Pluronics, also known as poloxamers, are amphiphilic triblock copolymers widely employed in drug delivery systems due to their tunable self-assembly and biocompatibility. Among them, Pluronic F68 (Poloxamer 188) exhibits thermoresponsive behavior in aqueous solution, forming ordered supramolecular structures at high concentrations and temperatures. In this work, we investigate the morphological and rheological properties of a 45 wt% Pluronic F68 aqueous system at different temperatures through a combination of experimental and computational approaches. Rheological measurements and Small-Angle X-ray Scattering (SAXS) confirm the formation of a body-centered cubic (BCC) structure at higher temperatures and highlight the emergence of viscoelastic solid-like behavior. To support and extend these findings, Dissipative Particle Dynamics (DPD) simulations are employed to model the nanostructure evolution and the impact of temperature on self-assembly and material properties. This integrated approach provides a consistent framework to characterize the temperature-induced transition from fluid-like to solid-like states and sets the groundwork for future simulation studies incorporating drug cargo. The results offer valuable insights into the design of thermoresponsive drug delivery systems and demonstrate the potential of DPD in capturing complex structure-property relationships in amphiphilic polymer systems.
- Keywords
- Dissipative particle dynamics, Drug delivery systems, Pluronics, Rheology, Self-assembly,
- MeSH
- Scattering, Small Angle MeSH
- Drug Carriers * chemistry MeSH
- Poloxamer * chemistry MeSH
- Surface Properties MeSH
- Rheology MeSH
- Temperature MeSH
- Particle Size MeSH
- Water * chemistry MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Drug Carriers * MeSH
- Poloxamer * MeSH
- Water * MeSH
Inbred mouse strains provide phenotypic homogeneity between individual mice. However, stochastic morphogenetic events combined with epigenetic changes due to exposure to environmental factors and ontogenic experience result in variability among mice with virtually identical genotypes, reducing the reproducibility of experimental mouse models. Here we used microscopic and cytometric techniques to identify individual patterns in gut-associated lymphoid tissue (GALT) that are induced by exposure to microbiota. By comparing germ-free (GF), conventional (CV) and gnotobiotic mice colonized with a defined minimal mouse microbiota (oMM12) MHC II-EGFP knock-in mice we quantified antigen-presenting cells (APCs) in the lamina propria, cryptopatches (CP), isolated lymphoid follicles (ILFs), Peyer's patches (PPs) and specific sections of the mesenteric lymphoid complex. We found that GF mice had a significantly larger outer intestinal surface area compared to CV and oMM12-colonized mice, which partially compensated for their lower density of the villi in the distal ileum. GF mice also contained fewer APCs than oMM12 mice in the Iamina propria of the villi and had a significantly smaller volume of the solitary intestinal lymphoid tissue (SILT). In both GF and oMM12 mice, PP follicles were significantly smaller compared to CV mice, although number was similar. Concomitantly, the number of pDCs in PPs was significantly lower in GF mice than in CV mice. Moreover, the cecal patch was dispersed into small units in GF mice whereas it was compact in CV mice. Taken together, we here provide further evidence that microbiota regulates SILT differentiation, the size and morphology of PPs, the cellular composition of mesenteric lymph nodes (MLNs) and the morphology of cecal patch. As such, microbiota directly affect not only the functional configuration of the immune system but also the differentiation of lymphoid structures. These findings highlight how standardized microbiota, such as oMM12, can promote reproducibility in animal studies by enabling microbiologically controlled experiments across laboratories.
- Keywords
- Germ-free and gnotobiotic models, Gut-associated lymphoid tissue (GALT), Lymphoid tissue morphogenesis, MHCII-EGFP knock-in mice, Microbiota-induced immunity, Phenotypic plasticity,
- MeSH
- Antigen-Presenting Cells immunology MeSH
- Germ-Free Life MeSH
- Lymphoid Tissue * immunology cytology microbiology MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Peyer's Patches immunology cytology MeSH
- Gastrointestinal Microbiome * immunology MeSH
- Intestinal Mucosa immunology microbiology cytology MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Targeted alpha therapy (TAT) is an effective option for cancer treatment. To maximize its efficacy and minimize side effects, carriers must deliver radionuclides to target tissues. Most of the nuclides used in TAT decay via the alpha cascade, producing several radioactive daughter nuclei with sufficient energy to escape from the original carrier. Therefore, studying these daughter atoms is crucial in the search for new carriers. Nanoparticles have potential as carriers due to their structure, which can prevent the escape of daughter atoms and reduce radiation exposure to non-target tissues. This work focuses on determining the released activity of 221Fr and 213Bi resulting from the decay of 225Ac labelled TiO2 nanoparticles. RESULTS: Labelling of TiO2 nanoparticles has shown high sorption rates of 225Ac and its progeny, 221Fr and 213Bi, with over 92 % of activities sorbed on the nanoparticle surface for all measured radionuclides. However, in the quasi-dynamic in vitro system, the released activity of 221Fr and 213Bi is strongly dependent on the nanoparticles concentration, ranging from 15 % for a concentration of 1 mg/mL to approximately 50 % for a nanoparticle concentration of 10 μg/mL in saline solution. The released activities of 213Bi were lower, with a maximum value of around 20 % for concentrations of 0.05, 0.025, and 0.01 mg/mL. The leakage of 225Ac and its progeny was tested in various biological matrices. Minimal released activity was measured in saline at around 10 % after 48 h, while the maximum activity was measured in blood serum and plasma at 20 %. The amount of 225Ac released into the media was minimal (<3 %). The in vitro results were confirmed in a healthy mouse model. The difference in %ID/g was clearly visible immediately after dissection and again after 6 h when 213Bi reached equilibrium with 225Ac. CONCLUSION: The study verified the potential release of 225Ac progeny from the labelled TiO2 nanoparticles. Experiments were performed to determine the dependence of released activity on nanoparticle concentration and the biological environment. The results demonstrated the high stability of the prepared 225Ac@TiO2 NPs and the potential release of progeny over time. In vivo studies confirmed our hypothesis. The data obtained suggest that the daughter atoms can escape from the original carrier and follow their own biological pathways in the organism.
- Keywords
- Actinium-225, Bismuth-213, Nanoparticles, Targeted alpha therapy, TiO(2),
- MeSH
- Actinium * chemistry MeSH
- Isotope Labeling MeSH
- Mice MeSH
- Nanoparticles * chemistry MeSH
- Radioisotopes * chemistry MeSH
- Titanium * chemistry MeSH
- Tissue Distribution MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Actinium-225 MeSH Browser
- Actinium * MeSH
- Radioisotopes * MeSH
- Titanium * MeSH
- titanium dioxide MeSH Browser
This study employed a simulation approach to model oxygen delivery in spontaneously breathing patients with chronic obstructive pulmonary disease (COPD). The model of respiratory and circulatory systems developed by Morozoff et al., originally designed for mechanically ventilated patients with a fixed fraction of inspired oxygen (FIO2), was adapted to incorporate the relationship between oxygen flow delivered through nasal cannula and FIO2, along with COPD-specific pathophysiological parameters. The effectiveness of constant and variable oxygen flow delivery was evaluated using a closed-loop control system with proportional (P) and proportional-integral-derivative (PID) controllers. The adapted model of respiratory and circulatory systems successfully reproduced SpO2 variations observed in COPD patients, capturing desaturation patterns during rapid eye movement sleep and daily activities. Simulations showed that continuous oxygen flow was inadequate for maintaining SpO2 within the target range. P and PID controllers improved SpO2 regulation, increasing time within the target range (88%-92%) to 80% and 74%, respectively, compared to a maximum of 55% achieved with a constant oxygen flow system. However, as airway resistance increased compared to the baseline case, the P-controller's performance declined considerably compared to PID-controller, highlighting the need for retuning controller to have the highest possible efficiency considering varying pathophysiological parameters. In addition, more advanced control strategies, such as model-based controllers, may enhance adaptability to dynamic patient conditions. These findings support the development of adaptive oxygen delivery strategies, optimizing treatment outcomes for spontaneously breathing COPD patients requiring long-term oxygen therapy.
- MeSH
- Models, Biological * MeSH
- Pulmonary Disease, Chronic Obstructive physiopathology metabolism MeSH
- Respiration * MeSH
- Oxygen * metabolism MeSH
- Humans MeSH
- Oxygen Inhalation Therapy * MeSH
- Feedback, Physiological * MeSH
- Feedback * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Oxygen * MeSH
Focused ultrasound stimulation (FUS) is rapidly gaining attention as a non-invasive and highly precise neuromodulatory technique with broad therapeutic potential in neurological and psychiatric disorders. While most reviews to date have emphasized in vivo and clinical studies, the cellular mechanisms underlying FUS remain underexplored. This study presents an innovative and thorough synthesis of FUS effects in in vitro neurological cell models, including SH-SY5Y, PC12, BV2 microglia, NSC-34 motor neurons, and human iPSC-derived neurons and astrocytes. These models offer essential insights into the mechanisms by which FUS influences intracellular calcium dynamics, mitigates oxidative stress, modulates inflammatory responses, and stimulates autophagy, thus facilitating neuroprotection and synaptic resilience in various disease contexts, including Parkinson's disease, Alzheimer's disease, schizophrenia, epilepsy, multiple sclerosis, OCD, and traumatic brain injury. Mapping disease-specific results with comprehensive FUS sonication parameters, this evaluation only focuses on cell-based systems, which is a fundamental advance. Additionally, it emphasizes the incorporation of new technology into FUS, such as acoustically responsive biomaterials, microbubble-assisted gene transfection, and nanoparticle-mediated medication delivery. The study highlights the increasing importance of AI in directing real-time FUS targeting and optimizing parameters, which is leading to tailored neuromodulation treatments. This study establishes a solid groundwork for the advancement of FUS in preclinical research by connecting the dots between cellular bioeffects and translational potential. It highlights the critical need for multidisciplinary methods, standardization, and the use of 3D organoid systems for next-generation brain treatments that fully use FUS.
BACKGROUND: Although mental disorders have long been considered complex dynamic systems, our understanding of the mutual interactions and temporal patterns of their symptoms remains limited. METHODS: In this longitudinal study, we examined the structure and dynamics of four key mental health indicators - depression, anxiety, post-traumatic stress disorder, and insomnia - in a representative sample of the Slovak population (effective N = 3,874) over 10 waves spanning 3.5 years. For each construct, a longitudinal panel network model was estimated. RESULTS: The temporal relationships between symptoms were mostly weak, with the autoregressive effects typically being stronger. In depression, anxiety, and insomnia, some causal chains and feedback loops were identified. In all constructs, both contemporaneous and between-person networks showed dense connections. CONCLUSIONS: The findings provide critical insights into the complexity of mental health development, offering potential targets for intervention and prevention strategies.
- Keywords
- anxiety, depression, insomnia, longitudinal analysis, mental health, network analysis, panel networks, posttraumatic stress disorder,
- MeSH
- Depression * epidemiology MeSH
- Adult MeSH
- Mental Health * MeSH
- Middle Aged MeSH
- Humans MeSH
- Longitudinal Studies MeSH
- Adolescent MeSH
- Young Adult MeSH
- Sleep Initiation and Maintenance Disorders * epidemiology MeSH
- Stress Disorders, Post-Traumatic * epidemiology MeSH
- Aged MeSH
- Anxiety * epidemiology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Slovakia epidemiology MeSH
Active Brownian particles (ABPs) are a generic model for synthetic active matter systems, such as active colloids, characterized by their ability to self-propel while also exhibiting Brownian motion. Under confinement, ABPs display propulsion-induced wall accumulation, a behavior that can be harnessed for microfluidic and lab-on-a-chip applications. We investigate ABPs confined in slit pores using overdamped Langevin dynamics and study their wall accumulation as a function of particle activity and slit width, at both gas and liquid densities. Furthermore, we examine the correspondence between confined ABPs and their equilibrium counterparts, confined fluid particles capable of completely wetting the slit walls.
- Publication type
- Journal Article MeSH
Euler and Cardan angles representation in biomechanical analysis allows straightforward description of joint rotations. However, application of Euler or Cardan angles can be problematic due to a singularity called gimbal lock. Quaternions offer an alternative way to describe rotation that avoids this problem, but they are not commonly used in biomechanics as they are complex and not inherently intuitive, specifically in dynamic models actuated by muscles. This study introduces a mathematical framework for describing muscle actions in dynamic quaternion-based musculoskeletal simulations. The proposed method estimates muscle torques in a quaternion-based musculoskeletal model. Its application is shown in a three-dimensional double-pendulum system actuated by muscle elements. Furthermore, the transformation of muscle moment arms obtained from muscle paths based on Euler or Cardan angles into a quaternion-based description is presented. The proposed method is advantageous for dynamic modeling of musculoskeletal models with complex kinematics and joints with large ranges of motion like the shoulder joint.
- Keywords
- Biomechanics, Moment arm, Musculoskeletal modeling, Quaternion,
- MeSH
- Models, Biological * MeSH
- Biomechanical Phenomena MeSH
- Muscle, Skeletal * physiology MeSH
- Humans MeSH
- Computer Simulation MeSH
- Shoulder Joint * physiology MeSH
- Range of Motion, Articular physiology MeSH
- Muscle Contraction * physiology MeSH
- Torque MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Most single-shot pulsed-field ablation (PFA) catheters require extensive repositioning for pulmonary vein isolation (PVI), posing a challenge for obtaining contiguous, durable lesions. OBJECTIVE: To determine 1-year outcomes of a single-shot, all-in-one mapping and ablation PFA catheter for treating paroxysmal atrial fibrillation (PAF). METHODS: After PVI with the large-lattice catheter with expandable tip (Sphere-360), follow-up included Holter monitoring at 180 and 365 days and scheduled/symptomatic trans-telephonic monitoring (TTM) or modeled insertable loop recorder (ILR) data. Efficacy outcomes were acute PVI and 12-month freedom from atrial arrhythmias (AA), after 90-day blanking. Optional invasive remapping at 75 days facilitated waveform refinement from PULSE1, PULSE2, to the optimized PULSE3. RESULTS: At 3 centers, 100 PAF patients underwent PFA with PULSE1 (n = 30), PULSE2 (n = 20), or PULSE3 (n = 50). Procedure, left atrial dwell, and fluoroscopy times were 57.9 ± 20.6, 22.2 ± 11.8 and 6.8 ± 5.7 minutes, respectively. All 395 targeted PVs were acutely isolated, with a transpired PVI time of 11.5 ± 6.0 minutes, using 4.0 ± 1.3 lesions/PV. There were no primary safety events (serious device-related events within 7 days post-PFA). PVI durability with PULSE3 (n = 40) was 98% (per-vein) and 93% (per-patient). One-year freedom from AA recurrence was 82.0% (95% CI:73.0%-88.3%) overall, and 88.0% (95%CI, 75.2%-94.4%) for PULSE3 patients. Of the ILR sub-cohort (n = 15 PULSE3 patients), 3 patients (20%) had recurrences, with an AA burden reduction from 26% (baseline) to 1.6% (post-ablation). CONCLUSION: The large lattice PFA catheter was efficient, safe, and effective in treating PAF. The observed high PVI durability translated to clinical effectiveness, even in continuously monitored patients.
- Keywords
- Atrial fibrillation, Burden, Catheter ablation, Mapping, Pulsed-field ablation,
- MeSH
- Time Factors MeSH
- Equipment Design MeSH
- Electrocardiography, Ambulatory MeSH
- Atrial Fibrillation * surgery physiopathology diagnosis MeSH
- Catheter Ablation * methods instrumentation MeSH
- Middle Aged MeSH
- Humans MeSH
- Follow-Up Studies MeSH
- Heart Conduction System * surgery physiopathology MeSH
- Aged MeSH
- Pulmonary Veins * surgery MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
Our ability to understand and control complex systems of many interacting parts remains limited. A key challenge is that we still do not know how best to describe-and quantify-the many-to-many dynamical interactions that characterize their complexity. To address this limitation, we introduce the mathematical framework of Integrated Information Decomposition, or [Formula: see text]ID. [Formula: see text]ID provides a comprehensive framework to disentangle and characterize the information dynamics of complex multivariate systems. On the theoretical side, [Formula: see text]ID reveals the existence of previously unreported modes of collective information flow, providing tools to express well-known measures of information transfer, information storage, and dynamical complexity as aggregates of these modes, thereby overcoming some of their known theoretical shortcomings. On the empirical side, we validate our theoretical results with computational models and examples from over 1,000 biological, social, physical, and synthetic dynamical systems. Altogether, [Formula: see text]ID improves our understanding of the behavior of widely used measures for characterizing complex systems across disciplines and leads to new more refined analyses of dynamical complexity.
- Keywords
- complexity, dynamical systems, information theory, integrated information,
- MeSH
- Computer Simulation MeSH
- Models, Theoretical * MeSH
- Publication type
- Journal Article MeSH
