Search Results (3,821)

Pharmaceutical waste is a challenge for the environment and public health in the European Union (EU). Although EU legislation requires Member States to establish collection systems for unwanted household pharmaceutical products, there is no common legal framework governing the application of extended producer responsibility (EPR) in this area, which has led to differences in the financing, organization, and effectiveness of national waste collection systems. Against this background, the aim of this work was to critically examine the role of EPR in the management of household pharmaceutical waste in the EU by analyzing its legal foundations, comparing selected national take-back systems, identifying the barriers to its implementation and indicating the key elements of a future EU regulatory framework. The analysis indicates that key elements of the future EPR framework for pharmaceutical products should include financing for producers through producer responsibility organizations (PROs), free and accessible collection of medicinal products from patients through community pharmacies, full cost compensation for collection point operators, common reporting requirements, environmentally differentiated producer contributions, consumer education, and independent public oversight. The future EU framework could build on good practices developed in Member States with established EPR systems and on the regulatory solutions adopted in EU environmental legislation. Full article

Tropane alkaloids (TA) constitute a class of plant specialized metabolites with important pharmaceutical applications, including the anticholinergic agents hyoscyamine and scopolamine and the local anesthetic cocaine. Over the past decade, advances in genomics, structural biology, and synthetic biology have substantially revised our understanding of TA biosynthesis, leading to the identification of numerous key biosynthetic enzymes and evolutionary mechanisms. This review comprehensively summarizes current knowledge of TA biosynthesis from precursor formation to structurally diverse end products. We describe the pathway from putrescine to tropinone, the stereoselective metabolic branching mediated by Tropinone Reductases, and the downstream biosynthesis of medicinal tropane alkaloids, calystegines, and cocaine. Particular emphasis is placed on recent discoveries concerning catalytic mechanisms, structural determinants of substrate specificity, metabolic compartmentalization, and the convergent evolution of TA biosynthesis in Solanaceae and Erythroxylaceae. We further integrate advances in genomics, evolutionary biology, and metabolic engineering to highlight emerging strategies for microbial production and pathway redesign. By providing a comprehensive synthesis of recent progress and critical perspectives on unresolved questions, this review offers an updated framework for understanding TA biosynthesis and supports future research in plant specialized metabolism, synthetic biology, and natural product engineering. Full article

Osteoarthritis (OA) is increasingly recognized as a mechanically driven whole-joint disease in which abnormal mechanotransduction initiates a cascade of mitochondrial dysfunction, chronic inflammation, and progressive cartilage degeneration. Among the mechanosensitive molecules identified to date, Piezo1 has emerged as a key mechanosensitive regulator linking pathological mechanical loading to intracellular calcium signaling and downstream cellular responses. Growing evidence indicates that persistent Piezo1 activation promotes mitochondrial calcium overload, excessive reactive oxygen species production, ATP depletion, mitochondrial membrane depolarization, and impaired mitophagy, ultimately amplifying chondrocyte dysfunction and extracellular matrix degradation. In parallel, mitochondrial damage triggers immunometabolic reprogramming through activation of the cGAS–STING pathway and the NLRP3 inflammasome. It also promotes pro-inflammatory cytokines, including interleukin-1β, tumor necrosis factor-α, and interleukin-6. Together, these responses may contribute to a self-perpetuating cycle of inflammation and tissue destruction. This review provides a comprehensive synthesis of recent advances regarding the role of Piezo1 in OA, focusing on the mechanistic links between mechanotransduction, mitochondrial dysfunction, mitophagy, and immunometabolic dysregulation. We further discuss the contribution of mitochondrial quality-control pathways, including PINK1/Parkin-, BNIP3-, and FUNDC1-mediated mitophagy, as well as alterations in mitochondrial dynamics involving DRP1, MFN1, MFN2, and OPA1. Emerging experimental models are discussed as valuable tools for accelerating therapeutic discovery. Finally, we critically evaluate current therapeutic strategies targeting the Piezo1–mitochondria axis, including mechanosensitive channel modulation, mitochondrial protection, mitophagy enhancement, gene therapy, biomaterial-assisted delivery, and nanomedicine. Collectively, current evidence supports the Piezo1–mitochondria–immune axis as an important mechanistic framework contributing to OA pathogenesis and as a potential therapeutic target. Integrating mechanobiology, mitochondrial medicine, and precision-engineered experimental models may facilitate the development of next-generation disease-modifying therapies capable of slowing or preventing osteoarthritis progression. Full article

Background/Objectives: Obesity is a chronic, progressive, and relapsing disease that requires long-term, multidisciplinary management rather than episodic weight-loss treatment. Although novel incretin-based anti-obesity pharmacotherapies, including GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists, have markedly improved the clinical management of obesity, weight reduction alone does not fully capture treatment success. Body composition, lean mass preservation, physical function, nutritional adequacy, psychological well-being, adherence, and long-term weight-loss maintenance are increasingly recognized as essential therapeutic outcomes. This narrative review critically examines the role of lifestyle medicine as a co-therapeutic strategy during modern anti-obesity pharmacotherapy, with particular attention to physical activity, nutrition, behavioral support, and individualized monitoring. Methods: A narrative literature search was conducted in PubMed up to June 2026. The review included studies addressing adults with overweight or obesity and evidence related to anti-obesity pharmacotherapy, physical activity, nutrition, body composition, functional outcomes, eating behavior, quality of life, treatment tolerability, adherence, weight regain, and long-term maintenance. Results: Current evidence indicates that incretin-based therapies produce substantial and clinically meaningful weight loss, but pharmacological efficacy may be limited by reductions in lean mass, gastrointestinal adverse events, inadequate nutritional intake, treatment discontinuation, and weight regain after drug withdrawal. Physical activity should be considered a therapeutic component rather than only a tool for increasing energy expenditure, as aerobic exercise supports cardiometabolic health and cardiorespiratory fitness, while resistance training helps preserve muscle strength, bone health, and functional capacity. Nutritional strategies are equally important, particularly during appetite suppression, to maintain adequate protein, fiber, fluids, micronutrients, and diet quality. Behavioral factors, including sleep, stress, mood, stigma, self-regulation, and the food environment, may influence adherence and long-term outcomes. Conclusions: Novel anti-obesity drugs should not be viewed as replacements for lifestyle medicine but as powerful tools within an integrated chronic-care model. The goal of treatment should move beyond maximal body-weight reduction to durable improvements in body composition, metabolic health, physical function, nutritional status, quality of life, and weight-loss maintenance. Full article

Background/Objectives: Medical training prepares students to diagnose known diseases and barely at all for the uncertainty that fills emergency practice, where symptom-based labels are common and nearly half of emergency medicine residents report difficulty discussing what remains unknown. This article sets out a six-category framework that separates medical uncertainty into distinct epistemological forms, so that communication can be matched to the uncertainty at hand. Methods: I used critical interpretive synthesis with iterative taxonomy development under prespecified ending conditions, arriving at six categories: (1) known and treatable, (2) unexplained, (3) untreatable, (4) heterogeneous, and (5) contested diseases, plus (6) depathologized conditions. Derivation ran iteratively against a purposive set of exemplar conditions, and existing uncertainty taxonomies were examined as alternatives. For each category I identified its epistemological features, the patient experience, and the communication it requires then built recommendations for teaching, assessment, and faculty development. Results: The framework supports structured reasoning and category-specific communication at three points in the emergency encounter: initial assessment, diagnostic testing, and disposition. Keeping a “known and treatable” category is what shows learners that apparently settled knowledge is provisional and context-dependent, which guards against false confidence. Categories are usefully assignable without being mutually exclusive; a condition may occupy several at once and may migrate as knowledge changes. Conclusions: The framework replaces generic advice to “tolerate ambiguity” with concrete tools for category recognition, emergency department safety-netting, disposition communication, and assessment. It is conceptually derived; its categories, scripts, and rubric require empirical validation through curriculum implementation and educational outcomes research. Full article

Fraud in herbal medicines and botanical supplements—such as biological substitution, dilution with inert material, undeclared active pharmaceutical ingredients (APIs), and intentional mislabeling—represents a significant and underestimated threat to public health. Beyond regulatory problems, fraudulent botanical products also compromise the scientific integrity of bioactive compound research. If pharmacological or clinical studies are carried out on adulterated material without knowing it, the resulting data on safety and efficacy become unreliable, and any conclusions drawn from such data are questionable. This review critically evaluates multi-platform metabolomics as an analytical decision-making framework for botanical fraud detection. Rather than cataloging available methods, we focus on the complete analytical pipeline: study design and sample strategy, multi-platform fingerprint acquisition and processing (NMR, GC-MS, LC-HRMS, HPTLC), and chemometric modeling, validation, and decision support. Particular emphasis is placed on data fusion across platforms and the requirements for producing decision-grade evidence—analytical outputs robust enough to support market monitoring and regulatory action. Full article

Artificial intelligence (AI) is increasingly being integrated into medical practice, offering promising tools to improve diagnostic accuracy and clinical efficiency. In the field of breast pathology, AI applications, particularly those based on deep learning (DL) and machine learning (ML), are emerging as decision-support tools in both diagnostic and prognostic workflows. This review provides a comprehensive overview of current AI-based approaches, with a focus on their clinical utility in tumor detection, histological classification, biomarker assessment, and prediction of treatment response. In addition to summarizing available AI platforms, the review critically examines their level of clinical validation, regulatory status, and integration into routine practice. Key challenges are also discussed. Overall, AI is expected to play an increasingly important role in supporting pathologists and advancing precision medicine in breast cancer management. Full article

Mesoporous silica nanoparticles (MSNs) have emerged as versatile nanocarriers for biomedical applications because of their unique physicochemical properties, including high surface area, large pore volume, excellent drug-loading capacity, controllable biodegradation, and facile surface functionalization. These characteristics have enabled the development of advanced drug delivery systems with enhanced therapeutic efficacy, targeted delivery, improved bioavailability, and reduced systemic toxicity. Recent advances in MSN synthesis, physicochemical properties, surface engineering, and functionalization strategies have significantly improved their biological performance and therapeutic potential. In particular, integrating polymers, lipids, and liposomes with MSN platforms has enhanced colloidal stability, circulation time, cellular uptake, and target specificity, thereby facilitating efficient, stimuli-responsive drug delivery. This review highlights MSN-based drug delivery systems in cancer therapy, where multifunctional nanocarriers enable site-specific delivery, controlled drug release, enhanced tumor accumulation, and reduced off-target effects. The review discusses the expanding roles of MSNs in antimicrobial therapy, wound healing, tissue engineering, and regenerative medicine, emphasizing their ability to promote localized therapeutic delivery, immunomodulation, angiogenesis, and tissue regeneration. The review discusses the diagnostic and theragnostic capabilities of MSNs for disease imaging and monitoring. It also critically evaluates current challenges related to biocompatibility, biodegradation, toxicity, biological barriers, large-scale manufacturing, clinical translation, and regulatory considerations. This review provides a comprehensive overview of recent progress, current limitations, and future opportunities for MSN-based platforms in targeted drug delivery and advanced biomedical applications, supporting their continued advancement toward clinical translation and precision medicine. Full article

Background/Objectives: Recurrent pregnancy loss (RPL) has traditionally been investigated predominantly through maternal factors, while the clinical role of paternal assessment remains inconsistently defined. Current guidelines differ substantially regarding semen analysis, sperm DNA fragmentation (SDF), genetic testing, and referral for andrological evaluation. This review aimed to compare contemporary guideline recommendations, critically appraise the directness, prognostic value, and clinical utility of the supporting evidence, and classify paternal assessment strategies as routine, selective, or investigational. Methods: A structured narrative review was conducted using PubMed and Scopus searches through June 2026. International RPL, obstetric, reproductive medicine, and andrology guidelines were compared. Evidence from systematic reviews, meta-analyses, clinical studies, and clinically relevant molecular investigations was evaluated according to its directness to RPL populations, diagnostic and prognostic value, and evidence that test-guided interventions improve miscarriage or live-birth outcomes. Results: Routine paternal assessment should include age, reproductive and medical history, body weight, lifestyle, medication exposure, and relevant environmental or occupational risks. Conventional semen analysis is appropriate primarily when RPL coexists with infertility or suspected male reproductive disease. SDF is the most extensively studied advanced paternal biomarker and is frequently elevated in RPL cohorts, but findings vary by assay and comparator population, while prospective prediction of subsequent live birth and benefit from SDF-directed treatment remain unproven. Parental karyotyping has established counselling value but should be risk-stratified. Sperm aneuploidy testing, oxidative stress assays, seminal microbiome profiling, epigenetic biomarkers, and biomarker-directed interventions remain investigational. Conclusions: Paternal assessment in RPL should be couple-based, clinically targeted, and evidence-informed. Current evidence supports routine clinical evaluation, selective use of semen analysis, SDF testing, genetic assessment, and reproductive urology referral, and restriction of unvalidated biomarkers and treatments to research settings. Full article

Lotus corniculatus is a superior leguminous forage with multiple values including forage, ecological, ornamental and medicinal uses. It is also an ideal material for plant bioreactors. As a core technical approach, genetic transformation overcomes the constraints of traditional breeding and facilitates the targeted improvement in stress resistance and agronomic traits in this species. This review summarizes the research progress of the Agrobacterium-mediated genetic transformation of L. corniculatus, focusing on key procedures such as explant selection, strain selection, infection and co-cultivation regimes, basal medium composition, phytohormone regulation, as well as bacteria elimination and transformant screening strategies. We further elaborate on the applications of this transformation system in enhancing tolerance to abiotic stresses (salt, drought and heat), regulating quality-related traits, and developing plant-based vaccine bioreactors. Additionally, this paper critically discusses the major bottlenecks and challenges constraining existing genetic transformation systems in L. corniculatus, and evaluates the prospects for establishing high-efficiency and genetically stable transformation platforms. This review aims to provide theoretical foundations and technical references for germplasm innovation, molecular breeding and comprehensive utilization of L. corniculatus. Full article

Background: The rapid integration of Artificial Intelligence (AI), specifically Clinical Decision Support Systems (CDSS), into healthcare offers substantial efficiency but introduces critical ethical and legal challenges, particularly the perpetuation of systemic bias against older adults (“Digital Ageism”). While technological advances may improve care, they can violate fundamental bioethical principles when models are trained on unrepresentative data. Aim: This article argues that traditional clinical risk-management models are structurally insufficient to address opaque algorithmic bias and presents a conceptual, multidimensional governance framework designed to prevent the codification of human ageism into AI infrastructure. Methods: Drawing on systemic failures observed during the COVID-19 pandemic, the normative model integrates legal and governance standards aligned with the EU AI Act, Explainable AI (XAI) tools, and a three-phase implementation protocol. Results: To illustrate potential application without overburdening medical staff, the article introduces a theoretical Targeted Escalation Protocol and an Autonomous High-Load Safety Mode. The latter applies deterministic hardcoded constraints to contain age-dominant outputs during acute surges while preserving attending-clinician authority. The framework is explored through an Intensive Care Unit (ICU) thought experiment. Conclusions: The framework provides a structured roadmap for policymakers, ethicists, and healthcare administrators to move from reactive defensive medicine toward proactive ethical safety, safeguarding the dignity of the aging population while aiming to mitigate institutional legal exposure. Full article

Donkeys and horses diverged approximately 4 million years ago and exhibit substantial genetic, chromosomal, and physiologic differences. Although mostly studied in horses, metabolic syndrome represents a broader metabolic dysfunction with systemic consequences, such as obesity and laminitis, that can impact the quality of life of equids. This review summarizes the current knowledge of glucose and insulin regulation in healthy horses and donkeys and examines the pathophysiology of equine metabolic syndrome (EMS) in comparison with donkey metabolic syndrome (DMS), including insulin dysregulation, impaired glucose transport, adipose tissue dysfunction, and emerging evidence of systemic meta-inflammation and oxidative stress. Compared with horses, donkeys demonstrate distinct patterns of adipose deposition, different metabolic profiles, and altered glucose and insulin dynamics following oral soluble carbohydrate intake. While our understanding of donkey medicine has expanded in recent years, gaps in knowledge remain regarding mechanistic insights into glucose metabolism and dysregulation in donkeys. Finally, we evaluate current and emerging therapeutic strategies, including dietary management, exercise, nutraceuticals, and pharmacologic interventions such as metformin and sodium–glucose cotransporter 2 inhibitors (SGLT2is). While these therapeutic approaches have demonstrated efficacy in horses, evidence in donkeys remains extremely limited. This highlights a critical need for species-specific research to elucidate the pathophysiological mechanisms and optimize therapeutic strategies for donkeys. Full article

This study examines the mediumistic paintings of Guo Fengyi (郭鳳怡 1942–2010) through the lens of Daoist inner contemplation (neiguan 內觀) and traditional Chinese medicine. Guo developed distinctive self-cultivation techniques, including Ziran Chaoneng Gong (自然超能功 Natural Superpower Qigong), Qi’e Gong (企鵝功 Penguin Qigong 氣功), and Liu Ling Shuzi Gong (劉陵數字功 Liu Ling Numerology Qigong), which resonate with ancient Chinese practices of Zhouyi (周易) divination, shamanic ritual, and Daoist visualization. Through sustained spiritual practice, she experienced what she understood as mystical revelations transmitted by the High Masters. Vivid visionary images repeatedly emerged in her consciousness, accompanied by an overwhelming sense of being guided by an unseen spiritual agency to depict an unknown transcendent realm. Following these experiences, she created nearly one thousand mediumistic paintings. Her work delves into inner landscapes of consciousness and energetic experience, expanding visual art research into the domain of “inner vision”. This study argues that Guo’s art challenges ocular-centric creative paradigms: her mode of “seeing” operates through the supersensory “eye of spirit” rather than physical sight, and artistic creation becomes a process of receiving higher-dimensional messages rather than singular self-expression. Her practice offers a critical reference for recovering the spiritual dimension in contemporary art and provides theoretical perspectives for comparative studies of international mediumistic artists such as Hilma af Klint (1862–1944) and Georgiana Houghton (1814–1884). Full article

Punica granatum L. (pomegranate) is one of the oldest medicinal plants known to humankind, valued across ancient civilisations for treating parasitic, microbial, and metabolic diseases. Its exceptionally rich phytochemical composition, dominated by punicalagins, ellagic acid, anthocyanins, flavonoids, piperidine alkaloids, and the unique conjugated fatty acid punicic acid, confers a remarkably broad spectrum of biological activities of direct relevance to contemporary veterinary medicine. While human-health applications have been extensively reviewed, a comprehensive synthesis of veterinary evidence across multiple species remains lacking. This review consolidates current preclinical and field knowledge on the pharmacological effects of pomegranate preparations in poultry, ruminants, swine, fish, companion animals, and laboratory models. In poultry—the most extensively studied taxon—dietary inclusion of pomegranate peel powder or extract consistently enhances growth performance, antioxidant status, and humoral immunity while exerting meaningful anticoccidial activity. The antiparasitic properties are compellingly supported by evidence against gastrointestinal nematodes of ruminants, tapeworms, schistosomes, and protozoa including Giardia, Cryptosporidium, and Leishmania spp., as well as monogenean fish parasites. Broad-spectrum antimicrobial activity extends to major veterinary pathogens such as Salmonella, Escherichia coli, Staphylococcus aureus (including MRSA), and Clostridium perfringens. Rodent models have validated antidiabetic, hepatoprotective, nephroprotective, and reproductive benefits, including improved post-thaw sperm quality and enhanced litter size. The safety profile is generally favourable at conventional doses, although high dietary inclusion elicits anti-nutritional effects from condensed tannins, and potential drug interactions via cytochrome P450 inhibition warrant clinical caution. Despite this substantial evidence, significant translational barriers persist, including extract heterogeneity, absence of pharmacokinetic data in target species, and scarcity of controlled clinical trials. By providing a species- and pathology-driven synthesis, this review identifies critical research priorities and highlights the immense potential of this ancient, accessible, and economically viable phytobiotic as a natural alternative to antibiotic growth promoters and synthetic antiparasitics in veterinary practice. Full article