Melatonin alleviates myocardial dysfunction through inhibition of endothelial-to-mesenchymal transition via the NF-κB pathway.

Endothelial-to-mesenchymal transition (EndMT) is a complex biological process of cellular transdifferentiation by which endothelial cells (ECs) lose their characteristics and acquire mesenchymal properties, leading to cardiovascular remodeling and complications in the adult cardiovascular diseases environment. Melatonin is involved in numerous physiological and pathological processes, including aging, and has anti-inflammatory and antioxidant activities. This molecule is an effective therapeutic candidate for preventing oxidative stress, regulating endothelial function, and maintaining the EndMT balance to provide cardiovascular protection. Although recent studies have documented improved cardiac function by melatonin, the mechanism of action of melatonin on EndMT remains unclear. The present study investigated the effects of melatonin on induced EndMT by transforming growth factor-ß2/interleukin-1ß in both in vivo and in vitro models. The results revealed that melatonin reduced the migratory ability and reactive oxygen species levels of the cells and ameliorated mitochondrial dysfunction in vitro. Our findings indicate that melatonin prevents endothelial dysfunction and inhibits EndMT by activating related pathways, including nuclear factor kappa B and Smad. We also demonstrated that this molecule plays a crucial role in restoring cardiac function by regulating the EndMT process in the ischemic myocardial condition, both in vessel organoids and myocardial infarction (MI) animal models. In conclusion, melatonin is a promising agent that attenuates EC dysfunction and ameliorates cardiac damage compromising the EndMT process after MI.

A 70% Ethanol Neorhodomela munita Extract Attenuates RANKL-Induced Osteoclast Activation and H2O2-Induced Osteoblast Apoptosis In Vitro.

The rapid aging of the population worldwide presents a significant social and economic challenge, particularly due to osteoporotic fractures, primarily resulting from an imbalance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation. While conventional therapies offer benefits, they also present limitations and a range of adverse effects. This study explores the protective impact of Neorhodomela munita ethanol extract (EN) on osteoporosis by modulating critical pathways in osteoclastogenesis and apoptosis. Raw264.7 cells and Saos-2 cells were used for in vitro osteoclast and osteoblast models, respectively. By utilizing various in vitro methods to detect osteoclast differentiation/activation and osteoblast death, it was demonstrated that the EN's potential to inhibit RANKL induced osteoclast formation and activation by targeting the MAPKs-NFATc1/c-Fos pathway and reducing H2O2-induced cell death through the downregulation of apoptotic signals. This study highlights the potential benefits of EN for osteoporosis and suggests that EN is a promising natural alternative to traditional treatments.

Enhanced Osteocyte Differentiation: Cathepsin D and L Secretion by Human Adipose-Derived Mesenchymal Stem Cells.

Adipose-derived mesenchymal stem cells (ASCs) have the potential to differentiate into bone, cartilage, fat, and neural cells and promote tissue regeneration and healing. It is known that they can have variable responses to hypoxic conditions. In the present study, we aimed to explore diverse changes in the cells and secretome of ASCs under a hypoxic environment over time and to present the possibility of ASCs as therapeutic agents from a different perspective. The expression differences of proteins between normoxic and hypoxic conditions (6, 12, or 24 h) were specifically investigated in human ASCs using 2-DE combined with MALDI-TOF MS analysis, and secreted proteins in ASC-derived conditioned media (ASC-derived CM) were examined by an adipokine array. In addition, genetic and/or proteomic interactions were assessed using a DAVID and miRNet functional annotation bioinformatics analysis. We found that 64 and 5 proteins were differentially expressed in hypoxic ASCs and in hypoxic ASC-derived CM, respectively. Moreover, 7 proteins among the 64 markedly changed spots in hypoxic ASCs were associated with bone-related diseases. We found that two proteins, cathepsin D (CTSD) and cathepsin L (CTSL), identified through an adipokine array independently exhibited significant efficacy in promoting osteocyte differentiation in bone-marrow-derived mesenchymal stem cells (BM-MSCs). This finding introduces a promising avenue for utilizing hypoxia-preconditioned ASC-derived CM as a potential therapeutic approach for bone-related diseases.

Epigallocatechin-3-Gallate Attenuates Myocardial Dysfunction via Inhibition of Endothelial-to-Mesenchymal Transition.

Cardiac tissue damage following ischemia leads to cardiomyocyte apoptosis and myocardial fibrosis. Epigallocatechin-3-gallate (EGCG), an active polyphenol flavonoid or catechin, exerts bioactivity in tissues with various diseases and protects ischemic myocardium; however, its association with the endothelial-to-mesenchymal transition (EndMT) is unknown. Human umbilical vein endothelial cells (HUVECs) pretreated with transforming growth factor ß2 (TGF-ß2) and interleukin 1ß (IL-1ß) were treated with EGCG to verify cellular function. In addition, EGCG is involved in RhoA GTPase transmission, resulting in reduced cell mobility, oxidative stress, and inflammation-related factors. A mouse myocardial infarction (MI) model was used to confirm the association between EGCG and EndMT in vivo. In the EGCG-treated group, ischemic tissue was regenerated by regulating proteins involved in the EndMT process, and cardioprotection was induced by positively regulating apoptosis and fibrosis of cardiomyocytes. Furthermore, EGCG can reactivate myocardial function due to EndMT inhibition. In summary, our findings confirm that EGCG is an impact activator controlling the cardiac EndMT process derived from ischemic conditions and suggest that supplementation with EGCG may be beneficial in the prevention of cardiovascular disease.

AMPK reduces macrophage endotoxin tolerance through inhibition of TGF-ß1 production and its signaling pathway.

Adenosine monophosphate-activated protein kinase (AMPK) is involved in suppression of the development of endotoxin tolerance, which is a driver of the immunosuppression induced by sepsis. However, the mechanism by which AMPK inhibits the development of endotoxin tolerance has not been clearly elucidated. Therefore, the present study was performed to investigate the mechanism by which the AMPK activator, metformin, inhibits the development of endotoxin tolerance. Lipopolysaccharide (LPS) increased the production of transforming growth factor (TGF)-ß1 in macrophages, which was inhibited by metformin and resveratrol. Knockdown of AMPKα1 inhibited the suppressive effect of metformin on LPS-induced TGF-ß1 production. TGF-ß neutralizing antibody and TGF-ß type I receptor inhibitor increased the production of TNF-α and IL-6 via LPS restimulation in tolerized macrophages. LPS increased Smad2 phosphorylation, but this was inhibited in cells treated with TGF-ß neutralizing antibody or metformin. Smad2 knockdown inhibited the development of endotoxin tolerance, as evidenced by increased TNF-α production in response to LPS restimulation in tolerized macrophages. TGF-ß1 expression was increased, and the levels of TNF-α and IL-6 production induced by LPS stimulation were decreased, in splenocytes of cecal ligation and puncture (CLP) model mice compared to sham-operated controls. However, metformin treatment suppressed the production of TGF-ß1, and enhanced the production of TNF-α and IL-6 induced by LPS stimulation in splenocytes of CLP mice. These results indicated that AMPK activation inhibits LPS-induced TGF-ß1 production and its signaling pathway, thus suppressing the development of endotoxin tolerance in macrophages.

A Low Concentration of Citreoviridin Prevents Both Intracellular Calcium Deposition in Vascular Smooth Muscle Cell and Osteoclast Activation In Vitro.

Vascular calcification (VC) and osteoporosis are age-related diseases and significant risk factors for the mortality of elderly. VC and osteoporosis may share common risk factors such as renin-angiotensin system (RAS)-related hypertension. In fact, inhibitors of RAS pathway, such as angiotensin type 1 receptor blockers (ARBs), improved both vascular calcification and hip fracture in elderly. However, a sex-dependent discrepancy in the responsiveness to ARB treatment in hip fracture was observed, possibly due to the estrogen deficiency in older women, suggesting that blocking the angiotensin signaling pathway may not be effective to suppress bone resorption, especially if an individual has underlying osteoclast activating conditions such as estrogen deficiency. Therefore, it has its own significance to find alternative modality for inhibiting both vascular calcification and osteoporosis by directly targeting osteoclast activation to circumvent the shortcoming of ARBs in preventing bone resorption in estrogen deficient individuals. In the present study, a natural compound library was screened to find chemical agents that are effective in preventing both calcium deposition in vascular smooth muscle cells (vSMCs) and activation of osteoclast using experimental methods such as Alizarin red staining and Tartrate-resistant acid phosphatase staining. According to our data, citreoviridin (CIT) has both an anti-VC effect and anti-osteoclastic effect in vSMCs and in Raw 264.7 cells, respectively, suggesting its potential as an effective therapeutic agent for both VC and osteoporosis.

Regulation of Inflammation-Mediated Endothelial to Mesenchymal Transition with Echinochrome a for Improving Myocardial Dysfunction.

Endothelial-mesenchymal transition (EndMT) is a process by which endothelial cells (ECs) transition into mesenchymal cells (e.g., myofibroblasts and smooth muscle cells) and induce fibrosis of cells/tissues, due to ischemic conditions in the heart. Previously, we reported that echinochrome A (EchA) derived from sea urchin shells can modulate cardiovascular disease by promoting anti-inflammatory and antioxidant activity; however, the mechanism underlying these effects was unclear. We investigated the role of EchA in the EndMT process by treating human umbilical vein ECs (HUVECs) with TGF-ß2 and IL-1ß, and confirmed the regulation of cell migration, inflammatory, oxidative responses and mitochondrial dysfunction. Moreover, we developed an EndMT-induced myocardial infarction (MI) model to investigate the effect of EchA in vivo. After EchA was administered once a day for a total of 3 days, the histological and functional improvement of the myocardium was investigated to confirm the control of the EndMT. We concluded that EchA negatively regulates early or inflammation-related EndMT and reduces the myofibroblast proportion and fibrosis area, meaning that it may be a potential therapy for cardiac regeneration or cardioprotection from scar formation and cardiac fibrosis due to tissue granulation. Our findings encourage the study of marine bioactive compounds for the discovery of new therapeutics for recovering ischemic cardiac injuries.

Different intraoperative decisions for undiagnosed paraganglioma: Two case reports.

BACKGROUND: Paragangliomas may be preoperatively misdiagnosed as non-functioning retroperitoneal tumors and are sometimes suspected only at the time of intraoperative manipulation. Without preoperative alpha blockade preparation, a hypertensive crisis during tumor manipulation and hypotension after tumor removal may result in critical consequences. Therefore, primary consideration should be given to the continuation or discontinuation of surgery on the basis of the possibility of gentle surgical manipulation and hemodynamic stabilization. We report two cases of paragangliomas detected intraoperatively. CASE SUMMARY: A 65-year-woman underwent laparoscopic small-bowel wedge resection. A hypertensive crisis occurred during manipulation of the mass, and an unrecognized catecholamine-producing paraganglioma was suspected. The surgeon and anesthesiologists believed that tumor excision could be performed with minimal manipulation of the tumor because the tumor was in a favorable location. Serious hemodynamic instability did not occur with aggressive use of vasoactive drugs. A week later, a 54-year-man underwent open resection of a 3-cm-sized retroperitoneal mass and showed the same findings during mass manipulation. For this patient, continuous manipulation of the mass seemed inevitable due to adhesion between the right adrenal gland and the mass in a narrow surgical field. The surgeon and anesthesiologists decided to cancel the surgical procedure and planned to perform a reoperation after alpha blockade therapy. Two weeks later, the tumor was uneventfully removed with small doses of vasoactive drugs. CONCLUSION: When an undiagnosed paraganglioma is suspected intraoperatively, reoperation after adequate preparation should be considered as an option to avoid fatal outcomes.

MicroRNA-26a/b-5p promotes myocardial infarction-induced cell death by downregulating cytochrome c oxidase 5a.

Myocardial infarction (MI) damage induces various types of cell death, and persistent ischemia causes cardiac contractile decline. An effective therapeutic strategy is needed to reduce myocardial cell death and induce cardiac recovery. Therefore, studies on molecular and genetic biomarkers of MI, such as microRNAs (miRs), have recently been increasing and attracting attention due to the ideal characteristics of miRs. The aim of the present study was to discover novel causative factors of MI using multiomics-based functional experiments. Through proteomic, MALDI-TOF-MS, RNA sequencing, and network analyses of myocardial infarcted rat hearts and in vitro functional analyses of myocardial cells, we found that cytochrome c oxidase subunit 5a (Cox5a) expression is noticeably decreased in myocardial infarcted rat hearts and myocardial cells under hypoxic conditions, regulates other identified proteins and is closely related to hypoxia-induced cell death. Moreover, using in silico and in vitro analyses, we found that miR-26a-5p and miR-26b-5p (miR-26a/b-5p) may directly modulate Cox5a, which regulates hypoxia-related cell death. The results of this study elucidate the direct molecular mechanisms linking miR-26a/b-5p and Cox5a in cell death induced by oxygen tension, which may contribute to the identification of new therapeutic targets to modulate cardiac function under physiological and pathological conditions.

Suppressing Pyroptosis Augments Post-Transplant Survival of Stem Cells and Cardiac Function Following Ischemic Injury.

The acute demise of stem cells following transplantation significantly compromises the efficacy of stem cell-based cell therapeutics for infarcted hearts. As the stem cells transplanted into the damaged heart are readily exposed to the hostile environment, it can be assumed that the acute death of the transplanted stem cells is also inflicted by the same environmental cues that caused massive death of the host cardiac cells. Pyroptosis, a highly inflammatory form of programmed cell death, has been added to the list of important cell death mechanisms in the damaged heart. However, unlike the well-established cell death mechanisms such as necrosis or apoptosis, the exact role and significance of pyroptosis in the acute death of transplanted stem cells have not been explored in depth. In the present study, we found that M1 macrophages mediate the pyroptosis in the ischemia/reperfusion (I/R) injured hearts and identified miRNA-762 as an important regulator of interleukin 1ß production and subsequent pyroptosis. Delivery of exogenous miRNA-762 prior to transplantation significantly increased the post-transplant survival of stem cells and also significantly ameliorated cardiac fibrosis and heart functions following I/R injury. Our data strongly suggest that suppressing pyroptosis can be an effective adjuvant strategy to enhance the efficacy of stem cell-based therapeutics for diseased hearts.

Resveratrol suppresses the reprogramming of macrophages into an endotoxin-tolerant state through the activation of AMP-activated protein kinase.

Resveratrol has been reported to have beneficial effects on sepsis by regulating the inflammatory response. However, it remains unclear if resveratrol plays a role in the development of endotoxin tolerance. Treatment with resveratrol in macrophages stimulated with primary lipopolysaccharide (LPS) resulted in the increased production of TNF-α and IL-6 induced by a 2nd dose of LPS (by 74.5 ± 12.9% and 63.4 ± 12%, respectively, compared to untreated cells, P < 0.05). This effect was inhibited by compound C, an AMPK inhibitor, and STO609, a calcium/calmodulin-dependent protein kinase-kinase (CaMKK) inhibitor. Resveratrol diminished the expression of interleukin-1 receptor-associated kinase M (IRAK-M) and Src homology 2 (SH2) domain-containing inositol-5-phosphatase 1 (SHIP1) by prolonging the exposure of cells to LPS (by 60.8 ± 16.3% and 70.3 ± 18.1%, respectively, compared to LPS only). The effect of resveratrol on the LPS-induced expression of IRAK-M and SHIP1 was inhibited by compound C or STO609. After a 2nd dose of LPS, resveratrol increased phosphorylation of ERK1/2, p38, and JNK in endotoxin tolerant macrophages. In vivo systemic administration of resveratrol prevented a significant increase in mortality rate by cecal ligation and puncture in LPS-induced endotoxin-tolerant mice. These results indicate that resveratrol induces AMPK activation through the Ca2+/CaMKKß pathway and suppresses the development of endotoxin tolerance by inhibiting LPS-induced expression of IRAK-M and SHIP1.

Donepezil-related inadequate neuromuscular blockade during laparoscopic surgery: A case report.

BACKGROUND: Donepezil is an acetylcholinesterase inhibitor used to improve cognition and delay disease progression in dementia patients by increasing acetylcholine levels. This drug may potentially interact with neuromuscular blocking agents (NMBAs) that act on muscular acetylcholine receptors during general anesthesia. Herein, we present a case of inadequate neuromuscular blockade with rocuronium, a nondepolarizing NMBA, in a dementia patient who had taken donepezil. CASE SUMMARY: A 71-year-old man was scheduled for laparoscopic gastrectomy. He had been taking donepezil 5 mg for dementia. General anesthesia was induced with propofol and remifentanil. The depth of neuromuscular blockade was monitored by train-of-four (TOF) stimulation. After the administration of rocuronium, the TOF ratio decreased at an unusually slow rate, and a TOF count of 0 was detected 7 min later. After intubation, a TOF count of 1 was detected within 1 min, and a TOF ratio of 12% was detected within 2 min. The TOF count remained at 4 even with an additional bolus and continuous infusion of rocuronium, suggesting resistance to this NMBA. Instead of propofol, an inhalation anesthetic was administered alongside another NMBA (cisatracurium). Then, the quality of neuromuscular blockade improved, and the TOF count remained at 0-1 for the next 70 min. No further problems were encountered with respect to surgery or anesthesia. CONCLUSION: Donepezil may be responsible for inadequate neuromuscular blockade during anesthesia, especially when total intravenous anesthesia is used.

Novel Therapeutic Effects of Pterosin B on Ang II-Induced Cardiomyocyte Hypertrophy.

Pathological cardiac hypertrophy is characterized by an abnormal increase in cardiac muscle mass in the left ventricle, resulting in cardiac dysfunction. Although various therapeutic approaches are being continuously developed for heart failure, several studies have suggested natural compounds as novel potential strategies. Considering relevant compounds, we investigated a new role for Pterosin B for which the potential life-affecting biological and therapeutic effects on cardiomyocyte hypertrophy are not fully known. Thus, we investigated whether Pterosin B can regulate cardiomyocyte hypertrophy induced by angiotensin II (Ang II) using H9c2 cells. The antihypertrophic effect of Pterosin B was evaluated, and the results showed that it reduced hypertrophy-related gene expression, cell size, and protein synthesis. In addition, upon Ang II stimulation, Pterosin B attenuated the activation and expression of major receptors, Ang II type 1 receptor and a receptor for advanced glycation end products, by inhibiting the phosphorylation of PKC-ERK-NF-κB pathway signaling molecules. In addition, Pterosin B showed the ability to reduce excessive intracellular reactive oxygen species, critical mediators for cardiac hypertrophy upon Ang II exposure, by regulating the expression levels of NAD(P)H oxidase 2/4. Our results demonstrate the protective role of Pterosin B in cardiomyocyte hypertrophy, suggesting it is a potential therapeutic candidate.

Avenanthramide C Prevents Neuronal Apoptosis via PI3K/Akt/GSK3ß Signaling Pathway Following Middle Cerebral Artery Occlusion.

Avenanthramides are a group of phenolic alkaloids that have been shown to have anti-inflammatory, anti-oxidant, anti-atherogenic, and vasodilation effects. The aim of the present study was to investigate the neuroprotective effect of avenanthramide-c (Avn-c) in focal brain ischemia and reperfusion injury using middle cerebral artery occlusion (MCAo) model with mice. Male C57BL/6 mice were divided into 4 groups: sham, control (MCAo), Avn-c, and Avn-c + LY294002 (phosphoinositide 3-kinase inhibitor) group. They were subjected to 60 min MCAo followed by reperfusion. Brain infarct volume and neurological deficit scores were measured after 24 h of reperfusion. We evaluated the blood brain barrier (BBB) integrity (ZO-1, VE-cadherin and occludin) and apoptosis (Bax, Bcl2, caspase3, Cytochrome C, and poly ADP ribose polymerase(PARP)-1). We also measured GSK3ß for evaluation of the downstream mechanism of Akt. We examined the effect of the Avn-c in the phosphoinositide 3-kinase pathway. Avn-c reduced neurological score and infarction size. Avn-c inhibited the MCAo-induced disruption of tight junction proteins. Avn-c decreased apoptotic protein expression (Bax, Cytochrome C, and cleaved PARP-1) and increased anti-apoptotic protein expression (Bcl2) after MCAo. Akt and GSK3ß were decreased in MCAo group and were restored in Avn-c group. This effect of Avn-c was abolished by PI3K inhibitor. In summary, Avn-c showed neuroprotective effects through PI3K-Akt-GSK3ß signaling pathway.

Antinociceptive role of neurotensin receptor 1 in rats with chemotherapy-induced peripheral neuropathy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect of anti-cancer drugs. Neurotensin receptors (NTSRs) are widely distributed within the pain circuits in the central nervous system. The purpose of this study was to determine the role of NTSR1 by examining the effects of an NTSR1 agonist in rats with CIPN and investigate the contribution of spinal serotonin receptors to the antinociceptive effect. METHODS: Sprague-Dawley rats (weight 150-180 g) were used in this study. CIPN was induced by injecting cisplatin (2 mg/kg) once a day for 4 days. Intrathecal catheters were placed into the subarachnoid space of the CIPN rats. The antiallodynic effects of intrathecally or intraperitoneally administered PD 149163, an NTSR1 agonist, were evaluated. Furthermore, the levels of serotonin in the spinal cord were measured by high-performance liquid chromatography. RESULTS: Intrathecal or intraperitoneal PD 149163 increased the paw withdrawal threshold in CIPN rats. Intrathecal administration of the NTSR1 antagonist SR 48692 suppressed the antinociceptive effect of PD 149163 given via the intrathecal route, but not the antinociceptive effect of intraperitoneally administered PD 149163. Intrathecal administration of dihydroergocristine, a serotonin receptor antagonist, suppressed the antinociceptive effect of intrathecally administered, but not intraperitoneally administered, PD 149163. Injecting cisplatin diminished the serotonin level in the spinal cord, but intrathecal or intraperitoneal administration of PD 149163 did not affect this reduction. CONCLUSIONS: NTSR1 played a critical role in modulating CIPN-related pain. Therefore, NTSR1 agonists may be useful therapeutic agents to treat CIPN. In addition, spinal serotonin receptors may be indirectly involved in the effect of NTSR1 agonist.

Isoliquiritigenin Derivatives Inhibit RANKL-Induced Osteoclastogenesis by Regulating p38 and NF-κB Activation in RAW 264.7 Cells.

Bone diseases may not be imminently life-threatening or a leading cause of death such as heart diseases or cancers. However, as aging population grows in almost every part of the world, they surely impose significant socioeconomic burden on the society, not to mention the patients and their families. Osteoporosis is the most common type of bone disease, which frequently develops in seniors, especially in postmenopausal women. Although currently several anti-osteoclastic drugs designed to suppress excessive osteoclast activation, a major cause of osteoporosis, are commercially available, accompanying adverse effects ranging from mild to severe have been reported as well. Natural products have become increasingly popular because of their effectiveness with fewer side effects. Isoliquiritigenin (ILG), a natural flavonoid from licorice, has been reported to suppress osteoclast differentiation and activation. In the present study, newly synthesized ILG derivatives were screened for their anti-osteoporotic activity as more potent substitute candidates to ILG. Out of the 12 ILG derivatives tested, two compounds demonstrated significantly improved bone loss in vitro by inhibiting both osteoclastogenesis and osteoclast activity. The results of the present study indicate that these compounds may serve as a potential drug for osteoporosis and warrant further studies to evaluate their in vivo efficacy.

miRNAs as potential biomarkers for the progression of gastric cancer inhibit CREBZF and regulate migration of gastric adenocarcinoma cells.

In our previous study, we identified three miRNAs (hsa-miR-421, hsa-miR-29b-1-5p, and hsa-miR-27b-5p) with two mRNAs (FBXO11 and CREBZF) that might play an important role in the development of gastric adenocarcinoma (GAC) from premalignant adenomas. However, the expression and function of these miRNAs have not been not well characterized. We investigated the roles of CREBZF and miRNAs as potential biomarkers for the progression of gastric cancer (GC) in low-/high-grade dysplasia and early gastric cancer patients using immunohistochemical staining and miRNA in situ hybridization. Considering that targets can modulate in GC, we analyzed the CREBZF expression in gastric cancer cell lines by RT-PCR and western blot analysis. We observed lower expression of CREBZF with increasing miRNAs in the MKN-74 gastric cancer cells compared to that in SNU-NCC-19. Next, the role of CREBZF in MKN-74 gastric cancer cells was investigated via cell viability and migration assays by miRNA/anti-miRNA modulation. Furthermore, we found that hsa-miR-421/hsa-miR-29b-1-5p target CREBZF and might play an important role in the migration of MKN-74 cells. This study suggests that increased CREBZF by hsa-miR-421/hsa-miR-29b-1-5p inhibition may be important to prevent the progression of gastric cancer in its early stage.

Effect of transportation method on preoperative anxiety in children: a randomized controlled trial.

BACKGROUND: This study was performed to evaluate the effect of a wagon as a transport vehicle instead of the standard stretcher car to reduce children's anxiety of separation from parents. The secondary goal was to evaluate whether this anxiolytic effect was related to age. METHODS: We divided 80 children (age 2-7 years) into two groups. The stretcher group was transferred to the operating room on a conventional stretcher car, whereas the wagon group was transferred using a wagon. The level of anxiety was evaluated three times using the Modified Yale Preoperative Anxiety Scale (mYPAS): in the waiting area (T0), in the hallway to the operating room (T1), and before induction of anesthesia (T2). RESULTS: The mYPAS score was significantly lower in the wagon group (36.7 [31.7, 51.7]) than in the stretcher group (51.7 [36.7, 83.3]) at T1 (P = 0.007). However, there was no difference in the mYPAS score between the two groups at T2 (46.7 [32.5, 54.2] vs. 51.7 [36.7, 75.0], respectively, P = 0.057). The baseline anxiety tended to be lower with increasing age (r = -0.248, P = 0.031). During transportation to the operating room, the increase in the mYPAS score (T1-T0) was greater as the age of children decreased in the stretcher group (r = -0.340, P = 0.034). However, no correlation was observed in the wagon group (r = -0.053, P = 0.756). CONCLUSION: The wagon method decreased preoperative anxiety, suggesting that it may be a good alternative for reducing preoperative anxiety in children.

A retrospective study of the relationship between postoperative urine output and one year transplanted kidney function.

BACKGROUND: Kidney transplantation (KT) is the most obvious method of treating a patient with end-stage renal disease. In the early stages of KT, urine production is considered a marker of successful reperfusion of the kidney after anastomosis. However, there is no clear conclusion about the relationship between initial urine output after KT and 1-year renal function. Thus, we investigated the factors that affect 1-year kidney function after KT, including urine output. METHODS: This retrospective study investigated the relationship between urine output in the 3 days after KT and transplanted kidney prognosis after 1-year. In total, 291 patients (129 living-donor and 162 deceased-donor transplant recipients) were analyzed; 24-h urine volume per body weight (in kilograms) was measured for 3 days postoperatively. The estimated glomerular filtration rate (eGFR), determined by the Modification of Diet in Renal Disease algorithm, was used as an index of renal function. Patients were grouped according to eGFR at 1-year after KT: a good residual function group, eGFR ≥60, and a poor residual function group, eGFR < 60. RESULT: Recipients' factors affecting 1-year eGFR include height (P = 0.03), weight (P = 0.00), and body mass index (P = 0.00). Donor factors affecting 1-year eGFR include age (P = 0.00) and number of human leukocyte antigen (HLA) mismatches (P = 0.00). The urine output for 3 days after KT (postoperative day 1; 2 and 3) was associated with 1-year eGFR in deceased-donor (P = 0.00; P = 0.00 and P = 0.01). And, postoperative urine output was associated with the occurrence of delayed graft function (area under curve (AUC) = 0.913; AUC = 0.984 and AUC = 0.944). CONCLUSION: Although postoperative urine output alone is not enough to predict 1-year GFR, the incidence of delayed graft function can be predicted. Also, the appropriate urine output after KT may differ depending on the type of the transplanted kidney. TRIAL REGISTRATION: Clinical Research Information Service of the Korea National Institute of Health in the Republic of Korea (KCT0003571).