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Pro- and Anti-tumorigenic effects of MSC secretome in Glioblastoma: mechanisms and therapeutic implications
No full textDespite advances in surgical resection, radiation, and chemotherapy, glioblastoma remains a lethal condition driven by intrinsic heterogeneity, therapy resistance, and an immunosuppressive tumour microenvironment. Mesenchymal stromal cells (MSCs) and their secretomes, comprising cytokines, growth factors, and extracellular vesicles, have emerged as promising therapeutic candidates due to their tumour-homing properties and anti-inflammatory and immunomodulatory potential. However, recent evidence reveals a paradox: MSC secretomes exhibit both anti-inflammatory/immunomodulatory potential and pro-tumorigenic activities, depending on MSC source, passage number, and environmental and manufacturing contexts. In this review, we critically examine the molecular mechanisms underlying these opposing effects, synthesising evidence on how MSC source, donor variability, passage number, and environmental priming/licensing (e.g., hypoxia, inflammatory licensing) dictate secretome composition and function. We identify critical manufacturing determinants, including the necessity for upper passage limits and standardised isolation protocols, and propose a translational framework that integrates mechanism-based potency assays, such as nuclear factor-κB (NF-κB) reporter systems and multi-donor mixed lymphocyte reactions, to predict clinical activity. Establishing these robust quality controls and mechanistic release and rejection criteria will be essential to resolve the functional plasticity of secretomes and enable the safe translation of MSC-based therapies for glioblastoma
Exploring patient satisfaction with community pharmacy services in the United Arab Emirates: Implications for quality improvement
Get PDFIntroduction: Patient satisfaction is a critical metric for enhancing service quality, meeting regulatory standards, and validating patient-reported outcomes in healthcare. Community pharmacies play a vital role in healthcare delivery, yet there is limited research on patient satisfaction with these services in the UAE.
Aims: This study aims to identify key factors influencing patient satisfaction with pharmaceutical care services provided by community pharmacies in the UAE.
Methods: A cross-sectional, questionnaire-based study was conducted from December 1st, 2023, to April 30th, 2024. A systematic intercept sampling method was used to ensure a representative sample of 505 patients from various regions of the UAE. Data were collected through structured questionnaires covering demographic details, pharmacy visit experiences, and satisfaction levels. Statistical analyses, including chi-square tests, t-tests, and binary logistic regression, were performed using SPSS 27.
Results: The study found that most participants most frequently used chain pharmacies (62.38%) and were highly satisfied with factors like lighting (91.29%) and pharmacist attentiveness (83.96%). Key drivers of satisfaction included convenient locations, accessible designs, and communication-related factors.. However, challenges such as the lack of private counseling areas (59.01%), limited access to medical files (77.62%), and inadequate prescription areas for private conversations (53.29%) were highlighted. Satisfaction was significantly lower in the Northern Emirates compared to Abu Dhabi, while differences involving Al Ain did not reach statistical significance. Providing sufficient time for medication advice (OR: 16.21, p < 0.001) and ease of waiting times (OR: 4.29, p = 0.016) improved satisfaction.
Conclusion: The findings underscore the importance of both environmental and interpersonal factors in shaping patient satisfaction with community pharmacies. Enhancing pharmacy accessibility, communication, and the quality of pharmacist-patient interactions can significantly improve patient experiences. Future research should further explore overall satisfaction and investigate targeted improvements in pharmacy practices across different regions and settings
Reduced occurrence of alpha waves during resting state predicts high ADHD traits in young adults
No full textBackground:
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition with significant cognitive and social impacts. Identifying reliable biomarkers for ADHD is crucial for developing personalised therapies. Electroencephalography (EEG) alpha oscillations (8–12 Hz) have been suggested as a potential biomarker, but findings have been inconsistent.
Methods:
This study aimed to investigate whether alpha oscillations in young adulthood are associated with high ADHD traits using EEG data from a large twin sample (N = 556) enriched with participants with ADHD and autism. We assessed whether alpha oscillations during rest were associated with high ADHD traits. In addition, we used twin modelling to estimate the heritability of EEG alpha measures and their relationship with ADHD traits.
Results:
Results showed that relative alpha peak amplitude was a significant predictor of ADHD traits when controlling for other factors such as age, sex and autistic traits. Specifically, we found that for each unit decrease in relative alpha peak amplitude (z-scored), the likelihood of being in the high ADHD trait group increased by approximately 26%. Further analysis suggested that group differences were due to a reduced occurrence (but not amplitude) of oscillatory bursts in the alpha range. Finally, our twin modelling results suggested that although these alpha measures are heritable, the genetic factors contributing to individual differences in alpha measures and ADHD traits were largely independent.
Conclusions:
Together, these findings suggest that reduced alpha oscillations, particularly the occurrence of alpha bursts, may serve as a potential biomarker for ADHD. Our results may have implications for neuromodulation therapies targeting alpha rhythms in ADHD, such as neurofeedback and transcranial alternating current stimulation
Food formulation: rheological and tribological determinants of oral processing and flavor perception
No full textUnderstanding how food behaves during oral processing requires going beyond its chemical composition to integrate rheological and tribological determinants that shape texture, mouthfeel, and ultimately flavor perception. This review examines how viscosity, microstructure, and flow properties govern aroma release and taste perception across liquid, semi-liquid, solid, and emulsion-based foods, while oral tribology elucidates lubrication regimes that drive sensations such as creaminess, smoothness, or astringency during mastication and bolus formation. Particular emphasis is placed on the interplay with saliva, whose proteins and physicochemical properties critically modulate lubrication and sensory dynamics. By combining rheological and tribological approaches termed “rheo-tribology” with sensory analysis, this work highlights integrated mechanisms of flavor release, from controlled diffusion in viscous matrices to tribological transitions at oral surfaces. Formulation strategies using hydrocolloids, proteins, fat replacers, and emulsifiers are detailed, showing how textural engineering can tailor perception and consumer acceptance, particularly in plant-based or reformulated products. Overall, the integration of rheology and tribology provides a comprehensive, physiologically relevant model of oral processing, offering predictive power for designing sensory-optimized foods that balance nutrition, functionality, and pleasure while addressing current challenges in health-driven reformulation and sustainable food innovation
Enhancing the Delegated Proof of Stake consensus mechanism for secure and efficient data storage in the Industrial Internet of Things
Get PDFThe rapid advancement of Industry 5.0 has accelerated the adoption of the Industrial Internet of Things (IIoT). However, challenges such as data privacy breaches, malicious attacks, and the absence of trustworthy mechanisms continue to hinder its secure and efficient operation. To overcome these issues, this paper proposes an enhanced blockchain-based data storage framework and systematically improves the Delegated Proof of Stake (DPoS) consensus mechanism. A four-party evolutionary game model is developed, involving agent nodes, voting nodes, malicious nodes, and supervisory nodes, to comprehensively analyze the dynamic effects of key factors—including bribery intensity, malicious costs, supervision, and reputation mechanisms—on system stability. Furthermore, novel incentive and punishment strategies are introduced to foster node collaboration and suppress malicious behaviors. The simulation results show that the improved DPoS mechanism achieves significant enhancements across multiple performance dimensions. Under high-load conditions, the system increases transaction throughput by approximately 5%, reduces consensus latency, and maintains stable operation even as the network scale expands. In adversarial scenarios, the double-spending attack success rate decreases to about 2.6%, indicating strengthened security resilience. In addition, the convergence of strategy evolution is notably accelerated, enabling the system to reach cooperative and stable states more efficiently. These results demonstrate that the proposed mechanism effectively improves the efficiency, security, and dynamic stability of IIoT data storage systems, providing strong support for reliable operation in complex industrial environments
Kommunikative Beschränkungen im Spiegel deutscher und britischer Tagebücher. Eine Analyse des Wandels metakommunikativer Äußerungen zwischen 1840 und 1960.
No full textThis paper is based on research we are conducting in an interdisciplinary project (linguistics and history), which analyses changing communicative norms and ideals between voice and silence as reflected in German and British diaries from 1840 to 1990. Combining approaches of qualitative close reading and software based coding (NVivo), we look at diarists‘ metacommunication pointing towards communicative options and constraints, affordances and risks, norms and ideals in the everyday life of ordinary people. For this contribution, we are using a data set compiling 20 British and 20 German diaries each from the 1840s and 1950s (i.e. 80 diaries in total) and focusing on diarists‘ recounting and metapragmatic reflections of communicative constraints. By analysing these, we argue, we can gain valuable insights into changes in communicative norms and their connections to broader sociopolitical, cultural and technological shifts going from the middle of the 19th to the middle of the 20th century
Firm prominence and price framing
Get PDFThis paper explores the strategic use of price framing in a duopoly where firms differ in their prominence and where both frame differentiation and frame complexity are sources of consumer confusion. It analyzes the interaction between the relative effectiveness of the two sources of consumer confusion and firms' prominence levels, and its impact on equilibrium outcomes. A parametric condition on firms' prominence delineates different equilibrium outcomes and synthesizes the interaction between firm prominence and consumer confusion. In equilibrium, firms do not always coordinate on the most effective source of confusion. The impact of consumer protection policy on market outcomes, especially consumer surplus, depends crucially on underlying market conditions, and can be ineffective or even detrimental to consumers
High-protein diets increase microbiota associated p-cresol production in the colon and reduce gut barrier function in a sex-dependent manner
Get PDFProtein is an essential nutrient, but the detrimental effects of excess dietary protein on gut health are often overlooked. Protein fermentation by colonic microbiota may impair barrier function by increasing toxic metabolite production. We previously identified sex-by-protein interactions affecting the microbiota and its metabolites in vitro. Do sex-by-protein interactions in colonic protein fermentation lead to a sexually dimorphic response in gut barrier function in vivo? We hypothesised that high-protein diets would elicit sex-specific effects on microbiota and barrier function. Twenty sibling-matched male (n = 10) and female (n = 10) piglets were fed high-protein (28%) or standard-protein (SP; 18%) diets for four weeks. Bacterial populations were assessed using 16 S rRNA sequencing, urinary metabolites via SPME/GC-MS, and gut barrier proteins via quantitative fluorescence immunohistology. High-protein diets increased bacteria-derived p-cresol and reduced E-cadherin and CD45 + protein expression without altering microbiota composition. Females on high-protein diets had greater abundances of Staphylococcus and Chryseobacterium, elevated p-cresol, and reduced ZO-1 expression compared to males. High-protein diets appear to reduce barrier function and increase protein-associated toxic metabolite production in sexually dimorphic manners in pigs. If these results are replicated in humans, it indicates requirements for sex-specific nutritional strategies
A unified framework for trend uncertainty assessment in climate data records: demonstration on global mean sea level
No full textTrends of essential climate variables are often estimated from climate data records to quantify changes in the Earth system. An understanding of the uncertainty in a trend is essential for accurately determining the significance of a trend and attributing its causes. Despite this importance, trend-uncertainty estimates rarely account for all known sources of uncertainty. Common approaches neglect measurement-system instability or neglect the impact of natural variability on trend uncertainty. Such neglect can result in over-confidence in trend estimates. This study addresses trend-uncertainty assessment, particularly the need to account for the combined effects of measurement instability and natural variability on the trend uncertainty. The study presents a novel, unified framework for trend estimation that combines available measurement uncertainty information with empirical modelling of natural climate variability to achieve a more accurate uncertainty estimate. The framework is demonstrated for a time series of global mean sea level observations, obtaining more realistic trend-uncertainty values. The framework is applicable to most other climate data records. Adopting this approach will enhance confidence in climate change analysis through more accurate trend-uncertainty assessment in climate studies