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Enhanced oral absorption and biodistribution to submandibular salivary glands of D-limonene in Sprague Dawley rats via a liquid-lipid formulation approach
No full textData source: Supplementary material, https://doi.org/10.1016/j.ijpharm.2025.125179Decreased saliva production due to salivary gland damage can result in difficulty speaking and swallowing, significantly reducing quality of life for head and neck cancer patients receiving radiotherapy. It is therefore imperative that treatment options are available to mitigate the effects of these debilitating side effects. D-limonene, a naturally occurring terpene, has shown protective effects on saliva production during radiotherapy treatment of mice, however the lipophilic nature of the molecule has necessitated a high oral dose to facilitate sufficient absorption. In this study, lipid-based drug delivery systems have been utilised to formulate D-limonene in order to reduce undesirable gastrointestinal side effects and increase solubility for enhanced absorption.
Lipid-based formulations produced up to 180-fold increased solubility over pure D-limonene, coupled with enhanced storage stability and protection against oxidation. Furthermore, pharmacokinetic evaluation of optimised lipid-based formulations in Sprague Dawley rats displayed up to a 51.25-fold increase in bioavailability relative to pure oral D-limonene. Finally, elevated levels of lipid-formulated D-limonene were localised within the submandibular salivary glands, indicating potential for local action on saliva production. Overall, the administration of D-limonene utilising lipid-based formulations shows significant promise for advancing prevention and treatment strategies for xerostomia
Search for a new scalar decaying into new spin-1 bosons in four-lepton final states with the ATLAS detector
No full textA search is conducted for a new scalar boson , with a mass distinct from that of the Higgs boson, decaying promptly into four leptons ( = , ) via an intermediate state containing two on-shell, promptly decaying new spin-1 bosons (d): →(d)(d) →4, where the (d) boson has a mass between 15 and 300 GeV, and the boson has a mass between either 30 and 115 GeV or 130 and 800 GeV. The search uses proton–proton collision data collected with the ATLAS detector at the Large Hadron Collider with an integrated luminosity of 139 fb(−1) at a centre-of-mass energy of √ = 13 TeV. No significant excess above the Standard Model background expectation is observed. Upper limits at 95% confidence level are set on the production cross-section times branching ratio, ( →) × Β( →(d)(d) →4), as a function of the mass of both particles, () and ()(d).The ATLAS Collaboratio
Changing the world for good? : mapping the long-term impacts of adult environmental education programs in South Australia /
No full text1 ethesis (xii, 238 pages) :illustrations (chiefly colour), charts (chiefly colour)Includes bibliographical references (pages 146-170)This research project, Changing the World for Good, aims to explore if and how adult-orientated Environmental and Sustainability Education (ESE) facilitates long-term outcomes and systemic impact. This study is part of a larger research project, Living Lightly Locally: SMARTer and Stronger through Citizen Science (LLL). The research is also framed by the researcher’s background in environmental policy and management and ESE. Living Smart (administered by Green Adelaide) was the focal case study for the research, complemented with data from the Australian Red Cross Climate-Ready Communities program. This research seeks to examine the current gap in understanding of the impact of ESE programs on fostering lasting change in individuals, households, communities and beyond.Thesis (Masters by research(Environmental Science))--University of South Australia, 2025
A new colorimetric using Zr oxide DGT technique for high-resolution measurement of labile Mo(VI) in sediment porewater
No full textData source: Supporting information, https://pubs.acs.org/doi/10.1021/acsestwater.4c01281?goto=supporting-infoUnderstanding the distribution of labile molybdenum (Mo(VI)) in sediment porewater is essential for managing Mo-contaminated environments. This study developed a two-dimensional (2D) high-resolution method combining diffusive gradients in thin films (DGT) with sodium thiocyanate coloration and computer-imaging densitometry (CID) to measure labile Mo(VI). Optimal color development occurred at 25 °C for 36 min using a reagent volume that was 100 times that of the binding gel. The method proved to be robust against variations in pH, ionic strength, and phosphate level. It was applied to sediment from the Luhun Reservoir, revealing increased Mo(VI) concentrations in overlying water, a decline near the sediment-water interface, a subsequent increase, and then a decrease with depth. These patterns suggest Mo(VI) originates from overlying water, binds to Fe/Mn (hydr)oxides below the interface, and interacts with dissolved sulfide in deeper layers. The DGT-CID technique offers a simple, field-applicable approach for accurate, high-resolution measurement of labile Mo(VI) and enhances our understanding of its spatial distribution in sediments, aiding effective environmental monitoring and remediation
Identification of new KCNT1-epilepsy drugs by In silico, cell, and drosophila modeling
No full textData source: supporting information, https://doi.org/10.1002/ana.78031Objective: Hyperactive KCNT1 potassium channels, caused by gain-of-function mutations, are associated with a range of epilepsy disorders. Patients typically experience drug-resistant seizures and, in cases with infantile onset, developmental regression can follow. KCNT1-related disorders include epilepsy of infancy with migrating focal seizures and sleep-related hypermotor epilepsy. There are currently no effective treatments for KCNT1 epilepsies, but suppressing overactive channels poses a potential strategy.
Methods: Using the KCNT1 channel structure we in silico screened a library of known drugs for those predicted to block the channel pore to inhibit channel activity. Cellular KCNT1 channel inhibition was analyzed using electrophysiology and Drosophila bang-sensitive assays were used to analyze seizure suppression. Brain penetration of one drug was analyzed using liquid chromatography–mass spectrometry in a mouse.
Results: Eight known drugs were investigated in vitro for their effects on patient-specific mutant KCNT1 channels, with 4 drugs showing significant reduction of K+ current amplitudes. The action of the 4 drugs was then analyzed in vivo and 2 were found to reduce the seizure phenotype in humanized Drosophila KCNT1 epilepsy models. One drug, antrafenine, was shown to cross the blood–brain barrier in mice.
Interpretation: This study identified a known drug, antrafenine, that reduces KCNT1 channel activity, reduces seizure activity in Drosophila, and crosses the blood–brain barrier in the mouse, suggesting its potential applicability as a new treatment for KCNT1 epilepsy. The sequential in silico, in vitro, and in vivo mechanism-based drug selection strategy used here may have broader application for other human disorders where a disease mechanism has been identified
Effects of a virtual iSupport Program on carers and people with dementia
No full textData source: Supporting Information, https://doi.org/10.1002/alz.70747Methods: We applied a pragmatic randomized controlled trial to evaluate a multicomponent program delivered virtually in four organizations (July 2022 to December 2024). The primary outcome was quality of life (QoL) of carers and PLWD at 12 months post-baseline, and the secondary outcomes were carers' self-efficacy, social support, reactions to behavior, PLWD's behavior frequency, hospital admissions, and emergency department presentations
Hippo signaling regulates the nuclear behavior and DNA binding times of YAP and TEAD to control transcription
No full textOver the past two decades, genetic and proteomic screens have identified the Hippo pathway as a complex signaling network that controls tissue growth and human cancer. Despite these advances, our understanding of how Hippo signaling regulates transcription is less clear. To address this, we used live microscopy to study the nuclear behavior of the major Hippo pathway transcription effectors, YAP and TEADs. We reveal that TEADs are a major determinant of YAP DNA binding and nuclear mobility, while YAP minorly influences TEADs. YAP and TEAD1 associate with DNA for longer periods in cells with intrinsically low Hippo pathway activity and upon acute Hippo pathway perturbation. TEAD1 binds the genome on a broad range of timescales, and this is extended substantially in nuclear condensates. Last, a cancer-associated YAP fusion protein exhibits substantially different biophysical behavior than either YAP or TEAD1. Thus, we reveal that Hippo signaling regulates transcription, in part, by influencing the DNA binding times of YAP and TEADs.Benjamin Kroeger, Samuel A. Manning, Varshini Mohan, Jieqiong Lou, Guizhi Sun, Sara Lamont, Alex J. McCann, Mathias Francois, Jose M. Polo, Elizabeth Hinde, Kieran F. Harve
Empirically testing for niche sports
No full textAlthough niching has been well explored across the marketing, strategy, and consumer behaviour literature, its application in the sport context to date has been atheoretical, resulting in pervasive inconsistencies within the sport marketing literature. Such inconsistency has derived from sport scholarship’s adoption of anecdotal and subjective descriptions of “niche sports.” This shortcoming is addressed first through an analysis of extant niche literature, to articulate a conceptual framework to realign and guide future niche marketing sport research. This framework is underpinned by marketing’s empirical generalisations and Dirichlet modelling, offering a parsimonious methodology to identify niche brands. An analysis of Australian sport participation is then performed, to empirically test for the presence of niche sports utilising the advocated framework. Data was obtained from Australia’s large-scale national population tracking survey AusPlay, with a final sample of 70,858 respondents and included 124 discrete sport and recreational activities.
The empirical analysis reveals several sports and recreation activities to exhibit characteristics of niche positioning: Crossfit, Mixed Martial Arts, Equestrian, and Walking. These activities feature a base of participants who exhibit an exceedingly high participation frequency, elevated rates of sole loyalty to the respective activity and a disposition for the chosen activity to fulfil a disproportionate share of their overall product category requirements. In practice, such niche sport brands require divergent marketing strategies focused upon product quality, maintaining customer relationships and reinforcing internal dynamic capabilities. The study concludes with a discussion of niche sport’s potential idiosyncratic features, to provide a roadmap for future research
Protocol summary and statistical analysis plan for the sodium bicarbonate for metabolic acidosis in the intensive care unit (SODa-BIC) trial
No full textBackground Metabolic acidosis is common in critically ill patients and is associated with increased risk of organ dysfunction, need for renal replacement therapy, and death. Despite its frequency and clinical relevance, the optimal treatment approach remains uncertain. Sodium bicarbonate is often used to correct acidosis, but its risk–benefit profile in this setting is unclear. Objective To describe the study protocol and statistical analysis plan for the sodium bicarbonate for metabolic acidosis in the intensive care unit (SODa-BIC) trial. Design, setting and participants Protocol for an international, multicentre, randomised, double-blind, parallel-group, superiority adaptive clinical trial. Five hundred (n = 500) adults with metabolic acidosis and receiving a continuous infusion of a vasopressor will be randomly assigned to sodium bicarbonate or placebo in a 1:1 ratio. SODa-BIC started recruiting in April 2023. It is anticipated that recruitment will be completed in 2026. Main outcome measures The primary outcome will be major adverse kidney events within 30 days (MAKE30). Secondary and tertiary outcomes include 30- and 90-day mortality, receipt of renal replacement therapy, and vasopressor-free and ICU-free days at day 30. All analyses will be conducted on an intention-to-treat basis. Results and conclusions SODa-BIC will evaluate whether sodium bicarbonate improves clinically meaningful outcomes in critically ill patients with metabolic acidosis. The trial has the potential to inform international practice guidelines and provide robust evidence to guide the treatment of a common and severe condition in the intensive care unit.Ary Serpa Neto, Mairead McNamara, Jamie Cooper, Tomoko Fujii, Alisa Higgins, Carol Hodgson, Leanlove Navarra, Alistair Nichol, Sandra Peake, Alvaro Rea-Neto, Paul Secombe, Emily See, Pam Taylor, Meredith Young, Fernando G. Zampieri, Paul Young, Rinaldo Bellomo, Andrew Ud
What is "Zone 2 Training"?: experts' viewpoint on definition, training methods, and expected adaptations
No full textBackground: The role of high-volume low-intensity training for enhancing endurance performance has gained growing interest in recent years. Specifically, so-called “zone 2 training” is currently receiving much attention, and many propose that this is the target intensity at which a large proportion of total endurance training should be performed. However, despite the popularity of this concept, there is no clear consensus among coaches, athletes, and scientists regarding the definition of zone 2 training.
Purpose: This commentary summarizes the perspectives, experience, and knowledge of an expert panel of 14 applied sport scientists and professional coaches with the aim of providing insight and a basis for definitional consensus on zone 2 training. Moreover, potential training strategies at this intensity are proposed, and the expected physiological adaptations when exercising at this intensity and related research gaps are also discussed.
Results: Experts reached consensus that zone 2 training should preferably be performed at intensities located immediately below the first lactate or ventilatory threshold through continuous, variable, or interval-type sessions. Furthermore, experts expected a broad range of central and peripheral adaptations from zone 2 training. These expected adaptations might not be unique to zone 2 and could also be induced with sessions performed at slightly higher and lower intensities.
Conclusions: This commentary provides practical insight and unified criteria regarding the preferred intensity, duration, and session type for the optimization of zone 2 training based on the perspectives of acknowledged sport scientists and professional coaches