Targeted Drug Delivery to the Spleen and Its Implications for the Prevention and Treatment of Cancer

The spleen, the largest secondary lymphoid organ, plays several vital roles in the body, including blood filtration, hematopoiesis, and immune regulation. Despite its importance, the spleen has not received substantial attention as a target organ for drug delivery. Most systemically administered colloidal and particulate drug carriers are cleared from the blood by the liver and spleen, making these two organs potential targets for drug accumulation. While various systems have been developed to target the liver, there is an urgent need to design spleen-targeted drug delivery systems that can evade clearance and degradation while delivering drugs efficiently to their target cells in the spleen. Targeting the spleen holds great potential for the treatment of a range of diseases, including blood disorders, immune and inflammatory diseases, infectious diseases, and cancer. It is also crucial for the development of effective vaccines. In this review, we explore different approaches used to target the spleen after systemic administration, and we discuss the factors that shift the biodistribution of drug carriers from the liver to the spleen. We focus on cell-specific delivery within the spleen, strategies to avoid degradation, and methods to achieve the efficient intracellular delivery of various drugs and genes. We also highlight the therapeutic implications of spleen-targeted drug delivery systems, particularly for the prevention and treatment of cancer

Postneonatal Cerebral Palsy in Europe: Prevalence and Clinical Characteristics According to Contributory Events: An SCPE Study.

Postneonatal cerebral palsy (PNCP) is rare and requires large databases to be studied over time. To study the time trend of prevalence of PNCP overall and by cause, and to describe the clinical characteristics of children with PNCP according to cause and compared with children with pre/peri/neonatal CP (PPNCP). The Surveillance of Cerebral Palsy in Europe (SCPE) database was used. Primary events (the first known chronological event in the causal chain) were classified according to the SCPE classification (six main and 19 sub-categories). Prevalence trends for children born during 1976-2012 were modelled using multilevel generalised linear models. The clinical characteristics of PNCP and PPNCP cases born after 1998 were reported as proportions. The prevalence rates of PNCP were 1.76 (95% confidence interval (CI) 1.37, 2.23) and 0.82 per 10,000 live births (95% CI 0.73, 0.92) in children born during 1976-1980 and 2006-2012, respectively. The models showed a 2% annual decline in overall prevalence (prevalence rate multiplied by 0.98 each year) and a 10% decline for infectious causes for every 5-year change. The prevalence rate in children born during 2006-2012 was 0.26 per 10,000 (95% CI 0.21, 0.32) for infectious causes, which remained the most frequent. No trend emerged for other causes. Unilateral spastic CP, associated impairments and severe gross motor dysfunction were more frequent in PNCP than in PPNCP, and PNCP showed predominantly grey matter injury (55.6%). Seventeen percent were born preterm. PNCP differed by cause, with cerebrovascular accidents presenting the least severe and hypoxic causes the most severe forms. Our study confirms the decrease in the prevalence of PNCP in children born up to 2012, particularly for CP, due to infectious causes, which remain the most frequent. Children with PNCP had more severe presentation overall than those with PPNCP, with severity depending on the cause. [Abstract copyright: © 2024 John Wiley & Sons Ltd.

Bridging the divide: Empowering marginalised student voices through reverse mentoring

This study explores the potential transformative effect of reverse mentoring in higher education, as a strategy to amplify the voices of students from marginalised and minoritised backgrounds. Against a backdrop of disparities in student outcomes, the project aimed to uncover barriers to academic success and unpick potential opportunities for inclusivity through the lived experiences of students. Via the implementation of a structured reverse mentoring framework, students served as mentors to academic staff, sharing insights from their own journeys to hopefully inform institutional practices and policies. The methodology included an interpretive phenomenological approach, with data collected through focus groups and mentoring sessions. Ten student mentors from diverse backgrounds were paired with ten academic staff members. Sessions were designed around student-led themes such as belonging, cultural adaptation, and support systems. The process inverted traditional hierarchies, empowering students to guide meaningful discussions whilst enabling staff to gain critical perspectives on systemic and interpersonal challenges. Key findings highlight recurring themes of health and wellbeing, social and institutional barriers, and belonging and inclusion. Within these themes students identified barriers such as stigma around disabilities, financial strain, and fragmented support systems, which disproportionately impact marginalised groups. The project’s outcomes underscore the value of reverse mentoring as a tool for personal and professional development, institutional change, and empowerment, and have allowed for recommendations to be made on an institutional level aimed at improving equality of outcomes. By bridging the divide between students and staff, this initiative demonstrates how reverse mentoring can promote equity, belonging, and actionable change in higher education. This study also contributes to the growing body of literature on inclusive practices in academia and highlights the potential of reverse mentoring to address systemic barriers, fostering a fairer and more socially responsible university community

Chain length effects of aliphatic monoamine on shape memory behaviors of copolybenzoxazines

The objective of this research is to investigate the effect of aliphatic amine chain lengths on shape memory polymers (SMPs) properties of benzoxazine resin. Bisphenol-A, paraformaldehyde, and different aliphatic amine chain lengths at 1:4:2 mol ratio are reacted at 120 °C for an hour. The synthesized samples are represented as BA-xMA, where x is the number of C atoms ranging from 6–18. It was found that shape fixity ratio (Rf) increased with short aliphatic chain, conversely to recovery ratio (Rr). Therefore, the self-copolymerization of poly(BA-xMA/BA-a)s are developed to improve the fixation ability. Interestingly, the cyclability of the copoly(BA-12dda/BA-a) at 60/40 is significantly enhanced reaching 34 cyclability where the Rr remains almost 100 %. Furthermore, the copoly(BA-12dda/BA-a) exhibits multiple-shape memory behavior resulting from a wide range of transition temperatures. The selfcopolymerization of benzoxazine reduces molecular complexity, enhances compatibility, and simplifies preparation steps, making benzoxazine-based SMPs highly promising for advanced shape memory polymer applications

Flexipill: A novel 3D printed flexible dose combination with a floating element.

Hypertension is highly prevalent worldwide, affecting approximately one in three adults. The pathophysiology of hypertension is multifactorial, which led recent guidelines to recommend the initiation of treatment with more than one antihypertensive agent. This exacerbates the existing issue of polypharmacy, particularly among geriatric patients. Polypharmacy can lead to a reduction in patient adherence to the treatment. As a result, many clinical studies have investigated using fixed-dose combinations to address this issue. These studies have demonstrated the effectiveness of a polypill in improving patient adherence. However, a polypill limits the flexibility for dose titration and personalisation of treatment. Therefore, when 3D printing was first introduced to pharmaceutical formulation, researchers recognised the potential of this technology for drug personalisation and the creation of more flexible drug combinations. Nonetheless, regulatory concerns still limit the translation of these research efforts into clinical applications that can benefit the patient. Consequently, this study seeks to bridge the existing gap by identifying a balanced approach between regulatory requirements and the concept of personalised drug combinations. The Flexipill is a flexible dose combination that does not require printing at the pharmacy level. It can be printed at a quality-controlled facility and assembled according to patient needs at the point of care. In this work, an antihypertensive Flexipill was printed, with each unit having different drug release profiles and formulation requirements. The propranolol HCl unit was printed as a floating unit to improve its solubility and bioavailability. It floated for 9 h, releasing over 90 % of the drug content. The enalapril maleate unit was formulated to avoid thermal degradation by printing at 150 °C, which is lower than its degradation temperature. Moreover, hydrochlorothiazide was formulated to provide immediate release of over 90 % of the drug within the first hour. [Abstract copyright: Copyright © 2025. Published by Elsevier B.V.

Structured Cardiac Assessment and Treatment Following Exacerbations of COPD (SCATECOPD): A Pilot Randomised Controlled Trial

Background/Objectives: Heart disease is common in COPD, yet it is underdiagnosed and undertreated. Heart failure (HF) is undiagnosed in up to 20% of hospital inpatients. Hospitalised exacerbations of COPD (ECOPD) confer high mortality and readmission rates, with an elevated temporal cardiac risk. We performed a pilot randomised controlled trial examining the feasibility and effect of inpatient structured cardiac assessment (SCA) to diagnose and prompt guideline-recommended treatment of heart disease. Methods: A total of 115 inpatients with ECOPD were randomised 1:1 to receive usual care (UC) or SCA, comprising transthoracic echocardiography, CT coronary artery calcium scoring, 24 h ECG, blood pressure, and diabetes assessment. Follow-up was for 12 months. The prevalence of underdiagnosis and undertreatment of heart disease were captured, and potential outcome measures for future trials assessed. Results: Among patients undergoing SCA, 42/57 (73.7%) received a new cardiac diagnosis and 32/57 (56.1%) received new cardiac treatment, compared with 11/58 (19.0%; p < 0.001) and 5/58 (8.6%; p < 0.001) in the UC group. More patients in the SCA group were newly diagnosed with HF (36.8% vs. 12.1%; p = 0.002). When heart disease was diagnosed, the proportion receiving optimal treatment at discharge was substantially higher in SCA (35/47 (74%) vs. 4/11 (34%); p = 0.029). The occurrence of a major adverse cardiovascular event (MACE) showed promise as an appropriate clinical outcome for a future definitive trial. MACEs occurred in 17.2% in usual care vs. 10.5% in SCA in one year, with a continued separation of survival curves during follow up, although statistical significance was not shown. Conclusions: A structured cardiac assessment during ECOPD substantially improved diagnosis and treatment of heart disease. HF and coronary artery disease were the most common new diagnoses. Future interventional trials in this population should consider MACEs as the primary outcome

Validation and application of a tool to assess self-confidence to do improvement

Introduction: Increasing improvement capability in the workforce is vital within healthcare. The type of quality improvement training to increase capability varies. One way to measure the impact of improvement training is self-confidence to do improvement. Objectives: Our objectives were to validate a tool to assess self-confidence to do improvement and to observe the degree of change before and after improvement training. We aimed to assess the degree of impact on self-confidence associated with varying exposure to quality improvement training. Methods: We used an online 10-item and 4-point scale to assess self-confidence before and after improvement training. Reliability analysis using Cronbach’s alpha was performed. The nature of the underlying construct was investigated using exploratory factor analysis and a full set of pre and post measures were used, and to compare individual question changes, a series of paired Wilcoxon tests were performed with Bonferroni post hoc corrections for multiple comparisons. To assess the differing lengths of programmes, individual results from each programme were combined meta-analytically with course duration added as a moderator. Results: 252 completed questionnaires were analysed at baseline and a full set of pre and post measures were available for 128 participants. Cronbach’s alpha for the tool was satisfactory at 0.93 (0.92–0.94) and measured a single underlying construct with an eigenvalue of 6.17. A significant increase in confidence to improve from before to after intervention was found (t(127) = 14.36, p<0.001, d=1.27 (95% CI 1.03–1.50)). Post-testing differences were significant (F(6,125) = 2.89, p=0.02) with shorter courses having significantly smaller increases in confidence. Conclusions: This manuscript provides a validated self-confidence tool to help assess improvement capability. Our tool offers a way to measure the impact of improvement capability on varying training durations and inform decisions about allocating staff time to this activity

Cyber Eyes Wide Open: Innovation, Art, and Collaborative Practice

This chapter showcases a collaboration between creatives, artists, academics, cyber security professionals and companies to create artworks that increased awareness of cyber security. The aim was to offer creative perspectives and practices into how cyber security might be better understood through creating visualizations, experiences and narratives that could enable communication and insight. Four cyber security businesses each provided a theme resulting in vibrant collaborations between the companies, four academics and eight artists. Eleven projects and forty two pieces of art were developed and exhibited in two exhibitions in the Northeast where over hundred people viewed the works. Evaluation indicated that the artworks had an impact, with people more aware of cyber security