Feasibility and Smokers' Evaluation of Self-Generated Text Messages to Promote Quitting.

INTRODUCTION: Cigarette smoking is a leading cause of preventable mortality. Mobile technologies, including text messaging, provide opportunities to promote quitting. Many text messaging-based cessation interventions contain content created by experts. However, smokers may be best persuaded by receipt of text messages they created based on their reasons for quitting, assisted or not by a motivational facilitator. This study assessed the feasibility and participants' evaluation of two ways to self-generate smoking cessation messages delivered via cell-phone. METHODS: We enrolled smokers (N = 24) and randomized them to: (1) behavioral counseling assistance plus self-generated messages, or (2) self-generated messages only. Both groups wrote: (1) their reasons for wanting to quit and then (2) text messages related to their reason(s) for quitting, Messages were delivered as text messages as well as with a link to verbatim self-recorded audio message for 10 days. At follow-up, participants evaluated the intervention. RESULTS: Participants composed and recorded messages and evaluated them and the intervention favorably. The counseling+message group wrote an average of 7.66 (SD = 4.86) text messages while the message-only wrote an average of 6.66 (SD = 2.93) messages. Most participants felt that the messages were of appropriate length, including the frequency and timing of message delivery. CONCLUSION: It is feasible for smokers to self-generate motivational text and audio messages concerning reasons for quitting, even among smokers without an immediate desire to quit. Participants evaluated the messages and intervention favorably. Future research should test self-generated messages in larger trials of self- versus expert-generated message. IMPLICATIONS: This study assessed the feasibility and participants' evaluation of two ways to self-generate smoking cessation messages delivered via cell-phone. It is feasible for smokers to self-generate motivational text and audio messages concerning reasons for quitting, even among smokers without an immediate desire to quit. Participants evaluated the messages and intervention favorable. Future research should test self-generated messages in larger trials of self- versus expert-generated messages.

Layer 4 pyramidal neuron dendritic bursting underlies a post-stimulus visual cortical alpha rhythm.

Alpha rhythms (9-11 Hz) are a dominant feature of EEG recordings, particularly over occipital cortex on cessation of a visual stimulation. Little is known about underlying neocortical mechanisms so here we constructed alpha rhythm models that follow cessation of cortical stimulation. The rhythm manifests following a period of gamma frequency activity in local V1 networks in layer 4. It associates with network level bias of excitatory synaptic activity in favour of NMDA- rather than AMPA-mediated signalling and reorganisation of synaptic inhibition in favour of fast GABAA receptor-mediated events. At the cellular level the alpha rhythm depended upon the generation of layer 4 pyramidal neuron dendritic bursting mediated primarily by PPDA-sensitive NR2C/D-containing NMDA receptors, which lack the magnesium-dependent open channel block. Subthreshold potassium conductances are also critical. The rhythm dynamically filters outputs from sensory relay neurons (stellate neurons in layer 4) such that they become temporally uncoupled from downstream population activity.

Genetic and environmental factors determining clinical outcomes and cost of warfarin therapy: a prospective study.

BACKGROUND: In this prospective cohort study, we have undertaken a comprehensive evaluation of clinical parameters along with variation in 29 genes (including CYP2C9 and VKORC1) to identify factors determining interindividual variability in warfarin response. METHODS: Consecutive patients (n=311) were followed up prospectively for 26 weeks. Several outcomes chosen to capture both warfarin efficacy and toxicity were assessed. Univariate and multiple regression analyses were undertaken to assess the combined effect of clinical and genetic factors. RESULTS: CYP2C9 was the most important gene determining initial anticoagulant control, whereas VKORC1 was more important for stable anticoagulation. Novel associations with some clinical outcomes were found with single nucleotide polymorphisms in the cytochrome 450 genes CYP2C18 and CYP2C19, which were independent of the associations observed with CYP2C9 and in genes encoding CYP3A5, protein S and clotting factor V, although the variability explained by these genes was small. On the basis of the results of microcosting, adverse events were shown to be a significant predictor of total cost. CONCLUSION: Accurate prediction of warfarin dose requirement needs to take into account multiple genetic and environmental factors, the contributions of which vary in the induction and maintenance phases of treatment.

High glucose-induced membrane translocation of PKC betaI is associated with Arf6 in glomerular mesangial cells.

Protein kinase C (PKC)-induced changes in glomerular mesangial cell (MC) phenotypic behavior has been implicated in diabetes. The activity of diacylglycerol-sensitive PKC isoforms in MCs is altered by ambient changes in glucose, but the regulation of PKC activity and subsequent intracellular signaling events are not yet clearly defined. Small GTP-binding proteins of the ADP-ribosylation factor (Arfs) family, may regulate protein kinase membrane recruitment and hence its activity in signaling events of non-polarized cells. Members of the ARF family may coordinate membrane dynamics and other cellular functions through their interaction with PKC. We studied the activation of Arf, PKC betaI and phospholipase D (PLD) in MCs cultured under normal or high glucose conditions. MCs cultured in high glucose medium exhibited predominantly cytosolic localization of PKC betaI, Arf3 and Arf6. However, phorbol ester (PMA) stimulation of cells cultured in high glucose significantly enhanced membrane association of PKC betaI and Arf6, but not Arf3. Using [3H]choline chloride to prelabel MCs and measuring [3H]choline-containing metabolite release as PLD activity, PMA stimulated a significant increase of PLD activity under high glucose condition. Our data suggest that Arf6 plays a specific role in activation of PKC betaI and PLD under high glucose condition, and may be a significant intracellular event in the change of the mesangial cell phenotype associated with diabetic nephropathy.