Using intervention mapping to develop a home-based parental-supervised toothbrushing intervention for young children

BACKGROUND: Dental caries in young children is a major public health problem impacting on the child and their family in terms of pain, infection and substantial financial burden on healthcare funders. In the UK, national guidance on the prevention of dental caries advises parents to supervise their child's brushing with fluoride toothpaste until age 7. However, there is a dearth of evidence-based interventions to encourage this practice in parents. The current study used intervention mapping (IM) to develop a home-based parental-supervised toothbrushing intervention to reduce dental caries in young children. METHODS: The intervention was developed using the six key stages of the IM protocol: (1) needs assessment, including a systematic review, qualitative interviews, and meetings with a multi-disciplinary intervention development group; (2) identification of outcomes and change objectives following identification of the barriers to parental-supervised toothbrushing (PSB), mapped alongside psychological determinants outlined in the Theoretical Domains Framework (TDF); (3) selection of methods and practical strategies; (4) production of a programme plan; (5) adoption and implementation and (6) Evaluation. RESULTS: The comprehensive needs assessment highlighted key barriers to PSB, such as knowledge, skills, self-efficacy, routine setting and behaviour regulation and underlined the importance of individual, social and structural influences. Parenting skills (routine setting and the ability to manage the behaviour of a reluctant child) were emphasised as critical to the success of PSB. The multi-disciplinary intervention development group highlighted the need for both universal and targeted programmes, which could be implemented within current provision. Two intervention pathways were developed: a lower cost universal pathway utilising an existing national programme and an intensive targeted programme delivered via existing parenting programmes. A training manual was created to accompany each intervention to ensure knowledge and standardise implementation procedures. CONCLUSIONS: PSB is a complex behaviour and requires intervention across individual, social and structural levels. IM, although a time-consuming process, allowed us to capture this complexity and allowed us to develop two community-based intervention pathways covering both universal and targeted approaches, which can be integrated into current provision. Further research is needed to evaluate the acceptability and sustainability of these interventions

Oleuropein derivatives from olive fruit extracts reduce α-synuclein fibrillation and oligomer toxicity

Aggregation of α-synuclein (αSN) is implicated in neuronal degeneration in Parkinson's disease and has prompted searches for natural compounds inhibiting αSN aggregation and reducing its tendency to form toxic oligomers. Oil from the olive tree (Olea europaea L.) represents the main source of fat in the Mediterranean diet and contains variable levels of phenolic compounds, many structurally related to the compound oleuropein. Here, using αSN aggregation, fibrillation, size-exclusion chromatography–multiangle light scattering (SEC-MALS)-based assays, and toxicity assays, we systematically screened the fruit extracts of 15 different olive varieties to identify compounds that can inhibit αSN aggregation and oligomer toxicity and also have antioxidant activity. Polyphenol composition differed markedly among varieties. The variety with the most effective antioxidant and aggregation activities, Koroneiki, combined strong inhibition of αSN fibril nucleation and elongation with strong disaggregation activity on preformed fibrils and prevented the formation of toxic αSN oligomers. Fractionation of the Koroneiki extract identified oleuropein aglycone, hydroxyl oleuropein aglycone, and oleuropein as key compounds responsible for the differences in inhibition across the extracts. These phenolic compounds inhibited αSN amyloidogenesis by directing αSN monomers into small αSN oligomers with lower toxicity, thereby suppressing the subsequent fibril growth phase. Our results highlight the molecular consequences of differences in the level of effective phenolic compounds in different olive varieties, insights that have implications for long-term human health

Prospect of vasoactive intestinal peptide therapy for COPD/PAH and asthma: a review

There is mounting evidence that pulmonary arterial hypertension (PAH), asthma and chronic obstructive pulmonary disease (COPD) share important pathological features, including inflammation, smooth muscle contraction and remodeling. No existing drug provides the combined potential advantages of reducing vascular- and bronchial-constriction, and anti-inflammation. Vasoactive intestinal peptide (VIP) is widely expressed throughout the cardiopulmonary system and exerts a variety of biological actions, including potent vascular and airway dilatory actions, potent anti-inflammatory actions, improving blood circulation to the heart and lung, and modulation of airway secretions. VIP has emerged as a promising drug candidate for the treatment of cardiopulmonary disorders such as PAH, asthma, and COPD. Clinical application of VIP has been limited in the past for a number of reasons, including its short plasma half-life and difficulty in administration routes. The development of long-acting VIP analogues, in combination with appropriate drug delivery systems, may provide clinically useful agents for the treatment of PAH, asthma, and COPD. This article reviews the physiological significance of VIP in cardiopulmonary system and the therapeutic potential of VIP-based agents in the treatment of pulmonary diseases

The potential of zwitterionic nanoliposomes against neurotoxic alpha-synuclein aggregates in Parkinson's Disease.

The protein α-synuclein (αSN) aggregates to form fibrils in neuronal cells of Parkinson's patients. Here we report on the effect of neutral (zwitterionic) nanoliposomes (NLPs), supplemented with cholesterol (NLP-Chol) and decorated with PEG (NLP-Chol-PEG), on αSN aggregation and neurotoxicity. Both NLPs retard αSN fibrillization in a concentration-independent fashion. They do so largely by increasing lag time (formation of fibrillization nuclei) rather than elongation (extension of existing nuclei). Interactions between neutral NLPs and αSN may locate to the N-terminus of the protein. This interaction can even perturb the interaction of αSN with negatively charged NLPs which induces an α-helical structure in αSN. This interaction was found to occur throughout the fibrillization process. Both NLP-Chol and NLP-Chol-PEG were shown to be biocompatible in vitro, and to reduce αSN neurotoxicity and reactive oxygen species (ROS) levels with no influence on intracellular calcium in neuronal cells, emphasizing a prospective role for NLPs in reducing αSN pathogenicity in vivo as well as utility as a vehicle for drug delivery