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Abstract Background Postoperative cognitive dysfunction (POCD) is one of the major complications after surgery, with devastating clinical outcomes. Although POCD is a condition with a multifactorial pathophysiology, blood-brain barrier (BBB) dysfunction and neuronal injury have been shown to play a critical role, especially in the elderly. Previous studies have demonstrated that the choice of anesthetics affect BBB permeability and neuroinflammation. However, most studies are carried out on animals, with limited research undertaken on humans. Therefore, we will compare the effect of intravenous anesthetics and inhaled anesthetics on BBB dysfunction and the change of inflammatory markers after surgery. Methods One hundred and fifty-four patients who are 60 years of age or older undergoing major surgery for more than 2 h will be randomly allocated to two anesthetics groups (intravenous, inhaled) in a 1:1 ratio. In the intravenous anesthetics group (group P), propofol will be infused with a target-controlled infusion (TCI) system throughout the entire surgery. In the inhaled anesthetics group (group G), bolus injection of propofol will be administered for loss of consciousness, and simultaneously sevoflurane will be initiated for the maintenance of anesthesia. The primary outcome is the change in serum S100 calcium binding protein β (S100β) at four time points: before induction of anesthesia, at the end of surgery, 4 h after surgery, postoperative day 1. Secondary outcomes include changes in the inflammatory markers, serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and C-reactive protein; the incidence of delirium; and the change in the cognitive function between groups. In patients pre-scheduled for postoperative intensive care unit admission, the cerebrospinal fluid/serum albumin quotient (Qalb) between the two groups will be compared before and after surgery, and change in inflammatory markers in serum and CSF will be analyzed in relation to the Qalb. Discussion The current study will compare the effect of intravenous versus inhaled anesthetics on blood-brain barrier permeability and, as a result, the difference in neuroinflammation in elderly patients. Also, the study results will provide additional information to develop intraoperative anesthetic strategies to reduce POCD. Trial registration The trial was prospectively registered at Clinical Trials protocol registration with identifier 2310-117-126 on April 9, 2024.

Arteriovenous malformations (AVMs) are characterized by direct connections between arteries and veins without intervening capillaries, with the concomitant formation of abnormal vascular networks associated with angiogenesis. However, the current understanding of the diagnosis and treatment of AVMs is limited, and no in vitro disease models exist at present for studying this condition. In this study, we produced endothelial cells (ECs) in two-dimensional cultures and three-dimensional (3D) blood vessel organoids (BVOs), comparing gene expression profiles between normal and AVM organoids. The normal and AVM organoids were examined via immunofluorescence staining using CD31 and phalloidin. The AVM organoids showed significantly higher expression levels of CD31 and phalloidin than the normal organoids. Genes such as FSTL1, associated with angiogenesis, showed significantly higher expression in the AVM organoids than in the normal organoids. In contrast, the MARCKS gene exhibited no significant difference in expression between the two types of organoids. The capillaries and related CSPG4 genes exhibited the lowest expression in the 3D AVM organoids. Furthermore, hsa-mir-135b-5p, a small RNA related to AVMs, showed elevated expression in AVM tissues and significantly higher levels in 3D AVM organoids. In our study, we were able to successfully establish AVM organoids (hBVOs) containing ECs and mural cells through advancements in stem cell and tissue engineering. These organoids serve as valuable models for investigating disease mechanisms, drug development, and screening potential therapeutic interventions in drug discovery. These findings contribute essential insights for the development of treatment strategies targeting AVMs.

Abstract Background Dexmedetomidine, one of the sedatives, has an analgesic effect. We aimed to investigate postoperative analgesia with dexmedetomidine as adjuvants for procedural sedation using perfusion index (PI). Methods In this prospective, randomized, case-control, observational study, 72 adult patients, 19–70 years, who were scheduled for chemoport insertion under monitored anesthesia care were performed. According to the group assignment, remifentanil or dexmedetomidine was simultaneously infused with propofol. The primary outcome was PI 30 min after admission to the post anesthesia care unit (PACU). And, pain severity using numerical rating scale (NRS) score and the relationship between NRS score and PI were investigated. Results During PACU staying, PI values were significantly different between the two groups PI values at 30 min after admission to the PACU were 1.3 (0.9–2.0) in the remifentanil group and 4.5 (2.9–6.8) in the dexmedetomidine group (median difference, 3; 95% CI, 2.1 to 4.2; P

Abstract Despite various intraoperative thermal strategies, core heat loss is considerable during liver transplantation and hypothermia is common. We tested whether forced-air prewarming prevents hypothermia during liver transplantation. Adult patients undergoing living donor liver transplantation were randomly assigned to non-prewarming group (n = 20) or prewarming group (n = 20). Patients in prewarming group underwent 30-min forced-air warming before anesthetic induction. During surgery, core temperature was measured in the pulmonary artery. The primary outcome was intraoperative hypothermia (

Abstract Endotracheal tube (ET) misplacement is common in pediatric patients, which can lead to the serious complication. It would be helpful if there is an easy-to-use tool to predict the optimal ET depth considering in each patient’s characteristics. Therefore, we plan to develop a novel machine learning (ML) model to predict the appropriate ET depth in pediatric patients. This study retrospectively collected data from 1436 pediatric patients aged

Abstract Risk factors for postoperative pulmonary complication (PPC) have not been determined according to preoperative respiratory spirometry. Thus, we aimed to find contributors for PPC in patients with restrictive or normal spirometric pattern. We analyzed 654 patients (379 with normal and 275 with restrictive spirometric pattern). PPCs comprised respiratory failure, pleural effusion, atelectasis, respiratory infection, and bronchospasm. We analyzed the association between perioperative factors and PPC using binary logistic regression. In particular, we conducted subgroup analysis on the patients stratified according to preoperative spirometry. Of 654 patients, 27/379 patients (7.1%) with normal spirometric pattern and 33/275 patients (12.0%) with restrictive spirometric pattern developed PPCs. Multivariable analysis demonstrated that high driving pressure was the only intraoperative modifiable factor increasing PPC risk (OR = 1.13 [1.02–1.25], p = 0.025). In the subgroup of patients with restrictive spirometric pattern, intraoperative driving pressure was significantly associated with PPC (OR = 1.21 [1.05–1.39], p = 0.009), whereas driving pressure was not associated with PPC in patients with normal spirometric pattern (OR = 1.04 [0.89–1.21], p = 0.639). In patients with restrictive spirometric pattern, greater intraoperative driving pressure is significantly associated with increased PPC risk. In contrast, intraoperative driving pressure is not associated with PPC in patients with normal spirometric pattern.

Abstract We evaluated the physiological benefits of performing lung recruitment maneuver (LRM) in the semi-lateral position compared in the supine position. Seventy-nine patients undergoing laparoscopic prostatectomy were randomly assigned to either the supine or semi-lateral group according to body position during the LRM. At the end of surgery, LRM (35 cmH2O for 20 s) was performed twice in the assigned posture. The primary outcome was the maximal decrease in systolic arterial pressure during LRM. Secondary outcomes were changes in PaO2/FiO2 and the regional lung volume distribution after LRM. The decrease in systolic arterial pressure during the LRM was significantly higher in the supine group than in the semi-lateral group (mean ± standard deviation, [−] 27.6 ± 14.6% vs. [−] 18.6 ± 9.9%, P = 0.001). Improvement in PaO2/FiO2 ratio after the LRM was evident in both groups but was more prominent in the semi-lateral group than in the supine group (median [interquartile range], 39.3% [20.2, 63.6] vs. 18.2% [8.4, 29.2], P = 0.001). Among the horizontal lung divisions, regional lung volume in the most dependent portion (the dorsal division) was significantly increased after the LRM only in the semi-lateral group (P = 0.024). Performing lung recruitment in a semi-lateral position protected against hemodynamic deterioration during the LRM and increased regional lung ventilation in the dependent portion of the lung, leading to an improvement in arterial oxygenation after laparoscopic procedures. Trial registration Clinical Research Information Service ( https://cris.nih.go.kr/ ). Identifier: KCT0003756.

Background In addition to vascular endothelial cells, vascular smooth muscle cells (VSMCs) are subject to continuous shear stress because of blood circulation. The angiogenic properties of VSMCs in extracranial arteriovenous malformations (AVMs) may exceed those of normal blood vessels if the body responds more sensitively to mechanical stimuli. This study was performed to investigate the hypothesis that rapid angiogenesis may be achieved by mechanical shear stress. Methods VSMCs were obtained from six patients who had AVMs and six normal controls. The target genes were set to angiopoietin-2 (AGP2), aquaporin-1 (AQP1), and transforming growth factor-beta receptor 1 (TGFBR1). Reverse-transcriptase polymerase chain reaction (RT-PCR) and real-time PCR were implemented to identify the expression levels for target genes. Immunofluorescence was also conducted. Results Under the shear stress condition, mean relative quantity values of AGP2, AQP1, and TGFBR1 in AVM tissues were 1.927±0.528, 1.291±0.031, and 2.284±1.461 when compared with neutral conditions. The expression levels of all three genes in AVMs were higher than those in normal tissue except for AQP1 under shear stress conditions. Immunofluorescence also revealed increased staining of shear stress-induced genes in the normal tissue and in AVM tissue. Conclusions Shear stress made the VSMCs of AVMs more sensitive. Although the pathogenesis of AVMs remains unclear, our study showed that biomechanical stimulation imposed by shear stress may aggravate angiogenesis in AVMs.

Abstract Background Vascular endothelial cells (ECs) are subject to continuous shear stress due to blood circulation. Mechanical stress due to high shear flow can also cause arteriovenous malformation (AVM) when ECs respond hyper-sensitively to shear flow. This study was conducted to test the hypothesis that angiogenesis could be promoted in response to mechanical stress via regulation of pro-angiogenic factors in AVM cells. Methods ECs were extracted from the tissue samples from six AVM patients and six normal patients. Shear stress at 7 dynes/cm2 were applied for 24 h. Before and after application of shear stress to each group, RT-PCR was performed to access the expression levels of angiopoietin2(AGP2), aquaporin1(AQP1) and TGFβR1. Immunofluorescences was also performed to evaluate the level of protein expressions. Results In both normal and AVM tissues, AGP2 and TGFβR1 under the shear stress showed increased expression in the ECs compared to the non-sheared samples. When AVMs and normal arterial vasculature were compared, the expression levels of both AGP2 and TGFβR1 in AVMs were higher when compared to normal arterial vasculature with or without shear stress. Immunofluorescence-based protein analysis also confirmed shear-induced AGP2 and TGFβR1 in both samples of normal and AVM patients. Conclusions AVMs exhibited higher sensitivity to shear stress by producing higher expressions of some marked genes and proteins that regulate the endothelial functions upon exposure to shear stress. While the physiological mechanism for AVMs remain elusive, our study shows the plausibility of physical stress imposed by the shearing flow can cause the occurrence of AVMs.

BackgroundArterial cannulation in elderly patients is difficult because of age-related morphological changes. Applying dynamic needle tip positioning (DNTP) that guides the catheter to position inside the vessel sufficiently may aid in successful cannulation.MethodsThis prospective study enrolled patients aged over 70 years, who were scheduled for elective surgery under general anaesthesia with arterial cannulation. The patients were randomly assigned to the DNTP (group D, n = 76) or the conventional short-axis view(group C, n = 75) group. The arterial depth, diameter, and arterial conditions(calcification, segmental stenosis, and tortuosity) were evaluated using ultrasound, before puncture. We recorded the first attempt success, cannulation time, the number of attempts, and cannulation-related complications.ResultsA total of 151 patients were enrolled in this study. The first attempt success rate in group D was significantly higher than that in group C (89% versus 72%; P = 0.0168). The median cannulation time per last attempt in group D versus group C was 25 versus 30 sec(P = 0.0001), and the overall cannulation time was 25 versus 35 sec(P = 0.0001), respectively. Arterial cannulation per last attempt and overall cannulation time were shorter in group D. The number of attempts was higher in group C (P = 0.0038). The occurrence rate of hematoma was significantly lower in group D (16% versus 47%, relative risk = 3.0, P = 0.0001).ConclusionsThe DNTP method may improve the first attempt success rate of arterial cannulation and reduce complications in elderly patients over 70 years of age.

Chalcones are a class of privileged scaffolds with high medicinal significance due to the presence of an α,β-unsaturated ketone functionality. Numerous functional modifications of chalcones have been reported, along with their pharmacological behavior. The present review aims to summarize the structures from natural sources, synthesis methods, biological characteristics against infectious and non-infectious diseases, and uses of chalcones over the past decade, and their structure–activity relationship studies are detailed in depth. This critical review provides guidelines for the future design and synthesis of various chalcones. In addition, this could be highly supportive for medicinal chemists to develop more promising candidates for various infectious and non-infectious diseases.

PURPOSE: To determine whether maternal attitude toward sex during pregnancy and health-related quality of life could influence sexual function of pregnant women. METHODS: In this study, 138 second and third trimester pregnant women completed self-report questionnaires during their visits to women's hospitals or community health centers to assess their general characteristics, attitude toward sex during pregnancy (PIES-M), health-related quality of life (EQ-5D), and sexual function (FSFI-6K). Multiple regression analysis was performed to test the research model with SPSS version 23. RESULTS: Pregnant women who had discontinued their sexual life after recognizing their pregnancy accounted for 27.5% of women questioned. The average sexual function score of pregnant women was higher in the second trimester than the third trimester. Attitude toward sex during pregnancy (β=−.38, p< .001), maintaining sexual life (β=.20, p=.028), health-related quality of life (β=.18, p=.030), and adverse symptoms during sex (β=.18, p=.042) were determinants of sexual function during pregnancy. CONCLUSION: Nurses in antenatal care units need to help pregnant women maintain a positive attitude toward sexual activity during pregnancy and manage their health-related quality of life to maintain their sexual life during pregnancy.

A complete redevelopment of the skin remains a challenge in the management of acute and chronic wounds. Recently, the application of extracellular vesicles (EVs) for soft tissue wound healing has received much attention. As fibroblasts are fundamental cells for soft tissues and skin, we investigate the proangiogenic factors in human normal fibroblast-derived EVs (hNF-EVs) and their effects on wound healing. Normal fibroblasts were isolated from human skin tissues and characterized by immunofluorescence (IF) and Western blotting (WB). hNF-EVs were isolated by ultracentrifugation and characterized using transmission electron microscopy and WB. The proangiogenic cargos in hNF-EVs were identified by a TaqMan assay and a protein array. Other in vitro assays, including internalization assays, cell counting kit-8 analysis, scratch wound assays, WBs, and tube formation assays were conducted to assess the effects of hNF-EVs on fibroblasts and endothelial cells. A novel scaffold-free noninvasive delivery of hNF-EVs with or without fibrin glue was applied onto full-thickness skin wounds in mice. The wound healing therapeutical effect of hNF-EVs was assessed by calculating the rate of wound closure and through histological analysis. Isolated hNF was confirmed by verifying the expression of the fibroblast markers vimentin, αSMA, Hsp70, and S100A4. Isolated hNF-EVs showed intact EVs with round morphology, enriched in CD81 and CD63, and devoid of the cell markers GM130, Calnexin, and Cytochrome C. Our TaqMan assay showed that hNF-EVs were enriched in miR130a and miR210, and protein arrays showed enriched levels of the proangiogenic proteins’ vascular endothelial growth factor (VEGF)-D and CXCL8. Next, we found that the internalization of hNF-EVs into hNF increased the proliferation and migration of hNF, in addition to increasing the expression of bFGF, MMP2, and αSMA. The internalization of hNF-EVs into the endothelial cells increased their proliferation and tube formation. A scaffold-free noninvasive delivery of hNF-EVs with or without fibrin glue accelerated the wound healing rate in full-thickness skin wounds in mice, and the treatments increased the cellular density, deposition, and maturation of collagens in the wounds. Moreover, the scaffold-free noninvasive delivery of hNF-EVs with or without fibrin glue increased the VEGF and CD31 expression in the wounds, indicating that hNF-EVs have an angiogenic ability to achieve complete skin regeneration. These findings open up for new treatment strategies to be developed for wound healing. Further, we offer a new approach to the efficient, scaffold-free noninvasive delivery of hNF-EVs to wounds.

BackgroundWe evaluated whether a simulation-based training with a vessel phantom improves the basic skills of a novice required for ultrasound-guided radial artery cannulation in real patients. In addition, we analysed whether repeated simulation training sets with an inter-training interval would accelerate the learning curve.MethodsFrom March 2019 to July 2019, twenty-one anesthesiology residents were randomized into either a simulation group (n = 11) or control group (n = 10). Residents performed a total of 84 ultrasound-guided radial artery cannulations in real patients. The simulation group participated in two sets of simulation training on a vessel phantom (10 sessions per set) with a one-month inter-training interval. Trainee's performance proficiency was scored using a developed checklist, and a learning curve for each training set was constructed. To evaluate the effectiveness of our training curriculum in skill transfer, each resident performed four ultrasound-guided radial artery cannulations in real patients. The primary outcome was first attempt success rate and the secondary outcome was dynamic needle-tip positioning ability in real patients.ResultsThe first attempt success rate and dynamic needle-tip positioning ability by ultrasound transducer were significantly higher in the simulation group than the control group (81.8% vs. 50%, P = 0.002 and 68.2% vs. 7.5%, P < 0.001, respectively). A reduced number of sessions was required to reach a plateau score on the learning curve in the repeated training set compared in the first-set (7 (5-8) vs. 3 (2-4), P = 0.003, respectively).ConclusionsSimulation-based training using a vessel phantom effectively improved the first attempt success rate for ultrasound-guided radial artery cannulation in real patients and the dynamic needle-tip positioning ability by ultrasound transducer in novice anesthesiology residents. In addition, repeated training curriculum accelerated the learning curve for recall skill proficiency and reduced inter-individual variability for skill acquisition.Clinical trial registrationClinical Research Information Service (KCT0003471, Principle investigator: Jeong Jin Min, Date of registration: 06/March/2019).

Tissue engineering and regenerative medicine (TERM) have paved a way for treating musculoskeletal diseases in a minimally invasive manner. The regenerative medicine cocktail involves the usage of mesenchymal stem/stromal cells (MSCs), either uncultured or culture-expanded cells along with growth factors, cytokines, exosomes, and secretomes to provide a better regenerative milieu in degenerative diseases. The successful regeneration of cartilage depends on the selection of the appropriate source of MSCs, the quality, quantity, and frequency of MSCs to be injected, and the selection of the patient at an appropriate stage of the disease. However, confirmation on the most favorable source of MSCs remains uncertain to clinicians. The lack of knowledge in the current cellular treatment is uncertain in terms of how beneficial MSCs are in the long-term or short-term (resolution of pain) and improved quality of life. Whether MSCs treatments have any superiority, exists due to sources of MSCs utilized in their potential to objectively regenerate the cartilage at the target area. Many questions on source and condition remain unanswered. Hence, in this review, we discuss the lineage differentiation potentials of various sources of MSCs used in the management of knee osteoarthritis and emphasize the role of tissue engineering in cartilage regeneration.

Angiogenesis is defined as the generation of new blood vessels or the sprouting of endothelial cells from a pre-existing vascular network. Angiogenesis occurs during the growth and development of an organism, the response of organs or tissues to injury, and during cancer development and progression. The majority of studies on stem-cell-derived extracellular vesicles (EVs) have used cell lines, and have primarily focused on well-known solitary proteins. Here, we isolated stem cells from human adipose tissue (ADSCs), and we isolated EVs from them (ADSC-EVs). The ADSC-EVs were characterised and 20 angiogenic proteins were analysed using an angiogenic antibody array. Furthermore, we analysed the ability of ADSC-EVs to induce angiogenesis in vitro and in vivo. ADSC-EVs were positive for CD81 and negative for GM130, calnexin, and cytochrome-C. ADSC-EVs showed typical EV spherical morphology and were ~200 nm in size. ADSC-EVs were found to contain angiogenic proteins as cargo, among which interleukin 8 (IL-8) was the most abundant, followed by chemokine (C-C motif) ligand 2 (CCL2), a tissue inhibitor of metalloproteinases 1 (TIMP-1), TIMP-2, and vascular endothelial growth factor-D (VEGF-D). ADSC-EVs treatment increased the proliferation, migration, total vessel length, total number of junctions, and junction density of endothelial cells in vitro. The results of an in vivo Matrigel plug assay revealed that ADSC-EVs induced more blood vessels in the Matrigel compared with the control. These results demonstrate that ADSC-EVs contain angiogenic proteins as cargo and promote angiogenesis in vitro and in vivo. Therefore, ADSC-EVs have potential for therapeutic use in ischaemia.

A new approach for using extracellular vesicles (EVs) to deliver tyrosine kinase inhibitors (TKIs) to enhance iodine avidity in radioactive iodine-refractory thyroid cancer is needed. We isolated and characterized primary human adipose-derived stem cells (ADSCs) and isolated their EVs. The EVs were characterized by transmission electron microscopy, nanoparticle tracking analysis, and western blotting. A new TKI was loaded into the EVs by incubation (37 °C; 10 min) or sonication (18 cycles; 4 s per cycle) with 2 s intervals and a 2 min ice bath every six cycles. TKI loading was confirmed and measured by mass spectrometry. EV uptake into radioactive iodine-refractory thyroid cancer cells (SW1736 cells) was confirmed by microscopy. We treated the SW1736 cells with vehicle, TKI, or TKI-loaded EVs (sonication TKI-loaded EVs [EVsTKI(S)]) and examined the expression of iodide-metabolizing proteins and radioiodine uptake in the SW1736 cells. ADSCs cells showed >99% of typical stem cell markers, such as CD90 and CD105. The EVs displayed a round morphology, had an average size of 211.4 ± 3.83 nm, and were positive for CD81 and Alix and negative for cytochrome c. The mass spectrometry results indicate that the sonication method loaded ~4 times more of the TKI than did the incubation method. The EVsTKI(S) were used for further experiments. Higher expression levels of iodide-metabolizing mRNA and proteins in the EVsTKI(S)-treated SW1736 cells than in TKI-treated SW1736 cells were confirmed. EVsTKI(S) treatment enhanced 125I uptake in the recipient SW1736 cells compared with free-TKI treatment. This is the first study that demonstrated successful delivery of a TKI to radioactive iodine-refractory thyroid cancer cells using EVs as the delivery vehicle. This approach can revert radioiodine-resistant thyroid cancer cells back to radioiodine-sensitive thyroid cancer cells.

Background and Objectives: The guidelines for cochlear implantation (CIs) are expanding, and the number of CI procedures performed on the elderly is increasing. The purpose of this study was to analyze the results and safety of cochlear implantation in the elderly, as well as to evaluate the predictive factors on CI outcomes. Subjects and Methods: The study included 56 patients aged ≥40 years, who received CIs between 2009 and 2020. They were divided into two groups: 27 younger adults (40-64 years) and 29 elderly (>64 years). The study compared their pre- and postoperative speech perception and category of auditory performance (CAP) scores, surgical complications, and hospitalization periods. It also evaluated associated factors in the elderly group by examining categorical and continuous variables and postoperative CAP score. Results: There was a significant improvement in speech recognition tests (both word and sentence) and CAP scores in both groups compared to the pre-implantation scores (p<0.001). Postoperative results were slightly lower in the elderly group than in younger adults for sentence recognition and CAP scores, except for word recognition. No significant associated factors were found on postoperative CAP scores, except for etiology. Postoperative CAP significantly improved in the sudden hearing loss group compared to the groups with other etiologies (p=0.045). The elderly group had more comorbidities than that in the younger adult group (p=0.026), but there were no significant differences in postoperative complications and hospitalization periods. Conclusions: While speech recognition and CAP scores were relatively lower in the elderly group compared to the younger adults, the elderly group showed significant improvements in audiological results after CI. Moreover, CI was safe and well tolerated in elderly patients. [ABSTRACT FROM AUTHOR]