Erosion protection benefits of stabilized SnF2 dentifrice versus an arginine–sodium monofluorophosphate dentifrice:results from in vitro and in situ clinical studies

OBJECTIVES: The aim of these investigations was to assess the ability of two fluoride dentifrices to protect against the initiation and progression of dental erosion using a predictive in vitro erosion cycling model and a human in situ erosion prevention clinical trial for verification of effectiveness. MATERIALS AND METHODS: A stabilized stannous fluoride (SnF(2)) dentifrice (0.454 % SnF(2) + 0.077 % sodium fluoride [NaF]; total F = 1450 ppm F) [dentifrice A] and a sodium monofluorophosphate [SMFP]/arginine dentifrice (1.1 % SMFP + 1.5 % arginine; total F = 1450 ppm F) [dentifrice B] were tested in a 5-day in vitro erosion cycling model and a 10-day randomized, controlled, double-blind, two-treatment, four-period crossover in situ clinical trial. In each study, human enamel specimens were exposed to repetitive product treatments using a standardized dilution of test products followed by erosive acid challenges in a systematic fashion. RESULTS: Both studies demonstrated statistically significant differences between the two products, with dentifrice A providing significantly better enamel protection in each study. In vitro, dentifrice A provided a 75.8 % benefit over dentifrice B (p < 0.05, ANOVA), while after 10 days in the in situ model, dentifrice A provided 93.9 % greater protection versus dentifrice B (p < 0.0001, general linear mixed model). CONCLUSION: These results support the superiority of stabilized SnF(2) dentifrices for protecting human teeth against the initiation and progression of dental erosion. CLINICAL RELEVANCE: Stabilized SnF(2) dentifrices may provide more significant benefits to consumers than conventional fluoride dentifrices

In vivo model for microbial invasion of tooth root dentinal tubules

ABSTRACT Objective Bacterial penetration of dentinal tubules via exposed dentine can lead to root caries and promote infections of the pulp and root canal system. The aim of this work was to develop a new experimental model for studying bacterial invasion of dentinal tubules within the human oral cavity. Material and Methods Sections of human root dentine were mounted into lower oral appliances that were worn by four human subjects for 15 d. Roots were then fixed, sectioned, stained and examined microscopically for evidence of bacterial invasion. Levels of invasion were expressed as Tubule Invasion Factor (TIF). DNA was extracted from root samples, subjected to polymerase chain reaction amplification of 16S rRNA genes, and invading bacteria were identified by comparison of sequences with GenBank database. Results All root dentine samples with patent tubules showed evidence of bacterial cell invasion (TIF value range from 5.7 to 9.0) to depths of 200 mm or more. A spectrum of Gram-positive and Gram-negative cell morphotypes were visualized, and molecular typing identified species of Granulicatella, Streptococcus, Klebsiella, Enterobacter, Acinetobacter, and Pseudomonas as dentinal tubule residents. Conclusion A novel in vivo model is described, which provides for human root dentine to be efficiently infected by oral microorganisms. A range of bacteria were able to initially invade dentinal tubules within exposed dentine. The model will be useful for testing the effectiveness of antiseptics, irrigants, and potential tubule occluding agents in preventing bacterial invasion of dentine

In vivo model for microbial invasion of tooth root dentinal tubules

Objective Bacterial penetration of dentinal tubules via exposed dentine can lead to root caries and promote infections of the pulp and root canal system. The aim of this work was to develop a new experimental model for studying bacterial invasion of dentinal tubules within the human oral cavity. Material and Methods Sections of human root dentine were mounted into lower oral appliances that were worn by four human subjects for 15 d. Roots were then fixed, sectioned, stained and examined microscopically for evidence of bacterial invasion. Levels of invasion were expressed as Tubule Invasion Factor (TIF). DNA was extracted from root samples, subjected to polymerase chain reaction amplification of 16S rRNA genes, and invading bacteria were identified by comparison of sequences with GenBank database. Results All root dentine samples with patent tubules showed evidence of bacterial cell invasion (TIF value range from 5.7 to 9.0) to depths of 200 mm or more. A spectrum of Gram-positive and Gram-negative cell morphotypes were visualized, and molecular typing identified species of Granulicatella, Streptococcus, Klebsiella, Enterobacter, Acinetobacter, and Pseudomonas as dentinal tubule residents. Conclusion A novel in vivo model is described, which provides for human root dentine to be efficiently infected by oral microorganisms. A range of bacteria were able to initially invade dentinal tubules within exposed dentine. The model will be useful for testing the effectiveness of antiseptics, irrigants, and potential tubule occluding agents in preventing bacterial invasion of dentine

Policy for sustainable entrepreneurship: a crowdsourced framework

Sustainable entrepreneurship—entrepreneurship with social and ecological gains as well as economic ones—has the potential to play a significant role in addressing societal and environmental challenges. However, sustainability and entrepreneurship have hitherto been addressed through separate policy regimes, and it is not clear how policymakers can encourage sustainable entrepreneurship specifically. The authors develop a policy framework for sustainable entrepreneurship, using an open innovation approach with policymakers, business executives, academics, entrepreneurs and other relevant actors, including an online crowdsourcing event with 150 participants. The framework incorporates five policy domains: creating awareness and skills; building networks; funding and investing; measuring impact and performance; and innovating government. The article proposes a modified version of the multi-level perspective (MLP) on how socio-technical transitions occur, since the findings suggest that policy can catalyze the facilitation and aggregation of innovations coming from the niche level, thereby evolving the socio-technical regime, in addition to the role of policy described in earlier work in stabilizing the socio-technical regime. Contributions to entrepreneurship policy literature include the policy domain of measuring impact and performance, as appropriate success measures are non-trivial in a triple bottom line environment, and the potential for open policy innovation in entrepreneurship policy. Contributions to sustainability policy literature include the requirements for support mechanisms and capacity building to empower individuals to contribute as innovators and entrepreneurs and not just consumers. The sustainable entrepreneurship framework can be applied by policymakers to develop context-specific policies: this is illustrated with a worked example of EU policy recommendations. The paper also outlines a method for crowdsourcing policy innovations

Policy for sustainable entrepreneurship: a crowdsourced framework

Sustainable entrepreneurship—entrepreneurship with social and ecological gains as well as economic ones—has the potential to play a significant role in addressing societal and environmental challenges. However, sustainability and entrepreneurship have hitherto been addressed through separate policy regimes, and it is not clear how policymakers can encourage sustainable entrepreneurship specifically. The authors develop a policy framework for sustainable entrepreneurship, using an open innovation approach with policymakers, business executives, academics, entrepreneurs and other relevant actors, including an online crowdsourcing event with 150 participants. The framework incorporates five policy domains: creating awareness and skills; building networks; funding and investing; measuring impact and performance; and innovating government. The article proposes a modified version of the multi-level perspective (MLP) on how socio-technical transitions occur, since the findings suggest that policy can catalyze the facilitation and aggregation of innovations coming from the niche level, thereby evolving the socio-technical regime, in addition to the role of policy described in earlier work in stabilizing the socio-technical regime. Contributions to entrepreneurship policy literature include the policy domain of measuring impact and performance, as appropriate success measures are non-trivial in a triple bottom line environment, and the potential for open policy innovation in entrepreneurship policy. Contributions to sustainability policy literature include the requirements for support mechanisms and capacity building to empower individuals to contribute as innovators and entrepreneurs and not just consumers. The sustainable entrepreneurship framework can be applied by policymakers to develop context-specific policies: this is illustrated with a worked example of EU policy recommendations. The paper also outlines a method for crowdsourcing policy innovations

Identification of a novel class of autotaxin inhibitors through cross-screening

Three novel series were generated in order to mimic the pharmacophoric features displayed by lead compound AM095, a Lysophosphatidic acid (LPA1) receptor antagonist. Biological evaluation of this array of putative LPA1 antagonists led us to the discovery of three novel series of inhibitors of the ecto-enzyme Autotaxin (ATX), responsible for LPA production in blood, with potencies in the range 1 – 4 μM accompanied with good (> 100 μg/mL) solubility

Relationship between mediation analysis and the structured life course approach

© The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association. Many questions in life course epidemiology involve mediation and/or interaction because of the long latency period between exposures and outcomes. In this paper, we explore how mediation analysis (based on counterfactual theory and implemented using conventional regression approaches) links with a structured approach to selecting life course hypotheses. Using theory and simulated data, we show how the alternative life course hypotheses assessed in the structured life course approach correspond to different combinations of mediation and interaction parameters. For example, an early life critical period model corresponds to a direct effect of the early life exposure, but no indirect effect via the mediator and no interaction between the early life exposure and the mediator. We also compare these methods using an illustrative real-data example using data on parental occupational social class (early life exposure), own adult occupational social class (mediator) and physical capability (outcome)

Childhood energy intake is associated with nonalcoholic fatty liver disease in adolescents

Background: Greater adiposity is an important risk factor for nonalcoholic fatty liver disease (NAFLD). Thus, it is likely that dietary intake is involved in the development of the disease. Prospective studies assessing the relation between childhood dietary intake and risk of NAFLD are lacking. Objective: This study was designed to explore associations between energy, carbohydrate, sugar, starch, protein, monounsaturated fat, polyunsaturated fat, saturated fat, and total fat intake by youth at ages 3, 7, and 13 y and subsequent (mean age: 17.8 y) ultrasound scan (USS)–measured liver fat and stiffness and serum alanine aminotransferase, aspartate aminotransferase, and γ-glutamyltransferase. We assessed whether observed associations were mediated through fat mass at the time of outcome assessment. Methods: Participants were from the Avon Longitudinal Study of Parents and Children. Trajectories of energy and macronutrient intake from ages 3–13 y were obtained with linear-spline multilevel models. Linear and logistic regression models examined whether energy intake and absolute and energy-adjusted macronutrient intake at ages 3, 7, and 13 y were associated with liver outcomes. Results: Energy intake at all ages was positively associated with liver outcomes; for example, the odds of having a USS-measured liver fat per 100 kcal increase in energy intake at age 3 y were 1.79 (95% CI: 1.14, 2.79). Associations between absolute macronutrient intake and liver outcomes were inconsistent and attenuated to the null after adjustment for total energy intake. The majority of associations attenuated to the null after adjustment for fat mass at the time liver outcomes were assessed. Conclusion: Higher childhood and early adolescent energy intake is associated with greater NAFLD risk, and the macronutrients from which energy intake is derived are less important. These associations appear to be mediated, at least in part, by fat mass at the time of outcome assessment

Agnoprotein Is an Essential Egress Factor during BK Polyomavirus Infection.

BK polyomavirus (BKPyV; hereafter referred to as BK) causes a lifelong chronic infection and is associated with debilitating disease in kidney transplant recipients. Despite its importance, aspects of the virus life cycle remain poorly understood. In addition to the structural proteins, the late region of the BK genome encodes for an auxiliary protein called agnoprotein. Studies on other polyomavirus agnoproteins have suggested that the protein may contribute to virion infectivity. Here, we demonstrate an essential role for agnoprotein in BK virus release. Viruses lacking agnoprotein fail to release from host cells and do not propagate to wild-type levels. Despite this, agnoprotein is not essential for virion infectivity or morphogenesis. Instead, agnoprotein expression correlates with nuclear egress of BK virions. We demonstrate that the agnoprotein binding partner α-soluble N-ethylmaleimide sensitive fusion (NSF) attachment protein (α-SNAP) is necessary for BK virion release, and siRNA knockdown of α-SNAP prevents nuclear release of wild-type BK virions. These data highlight a novel role for agnoprotein and begin to reveal the mechanism by which polyomaviruses leave an infected cell