High biocompatibility and three-dimensional printability of gels make them highly promising for the food industries. Appropriateness of gels for the food industry depends heavily on their mechanical characteristics and molecular dynamics. For identifying dynamic molecular information at the atomic level, molecular docking (MD) and molecular dynamics simulation (MDS) are thought to be viable methods. They can be used as a tool in creating food gels because they may investigate chemical bonding, particular binding sites, changes in spatial structure, and binding energy between molecules, as well as assess the ideal conformation. MD techniques can reveal the biopolymer interactions. Promising methods include data-driven protein engineering, which designs proteins using computer techniques. The history and evolution of MD techniques are discussed in this article, with a focus on their uses in the food-based gel field. Lastly, research avenues for enhancing the quality attributes of food-based gels via MD and MDS are discussed.
Environmental exposures are increasingly associated with kidney and cardiometabolic disease in children. This review summarizes current understanding of the potentially hazardous effects of air pollution, chemical toxicants, and heavy metal contamination on pediatric kidney health and cardiometabolic risk factors for chronic kidney disease (CKD), as well as the potentially protective effect of green space. We highlight the critical windows of childhood development, during which the kidneys may have varying susceptibility to environmental exposures. We also discuss challenges and possible solutions to adequately powered studies at the intersection of environmental health and pediatric kidney disease. Environmental exposures are both ubiquitous and modifiable. Therefore, elucidating the contribution of environmental exposures to the increasing global burden of CKD will be crucial to informing strategies for kidney disease prevention, starting in childhood. IMPACT: We summarize current evidence on the associations between environmental exposures-including air pollution, chemical toxicants, and heavy metal contamination-and pediatric kidney disease and related cardiometabolic risk factors, as well as the potentially protective effect of green space. We highlight how the impact of environmental exposures on the kidneys may vary during different critical windows of childhood development. Lastly, we discuss methodological challenges and potential solutions, such as using novel technologies and approaches to adequately power studies toward the goal of environmental intervention for chronic kidney disease (CKD) prevention.
Periprosthetic joint infections (PJIs) are one of the most dreaded complications of arthroplasty. Although relatively rare with an incidence of 1-2%, the absolute burden of PJIs is growing over time as the volume of performed arthroplasties increases. PJIs are associated with significant morbidity, mortality, and healthcare costs. Treatment is challenging and may require multiple revision surgeries, reimplantation, and/or amputation. The main issue is the delayed detection of PJIs, which permits progression of the infection into robust biofilms resistant to conventional antimicrobials. Early-detection strategies should focus on identifying infection during the pre-biofilm, planktonic phase, when it remains responsive to medical therapy. Implantable smart sensors are an innovative way to obtain local, real-time monitoring of the implant microenvironment to achieve this objective. In this translational review, an overview of PJIs and biofilm formation will first be provided. The current diagnostic approach to PJIs will then be reviewed along with its limitations to highlight opportunities for innovation. Fundamentals of smart sensor technology and examples of devices designed to detect markers of early infection will then be discussed. Research on smart sensors for the post-operative monitoring of orthopedic implants is in its infancy and has yet to be widely adopted into clinical practice. Strengths, limitations, and clinical significance of smart sensors in development will be discussed to inform recommendations on future directions. STATEMENT OF SIGNIFICANCE: Periprosthetic joint infection (PJI) is one of the most serious complications after hip and knee replacement surgery, yet current diagnostic tests often fail to detect infection early, when treatment is most effective. This review is the first to comprehensively evaluate the potential of implantable "smart sensors" that can monitor the joint environment in real time to detect early signs of infection. By comparing different sensor designs and highlighting both opportunities and limitations, our work bridges orthopaedic surgery, materials science, and bioengineering. These insights are significant for guiding future biomaterial-based diagnostics, with the long-term goal of improving outcomes for the rapidly growing population of patients undergoing joint replacement worldwide.
Measurement errors may be constant, change in predictable, systematic ways, or vary randomly and unpredictably. When discussing measurement errors, the distinction between systematic and random errors is often poorly characterized. Both systematic and random errors can occur at any stage of the testing process. Errors that occur during the measurement phase can be formally evaluated and quantified, for example, using CLSI evaluation protocol guidelines. Here, we assert that the assignment of measurement error labels, random and systematic, depends on the perspective of the observer and the availability of information. Random errors are usually quantified as imprecision or measurement uncertainty (MU), whereas systematic errors that remain approximately constant over time are quantified as biases. As more information becomes available, errors that were previously perceived as random may become predictable and thus considered systematic. Manufacturers/developers, users, and regulators of measurement procedures (MP) can have very different perspectives, including different levels of available knowledge, and these differences can affect perceptions of which errors are predictable. Therefore, whenever a bias is reported or discussed, its scope must be clearly stated. Similarly, whenever an imprecision or an uncertainty is stated, the sources of variation included in the estimate must also be detailed. Determining whether a source of error is systematic or random in each scenario ensures it can be meaningfully quantified and expressed.
Allogeneic transplantation is a cornerstone treatment for hematologic malignancies and organ failure, yet its success is limited by graft-versus-host disease (GvHD) and allograft rejection. Conventional broad-spectrum immunosuppression compromises protective graft-versus-leukemia (GvL) effects and anti-infectious immunity, creating an urgent need for precision tolerance strategies. CD4+Foxp3+ regulatory T cell (Treg)-directed strategies offer a promising solution but expanding stable, functional Tregs ex vivo and in vivo remains challenging. Given the pivotal role of the Tumor Necrosis Factor Receptor Superfamily (TNFRSF) in Treg biology, this review aims to critically examine how its members control Treg function and how these pathways can be leveraged for Treg‑based therapies. We systematically analyze key TNFRSF members - TNFR2, OX40, CD40, Fas, CD27, 4-1BB, GITR, and DR3 - detailing their dichotomous roles in Treg function and translational potential. We highlight how agonism of TNFR2 or DR3 offers selective Treg expansion while preserving GvL activity, and how CD27 and 4-1BB serve as valuable markers for isolating highly suppressive Treg subsets. We further discuss translational challenges, including the paradoxical effects of OX40 and GITR, which can either enhance or impair Treg function depending on the inflammatory milieu, and the vulnerability of Tregs to Fas-mediated apoptosis during ex vivo expansion. We also discuss CD40-CD40L blockade as a complementary strategy to empower endogenous Tregs. By synthesizing current knowledge, this review provides a rational roadmap for using selective agonism, blockade, or phenotypic selection to bolster Treg‑based therapies for GvHD, offering practical information for both laboratory and clinical efforts to optimize Treg manufacturing and achieve durable tolerance.
After hip fracture, older adults experience burdensome treatments and high mortality; they may therefore benefit from palliative care (PC). Best practices for PC integration during inpatient hip fracture care remain understudied. To determine frequency of inpatient PC process documentation for seriously ill older adults with hip fracture and explore clinicians' perspectives on observed documentation patterns. We used an explanatory sequential mixed-methods design. In a cohort of seriously ill adults ≥66 years old admitted for hip fracture from 2016-2019 at an academic health system, natural language processing was used to measure documentation of inpatient PC processes: healthcare proxy designations, code status limitations, goals of care conversations (GOCC), hospice discussions, and specialty PC. We then conducted semi-structured interviews (n=10) with clinicians, exploring perspectives on documentation rates. Transcripts were coded thematically using a mixed deductive-inductive approach. Among 1,433 hip fracture admissions, GOCC, hospice discussions, and specialty PC were documented in <25% each. Clinicians viewed these rates as reflective of under-documentation and under-delivery. Workflow barriers included lack of standardized processes and diffusion of responsibility across interdisciplinary teams. Emphasis on efficient perioperative optimization and minimizing prolonged hospitalizations competed with perceived time for delivery of GOCC and specialty PC. Clinicians described a rescue-oriented surgical culture in which the palliative value of surgical repair for hip fracture paradoxically limited surgeons' view on their role in GOCC. PC process documentation during hip fracture admissions was low. Limited standardization, role uncertainty, and cultural factors limited PC documentation and delivery, highlighting opportunities to strengthen PC integration in surgical care.
Although mentoring remains a fundamental part of medical training, the traditional approach of a senior mentor guiding a junior trainee often fails to meet the diverse and evolving needs of learners in radiology. While peer and near-peer mentoring approaches have shown promise, they often lack a scalable, structured framework. We present a cascade mentoring model embedded within the radiology training environment, in which senior trainees mentor junior residents, who then supervise undergraduate learners. This model is aligned with the European Society of Radiology's (ESR) competency-based framework through the European training curriculum for radiology (ETC). It sets out the specific responsibilities of faculty members, early career radiologists, senior residents, junior residents and undergraduates. Mentorship activities include case discussions, clinical teaching, research collaboration and providing structured feedback. The cascade approach fosters skill acquisition, professional development and research engagement at every level. Senior residents can refine their expertise through teaching, junior residents can reinforce their foundational knowledge by guiding undergraduates, and undergraduates can gain structured, early exposure to radiology. Anticipated benefits include enhanced departmental integration, improved teaching skills among residents, greater undergraduate engagement and an optimised faculty workload. The Cascade Mentoring Model is an innovative, sustainable educational strategy that is aligned with the ETC. It empowers residents to become future educators and promotes radiology as a speciality. When implemented, overseen and evaluated deliberately, it has the potential to enhance radiology education programmes throughout Europe. Cascade mentoring can also help mitigate the shortage of radiologists by enhancing training capacity and retention of early-career radiologists. CRITICAL RELEVANCE STATEMENT: The cascade mentoring model provides a structured, scalable approach to radiology education aligned with the European training curriculum. By optimising faculty workload, strengthening residents' teaching skills and fostering early engagement, it supports high-quality training, workforce retention and sustainable radiology education across Europe. KEY POINTS: Traditional mentoring in radiology lacks scalability and responsiveness to learner diversity needs. Cascade mentoring structures near-peer teaching across undergraduate, resident and faculty levels. Model aligns with the ESR European training curriculum competency-based framework. Cascade mentoring enhances skills, teaching capacity, research engagement and professional development. Scalable approach supports workforce retention and sustainable radiology education in Europe.
Accumulating evidence indicates that diabetes is associated with increased risk of several cancers. The strongest evidence has been reported for cancers of the breast, colorectum, endometrium, liver, pancreas, and gallbladder. However, distinguishing causal relationships from associations driven by shared risk factors such as obesity, aging, and lifestyle behaviors remains challenging. Several biological mechanisms have been proposed to explain these associations. Key pathways include the effects of insulin resistance and compensatory hyperinsulinemia on mitogenic signaling pathways, including PI3K/AKT/mTOR and MAPK, as well as the influence of adiposity, chronic inflammation, and altered metabolic substrates on tumor initiation and progression. Hyperglycemia may also contribute by promoting tumor metabolism and cellular proliferation, although its independent contribution remains debated. These mechanisms likely interact to create a protumorigenic metabolic environment in individuals with diabetes. Obesity, which frequently co-occurs with diabetes, further amplifies these risks through altered adipokine secretion and increased estrogen production, highlighting the interrelated contributions of metabolic and hormonal factors. The relationship between diabetes and cancer has important clinical implications. Diabetes has been associated with worse cancer prognosis and higher cancer-related mortality, highlighting the importance of integrated management strategies. The impact of antihyperglycemic therapy on cancer risk and progression has been extensively studied, and ongoing research continues to evaluate potential protective or tumor-modifying effects. In this article, we summarize the epidemiologic and pathophysiologic evidence describing the relationship between diabetes and cancer and discuss strategies for risk mitigation, screening, and management.
Atherosclerosis, a chronic inflammatory disease of the arterial wall, is a leading cause of cardiovascular diseases worldwide. The complex pathogenesis of atherosclerosis involves genetic predisposition, environmental factors, and immune responses. N-Methyl-d-aspartate receptors (NMDARs), a subclass of glutamate receptors, are critical for synaptic plasticity, learning, and memory in the central nervous system (CNS). Non-neuronal NMDARs are poorly understood compared to neuronal receptors, but there is a developing consensus that they have distinct structural and functional properties when activated by glutamate and NMDARs co-agonists. Emerging evidence indicates that non-neuronal NMDARs may participate in an array of physiological and pathophysiological processes, including but not limited to driving macrophage polarization, lipid dysregulation in macrophages, inflammation response, vascular smooth muscle cells phenotype switching and endothelial dysfunction, thereby fueling atherogenesis. This review discusses the association between NMDARs genes and atherosclerosis risk, molecular mechanisms underlying NMDARs-mediated regulation of atherosclerosis-related cells, and potential therapeutic implications. Besides, we introduce some pharmacological tools that can be used for studying NMDARs outside the CNS, which reflect modern subunit-selective agents to provide more precise insight into NMDARs mediate the various effects. Overall, the study of NMDARs may provide insights into the pathogenesis of atherosclerosis and lead to the development of more effective therapeutic strategies.
Zoonotic malaria, particularly Plasmodium knowlesi, has emerged as a growing public health concern across Southeast Asia, with increasing incidence reported in multiple countries. The recent detection of additional zoonotic Plasmodium species further complicates the epidemiological landscape, underscoring the expanding interface among humans, wildlife reservoirs, and mosquito vectors. Despite this trend, progress towards effective control and elimination remains limited, largely due to substantial gaps in entomological knowledge across many endemic regions. Currently, only a narrow range of vector control approaches is available, and these strategies are often ill-suited to the ecological and behavioural characteristics of zoonotic malaria transmission. A major challenge lies in the complexity of vector species assemblages in Southeast Asia. Some of the vectors belong to species complexes with high morphological similarity, making accurate taxonomic identification difficult. Misidentification of mosquito species can distort assessments of vector competence, biting behaviour, and ecological niche, leading to inaccurate inferences about transmission dynamics and potentially resulting in ineffective surveillance and misdirected vector control interventions. Compounding this issue are rapid landscape changes driven by deforestation, agricultural expansion, and habitat fragmentation, which alter mosquito bionomics. Growing evidence suggests that such environmental disturbances may promote outdoor and forest-associated biting, enhance vector adaptability, and shift transmission risk toward human settlements. Thus, this review synthesises current knowledge on the ecological, behavioural, and taxonomic complexities of zoonotic malaria vectors within a rapidly changing landscape. By critically examining challenges in vector identification, surveillance, and control, we highlight key gaps that impede effective intervention. Finally, we discuss pathways forward, emphasising the need for integrated, context-specific, and One Health-oriented strategies to address the unique challenges posed by zoonotic malaria transmission in Southeast Asia.
This study evaluated the effectiveness and acceptability of implementing a Fracture Liaison Service (FLS) and Information Technology (IT) platform into Australian general practices to improve osteoporosis management. Fracture Liaison Coordinators (FLCs) supported participating general practices in case-finding, and bone health education and assessment in at-risk individuals over 18 months from June 2022 to December 2023. Using the Compass IT platform, FLCs generated individualised patient management plans aligned with clinical guidelines for discussion between the general practitioner (GP) and patient. Initiation of bone protective medication occurred, as appropriate. Post-intervention surveys evaluated the effectiveness and acceptability of the intervention by participating GPs and patients. Overall, 1299 individuals and 66 GPs across 51 general practice sites participated in the study, an enrolment rate of 3.1% for invited GPs (n = 66/2118) and 4.7% for invited clinic sites (n = 51/1083). Three hundred and sixteen patients were newly identified with osteoporosis based on bone mineral density (BMD) assessment by dual energy x-ray absorptiometry (DXA) scan, spinal x-ray, or prior history of fragility fracture, who were not on treatment. Of these, 141 patients commenced osteoporosis treatment, a treatment rate of 45% (n = 141/316). In post-intervention evaluation surveys, 89% of participating GPs and 92% of patient respondents found the FLS service valuable and acceptable. This real-world study of a general practice-based FLS supported by a disease-specific IT platform improved osteoporosis diagnosis and management and was acceptable to both GPs and patients. Osteoporosis is under-diagnosed and under-treated in primary care. Our study found that implementing an integrated Fracture Liaison Service (FLS) and Information Technology (IT) platform into Australian general practices improved osteoporosis diagnosis and management and was acceptable to both general practitioners and patients. Wider implementation could complement and enhance hospital-based FLSs to improve bone health management in the community.
Glandular odontogenic cyst (GOC) is a less frequent odontogenic cyst with unpredictable clinical behavior and relatively high recurrence rate, posing a diagnostic and therapeutical challenges in oral and maxillofacial surgery. This study evaluated retrospectively management and outcomes in a cohort of individuals suffering from GOC, in the Department of Dentistry and The Fingerland Department of Pathology in Hradec Králové, Czech Republic. . Retrospective assessment was performed on 10 individuals with histologically confirmed GOC treated between year 2015 and 2025. Clinical and radiologic findings, surgical approaches and postoperative care were documented and discussed. . Totally,10 individuals (8 males, 2 females: median age 51.5 years) were treated. Lesion were predominantly located in the mandible, with one maxillary case only. Surgical treatment consisted of cyst extirpation with extraction of involved teeth. Recurrence occurred twice in maxillary case, and a suspected recurrence was noted in another individual. . Surgical extirpation of GOC yielded satisfactory outcomes even in recurrences, without the need for radical resective procedures. Prolonged follow-ups including radiological examination are essential.
Orphan nuclear receptors (ONRs) are members of the nuclear receptor superfamily initially identified without clearly defined endogenous high-affinity ligands. Nevertheless, increasing evidence demonstrates that they play essential roles in regulating metabolism, development, neural function, and tumorigenesis. Recent advances in structural biology, chemical biology, and systems biology have improved understanding of ligand recognition and regulatory mechanisms in these receptors. This review summarizes current progress in ONRs ligand research. ONRs are categorized according to their physiological roles in metabolic homeostasis, development and reproduction, and neuro-immune and cancer-related regulation, highlighting their involvement in diseases such as metabolic disorders, cancers, neurological diseases, and reproductive abnormalities. We discuss the structural basis of ligand recognition, focusing on conserved features of the ligand-binding domain (LBD) and structural variations, particularly in the α10 and AF-2 helices, that influence ligand accessibility and transcriptional regulation. Structural studies have revealed ligand-receptor complexes for representative ONRs, including ROR, HNF-4, REV-ERB, ERR, SF-1, and LRH-1, identifying ligand types such as lipids, heme, and phospholipids. In contrast, other receptors, including TR4, DAX-1, COUP-TFII, and Nur77, currently have only functional evidence supporting potential ligand interactions. Key strategies for ligand discovery include endogenous ligand co-purification, phenotype-based high-throughput screening, structural biology approaches, and structure-based virtual screening combined with molecular dynamics simulations. Major challenges include difficulties in endogenous ligand identification, context-dependent regulation, and limitations in achieving receptor subtype selectivity in drug development. Future progress will rely on integrating structural, biochemical, and multi-omics approaches to facilitate therapeutic targeting of ONRs.
Microplastics (MPs) have emerged as pervasive contaminants in aquatic environments and are increasingly recognized as a critical stressor in constructed wetlands (CWs). To systematically evaluate the behavior and fate of MPs, this review followed PRISMA guidelines, retrieving and screening over 405 peer-reviewed publications from 2019 to 2025 across Web of Science, Scopus, and Google Scholar. Using a rigorous inclusion criterion based on data quality and experimental relevance, 131 key studies were selected for in-depth synthesis and comparative analysis. Beyond serving as effective physical barriers that consistently achieve removal efficiencies exceeding 90%, CWs function as dynamic biogeochemical reactors where MPs undergo extensive aging, transformation, and biofilm colonization, thereby triggering complex long-term ecological risks. The roles of plants, substrates, microorganisms, and animals in MPs retention and transformation are critically evaluated, together with the influence of MPs properties (polymer type, size, and morphology) and wetland configurations on removal efficiency. Furthermore, the ecological responses of CWs under MPs exposure are comprehensively discussed. MPs exposure was found to significantly alter microbial community diversity, potentially inhibiting nitrogen removal and promoting greenhouse gas (CH4 and N2O) emissions. Particular attention is given to the aging behavior of MPs, additive release, pollutant adsorption, and their coupled ecological risks. Current challenges, such as the lack of standardized extraction methods and insufficient understanding of MPs-induced clogging, are identified. Finally, future research directions are proposed to enhance MPs management in CWs, aiming to balance pollutant removal performance, ecological safety, and long-term sustainability of wetland systems.
Creativity has been found to be a fundamental factor in innovation and generating new knowledge, and it is influenced by personality. The present study innovatively tested the personality-creativity relationship by resorting to the General Factor of Personality (GFP). Multiple measures were used for a comprehensive and unbiased estimation of the target relationship while controlling for the common method bias. The results showed that the GFP was consistently associated with multiple creativity indicators, with observed correlations above .60 for questionnaire-based measures and latent estimates ranging from .31 to .40 for performance-based abilities. Based on the findings, the present study indicates a stable association between the GFP and several core components of creativity. Additionally, the present study found that the GFP correlated with creative traits (.75) more strongly than creative abilities (.36), based on which we proposed a division of creative traits vs creative abilities. The reason for all found correlations can be attributed to the GFP being the most comprehensive personality structure encapsulating social characteristics, which is associated with multiple components of creativity. Suggestions for practical implications and future studies are discussed.
Multi-infarct dementia (MID) is a major subtype of vascular cognitive impairment, second only to Alzheimer's disease as a leading cause of dementia worldwide. Unlike neurodegenerative dementias, MID results from recurrent vascular insults, producing stepwise cognitive decline. Animal models have become indispensable for understanding MID mechanisms and testing therapies, yet no single model fully captures human disease complexity. This review synthesizes current knowledge of embolic, chronic cerebral hypoperfusion, hypertensive, and large animal models of MID. We compare methodological strategies, neuropathological features (including white matter injury, neuroinflammation, and blood-brain barrier disruption), and behavioral outcomes. Key limitations include poor replication of infarct heterogeneity, absence of comorbidities, and translational failures. Emerging directions such as multi-hit paradigms and mixed dementia models are discussed. We conclude that integrative, multifactorial models are essential for improving translational relevance and developing effective therapies.
Children's perspectives on optimal health care are rarely considered in health care research. These routine health assessments are carried out by Youth Health Care services (YHC), which provide school health care as part of preventive care for children. The aim of this study is to explore the perspectives of children aged 9 to 12 years old, on current routine health assessments in Dutch school health services and how these could be improved to better align their preferences and needs. We conducted a qualitative focus group study with Dutch primary school children, 9 to 12 years old, who received their routine health assessment from YHC in the past twelve months. Discussion topics included experiences with preventive youth health care services, preferences regarding involvement of parents, and suggestions for improvement of the services. Reflexive thematic analysis was conducted using the 6-step approach by Braun and Clarke. Six focus groups were conducted with in total 41 children. We identified four main themes; 'We want more! Monitoring health matters to children'; 'Feeling safe and comfortable: be the nice and sweet professional in a two-way conversation'; 'Parents know a lot, but not everything: mixed feelings on their role and presence', and 'Preventive youth health care should be organized more attractive'. Our sample of Dutch children perceived preventive routine health assessments as important to monitor their health and suggested more frequent and comprehensive assessments. The children's perspectives, provided relevant insights in how to design child-friendly preventive youth health care.
Anaphylaxis during pregnancy is a rare but potentially life-threatening condition for both mother and fetus, requiring rapid recognition and immediate treatment. Although the fundamental mechanisms of anaphylaxis in pregnancy are similar to those in nonpregnant women, physiological adaptations of pregnancy, peripartum exposures, and fetal considerations substantially complicate diagnosis, management, and prevention, contributing to variability in care and avoidable adverse outcomes. In this multidisciplinary review, experts in allergy-immunology, obstetrics, anesthesiology, and epidemiology synthesize current evidence on the epidemiology, triggers, pathophysiology, diagnostic challenges, management, outcomes, and prevention of anaphylaxis throughout pregnancy, labor, and delivery. We highlight how gestational cardiovascular and respiratory changes may obscure classic diagnostic features, emphasize the safety and critical importance of prompt intramuscular epinephrine use as first-line therapy, and review maternal and fetal outcomes associated with timely versus delayed intervention. Strategies for risk stratification, allergology workup, prevention of recurrence, and implementation of coordinated care pathways are discussed. This review underscores the need for increased awareness, structured interdisciplinary collaboration, and integration of prevention-focused strategies across obstetric and allergy care. By providing a practical, evidence-based framework, it aims to support health professionals in optimizing diagnosis, management, and maternal-fetal safety when anaphylaxis occurs during pregnancy.
The latest episode of cough syrup-associated pediatric deaths in India linked to the reported diethylene glycol (DEG) contamination reverberates a long-standing catastrophic history from the Elixir Sulfanilamide disaster in the USA to the similar incidents in Haiti, Panama, and Gambia. Such recurring preventable tragedies highlight continuing concerns on global pharmaceutical regulation enforcement, toxicological implications on public health, and drug safety, particularly in low- and middle-income countries. In spite of clearly established pharmacopeial limits of diethylene glycol and other excipients used in pharmaceutical industry, probable gaps in excipient verification, insufficient quality control measures, and patchy regulatory monitoring have continued to be discussed in relation to contaminated drug formulations reaching global markets. Existing conventional strategies to combat reoccurrences, such as mandatory analytical testing of excipients and final drug products, vendor qualification, and strict pharmacovigilance programs, are necessary but not sufficient. This article describes the toxicological aspects of diethylene glycol poisoning, provides a brief overview of the historical events, and critically examines the reasons behind recurrence of DEG-related poisonings. Further, it provides specific recommendations to eradicate such catastrophes by employing futuristic strategies using block chain technology and artificial intelligence-based solutions.
This review examines the bidirectional relationship between sleep instability and the pathogenesis of Alzheimer's disease, with particular emphasis on the hypothalamic orexinergic system as a key mechanistic link between these processes. Emerging evidence suggests that excessive orexin signaling contributes to insomnia and sleep fragmentation and may accelerate amyloid-β and tau accumulation by impairing glymphatic clearance and activating neurotoxic pathways. Conversely, progressive neurodegeneration can impair sleep-regulatory centers in the brainstem and hypothalamus, thereby creating a vicious cycle that may hasten cognitive decline. We further discuss therapeutic strategies targeting this pathway, with a focus on dual orexin receptor antagonists and complementary medical approaches. Notably, recent preclinical findings suggest that Panax ginseng extracts may inhibit orexin signaling and reactivate autophagy through the mammalian target of rapamycin pathway, thereby attenuating neuronal damage. By synthesizing current mechanistic insights and clinical evidence, this review proposes that modulation of the orexinergic system, through pharmacological and integrative approaches, may represent a promising strategy for delaying disease progression and improving quality of life in older adults.