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Pharmaceutical Formulations and Analytical Methods of Donepezil
No full textDonepezil is a selective acetylcholinesterase inhibitor widely prescribed for the symptomatic treatment of Alzheimer's disease. As therapeutic needs grow and delivery systems evolve, ensuring product quality, efficacy, safety and patient compliance becomes increasingly important. Meanwhile, pharmaceutical formulation innovations can improve clinical outcomes and usability, and analytical methods help ensure accurate assessment of drug behavior and quality control. This narrative review first provides a concise overview of donepezil's physicochemical properties and synthesis, then focuses on two interrelated domains: (i) pharmaceutical formulations and (ii) analytical methodologies. The former highlights advancements in novel delivery systems-such as liposomes, nanoparticles, microneedles, nasal gels, and long-acting injectable depots-developed to enhance brain targeting, prolong drug release, and reduce systemic side effects. The latter reviews validated analytical methods for quantifying and characterizing donepezil in pharmaceutical and biological matrices, with emphasis on RP-HPLC, LC-MS/MS, chiral separations, and emerging electrochemical and spectroscopic techniques. These analytical strategies are essential for evaluating formulation performance, monitoring drug stability, and ensuring regulatory compliance. Collectively, this review underscores that progress in both formulation design and analytical science is vital to optimizing donepezil-based therapies for Alzheimer's disease management
Dual-mode optical fiber sensor with polydopamine-functionalized surface and PDMS-enhanced temperature compensation for ultrasensitive HCG detection
No full textThis study introduces a temperature-compensated dual-mode optical fiber sensor for ultrasensitive human chorionic gonadotropin (HCG) detection, integrating polydopamine (PDA) nanostructures with polydimethylsiloxane (PDMS)-modified microcavities. The hybrid design synergistically enhances surface plasmon resonance (SPR) and Fabry-Pérot (FP) responses through engineered material interfaces. PDA enables efficient antibody immobilization via amine coupling, while PDMS simultaneously acts as a thermal expansion compensator and optical phase modulator, overcoming temperature-induced signal drift in conventional biosensors. The system demonstrates dual refractive index sensitivity (1875 nm/RIU) and differentiated temperature responses (-0.12 nm/ °C SPR vs. -0.61 nm/ °C FP), enabling environmental decoupling through matrix analysis. The sensor achieves record HCG detection performance with 1.54 nm/(mIU/mL) sensitivity and 0.01 mIU/mL detection limit. This materials-driven approach merges functional polymer engineering with photonic design, establishing a new paradigm for field-deployable lab-on-fiber biosensors. The work advances multiplexed optical sensing technologies for point-of-care diagnostics and smart medical materials development
Microbiota composition of the female reproductive tract and miscarriage: a systematic review and meta-analysis
No full textOnlinePublMiscarriage, the loss of a pregnancy before viability, can be sporadic or recurrent. Emerging evidence links miscarriage to specific microbiota compositions within the female reproductive tract (FRT). This systematic review aims to synthesise evidence on the association between sporadic and recurrent miscarriage and FRT microbiota composition, as assessed using metataxonomic profiling approaches. A systematic analysis of the 43 included studies, sampling the vaginal, cervical and endometrial microbiota supported an association between reduced Lactobacillus abundance and miscarriage, making it a potential target for therapeutic intervention. However, consistent changes in alpha and beta diversity were not observed and there was a lack of reproducibility for other compositional changes. This review also highlighted concerns about the significant bias introduced due to methodological variations and emphasises the need for future standardisation of microbial sampling, sequencing, and reporting to allow accurate comparison of results and to reduce research waste.Naomi Black, Ian Henderson, Siobhan Quenby, Joshua Odendaal & David A. MacIntyr
Cervical spine posture, but not head-end motion constraints, governs the kinematic and kinetic response in sub-injurious axial impacts
No full textAvailable online 22 December 2025Head-first impacts can produce traumatic cervical spine injuries resulting in tetraplegia. These injury patterns are thought to relate to the alignment of the loading vector relative to the spinal column. Pre-impact posture and subsequent head and intervertebral kinematics, including spinal buckling and head motion relative to the spine and torso, can generate complex spinal configurations. These motions often precede injury onset and can be observed with ex vivo models in which applied loads remain below injury thresholds. This study examined the kinematic response of the cervical spine to dynamic axial compression at sub-injurious severities, enabling interand intra-specimen comparisons across varying initial spinal postures and head motion constraints. Human cervical spine specimens (N = 7) were subjected to repeated 1 m/s axial impacts, while the applied head constraint (sagittal rotation and/or anterior translation) and initial posture (anterior eccentricity and curvature) were varied. Pre-impact head–T1 eccentricity and curvature, head-end motion during impact, intervertebral kinematics, and impact loads were recorded. Head-end anterior translation and flexion rotation were minimal across all constraint conditions ( 0.05). In contrast, greater initial curvature and eccentricity reduced stiffness and peak force, and increased deformation (p < 0.05). Greater initial curvature also produced larger changes in intervertebral flexion-extension during impact (p < 0.05). These results demonstrate that pre-impact posture dictates the cervical spine’s sub-injurious axial response at discrete anterior eccentricities, which may be further explored using computational models validated using this dataset.Darcy W. Thompson-Bagshaw, Ryan D. Quarrington, Peter A. Cripton, Claire F. Jone
Cost-efficient and stable electrolysis of reverse osmosis water using a Co-RuO₂-enabled PEM electrolyser
No full textThe durability of proton-exchange-membrane water electrolysers (PEMWE) is strongly influenced by the purity of the feedwater. Reverse osmosis (RO) is a cost-effective purification method, but the residual ions usually cause rapid degradation. Here we show that a standard PEMWE equipped with a cobalt-doped ruthenium dioxide (Co-RuO2) anode catalyst can operate stably for 2,000h at 1.0Acm -2 using RO-level impure water, with a degradation rate of 10.2muVh -1. The catalyst provides two complementary protections: Co sites selectively and reversibly capture chloride ions (Cl -), forming a shielding layer against anions corrosion, and strain-activated Ru sites create a proton-rich interface that blocks impurity cations. Together, these effects maintain electrode activity and membrane conductivity. As a result, RO water electrolysis achieves a durability comparable to pure water operation while retaining the cost benefits of seawater-derived purification, offering a practical route towards efficient and affordable hydrogen production.Hao Liu, Xiaogang Sun, Fei-Yue Gao, Yao Zheng, Shi-Zhang Qia
Psychological wellbeing outcomes across genders in childhood and adolescence aged 8–18 years: a population-level perspective
No full textThis study aimed to examine the difference in levels of psychological wellbeing outcomes of binary and nonbinary transgender and cisgender students aged 8–18 years in South Australia using population-level data. Student’s gender was imputed based on their self-reported gender (male, female, other) and parent-reported gender at school enrolment (male, female). Two groups represented cisgender students (n = 64,467), while four groups represented transgender and non-binary students (transgender boys, transgender girls, non-binary students presumed male at birth, non-binary students presumed female at birth; n = 1,016). A descriptive analysis was conducted to calculate the difference in levels of low, medium, and high psychological wellbeing across five outcomes: life satisfaction, optimism, happiness, sadness, and worries. Most transgender groups reported poorer outcomes than cisgender groups across most wellbeing indicators. Non-binary students, particularly those presumed female at birth, had the poorest psychological wellbeing outcomes. Like prior research, students with a gender other than male or female reported substantially poorer outcomes, indicating a need for holistic school and community services that assist transgender-specific social-emotional needs.Zara Boulton, Mary Brushe, Damien W. Riggs, Ashleigh Lin, Cristyn Davies, Tess Gregor
Malpractice in the machine age: Legal and ethical responses to machine learning in medical imaging
No full textObjectives Artificial intelligence (AI) and machine learning (ML) are increasingly integrated into diagnostic imaging. This review examines how AI adoption affects malpractice risk, the legal standard of care, liability distribution, and informed consent. It also evaluates regulatory developments and ethical concerns, including explicability, autonomy, and professional accountability. Key findings AI-supported image interpretation can improve diagnostic accuracy and efficiency. Its integration is reshaping expectations of reasonable clinical practice, with the potential for negligence claims both when clinicians fail to use validated systems and when they rely on insufficiently tested tools. Liability is uncertain because diagnostic responsibility is distributed across clinicians, healthcare organisations, and developers. Existing negligence frameworks assume human reasoning and struggle to accommodate opaque algorithmic decision-making, limiting courts' ability to assess whether AI-assisted diagnoses meet accepted standards. “Black box” models heighten automation bias, hinder legal scrutiny of error, and complicate professional accountability. Informed consent case law suggests AI involvement should be disclosed when it introduces material differences in risk or outcome, although this remains inconsistently applied. Ethical challenges include threats to patient trust, potential clinician deskilling, and reduced transparency in clinical communication. Regulatory initiatives such as the European Union’s General Data Protection Regulation and AI Act move toward clearer governance through requirements for data quality, human oversight, and post-market monitoring, yet explicit malpractice guidance remains under-developed globally. Conclusion Traditional legal and ethical frameworks insufficiently address accountability for AI-driven diagnostic errors. Clarifying responsibility, decision authority, and validation requirements is essential to safeguard patient safety and clinician protection. Implications for practice Clinical protocols should specify approved use cases, oversight expectations, documentation of AI involvement, and management of clinician-algorithm disagreement. Training should support critical review of outputs to mitigate automation bias.M.T. Chau, K.M. Spuur, S. White, A. Pyper, M. Crossma
Understanding polysulfide evolution in wine: insights from accelerated ageing and real-time cellaring in different packaging
No full textVolatile sulfur compounds (VSCs) and non-volatile biothiols play a crucial role in wine quality. Certain sulfhydryl compounds can react to form odourless polysulfides (RSSnSR′) that potentially contribute to the development of sulfur off-odours during winemaking and storage. This study investigated the evolution of sulfur species in Chardonnay and Shiraz wine during real-time and accelerated ageing in glass bottles with different closures and in aluminium cans. Moderate glutathione (GSH) accumulation was accompanied by disulfide formation, with GSH trisulfide (GS-S-SG), tetrasulfide (GS-S2-SG), and mixed cysteine-GSH tetrasulfide (Cys-S2-SG) displaying compound- and matrix-specific trends. Can packaging maintained higher amounts of VSCs, sulfur dioxide, and GSH, whereas closures with varying oxygen transmission had the most pronounced impact on glutathione disulfide (GS-SG) accumulation. Treatment with nitrogen gas or copper exhibited preservation effects under accelerated ageing. These findings highlight the role of wine packaging on polysulfide chemistry and clarify the effects of pre-bottling strategies for VSC management.Yu Hou, Marlize Z. Bekker, Tracey E. Siebert, Gal Y. Kreitman, David W. Jeffer
Refusing to forgive can have psychological benefits
No full textOffering forgiveness can confer benefits to victims in terms of enhanced sense of self. In the present research, we argue that refusing to forgive may also promote psychological benefits. Across three studies, a recall design (N = 300), an experiment (N = 327), and its pre-registered replication (N = 296), we examined the potential psychological benefits of refusing forgiveness and offering forgiveness compared to inaction. We found that refusing forgiveness (vs. inaction) resulted in greater feelings of power (n.s. Study 1), greater value integrity, and mediated by these, refusing to forgive increased state self-esteem. We also found that offering forgiveness (vs. inaction) resulted in greater feelings of power (n.s. Studies 1 and 2), greater value integrity, and greater state self-esteem. These findings demonstrate that while offering and refusing to forgive may be opposing responses to transgressions, both actions can provide psychological benefits for victims. This research offers support to victims who wish to express their genuine feelings of unforgiveness because the act of refusing forgiveness can have psychological benefits.Blake Quinney, Elena Zubielevitch, Tyler G. Okimot
Early high risk of cerebral palsy classification is predictive of cerebral palsy at 2 years: an implementation cohort study
No full textAvailable online 28 August 2025Objective: To determine the predictive accuracy of an early high risk of cerebral palsy (CP) classification for CP diagnosed by 2 years’ corrected age within an implementation study of international clinical CP guidelines. Design: Implementation cohort study. Setting: Eleven Australian neonatal intensive care units. Patients: 453 infants born 2019–21 <28 weeks’ gestation, or ≥28 weeks with other newborn-detectable risk factors for CP. Interventions: Implementation included providing professional development for clinicians, technology (smartphone app) and health network peer support. Infants were classified as high risk of CP if they had abnormal findings on at least two of the following three assessments: neonatal neuroimaging, General Movements Assessment at 3–4 months or Hammersmith Infant Neurological Examination. Main outcome measures: Baseline perinatal data and 2-year outcome data were collected from medical record review. Any parent-report of CP at the 2-year interview was confirmed by medical records and/or a paediatrician’s report. We calculated predictive values for high risk of CP classification for confirmed CP at 2 years. Results: We obtained 2-year outcomes from 425 infants (95%). High risk of CP was classified in 105 (25%) of these infants at a mean age of 3.5 months (SD 2.5). This classification demonstrated 91% sensitivity (95% CI 82% to 96%), 90% specificity (95% CI 86% to 93%) and 90% accuracy (95% CI 87% to 93%) for predicting CP, with a mean age of diagnosis of 10.8 months (SD 6.3). Conclusion: Being classified as high risk of CP using a combination of neuroimaging, General Movements Assessment and/or Hammersmith Infant Neurological Examination can predict CP by 2 years of age with high accuracy.Amanda KL Kwong, Abbey L Eeles, Peter J Anderson, Shankari Arunanthy, Nadia Badawi, Roslyn N Boyd, Kate LC Cameron, Paul B Colditz, Cathryn Crowle, Russell Dale, Lex W Doyle, Joanne M George, Pieter J Koorts, Katherine J Lee, Carly R Luke, Lynda McNamara, Catherine Morgan, Iona Novak, Joy E Olsen, Nadia G Reid, Paul Scuffham, Koa Whittingham, Jeanie LY Cheong, Alicia J Spittl