Advances in experimental medicine and biology最新文献

Bone implants and stents are medical devices that are commonly used to treat bone and cardiovascular diseases, respectively. Both require successful integration with the surrounding tissue to achieve long-term success. Osteointegration, the process by which the implant becomes integrated with the surrounding bone, is critical to the success of bone implants, while the stent healing process involves endothelialization, re-endothelialization, and neointimal formation. The healing process of bone is complex and influenced by various factors, including the properties of the implant material, the surgical technique, and patient factors such as age and overall health. Several materials have been developed for bone implants, including metals, ceramics, and polymers. The choice of material depends on the specific application, as each material has unique properties that affect its suitability for a particular use. For example, titanium is commonly used in orthopedic implants due to its biocompatibility, strength, and ability to promote osteointegration. The healing process of stents is influenced by the materials used and the stent design. Drug-eluting stents, which release drugs to reduce restenosis, have been developed to improve the healing process. Endothelialization, the formation of a layer of endothelial cells over the stent, is critical to the prevention of restenosis. Neointimal formation, the formation of new tissue over the stent, can cause restenosis and has been a major concern with bare-metal stents. Factors that affect osteointegration and stent healing process include implant surface properties, such as roughness and topography, as well as the size, shape, and placement of the implant. In addition, patient factors such as age, overall health, and medication use can also affect the healing process. In conclusion, successful integration with the surrounding tissue is critical to the long-term success of bone implants and stents. The choice of implant material, surgical technique, and patient factors all play a role in the healing process, and ongoing research is needed to improve the design and performance of these medical devices.

Background: Determining optical properties of biological tissues enables critical clinical insights, e.g., quantifying hemoglobin oxygenation in preterm infants or detecting malignant tissues in cancer diagnostics. In applications such as neonatal monitoring or endoscopic imaging, measurements at short distances (less than 1 cm) are essential due to space constraints.

Aim: This study aims to investigate the relationship between the tissue optical properties and the reflectance at short distances using a combination of experimental data and a modified Monte Carlo (MC) simulation.

Materials and methods: Twelve phantoms with different optical properties were created using silicone and validated using the commercial frequency domain near infrared spectroscopy system ISS Imagent. Reflectance measurements were conducted at precise source-detector separations ranging from 1.5 mm to 5 mm. Modified MC simulations incorporating the modified Henyey-Greenstein (MHG) and Gegenbauer (GB) phase functions were employed and simulated and measured data were compared.

Results: The reflectance data exhibited a clear dependence on absorption and scattering coefficients. The MHG and GB models provided better fits to experimental data compared to the traditional Henyey-Greenstein (HG) model. The median value of the intraclass correlation coefficient (ICC) among all the investigated separation distances and optical properties of 0.982 for MHG and 0.979 for GB confirms higher agreement with experimental data by using these phase functions compared to HG (ICC = 0.978).

Conclusion: The modified MC simulation enabled us to better simulate the experimental data. The MHG and GB models offer improved accuracy over traditional HG models, thus advancing optical imaging and diagnostic applications especially for measuring the peripheral oxygenation for preterm babies.

This study aimed to determine the changes in the time to nadir of mean arterial pressure (MAP) and oxygenated hemoglobin (O₂Hb) in the right and left prefrontal cortices (R-PFC and L-PFC, respectively) during repeated episodes of rapid hypotension. Four cycles of blood pressure reduction were induced via bilateral thigh occlusion at 250 mmHg followed by rapid deflation. Sixteen healthy male university students participated. MAP was recorded beat by beat, and O₂Hb was continuously monitored using near-infrared spectroscopy. The time from deflation to nadir was measured and compared across each deflation cycle. MAP and O₂Hb in the R-PFC and L-PFC reached their nadir values approximately 7 to 8 s post-deflation, with no significant changes observed across repetitions. These findings indicate that the time to nadir of MAP and O₂Hb in the R-PFC and L-PFC remains stable during repeated rapid hypotension.

In continuous-wave electron paramagnetic resonance (CW-EPR) imaging, many spectral projections are required to accurately reconstruct four-dimensional (4D) spectral-spatial data, which are used for oxygen mapping in tumors. The ability to obtain fewer spectral projections with less degradation of the resultant image quality is desirable because acquiring many spectral projections leads to a longer time for EPR imaging acquisition. The algebraic reconstruction technique (ART) is one of the most powerful image-reconstruction techniques for 4D spectral-spatial imaging. ART can be applied to incomplete sets of spectral projections. However, data sets of many spectral projections can provide reconstructed images of higher quality. In this study, we aimed to enhance acquisition speed by randomly collecting spectral projections and subsequently synthesizing those that had not been recorded. We applied this strategy to a numerical phantom and a mouse Hs766T xenograft model to confirm the feasibility of our concept. Random acquisition can prevent image degradation in linewidth mapping, which is the foundation for oxygen mapping with CW-EPR.

Background: The diaphragm muscle is the primary muscle involved in inspiration and is unique to mammals. Because the diaphragm is a constantly active muscle, its contraction may depend on oxidative phosphorylation and O₂ supply to create adenosine triphosphate. This study aimed to evaluate the role of intrinsic vasodilator nitric oxide (NO) in diaphragm O₂ dynamics.

Methods: Wistar male rats (n = 6, 10 wks old, 311 ± 14 g) were mechanically ventilated under isoflurane anesthesia. The diaphragm was exposed to measure microvascular partial O₂ pressure (PO₂mv) by phosphorescence quenching technique during electrical stimulation-induced diaphragm contractions (6 V, 2 ms, 2 Hz, 180 s). The 180 s of muscle contractions and PO₂mv measurement were repeated 10 min after endothelial NO synthase inhibition by the intra-arterial infusion of nitro-l-arginine methyl ester (L-NAME; eNOS inhibitor). The PO₂mv change during the transition from rest to contraction was fitted to a nonlinear regression model. Time delay, time constant (tau), rate constant (K), and nadir in PO₂mv were calculated and compared before and after eNOS inhibition. [Results] Diaphragm PO₂mv decreased during contractions both before and after eNOS inhibition. The time delay and K were not different before and after L-NAME. However, the L-NAME administration decreased the tau and nadir in PO₂mv (tau, 7.61 [5.18-13.41] vs. 3.36 [1.81-5.57] s; nadir, 7.45 [1.41-14.85] vs. 3.93 [0.89-9.47] mmHg; before vs. after eNOS inhibition, median [25-75 percentiles], P < 0.05, respectively).

Discussion: The time constant in PO₂mv is determined by oxygen supply to the capillaries and oxygen utilization. The faster time constant and lower nadir in PO₂mv possibly indicate the slower and lower oxygen supply to diaphragm capillaries after eNOS inhibition.

Conclusion: The NO has a crucial role in the diaphragm oxygen dynamics of intact rats.

Mobilization of critically ill patients within 72 hours of admission is associated with improved outcomes. Recently, the predictive value of regional cerebral oxygen saturation (rSO₂) measured via near-infrared spectroscopy (NIRS) has been emphasized. This study aimed to evaluate the differences in rSO₂ values depending on the availability of mobilization within 72 hours in the ICU. Eighty patients admitted to the emergency center between June 2020 and December 2022 were analyzed. Patients were assessed based on whether they could be mobilized within 72 hours (early mobilization group, EM) or later (non-early mobilization group, non-EM). During mobilization, prefrontal rSO₂ values were monitored. Regarding patient background, significant differences were noted between the groups, including delayed release in non-EM patients. rSO₂ values varied significantly, with the lowest values in the first half of end-sitting in both groups (non-EM 56.5 ± 4.8%, EM 58.6 ± 4.3%, p < 0.05). The rSO₂ value was also lower in the non-EM group than in the EM group (P < 0.014). A weak correlation was observed between rSO₂ and the number of days to first mobilization (r = -0.251, p = 0.025). The rSO₂ value may serve as a potential marker to guide the timing of mobilization in ICU patients.

A theoretical framework is presented to clarify the role of architectural and structural forces in ion selectivity. It expresses the relative free energy of bound ions in terms of a reduced subsystem corresponding to the local degrees of freedom coupled to the rest of the protein. The latter is separated into a first contribution that includes all the forces keeping the ion and the coordinating ligands confined to a microscopic sub-volume but do not prevent the ligands from adapting to a smaller ion, while the second contribution regroups the remaining forces that serve to dictate the precise geometry of the coordinating ligands best adapted to a given ion. The theoretical framework makes it possible to delineate two important limiting cases. In the limit where the geometric forces are dominant (rigid binding site), selectivity is controlled via the cavity size according to the familiar "snug-fit" mechanism of host-guest chemistry. In the limit where the geometric forces are negligible, the ion and ligands behave as a dynamical "confined droplet" that is free and adapt to the ion's size. In this case, selectivity is controlled by the number and the chemical type of ion-coordinating ligands.

Free energy calculations play a vital role in understanding protein behaviour at the molecular level. From protein folding and stability to ligand binding and enzyme catalysis, these calculations provide quantitative insights that are indispensable for both basic research and practical applications in fields such as drug discovery, protein engineering, and biotechnology. Due to the complex energy landscapes of proteins, traditional molecular dynamics simulations often fail to explore rare events or overcome high-energy barriers effectively. Enhanced sampling techniques, such as metadynamics, umbrella sampling, or replica exchange molecular dynamics, were developed to address these challenges, allowing for more efficient exploration of conformational space and improved accuracy in free energy predictions. These methods accelerate the sampling of relevant states and transitions, making it feasible to capture rare but biologically significant events. Recently, machine learning has also begun playing a crucial role in enhancing sampling efficiency, reducing the need for extensive computational resources. As computational power continues to increase and machine learning techniques are integrated with enhanced sampling algorithms, the scope and accuracy of free energy calculations will significantly improve, opening new avenues for more precise understanding and prediction of molecular interactions and biological processes.

This chapter explores the pivotal roles of planar lipid bilayers and liposomes in advancing our understanding of protein function. These artificial membrane systems serve as essential models that mimic natural cellular environments, providing a versatile platform for studying protein-lipid interactions. We delve into methods for assembling planar lipid bilayers and liposomes, examining their composition and diversity, and the techniques employed to integrate membrane proteins for functional analysis. We consider the influence of osmotic dynamics on membrane behavior and protein interactions through pressure gradients and review studies of signal transduction in artificial membrane systems aimed at elucidating how proteins interact with lipids to mediate cellular communication. We also discuss the contributions of these systems to structural studies, involving techniques like cryo-electron microscopy and X-ray crystallography, to reveal high-resolution insights into membrane protein conformations. Discussing challenges and limitations, we review the biological relevance and technical constraints that shape experimental outcomes. Looking forward, we consider innovations in lipid bilayer model systems and new research directions that promise to expand their utility. This chapter underscores the continued importance of these systems as indispensable tools in unraveling the complexities of protein function within biological membranes.

Introduction: Addiction professionals are affected by the traumas experienced by the individuals and the families they care for.

Aim: The aim of this study is the synthesis of research on the impact of Secondary Traumatic Stress (STS) on healthcare professionals working in the field of addiction.

Methodology: A mixed research synthesis of studies published in English from January 1, 2010, through June 10, 2024. The research was conducted using electronic databases, with keywords related to secondary trauma in the field of addiction. Out of 44 initially identified studies, 9 were selected that met the inclusion criteria.

Results: The results indicated that healthcare professionals working in the field of addiction experience considerable levels of STS. Three themes were derived from the synthesis of qualitative research studies: (a). "Opening the Pandora's Box," (b). "Defensive practice versus connecting and maintaining boundaries," and (c). "New paths in personal and professional development." Professionals in the landscape of addiction trauma and loss experience significant negative transformations in their experiences with themselves, others, and the world, affecting their emotions, thoughts, beliefs, value systems, and worldviews. Notwithstanding, witnessing clients remarkable resilience despite the traumas they endure and crediting clients for shaping their professional practice creates a meaningful space of shared personal growth. Support from colleagues, supervision, and continuous education were identified as critical factors in reducing negative consequences and promoting the professional and personal well-being of drug and alcohol workers.

Conclusion: Trauma can be frightening and unbearable for professionals to look at, but being there has a validating quality for the traumatized and creates feelings of safety, hope, and growth for both traumatized individuals and professionals. Maintaining clear boundaries between professional and client serves as a template for the latter's future relationships and is critical for preventing secondary trauma and promoting secondary post-traumatic growth. Overall, addressing secondary trauma requires a holistic approach involving trauma-informed education, self-care, and organizational support.