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Schizophrenia treatment based on sustained release of risperidone from poly(lactic-co-glycolic) acid implantable microarray patch
No full textSchizophrenia is one of the most severe mental disorders, affecting approximately 24 million people worldwide. Conventional treatments, such as drug-loaded implants and intramuscular injections, have several limitations, including pain during administration and the need for medical professionals to perform the procedure. In this study, a poly(lactic-co-glycolic) acid (PLGA)-based implantable microneedle patch (IMN) was developed for the transdermal delivery of risperidone (RIS) as a treatment for schizophrenia. RIS IMNs were prepared by sequentially casting gel-based formulations into microneedle (MN) molds. The patches were then characterized using microscopy, differential scanning calorimetry, and infrared spectroscopy, as well as through evaluations of MN insertion and RIS release. A selected formulation was further tested by evaluating its cytocompatibility and its ability to deliver RIS in a rat animal model. The RIS IMN demonstrated excellent mechanical properties, successfully inserting up to 378 nm into model skin, which is crucial for effective transdermal drug delivery. A biocompatibility study using human dermal fibroblasts showed no cytotoxicity, with cell viability and proliferation being close to 100%. The optimized formulation achieved a sustained in vitro release over 7 days, while ex vivo skin deposition and permeation studies showed over 65% RIS delivery efficiency. In vivo animal studies confirmed that RIS IMNs maintained therapeutic plasma concentrations throughout the nine-day experiment, with Cmax values of RIS and 9-OH RIS reaching 387.96 ± 194.02 and 139.89 ± 47.68 ng/mL at 6 and 96 h, respectively. In contrast, intramuscular injection showed a Cmax of 1756.70 ± 246.06 and 1377.38 ± 160.78 ng/mL at 2 and 6 h but lost therapeutic effect after just 24 h. These findings suggest that RIS IMNs offer significant clinical benefits for patients with schizophrenia, providing prolonged therapeutic effects with a simple, self-administering drug delivery system, reducing the need for frequent medical interventions.<br/
Associations between flavonoid-rich food and flavonoid intakes and incident unhealthy aging outcomes in older United States males and females
No full textBackgroundOur knowledge of the importance of flavonoid-rich foods in preventing unhealthy aging across its different domains is limited.ObjectivesThis study aimed to examine prospective associations between flavonoid-rich food and flavonoid intakes and indicators of unhealthy aging, namely frailty, impaired physical function, and poor mental health.MethodsWe followed up 62,743 females and 23,687 males, all aged ≥60 y, from the Nurses’ Health Study (1990–2014) and Health Professionals Follow-up Study (2006–2018), respectively. Both time-updated and change in intakes of a flavodiet score (an aggregate of intakes of major flavonoid-rich foods and beverages) and individual flavonoid-rich foods and beverages and time-updated intakes of total flavonoids and flavonoid subclasses were calculated from food frequency questionnaires collected at baseline and every subsequent 4 y. Associations with incident frailty, impaired physical function, and poor mental health, assessed from self-reported questionnaire responses, were examined with multivariable-adjusted Cox proportional hazards models.ResultsIn the Nurses’ Health Study, participants with the highest flavodiet scores, compared with the lowest, had a 15% lower risk of frailty (HRQ5vsQ1: 0.85; 95%CI: 0.80, 0.90), a 12% lower risk of impaired physical function (HRQ5vsQ1: 0.88; 95% CI: 0.84, 0.91), and a 12% lower risk of poor mental health (HRQ5vsQ1: 0.88; 95% CI: 0.82, 0.94). Increases in flavodiet scores and both higher intakes and increases in intakes of tea, red wine, apples, blueberries, and oranges tended to be associated with lower risks of all outcomes. Higher intakes of total flavonoids and all flavonoid subclasses tended to be associated with a lower risk of each outcome. Although fewer associations were observed among males in the Health Professionals Follow-up Study, those with the highest flavodiet scores had a lower risk of poor mental health.ConclusionsHigh intakes of flavonoid-rich foods may support healthy aging. Further research is needed, including examining sex-specific associations, as incorporating flavonoid-rich foods in the diet may be a simple strategy to support healthy aging.<br/
A decision framework for SMEs to address sustainability issues with Industry 4.0 technologies
No full textThis study investigates the adoption of Industry 4.0 technologies in Small and Medium Enterprises (SMEs) within emerging economies, focusing on sustainability and resource efficiency. Extant research often targets larger firms or developed economies, leaving SMEs in emerging markets underexplored. This study proposes a holistic framework for SMEs to enhance Industry 4.0 adoption, addressing sustainability goals while improving competitiveness. Twenty-five enablers of Industry 4.0 adoption were identified through a systematic literature review and validated their significance through a survey of 233 Indian manufacturing SMEs. Using Exploratory Factor Analysis, the enablers were clustered into five groups: Digital and Physical Technologies, Organizational, Supply Chain, Environmental, and Social. Fuzzy-AHP prioritized the enablers, while Fuzzy-DEMATEL explored their interrelationships. Sensitivity analysis validated the results, ensuring robustness. Analyzed results highlight organizational readiness, such as dedicated R&D teams and managerial support. Inter-organizational factors, such as supply chain integration and social enablers with effective policies, were also found to be pivotal. Digital technologies and environmental strategies emerged as factors dependent on robust organizational and policy support. Practical recommendations include targeted resource allocation, skill development, and policy interventions to support digital transformation. This research bridges gaps in Industry 4.0 adoption and advances SME participation in sustainable global supply chains.<br/
“Their teeth like fistfuls of hardened snow”: the duende, somatic response, and writing forward as forces of translationality
No full textThis chapter begins with a reconstruction of the circumstances around David Johnston’s debut as theatre translator – the production of Federico García Lorca’s Blood Wedding at the Edinburgh Festival in 1988 – and moves on to trace the various conceptual threads emerging from this formative experience and subsequently developed in Johnston’s scholarly work. It gives special prominence to Lorca’s notion of the duende, theorised here in terms of somatic response and related to Johnston’s influential idea of “writing forward”. The chapter argues that writing forward calls for immersing oneself in an experience of translationality prior to any attempts to (re)create this experience for a theatre audience – with all the uncertainties, anxieties, and contingencies that necessarily accompany such hermeneutic, representational, and mediating endeavours
Effects of rare coding variants in severe early-onset obesity genes in the population-based UK Biobank study
No full textContext Clinical case–based studies have identified rare pathogenic variants in several genes as causes of severe early-onset obesity, but their penetrance and interaction with polygenic susceptibility in the general population remain unclear. Objective We analyzed the United Kingdom Biobank (UKBB) whole-exome sequence data to assess the effects of heterozygous variants in 9 previously reported genes on adult body mass index (BMI) and recalled childhood adiposity. Methods Among 419 581 UKBB participants, we identified heterozygous carriers of coding variants that were (1) experimentally characterized as loss of function (LoF), or (2) bioinformatically predicted as rare (minor allele frequency &lt;0.1%) LoF. We assessed variant-level and gene-level population penetrance of obesity and associations with adult BMI and recalled childhood adiposity, and tested the statistical interaction between rare variant carriage and a BMI polygenic score. Results Considering experimentally characterized LoF variants (excluding MC4R), we identified 22 heterozygous and 2 homozygous variants in 3 autosomal recessive genes (POMC, PCSK1, LEPR), and 3 autosomal dominant genes (SH2B1, SIM1, KSR2) with at least 10 carriers in the UKBB. Obesity penetrance among carriers ranged from 8% to 29% (median 23%), and none was significantly different from noncarriers (24%, all P &gt; .05). For bioinformatically predicted rare LoF variants, gene-based burden tests showed that carriage of heterozygous variants in MC4R, PCSK1, and POMC was associated with higher adult BMI (effect sizes ranged from 0.5 to 2.5 kg/m2, all P &lt; .003), with no significant interaction effects with common variant polygenic risk of BMI. Conclusion This study provides the population-specific report of variant penetrance of known obesity genes and confirmed the heterozygous rare variant effects in MC4R, POMC, and PCSK1. We also underscore the utility of population-based studies in supporting variant classifications
Plant-based meat alternatives on the island of Ireland: changes in the market and comparisons with conventional meat
No full textThe plant-based meat alternative (PBMA) market and consumer base on the island of Ireland (IOI) has grown rapidly in recent years. Therefore, this study compared the changes in PBMAs available on the IOI over time and the nutritional profiles of PBMAs with meat counterparts. Three online audits of PBMAs available in Tesco’s and Sainsbury’s in 2021/2022, 2022/2023 and 2023/2024 were conducted. All on-pack information was extracted and analysed using descriptive statistics to identify trends over time. The nutritional content of selected categories of PBMAs identified in the 2023/2024 audit was compared to similar categories of meat using independent samples t-tests or Mann–Whitney-U tests. The number of PBMAs available on the IOI has increased over time (n = 350, n = 321 and n = 398), with a trend in slight improvements in A-scores observed for most categories. Compared to meat, PBMAs had significantly lower total and saturated fat contents and higher carbohydrate, fibre and sugar contents across most categories. The increase in PBMAs over time suggests that the development of new products is ongoing. However, the higher salt contents of PBMAs compared to meat in some categories and only slight improvements in A-scores suggest that focus should be redirected to product reformulation and refinement to improve the nutritional quality of PBMAs.<br/
Strengthening enforcement: the chain of enforcement theory and its application in cross-border cases
No full textThis Think Piece underpinned a presentation to the UNCTAD Working Group on Cross-Border Cartels in February 2025.It outlines the Chain of Enforcement Theory, emphasizing that enforcement is a sequential process where each stage builds upon the previous one. Since a chain is only as strong as its weakest link, enforcement efforts can be easily obstructed if a single stage fails. This theory is particularly relevant in cross-border cases, where enforcement faces unique challenges such as legal discrepancies, jurisdictional limitations, and lack of cooperation between authorities. This brief provides real-world examples of how agencies may overcome cross-border enforcement challenges. It underscores the importance of strengthening enforcement mechanisms and enhancing international cooperation to close regulatory gaps and combat anti-competitive practices effectively. It urges agencies to assess their vulnerabilities, develop in-house expertise, and proactively engage with foreign counterparts to improve enforcement efficiency
DeepPUFSCA: deep learning for physical unclonable function attack based on side channel analysis support
No full textPhysical Unclonable Function (PUF) poses a vulnerability since it could be imitated by machine learning attacks and side channel attacks, which break its physical uniqueness and unpredictable characteristic. Hence, many works are concerned with enhancing PUF design by introducing more nonlinear modules inside to differentiate approximating PUF behavior from the attacker side. However, the safety of these PUFs are still an open area and needs to be verified. In this paper, we propose DeepPUFSCA, which is a deep learning-based model that uniquely combines both challenge and side-channel information features during training to attack PUF. To gather the data, we conduct a design of an arbiter PUF on FPGA and measure its power consumption. Our intensive experiments on this dataset demonstrate that DeepPUFSCA outperforms other machine learning-based methods in terms of attacking accuracy, even the novel ensemble algorithms. Moreover, we also show that combined side channel information boosts the model performance compared to attacking with challenge-response only