A road map for designing and reporting clinical trials in paediatric dentistry

Background Unless clinical trials are well‐designed, there is a risk that they will not be usable to improve patient care. Aim This paper discusses some factors important in designing clinical trials in paediatric dentistry. It uses the prevention and management of dental caries in children as the lens through which to look at these. Findings Amongst the factors to consider are clear research questions and objectives; appropriate outcomes and outcome measures; sample size calculation and the level of randomisation; methods for random allocation; and operator/assessor training. Experts in trial design including statisticians and a trialist should be consulted early in the design process. The aspects of trial design unique to cariology trials such as ‘clustering’ of data items, mixed dentition issues and those related to trials involving children (communication, consent etc) should be considered. Comprehensive reporting of trial results is essential. Conclusion There are many readily available resources and tools to help the researcher design a trial of good quality that will yield results useful to the research community and beyond, to those who will implement the findings and ultimately those who will benefit from them

In vitro effects of selected medicinal plants shortlisted for clinical use in the Brazilian public health system in CYP3A4 mRNA gene expression, glutathione levels and P-glycoprotein activity and their implications for herb-drug interactions

The Brazilian Unified Public Health System (SUS) shortlisted various plant species of interest (RENISUS) for future clinical use. However, very little is known about their effects on metabolic and transporter proteins, which could potentially lead to herb-drug interactions (HDI). To evaluate this, we conducted in vitro preclinical studies on twenty-four plant extracts to disclose their effects on CYP3A4 mRNA gene expression, intracellular glutathione (GSH) levels, inhibition of γ-glutamyl transferase (GGT) in HepG2 cells and P- glycoprotein (P-gp) activity in vincristine resistant Caco-2 (Caco-2 VCR) cells. We also investigated whether four Brazilian native species were able to activate the human pregnane X receptor (hPXR) in transiently co-transfected HeLa cells. This preclinical research showed that all but two plant extracts were able to modulate at least one of the selected targets. CYP3A4 mRNA gene expression in HepG2 cells was significantly affected by half of the extracts. The antagonistic effect of Solanum paniculatum L. on hPXR could explain its ability to inhibit CYP3A4. GSH levels were affected by 80% of the extracts. There was depletion of intracellular GSH levels by Cordia verbenacea A. DC., Costus spicatus (Jacq.) Sw., Persea americana Mill., Salix alba L., Schinus terebinthifolia Raddi and Syzygium jambolanum (Lam.) DC. accompanied because of the inhibition of GGT activity. P-gp activity was modulated in a significant manner by 17% of the extracts. The approaches used for the conduction of in vitro preclinical studies in herbal medicines revealed a series of challenges faced especially by academics in order to anticipate cases of HDI. Clinicians have also to consider the presence of intrinsic factors such as genetic polymorphisms in each patient. The possible presence of undesirable interactions between RENISUS herbal medicines and essential drugs in SUS need eventually be clinically confirmed to attest our observed in vitro effects

Automating Cyberdeception Evaluation with Deep Learning

A machine learning-based methodology is proposed and implemented for conducting evaluations of cyberdeceptive defenses with minimal human involvement. This avoids impediments associated with deceptive research on humans, maximizing the efficacy of automated evaluation before human subjects research must be undertaken. Leveraging recent advances in deep learning, the approach synthesizes realistic, interactive, and adaptive traffic for consumption by target web services. A case study applies the approach to evaluate an intrusion detection system equipped with application-layer embedded deceptive responses to attacks. Results demonstrate that synthesizing adaptive web traffic laced with evasive attacks powered by ensemble learning, online adaptive metric learning, and novel class detection to simulate skillful adversaries constitutes a challenging and aggressive test of cyberdeceptive defenses

Photophysical study of Thioflavin T as fluorescence marker of amyloid fibrils

This is the accepted manuscript of the following article: Freire, S., de Araujo, M., Al-Soufi, W., & Novo, M. (2014). Photophysical study of Thioflavin T as fluorescence marker of amyloid fibrils. Dyes And Pigments, 110, 97-105. doi: 10.1016/j.dyepig.2014.05.004. © 2014 Elsevier B.V. This manuscript version is made available under the CC-BY-NC-ND 4.0 license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Thioflavin T is a highly sensitive fluorescent marker of amyloid fibrils that has been widely used for in vitro biomedical assays. However, neither its complex photophysical behavior nor its binding mode to amyloid fibrils are still well understood. We present a detailed analysis of the photophysical properties of Thioflavin T in various media, including solvents and solvent mixtures of different viscosities as well as fibrillar and globular proteins. We propose a model that explains the strong wavelength dependency of the Thioflavin T fluorescence and the large fluorescence enhancement in certain environments. We determine the binding affinities and the fluorescence properties of Thioflavin T bound to amyloid-β (1–42) fibrils and to bovine serum albumin and discuss the sensitivity and the specificity of this probe to amyloid aggregates. These results allow us to assess the suitability of Thioflavin T for quantitative determinations in biomedical studiesS.F. and M. H. A. thank the Xunta de Galicia and the Ministerio de Educación, Cultura y Deporte (Program "Ciencia sin Fronteras") for scholarship. M.N. and W.A. thank the Ministerio de Ciencia e Innovación and the Xunta de Galicia for their financial support (CTQ2010-21369, CN2012/314, GPC2013/052)S

Medication adherence among patients with Type 2 diabetes : a mixed methods study

This research was funded by the Saudi Arabian Ministry of Higher Education and the Saudi Culture Bureau in the form of Dr N Aloudah’s PhD which was undertaken and awarded by the University of Aberdeen, Scotland.Peer reviewedPublisher PD

"I just wanted a dentist in my phone"-designing evidence-based mHealth prototype to improve preschool children's oral and dental health: multimethod study of the codevelopment of an app for children's teeth

Background: Dental caries in preschool children is a global health concern. With increased access to technology and the disruption of health care during the pandemic, mobile health apps have been of interest as potential vehicles for individuals’ health maintenance. However, little is known about caring for their child’s teeth and what their preferences would be regarding the content or design of an oral health app. Objective: This study aims to co-design the prototype of an app named App for Children’s Teeth with parents, providing a source of information for them about caring for their children’s teeth and promoting positive dental habits. Methods: This multimethod study conducted user involvement research with a purposive sample of parents or carers of children aged ≤6 years to (1) understand their use of the internet through the eHealth Literacy Scale and interviews, (2) determine their opinions about content related to children’s oral health, and (3) collect feedback about the app’s acceptability using the Theoretical Framework of Acceptability. There were three stages: (1) interviews with parents to understand their needs, preferences, and abilities; (2) prototype design with app developers; and (3) parent feedback interviews using the think aloud method for data collection. Data were deductively analyzed using a codebook strategy, whereas data from the think aloud sessions were analyzed inductively using reflexive thematic analysis. Results: The prototype design stage involved 10 parents who reported using the internet for health information but found it to be scattered and contradictory. Parents generally welcomed the App for Children’s Teeth but expressed concerns about screen time and practicality. They suggested guidance regarding oral hygiene practices, teething symptoms, and pain relief. Parents appreciated features such as clear fonts, categorization according to their child’s age, and “In a Nutshell” bullet points. Topics that resonated with parents included information about teething, finding a dentist, and breastfeeding. They believed that the app aligned with their goals and offered suggestions for future developments, such as outlining the process of finding a dentist and incorporating a forum for parents to communicate and exchange ideas. Conclusions: The coproduction design approach highlighted parents’ need for solutions such as mobile health apps to access reliable information about oral health. Parents identified key design concepts for the app, including a simple and uncluttered interface, content categorization according to their child’s age, and practical guidance supported by visual aids. Despite potential challenges related to screen time restrictions, parents provided insights into how such an app could fit seamlessly into their lives

Radioactivity Backgrounds in ZEPLIN-III

We examine electron and nuclear recoil backgrounds from radioactivity in the ZEPLIN-III dark matter experiment at Boulby. The rate of low-energy electron recoils in the liquid xenon WIMP target is 0.75$\pm$0.05 events/kg/day/keV, which represents a 20-fold improvement over the rate observed during the first science run. Energy and spatial distributions agree with those predicted by component-level Monte Carlo simulations propagating the effects of the radiological contamination measured for materials employed in the experiment. Neutron elastic scattering is predicted to yield 3.05$\pm$0.5 nuclear recoils with energy 5-50 keV per year, which translates to an expectation of 0.4 events in a 1-year dataset in anti-coincidence with the veto detector for realistic signal acceptance. Less obvious background sources are discussed, especially in the context of future experiments. These include contamination of scintillation pulses with Cherenkov light from Compton electrons and from $\beta$ activity internal to photomultipliers, which can increase the size and lower the apparent time constant of the scintillation response. Another challenge is posed by multiple-scatter $\gamma$-rays with one or more vertices in regions that yield no ionisation. If the discrimination power achieved in the first run can be replicated, ZEPLIN-III should reach a sensitivity of $\sim 1 \times 10^{-8}$ pb$\cdot$year to the scalar WIMP-nucleon elastic cross-section, as originally conceived.Peer Reviewe