Search Results (1,409)

Background: Connexins (Cx) are a family of transmembrane proteins that form gap junctions and connexin hemichannels (HCs), enabling direct intercellular communication within the nervous system. Connexin 43 (Cx43), the principal astrocytic connexin, exhibits a context-dependent dual role: under physiological conditions it maintains tissue homeostasis and metabolic support, whereas under pathological conditions excessive activation of Cx43 hemichannels promotes neuroinflammation, excitotoxicity, blood–brain barrier disruption, and secondary neural tissue damage. Other connexin isoforms also contribute to the pathogenesis of neurological and psychiatric disorders through alterations in neuronal synchronization, glial signaling, and myelin integrity. Objective: To systematize current evidence on the role of key connexin isoforms in acute nervous system injuries—including stroke, traumatic brain injury, spinal cord injury, and peripheral nerve injury—as well as chronic disorders such as neurodegenerative diseases, epilepsy, and psychiatric disorders, with particular emphasis on the functional duality of connexin channels and the therapeutic potential of their selective modulation. Methods: A systematic literature search was conducted in the PubMed, Scopus, and Web of Science databases in accordance with the PRISMA framework and the PRISMA Extension for Scoping Reviews guidelines. The review included data from experimental models, postmortem brain studies, genetic association analyses, and pharmacological intervention studies. The retrieved studies were screened, assessed for eligibility, and integrated using a qualitative narrative synthesis approach. Results: In acute neural injuries, hyperactivation of Cx43 hemichannels amplifies inflammatory signaling, edema formation, and neuronal death, whereas selective HCs inhibitors reduce lesion volume and improve functional outcomes in experimental models. Connexin 36 (Cx36) contributes to cortical spreading depolarization and seizure propagation, while Connexin 32 (Cx32) and Connexin 47 (Cx47) are critically involved in oligodendrocyte function and white-matter demyelination. In PNI, Cx43 upregulation contributes to neuropathic pain, whereas mutations in Cx32 cause hereditary demyelinating neuropathies. In neurodegenerative diseases—including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis—Cx43 hemichannel activity promotes neuroinflammation and pathological protein accumulation, while reduced Cx32/Cx47 expression disrupts metabolic support of axons. In psychiatric disorders such as major depressive disorder, bipolar disorder, and schizophrenia, decreased astrocytic connexin expression (Cx43 and Cx30) has been associated with impaired glial–neuronal communication and cognitive–emotional dysfunction. In epilepsy, increased Cx43/Cx30 expression contributes to neuronal hypersynchronization and blood–brain barrier dysfunction, whereas selective hemichannel blockade suppresses seizure activity. Conclusions: Cx—particularly Cx43—occupies a central position in the molecular mechanisms of secondary neural injury and network dysfunction. The dual functional properties of gap junctions and hemichannels determine their context-dependent effects across neurological and psychiatric diseases. Selective inhibition of pathological HCs activity shows significant neuroprotective and anticonvulsant potential and represents a promising direction for the development of targeted therapeutic strategies. Further studies are required to determine optimal therapeutic time windows, tissue-specific effects, and the long-term safety of Cx modulation. Full article

This narrative review examines topical anti-inflammatory therapies in veterinary medicine through the lens of the One Health framework, integrating pharmacology, dermatology, ecotoxicology, food safety, and regulatory science. It discusses the interconnected roles of veterinarians, pharmacists, environmental scientists, public health authorities, and regulatory bodies in addressing antimicrobial resistance, environmental contamination, zoonotic transmission, and drug residues in food-producing animals. By emphasising cross-sector collaboration, the review highlights how coordinated strategies can enhance animal welfare, safeguard human health, and reduce ecological burden. The article analyses inflammatory conditions in companion and farm animals and compares systemic versus topical anti-inflammatory approaches. Particular attention is given to corticosteroids, NSAIDs, immunomodulators, pro-resolving lipid mediators, and plant-derived bioactives, alongside advances in vehicles such as lipid nanocarriers and biodegradable film-forming systems designed to minimise systemic absorption and environmental dispersion. Regulatory considerations, residue control, pharmacovigilance gaps, and sustainability-oriented formulation strategies are critically addressed. Topical anti-inflammatory therapies, when rationally designed and monitored under One Health principles, represent a strategic opportunity to improve therapeutic precision while limiting systemic toxicity and ecological impact. Future directions should prioritise translational research, eco-compatible formulation design, and harmonised regulatory frameworks. Full article

The capacity of the brain to adapt to experience has long been associated with synaptic plasticity; however, recent evidence demonstrates that experience-driven neural activity also modulates white matter organization through dynamic regulation of oligodendrocyte lineage cells and myelination. Activity-dependent myelination has emerged as a complementary form of neuroplasticity that contributes to circuit efficiency, temporal coordination, and cognitive function. This review aims to examine the neurobiological mechanisms linking cognitive stimulation and activity-dependent neuronal signaling with oligodendroglial dynamics and adaptive myelination. A narrative review of experimental and translational studies was conducted, focusing on evidence from animal models and human research exploring neuron–oligodendroglia interactions, neurotransmitter-mediated signaling, learning paradigms, physical exercise, and neuromodulatory interventions relevant to myelination and brain plasticity. Accumulating evidence indicates that cognitive stimulation, learning, and physical activity modulate neuronal firing patterns and neurotransmitter release, influencing oligodendrocyte precursor cell proliferation, differentiation, and myelin remodeling. Neurotransmitters such as glutamate, GABA, dopamine, and acetylcholine play key roles in neuron–oligodendroglia communication, largely through calcium-dependent intracellular signaling pathways. These mechanisms have been associated with experience-dependent circuit refinement across motor, cognitive, and stress-related paradigms. Rather than implying direct clinical effects, this review highlights oligodendroglial plasticity as a biologically plausible substrate through which cognitive and behavioral experiences may influence adaptive myelination and white matter integrity. Understanding these mechanisms provides a conceptual framework for future research exploring non-pharmacological approaches to modulate brain plasticity at the level of myelin. Full article

This article examines the assumed dichotomy between the Black church and the juke joint within African American cultural discourse. Often portrayed as moral opposites—one sacred and the other secular—this study argues that such a binary reflects a Eurocentric interpretive framework rather than the actual historical realities of Black communal life. Through cultural and historical analysis, the article asserts that both institutions originated from similar conditions of racial exclusion and served as complementary spaces that nurtured African American identity, resilience, and community connections. Using the film Sinners as a key cultural text, the study explores how contemporary media narratives complicate rigid distinctions between sacred and secular Black spaces, identities, music, and spirituality. The character Sammie illustrates the permeability between these spaces, embodying a cultural logic where spiritual refuge and expressive release coexist. The analysis places this view within the African philosophical concept of Ubuntu, which emphasizes relational identity and the inseparability and oneness of the Black community. Drawing on the scholarship of James H. Cone, the article also shows that spirituals and blues share roots in African diasporic musical traditions. These traditions demonstrate the deep interconnection between religious and secular forms of Black expression. Ultimately, the study concludes that the Black church and the juke joint should be understood not as opposing institutions but as interconnected cultural spaces that collectively sustain African American spiritual, social, and artistic life. Full article

This article presents an autoethnographic narrative account of curating and performing two pieces for solo piano and string orchestra—Climate Concerto by Brian Field and Eclogue by Gerald Finzi—to advocate for climate action. It discusses the selection of a concert venue that could be “thickly lived”, offering layers of cultural, historical and aesthetic resonance, and a concert date that could generate “interaction chains”, where engagement in one event motivates engagement in others. The article reflects on the multiple forms of loss brought about by the climate emergency, exploring Field’s musical portrayal of environmental loss and Finzi’s evocation of a harmonious human-nature relationship, which highlights a way of being-in-the-world that has been lost. In response to pervasive pessimism and dystopian narratives in climate communication, the discussion foregrounds hope as a powerful motivator for positive action, showing how the narrative scope of Field’s large-scale forms and the aesthetic beauty of Finzi’s music can elicit felt hope. The article also advocates for gentle musical activism for climate action, emphasising music’s capacity to cultivate relational sensitivity, ethical responsiveness, and collective responsibility toward each other and the world—even amid ecological crisis, social fragmentation, and uncertainty. Full article

Skin aging is a multifactorial process that is dependent on mechanisms linked to age and hormonal changes and on external factors, primarily chronic exposure to ultraviolet radiation. One of the key elements of this process is the quantitative and qualitative changes in collagen. In recent years, there has been particular interest in oral supplementation with hydrolyzed collagen (HC), which is promoted as one of the tools to support anti-aging treatments. The purpose of this narrative review is to synthesize the importance of collagen in skin structure and function, discuss changes occurring during aging, and analyze current data on oral collagen supplementation. The following sections discuss the structure and function of collagen, its importance for skin integrity, the main mechanisms of collagen aging, available sources and forms of supplementation, as well as the clinical efficacy, safety, and interpretive limitations of the current literature. Oral supplementation with hydrolyzed collagen at doses of 2.5–10 g/day for at least 8–12 weeks is associated with improved skin hydration and elasticity, as well as a reduction in wrinkle depth, although study results are inconsistent, and the effect may be weaker in studies of the highest methodological quality and those free from industry funding. In clinical trials, hydrolyzed collagen preparations are typically highly purified (>90–97%) with minimal additives, enabling the isolated effect of the peptides to be evaluated. Future research should focus on independent, long-term randomized controlled trials, direct comparisons of commercial versus purified collagen peptides, and the contribution of synergistic additives to bioavailability and clinical efficacy. Such studies are essential to refine dosing recommendations and strengthen evidence-based use in both cosmetic and clinical settings. Full article

Chronic kidney disease is rising worldwide, and kidney transplantation remains the preferred modality of kidney replacement therapy. However, long-term graft survival continues to be limited by chronic alloimmune injury, particularly antibody-mediated rejection (ABMR) and its chronic active form. This narrative review synthesizes contemporary evidence on the immunopathogenesis, epidemiology, diagnosis, and management of kidney allograft rejection, with a deliberate focus on studies from the last five years and on United States and European cohorts. We summarize current concepts of T cell–mediated rejection (TCMR), ABMR, mixed and donor-specific antibody (DSA)–negative phenotypes, and the evolution of the Banff classification, highlighting how chronic active ABMR has emerged as a leading cause of death-censored graft loss. We then critically appraise the conventional diagnostic triad of creatinine/eGFR, DSA, and biopsy and review emerging tools, including donor-derived cell-free DNA, urinary chemokines such as CXCL9 and CXCL10, additional blood- and urine-based biomarkers, and biopsy transcriptomics. We also examine how artificial intelligence and machine learning may support digital pathology, multimodal risk prediction, and data integration, while recognizing the current challenges of biological interpretability, external validation, and clinical implementation. Finally, we propose a rejection-focused precision-medicine framework and outline key research gaps, including multicenter validation, trial-ready endpoints, and governance for AI-enabled pathways. Overall, the field is moving from isolated diagnostic signals toward integrated, biologically informed, and clinically actionable approaches to rejection detection and risk stratification. Full article

The importance of Structural Health Monitoring (SHM) in maintaining safety, reliability of bridges in service, and in their lifespan, cannot be overstated. Available studies show there is still much to be gleaned in addressing challenges in optimization of sensors in their placement to achieve efficiency in integration as well as in making determinations concerning precision in measurements. The current study aimed to provide a narrative review of the research conducted between 2010 and 2025 on the application of sensor techniques for the detection of different forms of degradation in bridge structures. The main results, in terms of KPIs on precision, spatial, and temporal information, are reviewed and compared, and the results are provided in the form of a framework that highlights the achievements and the challenges in the field. Full article

Myositis ossificans (MO) is a benign, self-limiting heterotopic ossification process that typically develops within soft tissues following trauma, although non-traumatic forms have also been described. Despite its benign nature, MO frequently represents a diagnostic challenge, particularly in its early stages when imaging findings may mimic aggressive soft-tissue tumors, leading to unnecessary biopsies or surgical interventions. This narrative review provides an updated overview of the classification, pathophysiology, and imaging features of myositis ossificans, with a specific focus on the time-dependent evolution of radiologic appearances across different imaging modalities. Radiologic findings are discussed according to disease stage, highlighting key diagnostic clues such as the zonal phenomenon and peripheral maturation pattern. In addition, the main entities included in the differential diagnosis are reviewed, with particular emphasis on imaging features that help distinguish myositis ossificans from soft-tissue sarcomas and other calcified or ossified lesions. Finally, current management strategies and the role of imaging in patient follow-up are summarized. A thorough understanding of the evolving imaging spectrum of myositis ossificans is essential for radiologists and clinicians to achieve an accurate diagnosis, guide appropriate management, and avoid overtreatment. Full article

Tension-type headache (TTH) is the most prevalent primary headache disorder worldwide, contributing substantially to individual disability and global socioeconomic burden. Despite its high prevalence, TTH remains clinically heterogeneous, with episodic and chronic forms influenced by the dynamic interplay of peripheral, central, psychosocial, and lifestyle-related mechanisms. Peripheral musculoskeletal factors, including craniocervical muscle alterations and myofascial trigger points, interact with central sensitization processes, while psychosocial stressors, coping strategies, and lifestyle habits such as sleep and physical activity modulate pain perception and chronification risk. Current approaches often address these domains in isolation, limiting therapeutic effectiveness and the understanding of interindividual variability. This narrative review critically synthesizes evidence on the multifactorial determinants of TTH, providing an integrative conceptual framework. We systematically searched PubMed, Scopus, and Web of Science for articles published between 2010 and 2025, including conceptually or methodologically foundational studies outside this range. Relevant studies were selected based on predefined inclusion criteria and synthesized narratively to highlight key mechanisms and contributing factors. The proposed model emphasizes multidimensional assessment, incorporating peripheral musculoskeletal evaluation, central pain modulation, psychosocial profiling, and lifestyle factors, thereby providing a conceptual basis for future personalized management approaches. Recognizing TTH as a dynamic, multidimensional condition may inform clinical assessment and patient-centered interventions, while also highlighting key gaps for future longitudinal and multimodal research aimed at validating the framework and improving individualized therapeutic strategies. The evidence presented is primarily narrative and observational, and clinical applicability should be confirmed in future studies. Full article

Reconstruction in head and neck surgery requires restoration of complex functions, including speech, swallowing, and breathing, while preserving as much facial form and patient identity as possible. Over the past decade, advances in preoperative digital planning, intraoperative technologies, and robotic platforms have reshaped reconstructive strategies, giving rise to the concept of hybrid reconstruction. Hybrid approaches integrate free tissue transfer with computer-aided design and manufacturing (CAD/CAM), virtual surgical planning, intraoperative navigation, and robot-assisted microsurgery to enhance precision, reproducibility, and functional outcomes. This narrative review examines the principles and applications of hybrid reconstruction in head and neck surgery with particular emphasis on osseous reconstruction of the mandible, maxilla, and midface. The roles of intraoperative navigation and robotic assistance as enabling tools are discussed, along with their potential benefits and current limitations. Functional and morphologic outcomes, patient-reported quality of life, and challenges related to cost, access, training, and evidence heterogeneity are critically reviewed. Hybrid reconstruction represents an advancement toward outcomes-driven, patient-centered care; however, thoughtful integration of emerging technologies and continued emphasis on rigorous outcome assessment are essential to guide responsible adoption in contemporary head and neck reconstructive surgery. Full article

Background/Objectives: Beeswax, a complex natural secretion primarily derived from Apis mellifera and Apis cerana, has evolved from an ancient remedy into a multifunctional excipient and bioactive material in modern pharmaceutical sciences. This review evaluates its physicochemical properties, pharmaceutical applications, and emerging biomedical potential, while addressing current quality and regulatory challenges. Methods: A narrative review was conducted by analyzing literature on the chemical composition, functional properties, conventional uses, advanced drug delivery applications, pharmacological activities, and quality control of beeswax, emphasizing structural characteristics, formulation roles, and integration into innovative delivery technologies. Results: Beeswax is a lipid-based matrix composed of over 300 constituents, including wax esters, hydrocarbons, and free fatty acids, conferring thermoplasticity, biocompatibility, and structural stability. Traditionally, it functions as a stiffening agent, viscosity modifier, and emulsion stabilizer in topical formulations, forming an occlusive barrier that enhances skin hydration. In advanced systems, it serves as a solid lipid matrix in nanostructured lipid carriers (NLCs), microspheres, and 3D-printed tablets, enabling controlled drug release and improved bioavailability of lipophilic compounds. It also exhibits antimicrobial, anti-inflammatory, and wound-healing activities, while beeswax-derived policosanols show potential cardiovascular and gastroprotective benefits. However, concerns regarding paraffin adulteration and pesticide contamination highlight the need for stringent analytical and regulatory oversight. Conclusions: With rigorous quality control and sustainable sourcing, beeswax remains a versatile, eco-friendly material bridging traditional medicine and advanced pharmaceutical innovation. Full article

Introduction: Caffeine is the most widely consumed psychoactive stimulant worldwide and acts primarily through antagonism of adenosine A1 and A2A receptors, thereby reducing sleep pressure and promoting wakefulness. Although its alerting and performance-enhancing effects are well established, its influence on sleep-related electroencephalography (EEG) has been investigated across diverse paradigms with substantial methodological heterogeneity. This systematic and mechanistic review aimed to synthesize human evidence on how caffeine affects sleep architecture, quantitative sleep EEG, and neurophysiological markers of sleep homeostasis, and to interpret these findings within current models of adenosine-mediated sleep–wake regulation. Materials and methods: A systematic search of PubMed/MEDLINE, Web of Science, Scopus, Embase, PsycINFO, ResearchGate, and Google Scholar was conducted for studies published between January 1980 and January 2026, with the final search performed on 10 January 2026. Eligible studies were original human investigations examining caffeine exposure or administration and reporting sleep-related EEG outcomes, including polysomnographic sleep staging, spectral EEG analyses, or other EEG-derived sleep metrics. Two reviewers independently screened records and assessed eligibility, with disagreements resolved by consensus. Data on study design, participant characteristics, caffeine interventions, EEG methodology, and outcomes were extracted using a predefined form. Risk of bias was evaluated using the RoB 2 and ROBINS-I tools. Owing to marked heterogeneity across studies, findings were synthesized narratively within a mechanistic interpretive framework. Results: Thirty-two studies were included. Across highly heterogeneous paradigms—including acute bedtime or evening dosing, daytime or repeated caffeine use before nocturnal sleep, administration during prolonged wakefulness followed by recovery sleep, withdrawal protocols, and ambulatory/home EEG monitoring—the most consistent finding was suppression of low-frequency NREM EEG activity, particularly slow-wave activity and the lowest delta frequencies. Caffeine frequently increased faster EEG activity, including sigma/spindle and beta ranges, producing a lighter, more aroused, and more wake-like sleep EEG profile. These effects were especially prominent during early-night NREM sleep and in recovery sleep after sleep deprivation, where caffeine attenuated the expected homeostatic rebound in low-frequency power. REM-related effects were less consistent, but some studies reported delayed REM timing and subtler alterations in REM EEG. Emerging evidence further suggests that caffeine increases EEG complexity and shifts sleep dynamics toward a more excitation-dominant state. Several studies indicated that quantitative EEG measures were more sensitive than conventional sleep-stage variables in detecting caffeine-related sleep disruption. Dose, timing, habitual caffeine use, withdrawal state, age, circadian context, and adenosinergic genetic variation, particularly involving ADORA2A, moderated the magnitude of effects. We also highlighted the connection between current results and sports and sports science. Conclusions: Caffeine reliably alters the neurophysiological architecture of human sleep in a direction consistent with reduced sleep depth and weakened homeostatic recovery. The overall evidence supports a mechanistic model centered on adenosine receptor antagonism, attenuation of sleep-pressure build-up and expression, and a shift toward greater cortical arousal during sleep. Sleep EEG appears to be a sensitive marker of these effects, often revealing physiological disruption even when conventional sleep architecture changes are modest. Future research should prioritize larger and more diverse samples, pharmacokinetic and pharmacogenetic characterization, and ecologically valid high-resolution sleep monitoring to clarify the real-world and functional consequences of caffeine-induced EEG changes. Full article

The dominant agri-food system’s well-documented failures—biodiversity loss, deepening rural inequalities, and the erosion of small-scale farming livelihoods—have elevated SSE initiatives and social innovation in the agri-food sector and bioeconomy from a niche policy concern to a structural priority. This paper examines how SSE arrangements drive meaningful transformation in agri-food chains while advancing sustainable development at local and regional scales. Through a narrative review of interdisciplinary peer-reviewed literature and key institutional sources, the paper synthesizes evidence that SSE initiatives generate transformation through three interconnected mechanisms: (a) the reconfiguration of governance structures; (b) the deepening of producer–consumer relationships through spatial proximity and relational transparency; and (c) the more equitable redistribution of value across agri-food territories. These findings suggest that place-based SSE models occupy a central—rather than peripheral—role in sustainability transitions and local development. The paper presents a structured analytical framework linking SSE practices to agri-food chain transformation and develops nine concrete policy implications for scaling and sustaining SSE innovations through coordinated collaboration among public, private, and social economy stakeholders. The findings contribute to a sharper understanding of the conditions under which SSE-driven models can foster sustainable, socially inclusive, and community-oriented agri-food systems and of why the solidarity dimension, rather than organisational form alone, is the decisive criterion for identifying genuinely transformative initiatives. Full article

Adult intussusception is a rare cause of intestinal obstruction that differs markedly from the pediatric form in etiology, clinical presentation, and management. In contrast to predominantly idiopathic pediatric cases, adult intussusception is usually associated with an underlying structural lesion, particularly malignancy in colonic involvement. This narrative review summarizes current evidence regarding the epidemiology, etiologic spectrum, clinical features, diagnostic evaluation, and management of adult colo-colic and sigmoido-rectal intussusception. Clinical presentation is often nonspecific, and distal variants may mimic rectal prolapse or large bowel obstruction, contributing to delayed diagnosis. Contrast-enhanced computed tomography represents the diagnostic modality of choice, enabling the identification of lead points and associated complications. Surgical resection remains the cornerstone of treatment due to the high risk of malignancy, while nonoperative management is reserved for carefully selected cases. Improved recognition of atypical presentations and individualized, imaging-guided management are essential to optimize outcomes in this uncommon but clinically significant condition. Full article