Search Results (458)

Sewage sludge, a byproduct of wastewater treatment, can be converted into biochar, offering a sustainable solution for waste management and water treatment. Although biochars from biomass have been widely studied, sewage sludge-derived biochars remain underexplored. This study investigated the use of alkaline-treated sewage sludge-derived biochar (AlBC) as an adsorbent for three water pollutants: caffeine (CAF), carbamazepine (CBZ), and 17α-ethinyl estradiol (EE2). A comprehensive analysis was conducted to explore the kinetic and thermodynamic behaviors of these pollutants under varying conditions, such as different adsorbent dosage, temperature, and water matrix values. The AlBCSS showed enhanced surface area and improved adsorption capacity, with EE2 being preferentially adsorbed (q_e: 9.51 mg g⁻¹), followed by CAF (6.12 mg g⁻¹) and CBZ (4.58 mg g⁻¹). Adsorption followed the Langmuir isotherm for CAF and CBZ, and the Freundlich isotherm for EE2, while kinetics were best described by the pseudo-second-order and Elovich models. Thermodynamic analysis revealed that the adsorption process was spontaneous, primarily driven by physical interactions. Factors such as dosage, temperature, and pollutant concentration influenced adsorption, with no saturation observed at higher concentrations. The natural water matrix had a minimal effect on removal efficiency (40–100%), whereas AlBC exhibited promising results after four adsorption cycles. These results highlight the potential of sewage sludge-derived biochar as a sustainable adsorbent for emerging water pollutants, supporting circular economy practices in wastewater management. Full article

Background/Objectives: Nanoemulsions and microemulsions are promising drug delivery systems capable of enhancing the solubility, stability, and bioavailability of active pharmaceutical ingredients, particularly for central nervous system (CNS) disorders. This study presents a bibliometric analysis of scientific publications on intranasal nanoemulsions from 2004 to 2024, based on data from the Scopus database. Methods: A total of 379 articles were analyzed using Bibliometrix and VOSviewer to identify publication trends, leading countries and institutions, prominent journals, and keyword networks. Results: Publications grew significantly over the last decade, with India, the United States, and China leading in volume. Keyword analysis revealed strong thematic clusters related to “brain targeting,” “drug delivery,” and “intranasal administration,” highlighting this route’s potential for bypassing the blood–brain barrier. The most studied compounds included curcumin, quercetin, carbamazepine, diazepam, and insulin, each with therapeutic applications in neurodegenerative and psychiatric disorders. Conclusions: The findings highlight growing interest in intranasal nano- and microemulsions as a non-invasive and efficient CNS delivery strategy. Future research can bridge translational gaps, enhancing efficacy and safety while meeting regulatory expectations for patient-centered drug development. This study provides a comprehensive overview of current trends and serves as a guide for advancing innovative intranasal delivery platforms. Full article

Background: Paroxysmal dyskinesias (PDs) are rare, episodic movement disorders characterized by sudden and involuntary hyperkinetic motor events. In paediatric populations, their diagnosis is often complicated by clinical overlap with epilepsy and other neurological conditions. Genetic underpinnings have increasingly been recognized as key to understanding phenotypic heterogeneity and guiding treatment. Objectives: This systematic review aims to provide a comprehensive overview of paediatric PD, with a focus on genetic aetiologies, clinical features, subtype classification, and therapeutic approaches, including genotype–treatment correlations. Methods: We systematically reviewed the literature from 2014 to 2025 using PubMed. Inclusion criteria targeted paediatric patients (aged 0–18 years) with documented paroxysmal hyperkinetic movements and genetically confirmed or clinically suggestive PD. Data were extracted regarding demographics, dyskinesia subtypes, age at onset, genetic findings, and treatment efficacy. Gene categories were classified as PD-specific or pleiotropic based on functional and clinical features. Results: We included 112 studies encompassing 605 paediatric patients. The most common subtype was Paroxistic Kinesigenic Dyskinesia (PKD). Male sex was more frequently reported. The mean onset age was 5.99 years. A genetic diagnosis was confirmed in 505 patients (83.5%), involving 38 different genes. Among these, PRRT2 was the most frequently implicated gene, followed by SLC2A1 and ADCY5. Chromosomal abnormalities affecting the 16p11.2 region were identified in ten patients, including deletions and duplications. Among the 504 patients with confirmed monogenic variants, 390 (77.4%) had mutations in PD-specific genes, while 122 (24.2%) carried pleiotropic variants. Antiseizure drugs—particularly sodium channel blockers such as carbamazepine and oxcarbazepine—were the most frequently reported treatment, with complete efficacy documented in 59.7% of the studies describing their use. Conclusions: Paediatric PDs exhibit significant clinical and genetic heterogeneity. While PRRT2 remains the most common genetic aetiology, emerging pleiotropic genes highlight the need for comprehensive diagnostic strategies. Sodium channel blockers are effective in a subset of genetically defined PD, particularly PRRT2-positive cases. Patients with pathogenic variants in other genes, such as ADCY5 and SLC2A1, may benefit from specific therapies that can potentially change their clinical course and prognosis. These findings support genotype-driven management approaches and underscore the importance of genetic testing in paediatric movement disorders. Full article

Background: Accurate assessment of CYP2C induction-mediated drug–drug interactions (DDIs) remains a challenge, despite the importance of CYP2C enzymes in drug metabolism. Limitations in available models and scarce clinical induction data have hampered quantitative preclinical DDI risk evaluation. Methods: In this study, the authors utilized an all-human hepatocyte triculture system to capture CYP2C induction using the perpetrators rifampicin, efavirenz, carbamazepine, and apalutamide. In vitro induction parameters were quantified by measuring changes in both mRNA and enzyme activities for CYP2C8, CYP2C9, and CYP2C19. These induction parameters, along with CYP-specific intrinsic clearance (CL_int) for the victim compounds, were incorporated into a physiologically based pharmacokinetic (PBPK) model, and pharmacokinetics (PK) of known CYP2C substrates were predicted with and without co-administration of perpetrator compounds using clinical dosing regimens. The results were quantitatively compared with the currently utilized mechanistic static modeling (MSM) approach and the reported clinical DDI outcomes. Results: By incorporating the measured f_m of CYP2C substrates into PBPK modeling, we observed a lower propensity to over- or underpredict the exposure of these substrates as victims of CYP2C induction-based DDIs when co-administered with known perpetrators, which resulted in an excellent correlation to observed clinical outcomes. The MSM approach predicted the CYP3A4 induction-based DDI risk accurately but could not capture CYP2C induction with similar precision. Conclusions: Overall, this is the first study that demonstrates the utility of PBPK modeling as a complementary approach to MSM for CYP2C induction-based DDI risk assessment. Full article

Certain foods and specific drugs have been linked to epilepsy in the literature. Here, we query PubMed citations for the co-occurrence of epilepsy with foods and drugs, using a list of 217,776 molecules from the HMDB. Notably, the top associations with epilepsy include approved drugs and drug families, diagnostic markers, inducers, and vitamins. Drugs include fosphenytoin (40%), topiramate (37%), valproic acid (34%), hydantoin (20%), phenytoin (31%), carbamazepine (33%), carbamazepine-10,11-epoxide (40%), trimethadione (31%), gabapentin (14%), pregabalin (11%), flunarizine (7%), fenfluramine (4%), bumetanide (4%), KBr (18%), cannabidiol (14%), clonazepam (22%), nitrazepam (10%), diazepam (7%), lorazepam (6%), midazolam (3%), amobarbital (21%), phenobarbital (16%), flumazenil (7%) allopregnanolone (7%), pregnanolone (6%), epipregnanolone (6%), 3-hydroxypregnan-20-one (6%), and vitamin B6 (6%). Drug families and scaffolds include imidazolidine (18%), succinimide (10%), acetamide (7%), 2-pyrrolidinone (7%), pyrrolidine (6%), tetrahydropyridine (6%), and isoxazole (4%). Investigational compounds include cyano-7-nitroquinoxaline-2,3-dione (5%). Diagnostic markers include exametazime (10%) and quinolinic acid (3%). Inducers include flurothyl (37%), pentetrazol (32%), pilocarpine (25%), (+)-Bicuculline (8%), and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP, 6%). Our analysis highlights frequently cited associations between epilepsy and specific drugs and highlights the importance of supplementing nutrients with vitamin B6 and the ketogenic diet, which increases the gamma-aminobutyric acid (GABA)/glutamate ratio. As such, our study offers dietary approaches in the treatment of this neurodegenerative disease. Full article

Cost-effective procedures usually cannot achieve complete removal of priority contaminants present in water at very low concentrations (as pesticides or pharmaceuticals). Advanced oxidation processes (AOPs) represent promising technologies for removing priority contaminants from water at trace concentrations, yet practical implementation remains limited due to technical and economic constraints. This study presents an innovative flow-through photodegradation device designed to overcome current limitations while achieving efficient contaminant removal at industrial scale. The device integrates a UVC 254 nm lamp-equipped flow chamber with automated dosing pumps for hydrogen peroxide and/or solid catalyst suspensions, coupled with a 30 nm porous membrane filtration system for catalyst recirculation. This configuration optimizes light–catalyst–pollutant contact while enabling combined catalytic processes. Performance evaluation using acesulfame (ACE) and iohexol (IHX) as model contaminants demonstrated rapid and effective removal. IHX degradation with UVC and 75 μM H₂O₂ achieved complete removal with t₉₅% = 7.23 ± 1.21 min (pseudo-order 0.25, t₁/₂ = 3.27 ± 0.39 min), while ACE photolysis (with UVC only) required t₉₅% = 14.88 ± 2.02 min (pseudo-order 1.27, t₁/₂ = 2.35 ± 0.84 min). The introduction of t₉₅% as a performance metric provides practical insights for near-complete contaminant removal requirements. Real-world efficacy was confirmed using tertiary wastewater treatment plant effluents containing 14 μg/L IHX, achieving complete removal within 8 min. However, carbamazepine degradation proved slower (t₉₅% > 74 h), highlighting the need for combined catalytic approaches for recalcitrant compounds. Spiking experiments (1000 μg/L) revealed concentration-dependent kinetics and synergistic effects between co-present contaminants. Analysis identified degradation byproducts consistent with previous studies, including tri-deiodinated iohexol (474.17 Da) intermediates. This scalable system, constructed from commercially available components, demonstrates potential for cost-effective industrial implementation. The modular design allows adaptation to various contaminants through adjustable AOP combinations (UV/H₂O₂, photocatalysts, ozone), representing a practical advancement toward addressing the gap between laboratory-scale photocatalytic research and full-scale water treatment applications. Full article

Objectives: Transforming poorly soluble crystalline drugs into their amorphous form is a well-established strategy in pharmaceutical science to enhance their solubility and improve their clinical efficacy. However, developing amorphous forms of organic drugs for pharmaceutical applications presents significant technical hurdles due to the lack of suitable analytical tools for the amorphization process. Carbamazepine is a crystalline BCS class II drug commonly used for epilepsy and trigeminal neuralgia, whose clinical efficacy is compromised by its low solubility and slow dissolution. Therefore, this study focuses on investigating the amorphization of carbamazepine to enhance its solubility by using a micro-droplet precipitation system. Methods: These micro-droplets serve as individual reactors, enabling homogeneous nucleation for precipitation of carbamazepine. During crystallization, carbamazepine undergoes an intermediate liquid–liquid phase transition characteristic of two-step nucleation. By varying the solvent’s composition (methanol/water), we characterized the kinetics and stability of the intermediate liquid phase under various conditions. Results: Our results indicate that carbamazepine can undergo either a one-step liquid-to-amorphous-solid phase transition or a two-step liquid-to-crystalline-solid phase transition. Notably, both transitions pass through a liquid-to-dense-liquid phase separation process starting from the supersaturated solution, where the generated intermediate phases exhibit different sizes and numbers that are influenced by the solvent and its concentration. Conclusions: Our findings not only elucidate the mechanism underlying the carbamazepine phase transition but also propose a novel method for studying the amorphous process, which could be broadly applicable to other poorly soluble pharmaceutical compounds and may be helpful to amorphous formulations production, potentially offering significant improvements in drug efficacy and patient compliance. Full article

Background/Objectives: Pain—whether acute, chronic, or neuropathic—remains a leading cause of disability and reduced quality of life worldwide. Despite advances in pharmacologic options, interindividual variability in response and susceptibility to adverse effects continues to challenge clinicians. In recent years, pharmacogenetics has emerged as a promising approach to optimize analgesic selection and dosing based on patient-specific genetic profiles. This perspective examines current pharmacogenetic evidence in pain management, focusing on validated biomarkers and their clinical implications. Methods: A narrative review was conducted of recent literature addressing the impact of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of analgesic agents. Particular focus was given to genes involved in drug metabolism and transport as well as receptor signaling, along with the clinical applications of genotype-informed prescribing. Results: Substantial evidence indicates that genetic variants significantly influence patient responses to analgesics, contributing to both inadequate pain relief and heightened sensitivity to adverse effects. The main pharmacogenetic biomarkers appear to be CYP2C9 (for NSAIDs), CYP2D6 (for opioids and tricyclic antidepressants), CYP2C19 (for tricyclic antidepressants) and HLA-B*15:02 and HLA-A*31:01 for carbamazepine. PGx-informed strategies have shown promise in improving analgesic effectiveness, reducing opioid-related complications, and supporting opioid-sparing protocols. Conclusions: Pharmacogenetic screening represents a valuable tool for personalizing pain management. Incorporating validated pharmacogenetic biomarkers into clinical practice could improve treatment outcomes and patient safety. Further research, infrastructure development, and clinician education are essential for scaling PGx implementation in pain care. Full article

Background: Carbamazepine (CBZ) is associated with severe cutaneous adverse reactions in individuals carrying the HLA-B*15:02 allele, which is prevalent in Asian populations. Genetic screening before the initiation of CBZ is recommended, yet screening is not always undertaken. Objectives: To determine the effect of implementing computerized physician order entry (CPOE) reminders on the screening rates of HLA-B*15:02 before CBZ prescription. Methods: We conducted a retrospective analysis of 1611 patients who were prescribed CBZ between 2012 and 2023 in a regional hospital in Taiwan. The intervention involved integrating automated HLA-B*15:02 screening reminders into the CPOE system in outpatient settings. Patients were divided into an outpatient (intervention) group and an inpatient (control) group, and their data were analyzed before and after the intervention. Screening rates were compared using Fisher’s exact test, and subgroup analyses were conducted on the basis of age group and physician specialty. Results: After the intervention, the outpatient group exhibited an increase in screening rate from 23.7% to 55.6% (p < 0.001). However, no significant change was observed in the inpatient group. Subgroup analysis revealed major improvements among neurologists and patients aged 41–80 years in outpatient settings. Conclusions: Implementing CPOE reminders substantially improves rates of screening for HLA-B*15:02 in outpatient settings, indicating the effectiveness of informatic interventions in enhancing adherence to pharmacogenomic guidelines. Extending such interventions to inpatient settings may further mitigate the risk of CBZ-induced severe cutaneous adverse reactions. Full article

Orofacial pain encompasses a spectrum of disorders ranging from musculoskeletal disorders, such as myofascial pain, and temporomandibular disorders to neuropathic situations, such as trigeminal neuralgia and painful post-traumatic trigeminal neuropathy, and neurovascular pain such as orofacial migraine and cluster orofacial pain. Each require tailored prophylactic pharmacotherapy, such as carbamazepine, gabapentin, pregabalin, amitriptyline, metoprolol, and topiramate. Yet a substantial subset of patients remains refractory. Botulinum toxin type A (BoNT-A) has demonstrated growing efficacy in the treatment of multiple forms of orofacial pain, which covers the whole range of these disorders. We describe the analgesic properties of BoNT-A for each of the three following orofacial pain disorders: neuropathic, myofascial, and neurovascular. Then, we conclude with a section on the neuromodulatory mechanisms of BoNT-A. This lays the basis for the generation of a hypothesis for the segmental therapeutic action of BoNT-A on the whole range of orofacial pain disorders. In addition, the advantage of BoNT-A for providing a safe sustained effect after a single application for chronic pain prophylaxis is discussed, as opposed to the daily use of current conventional prophylactic medications. Finally, we summarize the clinical applications of BoNT-A for chronic orofacial pain therapy. Full article

Background: Precision medicine refers to the formulation of personalized drug regimens according to the individual characteristics of patients to achieve optimal efficacy and minimize adverse reactions. Additive manufacturing (AM), also known as three-dimensional (3D) printing, has emerged as an optimal solution for precision drug delivery, enabling customizable and the fabrication of multifunctional structures with precise control over morphology and release behavior in pharmaceutics. However, the influence of 3D printing parameters on the printed tablets, especially regarding in vitro and in vivo performance, remains poorly understood, limiting the optimization of manufacturing processes for controlled-release profiles. Objective: To establish the fabrication process of 3D-printed controlled-release tablets via comprehensively understanding the printing parameters using fused deposition modeling (FDM) combined with hot-melt extrusion (HME) technologies. HPMC-AS/HPC-EF was used as the drug delivery matrix and carbamazepine (CBZ) was used as a model drug to investigate the in vitro drug delivery performance of the printed tablets. Methodology: Thermogravimetric analysis (TGA) was employed to assess the thermal compatibility of CBZ with HPMC-AS/HPC-EF excipients up to 230 °C, surpassing typical processing temperatures (160–200 °C). The formation of stable amorphous solid dispersions (ASDs) was validated using differential scanning calorimetry (DSC), hot-stage polarized light microscopy (PLM), and powder X-ray diffraction (PXRD). A 15-group full factorial design was then used to evaluate the effects of the fan speed (20–100%), platform temperature (40–80 °C), and printing speed (20–100 mm/s) on the tablet properties. Response surface modeling (RSM) with inverse square-root transformation was applied to analyze the dissolution kinetics, specifically t_50% (time for 50% drug release) and Q_4h (drug released at 4 h). Results: TGA confirmed the thermal compatibility of CBZ with HPMC-AS/HPC-EF, enabling stable ASD formation validated by DSC, PLM, and PXRD. The full factorial design revealed that printing speed was the dominant parameter governing dissolution behavior, with high speeds accelerating release and low speeds prolonging release through porosity-modulated diffusion control. RSM quadratic models showed optimal fits for t_50% (R² = 0.9936) and Q_4h (R² = 0.9019), highlighting the predictability of release kinetics via process parameter tuning. This work demonstrates the adaptability of polymer composite AM for tailoring drug release profiles, balancing mechanical integrity, release kinetics, and manufacturing scalability to advance multifunctional 3D-printed drug delivery devices in pharmaceutics. Full article

Pharmaceuticals are increasingly being detected in coastal ecosystems globally, but contamination and bioaccumulation levels are understudied in temporarily closed estuaries. In these systems, limited freshwater inputs and periodic closure may predispose them to pharmaceutical accumulation. We quantified in situ water column pharmaceutical levels at five sites in a temporarily closed model urban estuary (Zandvlei Estuary) in Cape Town, South Africa, that has been heavily anthropogenically modified. The results indicate an almost 100-fold greater concentration of pharmaceuticals in the estuary relative to False Bay, into which the estuary discharges, with acetaminophen (max: 2.531 µg/L) and sulfamethoxazole (max: 0.138 µg/L) being the primary pollutants. Acetaminophen was potentially bioaccumulative, while nevirapine, carbamazepine and sulfamethoxazole were bioaccumulated (BAF > 5000 L/kg) by sandprawns (Kraussillichirus kraussi), which are key coastal endobenthic ecosystem engineers in southern Africa. The assimilative capacity of temporarily closed estuarine environments may be adversely impacted by wastewater discharges that contain diverse pharmaceuticals, based upon the high bioaccumulation detected in key benthic engineers. Full article

In response to the European Union’s revised Urban Wastewater Treatment Directive, which mandates enhanced monitoring and advanced treatment of micropollutants, this study was conducted. It took place within the Coastal Landscape Park (CLP), a Natura 2000 protected area in northern Poland. The focus was on the municipal wastewater treatment plant in Jastrzębia Góra, located in a region exposed to seasonal tourist pressure and discharging effluent into the Czarna Wda River. A total of 90 wastewater samples were collected during five monitoring campaigns (July, September 2021; February, May, July 2022) and analysed for 13 pharmaceuticals and personal care products (PPCPs) using ultra-high-performance liquid chromatography tandem mass spectrometry with electrospray ionisation (UHPLC-ESI-MS/MS). The monitoring included both untreated (UTWW) and treated wastewater (TWW) to assess the PPCP removal efficiency and persistence. The highest concentrations in the treated wastewater were observed for metoprolol (up to 472.9 ng/L), diclofenac (up to 3030 ng/L), trimethoprim (up to 603.6 ng/L) and carbamazepine (up to 2221 ng/L). A risk quotient (RQ) analysis identified diclofenac and LI-CBZ as priority substances for monitoring. Multivariate analyses (PCA, HCA) revealed co-occurrence patterns and seasonal trends. The results underline the need for advanced treatment solutions and targeted monitoring, especially in sensitive coastal catchments with variable micropollutant presence. Full article

Untreated sewage sludge (SS) and misused stabilization technologies have contributed to great contamination and the accumulation of various pollutants in agricultural soils. Regarding micro-pollutants’ degradation, scalable and effective technologies are still scarce. Although many attempts at composting adaptations have been discussed, only a few have been tested individually under outdoor conditions. To investigate different composting methods (bioaugmentation and semipermeable cover) for the removal of micro-pollutants frequently found in SS, we performed a set of on-site experiments. Windrows of SS and olive pruning were used as the compostable material and were subjected to (i) bioaugmentation with the fungus Penicillium oxalicum, (ii) covered composting, (iii) covered and bioaugmented composting, and (iv) a conventional composting pile, which was included as a control. The entire experiment lasted 99 days. Bioaugmentation without cover increased the phosphorus content, favored a reduction in heavy metal content, and was the only treatment that reduced carbamazepine at the end of the process. Moreover, the inoculation of P. oxalicum under semipermeable cover increased the richness, diversity, and dominance of specific microbial taxa and total bacterial abundance. The four mature composts obtained met the standards required to be classified in the B fertilizer category, showing that we reduced most of the micro-pollutants, and passed the germination test. Full article

Cumulative inhibition of voltage-gated Na⁺ channel current (I_Na) caused by high-frequency depolarization plays a critical role in regulating electrical activity in excitable cells. As discussed in this review paper, exposure to certain small-molecule modulators can perturb I_Na during high-frequency stimulation, influencing the extent of cumulative inhibition and electrical excitability in excitable cells. Carbamazepine differentially suppressed transient or peak (I_Na(T)) and late (I_Na(L)) components of I_Na. Moreover, the cumulative inhibition of I_Na(T) during pulse-train stimulation at 40 Hz was enhanced by lacosamide. GV-58 was noted to exert stimulatory effect on I_Na(T) and I_Na(L). This stimulated I_Na was not countered by ω-conotoxin MVIID but was effectively reversed by ranolazine. GV-58′s exposure can slow down I_Na inactivation elicited during pulse-train stimulation. Lacosamide directly inhibited I_Na magnitude as well as promoted this cumulative inhibition of I_Na during pulse-train stimuli. Mirogabalin depressed I_Na magnitude as well as modulated frequency dependence of the current. Phenobarbital can directly modulate both the magnitude and frequency dependence of ionic currents, including I_Na. Previous investigations have shown that exposure to small-molecule modulators can perturb I_Na under conditions of high-frequency stimulation. This ionic mechanism plays a crucial role in modulating membrane excitability, hereby supporting the validity of these findings. Full article