Search Results (79)

This essay argues for the reciprocal benefits of joining the new theories of matter emerging out of critical posthumanism and the psychedelic drugs currently experiencing a so-called “renaissance” in global north societies. While the former’s twin emphasis on relationality and embodiment is perfectly suited to capture and ground the ontological, epistemological, and ethical implications of psychedelic experiences of interconnectedness and transformation, these substances are in turn powerful companions through which to enact a “posthuman phenomenology” that helps us with the urgent task to “access, amplify, and describe” our deep imbrication with our more-than-human environments. In other words, I argue that while the “new materialism” emerging out of posthumanism can help elaborate a psychedelic rationality, psychedelics can in turn operate as educators in materiality. It is from this materialist perspective that we can best make sense of psychedelics’ often touted potential for social transformation and the enduring suspicion that they are somehow at odds with the “ontoepistemological order” of modernity. From this point of view, I contend that a crucial critical move is to push against the common trope that this opposition is best expressed as a turn from the narrow scientific and “consumerist materialism” of modern Western societies to more expansive “spiritual” worldviews. Pushing against this science-–spirituality binary, which in fact reproduces modern “indivi/dualism” by confining psychedelic experience inside our heads, I argue instead that what is in fact needed to think through and actualize such potentials is an increased attention to our material transcorporeality. In a nutshell, if we want psychedelics to inform social change, we must be more, not less, materialist—albeit by redefining matter in a rather “weird”, non-reductive way and by redefining consciousness as embodied. By the end of the essay, attaching psychedelics to a new materialism will enable us to formulate a “material spirituality” that establishes psychedelics’ political value less in an idealistic or cognitive “politics of consciousness” and more in a “materialization of critique”. Full article

Neonatal calves possess an immature and naïve immune system and are reliant on the intake of maternal colostrum for the passive transfer of immunoglobulins. Maternal antibodies delivered to the calf via colostrum, are crucial to prevent calfhood diseases and death. Failure of transfer of passive immunity (FTPI) is a condition in which calves do not acquire enough maternal antibodies, mostly in the form of IgG, due to inadequate colostrum quality or delayed colostrum feeding. The diagnosis and risk factors for FTPI have been widely studied in dairy cattle; however, in beef calves, the research interest in the topic is relatively recent, and the most adequate diagnostic and preventative methods are still in development, making it difficult to define recommendations for the assessment and prevention of FTPI in cow–calf operations. The objective of this scoping review is to identify the published literature on best practices for colostrum management and transfer of passive immunity (TPI) in neonatal beef calves. The literature was searched using three electronic databases (CAB Direct, Scopus, and PubMed) for publications from 2003 to 2025. The search process was performed during the period from May to July 2023, and was repeated in January 2025. All screening processes were performed using Covidence systematic review software (Veritas Health Innovation, Melbourne, Australia). A total of 800 studies were initially identified through database searches. After removing duplicates, 346 studies were screened based on their titles and abstracts, leading to the exclusion of 260 studies. The remaining 86 studies underwent full-text screening, and 58 studies were considered eligible for data extraction. Hand-searching the references from published review papers on the subject yielded an additional five studies, bringing the total to 63 included articles. The prevalence of FTPI has been estimated to be between 5.8% and 34.5% in beef calves. Factors studied related to colostrum management include quality and quantity of colostrum intake, the timing and method of colostrum feeding, and the microbial content of the colostrum. Studies on risk factors related to the calf include the topics calf sex, twin status, calf vigor, weight, month of birth, cortisol and epinephrine concentrations, and the administration of nonsteroidal anti-inflammatory drugs to calves after difficult calving. The dam-related risk factors studied include dam body condition score and udder conformation, breed, parity, genetics, prepartum vaccinations and nutrition, calving area and difficulty, and the administration of nonsteroidal anti-inflammatory drugs at C-section. Most importantly for beef systems, calves with low vigor and a weak suckling reflex are at high risk for FTPI; therefore, these calves should be given extra attention to ensure an adequate consumption of colostrum. While serum IgG levels of < 8 g/L or < 10 g/L have been suggested as cutoffs for the diagnosis of FTPI, 16 g/L and 24 g/L have emerged as cutoffs for adequate and optimal serum IgG levels in beef calves. Several field-ready diagnostics have been compared in various studies to the reference standards for measuring indicators of TPI in beef calves, where results often differ between models or manufacturers. Therefore, care must be taken when interpreting these results. Full article

Atrial fibrillation (AF) is the most common sustained arrhythmia and a major contributor to stroke and cardiovascular morbidity. However, current approaches to rhythm control and stroke prevention are often limited by variable treatment responses and population-based risk stratification tools that fail to capture individual disease mechanisms. Digital twin technology—computational models built using patient-specific anatomical and physiological data—has emerged as a promising approach to address these limitations. In the context of AF, left atrial (LA) digital twins integrate structural, electrophysiological, and hemodynamic information to simulate arrhythmia behavior, therapeutic response, and thromboembolic risk with high mechanistic fidelity. Recent applications include stroke risk prediction using computational fluid dynamics, in silico testing of antiarrhythmic drugs, and virtual planning of catheter ablation strategies. These models have shown potential to enhance the personalization of care, offering a more nuanced and predictive framework than conventional scoring systems or imaging alone. Despite promising progress, challenges related to model personalization, computational scalability, and clinical validation remain. Nevertheless, LA digital twins are poised to advance the precision management of AF by bridging in silico modeling with real-world decision-making. This review summarizes the current state and future directions of left atrial digital twin models in AF, focusing on their application in stroke risk prediction, pharmacologic decision-making, and ablation strategy optimization. Full article

Background/Objectives: Quality by Design (QbD) has revolutionized pharmaceutical development by transitioning from reactive quality testing to proactive, science-driven methodologies. Rooted in ICH Q8–Q11 guidelines, QbD emphasizes defining Critical Quality Attributes (CQAs), establishing design spaces, and integrating risk management to enhance product robustness and regulatory flexibility. This review critically examines QbD’s theoretical frameworks, implementation workflows, and industrial applications, aiming to bridge academic research and commercial practices while addressing emerging challenges in biologics, advanced therapies, and personalized medicine. Methods: The review synthesizes regulatory guidelines, case studies, and multidisciplinary tools, including Design of Experiments (DoE), Failure Mode Effects Analysis (FMEA), Process Analytical Technology (PAT), and multivariate modeling. It evaluates QbD workflows—from Quality Target Product Profile (QTPP) definition to control strategies—and explores advanced technologies like AI-driven predictive modeling, digital twins, and continuous manufacturing. Results: QbD implementation reduces batch failures by 40%, optimizes dissolution profiles, and enhances process robustness through real-time monitoring (PAT) and adaptive control. However, technical barriers, such as nonlinear parameter interactions in complex systems, and regulatory disparities between agencies hinder broader adoption. Conclusions: QbD significantly advances pharmaceutical quality and efficiency, yet requires harmonized regulatory standards, lifecycle validation protocols, and cultural shifts toward interdisciplinary collaboration. Emerging trends, including AI-integrated design space exploration and 3D-printed personalized medicines, promise to address scalability and patient-centric needs. By fostering innovation and compliance, QbD remains pivotal in achieving sustainable, patient-focused drug development. Full article

Background/Objectives: Herein, we demonstrate the development and characterization of ceftriaxone (CTX)-loaded liposomal nanoparticles (NPs) intended to be applicable to the management of lower respiratory tract infections (LRTIs) associated with resistant bacteria. Methods: The CTX-loaded liposomal NPs were fabricated by a thin film hydration approach. Results: The particle size of the NPs, determined by a Zetasizer, was within the range of 90–536 nm. Microscopic examination by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) revealed that particles are spherical in shape and have retained their original morphology even after freeze-drying. Attenuated total reflection-Fourier transform infrared (ATR-FTIR), differential scanning calorimetry (DSC), thermogravimetric (TG), and powder X-ray diffraction (PXRD) spectra exhibited that CTX is incorporated into the liposomes with no possible interaction between drug and excipients. The formation of the CTX-loaded liposomal NPs was dependent on the concentrations of phospholipids, cholesterol and mannitol; however, no considerable differences were observed in entrapment efficiency and loading capacity of CTX formulations (F6–F10). Using a twin-stage impinger (TSI), the in vitro aerosolization of the formulations were carried out at a flow rate of 60 ± 5 L/min and CTX was determined by a validated HPLC method and the prepared liposomal formulations produced promising fine particle fraction (FPF) between 47 and 62%. The prepared formulation (F6) showed prolonged CTX release of 94.0% ± 5.7 and 95.9% ± 3.9 at 24 h and 48 h, respectively. The drug release followed the Hixon–Crowell model, with CTX being transported through Fickian diffusion. Conclusions: These results highlight the prepared CTX-loaded inhaled liposomal formulation would be suitable for pulmonary delivery and extend the successful antibiotic delivery strategies for the effective management of LRTIs. Full article

Background/Objectives: Evans’ syndrome (ES) is a rare autoimmune disorder characterized by the simultaneous or sequential onset of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Given its rarity, available data concerning the clinical course and optimal management in pregnancy are limited. Methods: We present the case of a 32-year-old woman who experienced ES during her first pregnancy. She had been previously diagnosed with childhood-onset SLE at the age of 14 but had been in treatment-free remission since the age of 24. The treatment of both AIHA and ITP included intravenous immunoglobulins, cyclosporine-A, high dosage oral corticosteroids, and, in the second trimester, rituximab. The delivery was planned at 34 + 6 weeks of gestation (GW); no immunological alterations or infectious complications were detected in the newborn. The post-delivery period was uncomplicated, and the mother was discharged with a normal blood count. A narrative review of available ES cases during pregnancy is also presented. Results: A total of 16 patients with ES in pregnancy were reported, including the one we described. None of them developed major bleedings during gestation, while a case of abruptio placentae with delayed postpartum hemorrhage occurred. ITP was difficult to treat in 4/16 women after delivery; 4/16 patients also developed gestational hypertensive disorders. Perinatal outcomes include 13/17 healthy newborns and 4/17 stillbirths (2 of them were twins), of which 1 was due to fetal AIHA. Gestational age at birth was before 37 GW in 8/17. In 15/16 women, ES resolved after delivery. Conclusions: The occurrence of ES during pregnancy has been rarely reported; it constitutes a clinical challenge due to the need for multiple treatments, including conventional immunosuppressants and/or biologic drugs as steroid-sparing agents. After delivery, ES appeared to be less resistant to treatment than it was during pregnancy. Full article

Background/Objectives: Guidelines recommend adjusting amikacin dosing based on patients’ renal function. Nevertheless, for critically ill cancer patients, the renal function equations based on serum creatinine levels have low or no correlation with amikacin clearance. Considering this, using real-world data, we built an amikacin PBPK model to predict amikacin plasma concentrations in critically ill oncologic patients stratified by renal impairment levels. Further, the model was applied for dose stratification and individualization (digital twin strategy) in this population. Methods: In the Therapeutic Drug Monitoring (TDM) study, 368 amikacin pharmacokinetic analyses from 184 critically ill cancer patients were enrolled in three cohorts. A full-body PBPK model was developed using PK-Sim v. 11.3. Results: The final PBPK model accounted for two groups of critically ill cancer patients with mild (creatinine clearance; CLcr ≥ 60 mL/min) or severe (CLcr < 60 mL/min) renal dysfunction. In the dose stratification strategy, at the 7th dose, cancer patients with CLcr ≥ 60 mL/min under regimens 20 mg/kg (q24h); 25 mg/kg (q24h); 25 mg/kg (q48h); and 30 mg/kg (q72h) have probability of ≥69% of the patients achieving the efficacy target (AUC/MIC > 80, MIC of 4 mg/L), while cancer patients with CLcr < 60 mL/min under regimens 7.5 mg/kg (q24h); 15 mg/kg (q24h); 15 mg/kg (q48h); and 20 mg/kg (q36h) have ≥90% probability of achieving the same efficacy target. Conclusions: Our MIPD approach demonstrates potential in optimizing amikacin dosing for critically ill cancer patients. However, it does not eliminate the need for TDM due to unexplained variability still not accounted for by the PBPK model. Full article

Background/Objectives: This study evaluates the efficacy of twin screw melt granulation (TSMG), and hot-melt extrusion (HME) techniques in enhancing the solubility and dissolution of simvastatin (SIM), a poorly water-soluble drug with low bioavailability. Additionally, the study explores the impact of binary polymer blends on the drug’s miscibility, solubility, and in vitro release profile. Methods: SIM was processed with various polymeric combinations at a 30% w/w drug load, and a 1:1 ratio of binary polymer blends, including Soluplus^® (SOP), Kollidon^® K12 (K12), Kollidon^® VA64 (KVA), and Kollicoat^® IR (KIR). The solid dispersions were characterized using modulated differential scanning calorimetry (M-DSC), powder X-ray diffraction (PXRD), and Fourier-transform infrared spectroscopy (FTIR). Dissolution studies compared the developed formulations against a marketed product. Results: The SIM-SOP/KIR blend showed the highest solubility (34 µg/mL), achieving an approximately 5.5-fold enhancement over the pure drug. Dissolution studies showed that SIM-SOP/KIR formulations had significantly higher release profiles than the physical mixture (PM) and pure drug (p < 0.01). Additionally, their release was similar to a marketed formulation, with 100% drug release within 30 min. In contrast, the SIM-K12/KIR formulation exhibited strong miscibility, but limited solubility and slower release rates, suggesting that high miscibility does not necessarily correlate with improved solubility. Conclusions: This study demonstrates the effectiveness of TSMG, and HME as effective continuous manufacturing technologies for improving the therapeutic efficacy of poorly water-soluble drugs. It also emphasizes the complexity of polymer–drug interactions and the necessity of carefully selecting compatible polymers to optimize the quality and performance of pharmaceutical formulations. Full article

In order to reproduce pharmacokinetics (PK) profiles seen in vivo, the Hollow Fiber Infection Model (HFIM) is a useful in vitro module in the evaluation of antimicrobial resistance. In order to reduce the consumption of culture medium and drugs, we developed a hollow fiber microreactor applicable to the HFIM by integrating the HFIM function. Next, we constructed a novel control method by using the “digital twin” of the microreactor to achieve precise concentration control. By integrating functions of the HFIM, the extra-capillary space volume was reduced to less than 1/10 of conventional HFIM. The control method with the digital twin can keep drug concentration in the extra-capillary space within an error of 10% under simulated drug destruction. The control method with the digital twin can also stabilize the drug concentration both in the intra-capillary space and the extra-capillary space within 15 min. Full article

Rhein is a natural active ingredient in traditional Chinese medicine that has attracted much attention due to its wide range of pharmacological activities. However, its clinical application is limited by low water solubility, poor oral absorption, and potential toxicity to the liver and kidneys. Recently, advanced extraction and synthesis techniques have made it possible to develop derivatives of rhein, which have better pharmacological properties and lower toxicity. This article comprehensively summarizes the biological activity and action mechanism of rhein. Notably, we found that TGF-β1 is the target of rhein improving tissue fibrosis, while NF-κB is the main target of its anti-inflammatory effect. Additionally, we reviewed the current research status of the pharmacokinetics, toxicology, structural optimization, and potential drug applications of rhein and found that the coupling and combination therapy of rhein and other active ingredients exhibit a synergistic effect, significantly enhancing therapeutic efficacy. Finally, we emphasize the necessity of further studying rhein’s pharmacological mechanisms, toxicology, and development of analogs, aiming to lay the foundation for its widespread clinical application as a natural product and elucidate its prospects in modern medicine. Full article

The human gastrointestinal microbiota plays a vital role in maintaining host health and preventing diseases, prompting the creation of simulators to replicate this intricate system. The Simulator of the Human Intestinal Microbial Ecosystem (SHIME^®), a multicompartment dynamic simulator, has emerged as a pivotal in vitro model for studying the interactions and interferences within the human gut microbiota. The continuous and real-time monitoring hallmarks, along with the programmatically flexible setup, bestow SHIME^® with the ability to mimic the entire human intestinal ecosystem with high dynamics and stability, allowing the evaluation of various treatments on the bowel microbiota in a controlled environment. This review outlines recent developments in SHIME^® systems, including the M-SHIME^®, Twin-SHIME^®, Triple-SHIME^®, and Toddle SHIME^® models, highlighting their applications in the fields of food and nutritional science, drug development, gut health research, and traditional Chinese medicine. Additionally, the prospect of SHIME^® integrating with other advanced technologies is also discussed. The findings underscore the versatility of SHIME^® technology, demonstrating its significant contributions to current gut ecosystem research and its potential for future innovation in microbiome-related fields. Full article

Background: This study explores the development and characterization of spray-dried composite microparticles consisting of levofloxacin (LVX, a broad-spectrum antibiotic), and ambroxol (AMB, a mucolytic agent that has antibacterial and antibiofilm properties), for the intended application of the drug against lower respiratory tract infections (LRTIs). Methods: A range of LVX to AMB mass ratios (1:1, 1:0.5, and 1:0.25) were prepared, with and without the use of the dispersibility enhancer leucine (LEU), and spray-dried following pre-optimized parameters to achieve the required particle size (1–5 µm) and flow properties. The formulations were characterized by attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy, scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), and a thermogravimetric analysis (TGA). The in vitro aerosolization performance of the new formulation was evaluated with a twin-stage impinger (TSI) at a flow rate of 60 ± 5 L/min. Using a validated RP-HPLC method, LVX and AMB were quantitatively determined. Results: The combined spray-dried LVX, AMB, and LEU particles were spherically shaped with sizes ranging from 1.9 to 2.9 µm, thus complying with the size requirements for effective deep lung deposition. The dispersibility enhancer leucine produced a high yield and enhanced the flow properties and aerosolization characteristics of the spray-dried formulations. The LVX to AMB mass ratios showed a remarkable impact on the aerosolization properties, with the LVX to AMB 1:1 mass ratio demonstrating the best flow and FPFs for both drugs. There must be a balanced ratio of these components for spray drying the composite particles to obtain composite particles of the required size and with the appropriate flow property. The addition of 5% of LEU significantly (p < 0.005) improved the FPF of all the formulations, probably by enhancing the surface hydrophobicity of the composite particles. Conclusions: The spray-dried combined antibiotics formulation has a strong potential for efficient lung delivery intended for the management of LRTIs. Full article

Background/Objectives: This study focuses on the ability of vaping technology to deliver beclomethasone dipropionate compared to nebulization. Methods: An in vitro comparison of aerosol properties in terms of respirable dose with the Glass Twin Impinger and the mass median aerodynamic diameter using the Next Generation Impactor was performed. The respirable dose delivered in a vaping drug delivery system (VDDS) puff as a function of concentration was quantified by high-pressure liquid chromatography coupled with an ultraviolet detector. Results: The mass of drug contained in a single puff of 55 mL of aerosol varied between 0.94 and 1.95 µg for a refill liquid concentration range of 400 to 1600 µg/mL. The analysis of the particle size distribution shows an advantage for a VDDS in producing smaller particles compared to nebulization (1.56 ± 0.05 µm vs. 2.30 ± 0.19 µm). In total, 81 puffs are needed to reach the dose equivalent to nebulized beclomethasone dipropionate under these specific experimental conditions, which corresponds to an aerosol duration of about 4 min (i.e., four times lower than the jet nebulizer) and a patient administration time of about 45 min (i.e., three times higher than the jet nebulizer). Conclusions: The results show the potential of vaping devices as an alternative to nebulizers for the administration of beclomethasone dipropionate in an equivalent respirable dose. Full article

There have recently been rapid developments in smart healthcare systems, such as precision diagnosis, smart diet management, and drug discovery. These systems require the integration of the Internet of Things (IoT) for data acquisition, Digital Twins (DT) for data representation into a digital replica and Artificial Intelligence (AI) for decision-making. DT is a digital copy or replica of physical entities (e.g., patients), one of the emerging technologies that enable the advancement of smart healthcare systems. AI and Machine Learning (ML) offer great benefits to DT-based smart healthcare systems. They also pose certain risks, including security risks, and bring up issues of fairness, trustworthiness, explainability, and interpretability. One of the challenges that still make the full adaptation of AI/ML in healthcare questionable is the explainability of AI (XAI) and interpretability of ML (IML). Although the study of the explainability and interpretability of AI/ML is now a trend, there is a lack of research on the security of XAI-enabled DT for smart healthcare systems. Existing studies limit their focus to either the security of XAI or DT. This paper provides a brief overview of the research on the security of XAI-enabled DT for smart healthcare systems. It also explores potential adversarial attacks against XAI-enabled DT for smart healthcare systems. Additionally, it proposes a framework for designing XAI-enabled DT for smart healthcare systems that are secure and trusted. Full article

Background/Objectives: Amorphization of an active pharmaceutical ingredient (API) can improve its dissolution and enhance bioavailability. Avoiding solvents for drug amorphization is beneficial due to environmental issues and potential solvent residues in the final product. Methods: Dry amorphization using a twin-screw extruder is presented in this paper. A blend of mesoporous silica particles and crystalline itraconazole was processed using a pharma-grade laboratory scale twin-screw extruder. The influence of different screw configurations and process parameters was tested. Particle size and shape are compared in scanning electron microscopy (SEM) images. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) are used to determine the residual amount of crystalline itraconazole in the final product. Results: An optimized screw configuration for the process was found which leads to more than 90% amorphous API when processed at room temperature. Full amorphization was reached at 70 °C. The specific mechanic energy (SME) introduced into the material during twin-screw processing is crucial for the dry amorphization. The higher the SME, the lower the residual amount of crystalline API. Two months after processing, however, recrystallization was observed by XRD. Conclusions: Dry processing using a twin-screw extruder is continuous, free of solvents and can be performed at low temperatures. This study proves the concept of twin-screw processing with mesoporous silica for dry amorphization of itraconazole. Full article