Search Results (307)

Background: Xylazine, an adulterant in the illicit opioid supply, heightens the risks of overdose, withdrawal severity, and severe wounds among people who use opioids (PWUO). Despite increasing prevalence, gaps remain regarding xylazine awareness in the drug supply and effective harm reduction interventions to address it. Methods: We conducted a cross-sectional survey of 703 PWUO in Baltimore, MD (2023–2025), to assess xylazine awareness, perceptions, and experiences. Multivariable logistic regression models examined correlates of xylazine awareness and self-reported xylazine-attributed wounds. Results: 84.8% of White participants, 48.6% Black participants, 64.3% of males, and 51.4% females had heard of xylazine. Nearly half (45%) of those who used xylazine reported that it caused more severe withdrawal symptoms. In the multivariable model of xylazine awareness, the largest odds ratios were year of survey administration (2024 vs. 2023: aOR = 4.30, 95% CI = 2.91–6.37; 2025 vs. 2023: aOR = 6.32, 95% CI = 3.31–12.07) and White race (aOR = 3.22, 95% CI = 1.85–5.57). Other significant demographic variables included education and gender. In the multivariable model of xylazine-attributed wounds, survey year 2025 vs. 2023 (aOR = 2.65, 95% CI = 1.06–6.61) and injection drug use in the prior year (aOR = 17.74, 95% CI = 5.58–56.39) were statistically significant. Conclusions: Awareness of xylazine in the drug supply remains incomplete among PWUO, with differences by race, age, and gender. The finding of a strong association of xylazine-attributed wounds and injection drug use should be the focus of future research. These findings underscore the need for enhanced surveillance systems, peer education, and community-based harm reduction strategies. Real-time monitoring and rapid response strategies are essential to protect against health risks of toxic adulterants, such as xylazine, medetomidine, and BTMP, in the drug supply. Full article

This review examines convergent neurobiological mechanisms linking stress and drugs that drive stress-induced drug-related behaviors. It first outlines the main theoretical frameworks explaining substance use disorders (SUDs), emphasizing vulnerability factors—particularly stressful life events—that increase addiction risk. The analysis integrates preclinical evidence demonstrating that chronic stress facilitates cross-sensitization to psychostimulants and accelerates drug self-administration, underscoring how stress and drugs converge on glutamatergic and dopaminergic transmission within the Nucleus Accumbens (NAc). Special attention is given to the glial cells, particularly microglia and astrocytes, in mediating stress-induced neuroimmune activation and glutamate dysregulation in the NAc. Three major themes related to microglia–astrocyte crosstalk are addressed: (i) the contribution of these glial cells to neuroimmune and glutamatergic alterations induced by stress; (ii) their role in synaptic and structural plasticity changes within the NAc; and (iii) the mechanisms by which stress and drug exposure reshape glial–neuronal communication, driving the comorbidity between stress and SUDs. A dedicated section focuses on key neuroimmune signaling pathways—particularly the TNF-α/NF-κB axis—and their involvement in stress-induced vulnerability to cocaine addiction. Finally, the review discusses preclinical evidence supporting the therapeutic potential of repurposed glutamate-modulating agents as promising pharmacological candidates for treating comorbid stress and cocaine-use disorder. Full article

The United States is currently facing a drug overdose epidemic. The nucleus accumbens core (NAcore), a brain region critical for reward and aversion behaviors, undergoes structural and functional synaptic adaptations in response to chronic drug exposure. However, the molecular mechanisms underlying these adaptations remain poorly understood. In this study, we investigate the role of dual-specificity phosphatase 5 (DUSP5), a phosphatase known to deactivate extracellular signal-regulated kinase (ERK), in cocaine-induced neuroplasticity. While prior research has linked other DUSP family members to various drugs of abuse, the specific role of DUSP5 in cocaine addiction remains unexplored. We hypothesized that lack of DUSP5 contributes to cocaine-induced maladaptive synaptic plasticity in NAcore. To test this, we employed a rat cocaine self-administration model and molecular analyses and mined publicly available single-cell RNA sequencing data from cocaine-treated NAcore. Our findings reveal a role for DUSP5 in cocaine-related synaptic and behavioral adaptations, highlighting DUSP5 and DUSP5-associated signaling pathways as potential mechanisms underlying substance use disorders and as candidates for therapeutic intervention. Full article

Injectable hydrogels (IHs) have gained considerable interest in biomedical and aesthetic applications due to their minimally invasive delivery, selective localization, and sustained release of bioactive agents. They exhibit flowability during administration and undergo in situ gelation under physiological conditions. These behaviors are influenced by their tunable structural, physical, mechanical, and viscoelastic properties, modulating performance. Rheological parameters, including viscosity (η), storage modulus (G′), loss modulus (G″), and yield stress (τ_y) of IHs with time (t), shear rate ($\stackrel{·}{\gamma }$), and frequency (f), explaining their shear thinning, thixotropy, viscoelasticity, and gelatin kinetics, serve as key quantitative indicators of their injectability, self-healing capability, and structural and mechanical stability. The rheological characteristics reflect molecular interactions and crosslinking mechanisms within IH networks, thereby linking formulation to provide overall performance, including injectability, biodegradability, and controlled release. This review summarizes recent advances in IHs for diverse applications, with a primary focus on their rheological properties. It also briefly addresses their composition, intermolecular interactions, and correlated function and performance. The applications discussed include hemostatic and wound dressings, tissue engineering and regenerative medicine scaffolds, drug delivery systems, reconstructive and aesthetic materials, and functional bioinks for 3D printing. Overall, this review demonstrates that rheological characterization provides an essential framework for the rational engineering of next-generation IH systems. Full article

The increasing prevalence of antimicrobial resistance in livestock pathogens necessitates the development of effective alternatives to conventional antibiotics. This review aims to assess the potential of antimicrobial peptides (AMPs) as alternatives to traditional antibiotics in farm animal production systems, examining their mechanisms of action, efficacy, and applications. A thorough examination of recent literature was conducted to evaluate the properties, classification, and mechanisms of action of AMPs, their natural occurrence, and their applications in poultry, swine, and ruminant production. The review also compared AMPs with conventional antibiotics, antifungals, and antiparasitic drugs. Specific AMPs have shown effectiveness against livestock pathogens, including Escherichia coli, Salmonella, and Clostridium perfringens, along with drug-resistant fungi. One of the primary benefits of AMPs is their strong antimicrobial activity against a wide range of pathogens relevant to farm animal health. Innovative delivery systems, such as self-assembly techniques and nanoparticle encapsulation, can tackle the stability and bioavailability issues associated with AMP administration in farm settings. AMPs represent promising alternatives to conventional antimicrobials in livestock production, offering significant benefits, including a reduced risk of resistance development, immunomodulatory effects, and broad-spectrum activity. However, addressing disadvantages related to production costs, stability, and delivery systems is crucial for their successful commercial application. Integrating AMPs into sustainable farming, after overcoming their shortcomings, could significantly contribute to global efforts to combat antimicrobial resistance. Full article

Background and Objectives: Hereditary angioedema caused by C1 inhibitor deficiency (HAE-C1-INH) is a rare genetic condition characterized by recurrent, potentially life-threatening episodes of angioedema. Long-term prophylaxis (LTP) is essential for decreasing the frequency and severity of attacks. This study aims to compare the safety profiles of two first-line LTP therapies, both of which inhibit kallikrein: berotralstat (oral) and lanadelumab (subcutaneous), using data from the WHO’s VigiBase pharmacovigilance database. Materials and Methods: The study employed a retrospective quantitative design, utilizing the World Health Organization’s pharmacovigilance database, VigiAccess, which contains individual case safety reports of adverse drug reactions (ADRs) to identify cases of ADRs associated with HAE-C1-INH long-term prophylaxis. Results: A total of 644 reports for berotralstat and 3432 reports for lanadelumab were analyzed. Berotralstat was mainly associated with gastrointestinal adverse events (47.9%), while lanadelumab was linked to injection site reactions (45.9%), infections (23.3%), musculoskeletal and connective tissue disorders (10%), immune system disorders (5.3%), vascular disorders (4.7%), and metabolic issues (3.9%). Female patients were more frequently affected in both groups. Statistically significant differences were observed, reflecting the differences in administration methods and pharmacological profiles between the two drugs. Limitations include the self-reported nature of the data and the absence of detailed clinical information. Conclusions: The results confirmed the literature’s data on the gastrointestinal adverse effects of berotralstat, as well as site reactions and infections associated with lanadelumab. Notably, musculoskeletal and connective tissue disorders, immune system disorders, vascular disorders, and metabolic issues occurred more frequently in patients using lanadelumab. Full article

Background: hearing loss represents, today, one of the most significant health problems affecting the world’s population. This clinical condition, particularly manifest in adulthood, can arise or be aggravated by both the presence of specific pathologies and by taking multiple classes of drugs at the same time. Methods: to understand this relationship, the present non-interventional observational study aimed to investigate the relationship between worsening hearing abilities in 1651 patients aged between 18 and 99 years. In particular, the thorough history of patients allowed us to evaluate the pathological profiles, pharmacological profiles, and therapeutic regimens adopted. This allowed us to evaluate its association with self-reported hearing loss, assessed through the administration of the HHIE-S-It questionnaire. Furthermore, given the presence of multimorbidity, the possible correlation between self-reported hearing loss and the specific classes of drugs, categorized using the Anatomical Therapeutic Classification (ATC) system, was evaluated. Results: the results highlighted how patients taking drugs, both in mono- and polytherapy regimens, had higher hearing deficits than patients not taking drugs. Furthermore, an apparent dose–response effect, in which the risk of moderate to severe impairment progressively increased with the number of drugs taken, was also observed. Different classes of drugs, particularly those used for the treatment of diseases of the cardiovascular system, as well as drugs for acid-related disorders, were significantly linked to an increased risk of perceived hearing impairment. On the contrary, agents belonging to the antidiabetic category have proven to be drugs capable of offering a potential protective effect. Conclusion: this study highlighted how both the number of drugs taken and some specific categories of drugs can contribute to perceived hearing impairment. While this evidence highlights the importance of integrating audiological evaluation into the management of patients in polypharmacy, the cross-sectional nature of the design precludes the inference of causality. This evidence still favors safer and more personalized therapeutic strategies. Full article

Oral administration remains the most patient-friendly drug delivery route, yet its efficacy is limited by physiological barriers including gastric degradation and inefficient cellular uptake. pH-responsive nanogels have shown promise for gastrointestinal drug delivery, though their effectiveness is often constrained by poor membrane interaction. Inspired by natural membrane-anchoring mechanisms, a series of comb-like anionic polymers were designed via grafting alkylamines of different chain lengths (C₁₀, C₁₄, C₁₈) at varying densities (10–30%) onto a biodegradable poly(L-lysine isophthalamide) (PLP) backbone. These pH-responsive comb-like polymers self-assembled into nanogels for loading the hydrophobic chemotherapeutic agent camptothecin. The alkyl length and grafting density significantly influenced pH-responsive behavior, membrane disruption, and drug release profiles. The optimal formulation—the nanogel prepared with PLP grafted 30% C₁₄—achieved a high drug-loading capacity, ideal particle size and stability, and offered superior protection in acidic conditions (only 7 ± 5% release at pH 1.2 over 24 h), while enabling rapid intestinal release (78 ± 2% at pH 7.4 within 24 h). The nanogels significantly enhanced cellular uptake, cytoplasmic delivery, and cytotoxicity against colorectal carcinoma cells. This study demonstrates the key role of hydrophobic modification in designing effective oral nanocarriers, providing a promising platform for the treatment of intestinal diseases. Full article

Background: Antimicrobial resistance (AMR) is a critical global health issue. Like other low- and middle-income countries, the misuse of antimicrobial medicine, including widespread self-medication, exacerbates AMR in Bangladesh. Making future generations aware of AMR through educational interventions is an effective tool in combating AMR. This research focuses on understanding the effects of AMR awareness interventions on the knowledge, attitudes, and behaviors of the schoolchildren in the selected district of Bangladesh. Methods: In this study, 241 students of the 12- to 16-year-old age group participated in a two-day program. The programs include four hours of activities, including reading comics and coloring books, presentations, quizzes, and watching an animation about AMR on the first day, followed by an art competition on the second day. To assess changes in knowledge earlier and after the intervention, pre- and post-tests were conducted. Results: This pilot study demonstrates that using age-appropriate interactive educational tools can significantly improve students’ knowledge about AMR, showing a mean difference of 1.28 (p < 0.001). The regulatory step of the Directorate General of Drug Administration, incorporating red identification marks on antibiotic packaging, makes it easier and shows that 93.36% of students could identify antibiotics, which helps them to be aware of these types of medicines. Interventions were equally effective for boys and girls and science and commerce students, and these helped participants recognize the inappropriate practices of antibiotic use in their daily lives. Conclusions: This study identified the importance of incorporating AMR issues into the educational curriculum to address AMR for future generations. Full article

Arterial hypertension is a major contributor to cardiovascular disease, the leading cause of death globally. Previously, our research group has demonstrated that both organic extracts from Heliopsis longipes roots and affinin—its principal bioactive compound—induce vasodilation and exert antihypertensive effects in L-NAME-induced hypertensive rats. However, the poor water solubility of these extracts limits their oral administration and dosing. To address this limitation, a self-microemulsifying drug delivery system (HL-SMDS) was developed from an ethanolic extract of H. longipes root to enhance its aqueous solubility and oral bioavailability. This study evaluated the antihypertensive efficacy of HL-SMDS in spontaneously hypertensive and L-NAME-induced hypertensive rat models, as well as its effects on endothelial reactivity. HL-SMDS significantly reduced systolic blood pressure in both models, demonstrating greater efficacy than the crude extract, likely due to improved solubility and systemic bioavailability of the active constituents. Moreover, HL-SMDS enhanced endothelial function in aortas from L-NAME-treated rats. These findings support the potential of HL-SMDS as a lipid-based phytopharmaceutical formulation that improves the oral bioavailability and antihypertensive effect of the ethanolic extract of H. longipes root. HL-SMDS offers a promising strategy for the development of phytopharmaceutical drugs to treat hypertension. Full article

With ketamine gaining attention as a therapeutic drug, oral administration offers an effective alternative to traditional parenteral routes. However, a significant gap remains in understanding its use via voluntary ingestion. This preliminary study aimed to explore the feasibility of oral ketamine self-administration in mice (Mus musculus), while investigating the effects of low concentrations on the brain, liver, and kidney. Adult mice were divided into three groups and received ketamine in their drinking water for 16 days at 0 (control), 5 (K5), or 10 mg/L (K10). A transient decrease in water consumption was observed in both sexes in the K10 group; however, only females in this group showed differences in ketamine intake between groups on some days. Oxidative stress markers measured in the brain, liver, and kidney only revealed higher catalase activity in the brains of females. No significant alterations were observed in liver and kidney function in either sex, nor in inflammation, apoptosis, or DNA damage in kidney tissues. Overall, these findings support the viability of voluntary oral ketamine administration and accentuate the need to refine the proposed model, not only to prevent water consumption inhibition but also to extend the exposure period, explore potential sex-related differences in ketamine intake, and further confirm the safety of oral ketamine administration. Full article

Oral administration remains the preferred drug delivery route but faces formidable gastrointestinal barriers, including enzymatic degradation, solubility limitations, and poor epithelial absorption. Zein-based nanocarriers (ZBNs), derived from maize prolamin, provide a transformative platform to address these challenges. This review synthesizes recent advances in ZBNs’ design, highlighting their intrinsic advantages: structural stability across pH gradients, self-assembly versatility, and a surface functionalization capacity. Critically, we detail how engineered ZBNs overcome key barriers, such as enzymatic/chemical protection via hydrophobic encapsulation, the enhanced mucus penetration or adhesion through surface engineering, and improved epithelial transport via ligand conjugation. Applications demonstrate their efficacy in stabilizing labile therapeutics, enhancing the solubility of BCS Class II/IV drugs, enabling pH-responsive release, and significantly boosting oral bioavailability. Remaining challenges in scalability and translational predictability warrant future efforts toward multifunctional systems, bio-interfacial modeling, and continuous manufacturing. This work positions ZBNs as a potential platform for the oral delivery of BCS Class II–IV drugs’ in the biopharmaceutics classification system. Full article

The opioid drug overdose death rate remains a significant public health crisis in the U.S., where an opioid epidemic has led to a dramatic rise in overdose deaths over the past two decades. Since 1999, opioids have been implicated in approximately 75% of the nearly one million drug-related deaths. Research indicates that the epidemic is caused by both over-prescribing and social and psychological determinants such as economic stability, hopelessness, and social isolation. Impeding this research is the lack of measurements of these social and psychological constructs at fine-grained spatial and temporal resolution. To address this issue, we sourced data from Reddit, where people share self-reported experiences with opioid substances, specifically using opioid drugs through different routes of administration. To achieve this objective, an opioid overdose dataset is created and manually annotated in binary and multi-classification, along with detailed annotation guidelines. In traditional manual investigations, the route of administration is determined solely through biological laboratory testing. This study investigates the efficacy of an automated tool leveraging natural language processing and transformer model, such as RoBERTa, to analyze patterns of substance use. By systematically examining these patterns, the model contributes to public health surveillance efforts, facilitating the identification of at-risk populations and informing the development of targeted interventions. This approach ultimately aims to enhance prevention and treatment strategies for opioid misuse through data-driven insights. The findings show that our proposed methodology achieved the highest cross-validation score of 93% for binary classification and 91% for multi-class classification, demonstrating performance improvements of 9.41% and 10.98%, respectively, over the baseline model (XGB, 85% in binary class and 81% in multi-class). Full article

Background: Self-emulsifying drug delivery system (SEDDS) is widely used to improve the oral bioavailability of hydrophobic drugs. Emulsion droplet size was revealed to be a critical parameter that influences the thermodynamic stability, drug solubility, and drug absorption of the SEDDS. A high proportion of surfactant and/or co-surfactant was usually employed to reduce the particle size, which may lead the low drug loading and undesirable gastrointestinal toxicity. Methods: This manuscript proposed a novel strategy to reduce the particle size of emulsions using the hybrid of medium and long-chain triglyceride (MCT and LCT) SEDDS without promoting the concentration of surfactants and co-surfactants. The composition of SEDDS was selected based on the drug solubility. Particle size distribution and zeta potential of emulsion particles were determined using the dynamic light scattering technique. The bioavailability of formulations was evaluated in a mouse model. Results: The particle size of the emulsion was reduced from 113.50 ± 0.34 nm (MCT SEDDS) and 371.60 ± 6.90 nm (LCT SEDDS) to 21.23 ± 0.30 nm (MCT&LCT SEDDS). Progesterone, a poorly water-soluble drug, was selected as the model drug in the investigation of SEDDS. The hybrid of MCT&LCT progesterone SEDDS exhibited reduced particle size, enlarged self-emulsifying ranges, and increased drug content in the aqueous phase after lipolysis compared with the conventional mono-MCT or LCT SEDDS. In addition, the bioavailability of progesterone in the MCT&LCT SEDDS formulation was 3.82-fold higher than that of Utrogestan^® (a clinical oral administrated product) in a mouse model. Full article

Gas bubbles are one of the main disturbances encountered when dispensing drugs of microliter volumes using portable miniaturized systems based on piezoelectric diaphragm micropumps. The presence of a gas bubble in the pump chamber leads to the inaccurate administration of the required dose due to its impact on the flowrate. This is particularly important for highly concentrated drugs such as insulin. Different types of sensors are used to detect gas bubbles: inline on the fluidic channels or inside the pump chamber itself. These solutions increase the complexity, size, and cost of the microdosing system. To address these problems, a radically new approach is taken by utilizing the sensing capability of the piezoelectric diaphragm during micropump actuation. This work demonstrates the workflow to build a self-sensing micropump based on artificial intelligence methods on an embedded system. This is completed by the implementation of an electronic circuit that amplifies and samples the loading current of the piezoelectric ceramic with a microcontroller STM32G491RE. Training datasets of 11 micropumps are generated at an automated testbench for gas bubble injections. The training and hyper-parameter optimization of artificial intelligence algorithms from the TensorFlow and scikit-learn libraries are conducted using a grid search approach. The classification accuracy is determined by a cross-training routine, and model deployment on STM32G491RE is conducted utilizing the STM32Cube.AI framework. The finally deployed model on the embedded system has a memory footprint of 15.23 kB, a runtime of 182 µs, and detects gas bubbles with an accuracy of 99.41%. Full article