent, high-risk area of concern. Yet, we have little understanding of the supports and barriers to safe medication management in the Canadian home care environment. There is a clear need to engage the providers and recipients of care in studying and improving medication safety with collaborative approaches to exploring the nature and safety of medication management in home care.</p> <p>Methods</p> <p>A socio-ecological perspective on health and health systems drives our iterative qualitative study on medication safety with elderly home care clients, family members and other informal caregivers, and home care providers. As we purposively sample across four Canadian provinces: Alberta (AB), Ontario (ON), Quebec (QC) and Nova Scotia (NS), we will collect textual and visual data through home-based interviews, participant-led photo walkabouts of the home, and photo elicitation sessions at clients' kitchen tables. Using successive rounds of interpretive description and human factors engineering analyses, we will generate robust descriptions of managing medication at home within each provincial sample and across the four-province group. We will validate our initial interpretations through photo elicitation focus groups with home care providers in each province to develop a refined description of the phenomenon that can inform future decision-making, quality improvement efforts, and research.</p> <p>Discussion</p> <p>The application of interpretive and human factors lenses to the visual and textual data is expected to yield findings that advance our understanding of the issues, challenges, and risk-mitigating strategies related to medication safety in home care. The images are powerful knowledge translation tools for sharing what we learn with participants, decision makers, other healthcare audiences, and the public. In addition, participants engage in knowledge exchange throughout the study with the use of participatory data collection methods.</p

Replication and active partition of integrative and conjugative elements (ICEs) of the SXT/R391 family : the line between ICEs and conjugative plasmids is getting thinner

Integrative and Conjugative Elements (ICEs) of the SXT/R391 family disseminate multidrug resistance among pathogenic Gammaproteobacteria such as Vibrio cholerae. SXT/R391 ICEs are mobile genetic elements that reside in the chromosome of their host and eventually self-transfer to other bacteria by conjugation. Conjugative transfer of SXT/R391 ICEs involves a transient extrachromosomal circular plasmid-like form that is thought to be the substrate for single-stranded DNA translocation to the recipient cell through the mating pore. This plasmid-like form is thought to be non-replicative and is consequently expected to be highly unstable. We report here that the ICE R391 of Providencia rettgeri is impervious to loss upon cell division. We have investigated the genetic determinants contributing to R391 stability. First, we found that a hipAB-like toxin/antitoxin system improves R391 stability as its deletion resulted in a tenfold increase of R391 loss. Because hipAB is not a conserved feature of SXT/R391 ICEs, we sought for alternative and conserved stabilization mechanisms. We found that conjugation itself does not stabilize R391 as deletion of traG, which abolishes conjugative transfer, did not influence the frequency of loss. However, deletion of either the relaxase-encoding gene traI or the origin of transfer (oriT) led to a dramatic increase of R391 loss correlated with a copy number decrease of its plasmid-like form. This observation suggests that replication initiated at oriT by TraI is essential not only for conjugative transfer but also for stabilization of SXT/R391 ICEs. Finally, we uncovered srpMRC, a conserved locus coding for two proteins distantly related to the type II (actin-type ATPase) parMRC partitioning system of plasmid R1. R391 and plasmid stabilization assays demonstrate that srpMRC is active and contributes to reducing R391 loss. While partitioning systems usually stabilizes low-copy plasmids, srpMRC is the first to be reported that stabilizes a family of ICEs