Topical ferumoxytol nanoparticles disrupt biofilms and prevent tooth decay in vivo via intrinsic catalytic activity

Ferumoxytol is a nanoparticle formulation approved by the U.S. Food and Drug Administration for systemic use to treat iron deficiency. Here, we show that, in addition, ferumoxytol disrupts intractable oral biofilms and prevents tooth decay (dental caries) via intrinsic peroxidase-like activity. Ferumoxytol binds within the biofilm ultrastructure and generates free radicals from hydrogen peroxide (H2O2), causing in situ bacterial death via cell membrane disruption and extracellular polymeric substances matrix degradation. In combination with low concentrations of H2O2, ferumoxytol inhibits biofilm accumulation on natural teeth in a human-derived ex vivo biofilm model, and prevents acid damage of the mineralized tissue. Topical oral treatment with ferumoxytol and H2O2 suppresses the development of dental caries in vivo, preventing the onset of severe tooth decay (cavities) in a rodent model of the disease. Microbiome and histological analyses show no adverse effects on oral microbiota diversity, and gingival and mucosal tissues. Our results reveal a new biomedical application for ferumoxytol as topical treatment of a prevalent and costly biofilm-induced oral disease

Topical Ferumoxytol Nanoparticles Disrupt Biofilms and Prevent Tooth Decay in Vivo Via Intrinsic Catalytic Activity

Ferumoxytol is a nanoparticle formulation approved by the U.S. Food and Drug Administration for systemic use to treat iron deficiency. Here, we show that, in addition, ferumoxytol disrupts intractable oral biofilms and prevents tooth decay (dental caries) via intrinsic peroxidase-like activity. Ferumoxytol binds within the biofilm ultrastructure and generates free radicals from hydrogen peroxide (H2O2), causing in situ bacterial death via cell membrane disruption and extracellular polymeric substances matrix degradation. In combination with low concentrations of H2O2, ferumoxytol inhibits biofilm accumulation on natural teeth in a human-derived ex vivo biofilm model, and prevents acid damage of the mineralized tissue. Topical oral treatment with ferumoxytol and H2O2 suppresses the development of dental caries in vivo, preventing the onset of severe tooth decay (cavities) in a rodent model of the disease. Microbiome and histological analyses show no adverse effects on oral microbiota diversity, and gingival and mucosal tissues. Our results reveal a new biomedical application for ferumoxytol as topical treatment of a prevalent and costly biofilm-induced oral disease

How to Intervene in the Caries Process in Older Adults: A Joint ORCA and EFCD Expert Delphi Consensus Statement

Aim: To provide recommendations for dental clinicians for the management of dental caries in older adults with special emphasis on root caries lesions. Methods: A consensus workshop followed by a Delphi consensus process were conducted with an expert panel nominated by ORCA, EFCD, and DGZ boards. Based on a systematic review of the literature, as well as non-systematic literature search, recommendations for clinicians were developed and consented in a two-stage Delphi process. Results: Demographic and epidemiologic changes will significantly increase the need of management of older adults and root caries in the future. Ageing is associated with a decline of intrinsic capacities and an increased risk of general diseases. As oral and systemic health are linked, bidirectional consequences of diseases and interventions need to be considered. Caries prevention and treatment in older adults must respond to the patient’s individual abilities for self-care and cooperation and often involves the support of caregivers. Systemic interventions may involve dietary counselling, oral hygiene instruction, the use of fluoridated toothpastes, and the stimulation of salivary flow. Local interventions to manage root lesions may comprise local biofilm control, application of highly fluoridated toothpastes or varnishes as well as antimicrobial agents. Restorative treatment is often compromised by the accessibility of such root caries lesions as well as the ability of the senior patient to cooperate. If optimum restorative treatment is impossible or inappropriate, longterm stabilization, e.g., by using glass-ionomer cements, and palliative treatments that aim to maintain oral function as long and as well as possible may be the treatment of choice for the individual

How to Intervene in the Caries Process in Children: A Joint ORCA and EFCD Expert Delphi Consensus Statement

This paper provides recommendations for dentists for the treatment of dental caries in children, with an emphasis on early childhood caries (ECC), primary teeth, and occlusal surfaces in permanent teeth. A consensus workshop followed by an e-Delphi consensus process was conducted with an expert panel nominated by the European Organization for Caries Research (ORCA) and European Federation of Conservative Dentistry (EFCD)/German Association of Conservative Dentistry (DGZ) boards. Based on 3 systematic reviews and a nonsystematic literature search, recommendations were developed. The caries decline has led to a more polarized disease distribution in children and adolescents along social gradients which should be taken into account when managing the caries process at all levels, such as the individual, the group, or a population. The control or reduction of caries activity is the basis for successful caries management. In children, caries management requires adequate daily oral hygiene and fluoride application via toothpaste, ensured by caregivers, and especially for ECC prevention an emphasis on sugar intake reduction is needed. These noninvasive interventions are also suitable to arrest or control initial or even cavitated dentine caries lesions in the absence of irreversible pulpitis. Fluoride varnish or silver diammine fluoride can be added as supplementary agents. In pits and fissures, composite resin materials can be used as preventive sealants and for defect-oriented minimally invasive restorations. In primary molars, preformed metal crowns are more successful than multisurface fillings, especially in caries-active patients. With persisting high caries activity, multiple lesions, and limited cooperation, caries control should consist of robust measures with high success rates, even including extraction in selected cases. This applies especially to treatments performed under general anesthesia

How to Intervene in the Caries Process in Older Adults: A Joint ORCA and EFCD Expert Delphi Consensus Statement

Aim: To provide recommendations for dental clinicians for the management of dental caries in older adults with special emphasis on root caries lesions. Methods: A consensus workshop followed by a Delphi consensus process were conducted with an expert panel nominated by ORCA, EFCD, and DGZ boards. Based on a systematic review of the literature, as well as non-systematic literature search, recommendations for clinicians were developed and consented in a two-stage Delphi process. Results: Demographic and epidemiologic changes will significantly increase the need of management of older adults and root caries in the future. Ageing is associated with a decline of intrinsic capacities and an increased risk of general diseases. As oral and systemic health are linked, bidirectional consequences of diseases and interventions need to be considered. Caries prevention and treatment in older adults must respond to the patient's individual abilities for self-care and cooperation and often involves the support of caregivers. Systemic interventions may involve dietary counselling, oral hygiene instruction, the use of fluoridated toothpastes, and the stimulation of salivary flow. Local interventions to manage root lesions may comprise local biofilm control, application of highly fluoridated toothpastes or varnishes as well as antimicrobial agents. Restorative treatment is often compromised by the accessibility of such root caries lesions as well as the ability of the senior patient to cooperate. If optimum restorative treatment is impossible or inappropriate, long-term stabilization, e.g., by using glass-ionomer cements, and palliative treatments that aim to maintain oral function as long and as well as possible may be the treatment of choice for the individual

European Organization for Caries Research Workshop: Methodology for Determination of Potentially Available Fluoride in Toothpastes

Toothpastes are the most universally accepted form of fluoride delivery for caries prevention. To provide anti-caries benefits, they must be able to release fluoride during the time of tooth brushing or post brushing into the oral cavity. However, there is no standard accepted procedure to measure how much fluoride in a toothpaste may be (bio) available for release. The European Organization for Caries Research proposed and supported a workshop with experts in fluoride analysis in toothpastes and representatives from industry. The objective of the workshop was to discuss issues surrounding fluoride analysis in toothpaste and reach consensus on terminology and best practices, wherever the available evidence allowed it. Participants received a background paper and heard presentations followed by structured discussion to define the problem. The group also reviewed evidence on the validity, reliability and feasibility of each technique (namely chromatography and fluoride electroanalysis) and discussed their strengths and limitations. Participants were able to reach a consensus on terminology and were also able to identify and summarize the advantages and disadvantages of each technique. However, they agreed that most currently available methods were developed for regulatory agencies several decades ago, utilizing the best available data from clinical trials then, but require to be updated. They also agreed that although significant advances to our understanding of the mechanism of action of fluoride in toothpaste have been achieved over the past 4 decades, this clearly is an extraordinarily complex subject and more work remains to be done

Car dependent practices: findings from a sequence pattern mining study of UK time use data

This paper identifies three main understandings of the notion of 'car dependence' in transport research: a micro-social understanding (dependence as an attribute of individuals), a macro approach (attribute of societies or local areas as whole), and a meso-level understanding, where it refers to trips – or rather to the activities that people travel to undertake. While the first two approaches have been dominant, this paper further develops the third, addressing questions as to whether and why certain activities are inherently more difficult to switch away from the car. At the theoretical level, it builds on theories of social practice to put forward the notion of ‘car dependent practices’. At the empirical level, it demonstrates that the application of sequence pattern mining techniques to time use data allows the identification of car and mobility intensive activities, arguably representing the trace of car dependent practices. Overall, the findings of this mining exercise suggest that the emphasis of existing literature on escorting children, shopping and carrying heavy goods as car dependent trip purposes is not misplaced. Our analysis adds to this knowledge by contextualising the information by providing detailed quantitative analysis of a larger, richer set of activities hitherto overlooked in transport policy. The article concludes by illustrating the policy implications of the approach adopted and the findings generated, discussing possible strategies to steer practices in a more sustainable direction by creating material alternatives to the 'cargo function' of car travel

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV

A search for new physics is presented based on an event signature of at least three jets accompanied by large missing transverse momentum, using a data sample corresponding to an integrated luminosity of 36 inverse picobarns collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector at the LHC. No excess of events is observed above the expected standard model backgrounds, which are all estimated from the data. Exclusion limits are presented for the constrained minimal supersymmetric extension of the standard model. Cross section limits are also presented using simplified models with new particles decaying to an undetected particle and one or two jets