The anti-caries efficacy of a dentifrice containing 1.5% arginine and 1450ppm fluoride as sodium monofluorophosphate assessed using Quantitative Light-induced Fluorescence (QLF)

AbstractObjectiveTo compare the efficacy of a new dentifrice containing 1.5% arginine, an insoluble calcium compound and 1450ppm fluoride to arrest and reverse naturally occurring buccal caries lesions in children relative to a positive control dentifrice containing 1450ppm fluoride alone.Study designParticipants from Chengdu, Sichuan Province, China tested three dentifrices: a new dentifrice containing 1.5% arginine, an insoluble calcium compound, and 1450ppm fluoride, as sodium monofluorophosphate, a positive control dentifrice containing 1450ppm fluoride, as sodium fluoride, in a silica base, and a matched negative control dentifrice without arginine and fluoride. Quantitative Light-induced Fluorescence (QLF) was used to assess buccal caries lesions at baseline and after 3 and 6 months of product use.Results438 participants (initial age 9–13 years (mean 11.1±0.78) and 48.6% female) completed the study. No adverse events attributable to the products were reported during the course of the study. The subject mean ΔQ (mm2%), representing lesion volume, was 27.26 at baseline. After 6 months of product use, the ΔQ values for the arginine-containing, positive and negative control dentifrices were 13.46, 17.99 and 23.70 representing improvements from baseline of 50.6%, 34.0% and 13.1%. After 6 months product use, the differences between the pair wise comparisons for all three groups were statistically significant (p<0.01). The arginine-containing dentifrice demonstrated an improvement after only 3 months that was almost identical to that achieved by the conventional 1450ppm fluoride dentifrice after 6 months.ConclusionThe new dentifrice containing 1.5% arginine, an insoluble calcium compound, and 1450ppm fluoride provides statistically significantly superior efficacy in arresting and reversing buccal caries lesions to a conventional dentifrice containing 1450ppm fluoride alone

Molecular Basis and Differentiation-Associated Alterations of Anion Secretion in Human Duodenal Enteroid Monolayers

Background & Aims: Human enteroids present a novel tool to study human intestinal ion transport physiology and pathophysiology. The present study describes the contributions of Cl- and HCO3 - secretion to total cyclic adenosine monophosphate (cAMP)-stimulated electrogenic anion secretion in human duodenal enteroid monolayers and the relevant changes after differentiation. Methods: Human duodenal enteroids derived from 4 donors were grown as monolayers and differentiated by a protocol that includes the removal of Wnt3A, R-spondin1, and SB202190 for 5 days. The messenger RNA level and protein expression of selected ion transporters and carbonic anhydrase isoforms were determined by quantitative real-time polymerase chain reaction and immunoblotting, respectively. Undifferentiated and differentiated enteroid monolayers were mounted in the Ussing chamber/voltage-current clamp apparatus, using solutions that contained as well as lacked Cl- and HCO3 -/CO2, to determine the magnitude of forskolin-induced short-circuit current change and its sensitivity to specific inhibitors that target selected ion transporters and carbonic anhydrase(s). Results: Differentiation resulted in a significant reduction in the messenger RNA level and protein expression of cystic fibrosis transmembrane conductance regulator, (CFTR) Na+/K+/2Cl- co-transporter 1 (NKCC1), and potassium channel, voltage gated, subfamily E, regulatory subunit 3 (KCNE3); and, conversely, increase of down-regulated-in-adenoma (DRA), electrogenic Na+/HCO3 - co-transporter 1 (NBCe1), carbonic anhydrase 2 (CA2), and carbonic anhydrase 4 (CA4). Both undifferentiated and differentiated enteroids showed active cAMP-stimulated anion secretion that included both Cl- and HCO3 - secretion as th

Sources and contributions of wood smoke during winter in London: Assessing local and regional influences

Determining the contribution of wood smoke to air pollution in large cities such as London is becoming increasingly important due to the changing nature of domestic heating in urban areas. During winter, biomass burning emissions have been identified as a major cause of exceedances of European air quality limits. The aim of this work was to quantify the contribution of biomass burning in London to concentrations of PM2:5 and determine whether local emissions or regional contributions were the main source of biomass smoke. To achieve this, a number of biomass burning chemical tracers were analysed at a site within central London and two sites in surrounding rural areas. Concentrations of levoglucosan, elemental carbon (EC), organic carbon (OC) and KC were generally well correlated across the three sites. At all the sites, biomass burning was found to be a source of OC and EC, with the largest contribution of EC from traffic emissions, while for OC the dominant fraction included contributions from secondary organic aerosols, primary biogenic and cooking sources. Source apportionment of the EC and OC was found to give reasonable estimation of the total carbon from non-fossil and fossil fuel sources based upon comparison with estimates derived from 14C analysis. Aethalometer-derived black carbon data were also apportioned into the contributions frombiomass burning and traffic and showed trends similar to those observed for EC. Mean wood smoke mass at the sites was estimated to range from 0.78 to 1.0 μgm-3 during the campaign in January–February 2012. Measurements on a 160m tower in London suggested a similar ratio of brown to black carbon (reflecting wood burning and traffic respectively) in regional and London air. Peaks in the levoglucosan and KC concentrations were observed to coincide with low ambient temperature, consistent with domestic heating as a major contributing local source in London. Overall, the source of biomass smoke in London was concluded to be a background regional source overlaid by contributions from local domestic burning emissions. This could have implications when considering future emission control strategies during winter and may be the focus of future work in order to better determine the contributing local sources

Innovative moments and poor outcome in narrative therapy

To analyse a poor outcome case of narrative therapy with a woman victim of intimate violence. Method: The Innovative Moments Coding System: version 1 was applied to all sessions to track the innovative moments (i-moments) in the therapeutic process. I moments are the narrative details that occur in psychotherapeutic conversations that are outside the influence of the problematic narrative. This research aims to describe the processes involved in the stability of meanings in psychotherapy through a dialogical approach to meaning making. Findings: Contrarily to what usually occurs in good outcome cases, re-conceptualization i-moments are absent. Moreover, two specific types of i-moments emerged with higher duration: reflection and protest. Qualitative analysis showed that the potential meanings of these i-moments were surpassed by a return to the problematic narrative. Conclusion: The therapeutic stability seems to be maintained by a systematic return to the problematic narrative after the emergence of novelties. This process was referred from a dialogical perspective as a mutual in-feeding of voices, one that emerges in the i-moment and another one that supports the problematic narrative, which is maintained by an oscillation between these two types of voices during therapy.This article was supported by the Portuguese Foundation for Science and Technology (FCT), by the Grant PTDC/PSI/72846/2006 (Narrative Processes in Psychotherapy, 2007-2010) and by the PhD Grant SFRH/BD/16995/2004

Making sense of leadership development: Developing a community of education leaders

In education literature there is a distinct lack of scholarly work on issues of leadership other than on functional leadership at lower levels or high-level individual leadership activity which dominates existing studies. This empirical research is based on the result of a merger of education providers within the North East of England. A crucial aspiration of the newly merged organisation was to provide an overarching innovative leadership structure to facilitate integrated leadership. The specific focus of this article is participants of a bespoke postgraduate learning intervention. The authors apply sense-making theory to identify how student-leaders undertaking a leadership development intervention developed to become a community of education leaders. The reflective accounts of the student-leaders indicated a combined approach of distributed, shared and collaborative leadership. Whilst the study was conducted in the UK, the concepts and ideas are likely to have international application

Opioid activation of toll-like receptor 4 contributes to drug reinforcement

Opioid action was thought to exert reinforcing effects solely via the initial agonism of opioid receptors. Here, we present evidence for an additional novel contributor to opioid reward: the innate immune pattern-recognition receptor, toll-like receptor 4 (TLR4), and its MyD88-dependent signaling. Blockade of TLR4/MD2 by administration of the nonopioid, unnatural isomer of naloxone, (+)-naloxone (rats), or two independent genetic knock-outs of MyD88-TLR4-dependent signaling (mice), suppressed opioid-induced conditioned place preference. (+)-Naloxone also reduced opioid (remifentanil) self-administration (rats), another commonly used behavioral measure of drug reward. Moreover, pharmacological blockade of morphine-TLR4/MD2 activity potently reduced morphine-induced elevations of extracellular dopamine in rat nucleus accumbens, a region critical for opioid reinforcement. Importantly, opioid-TLR4 actions are not a unidirectional influence on opioid pharmacodynamics, since TLR4−/− mice had reduced oxycodone-induced p38 and JNK phosphorylation, while displaying potentiated analgesia. Similar to our recent reports of morphine-TLR4/MD2 binding, here we provide a combination of in silico and biophysical data to support (+)-naloxone and remifentanil binding to TLR4/MD2. Collectively, these data indicate that the actions of opioids at classical opioid receptors, together with their newly identified TLR4/MD2 actions, affect the mesolimbic dopamine system that amplifies opioid-induced elevations in extracellular dopamine levels, therefore possibly explaining altered opioid reward behaviors. Thus, the discovery of TLR4/MD2 recognition of opioids as foreign xenobiotic substances adds to the existing hypothesized neuronal reinforcement mechanisms, identifies a new drug target in TLR4/MD2 for the treatment of addictions, and provides further evidence supporting a role for central proinflammatory immune signaling in drug reward.M. R. Hutchinson... J. Thomas, K. van Steeg... A. A. Somogyi... et al

Designing a broad-spectrum integrative approach for cancer prevention and treatment

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notablesuccesses in some cancers; however, significant problems remain with this approach. Many targetedtherapies are highly toxic, costs are extremely high, and most patients experience relapse after a fewdisease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistantimmortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are notreliant upon the same mechanisms as those which have been targeted). To address these limitations, aninternational task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspectsof relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a widerange of high-priority targets (74 in total) that could be modified to improve patient outcomes. For thesetargets, corresponding low-toxicity therapeutic approaches were then suggested, many of which werephytochemicals. Proposed actions on each target and all of the approaches were further reviewed forknown effects on other hallmark areas and the tumor microenvironment. Potential contrary or procar-cinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixedevidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of therelationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. Thisnovel approach has potential to be relatively inexpensive, it should help us address stages and types ofcancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for futureresearch is offered