Safe and effective sedation depends on various factors, such as the choice of sedatives, sedation techniques used, experience of the sedation provider, degree of sedation-related education and training, equipment and healthcare worker availability, the patient’s underlying diseases, and the procedure being performed. The purpose of these evidence-based multidisciplinary clinical practice guidelines is to ensure the safety and efficacy of sedation, thereby contributing to patient safety and ultimately improving public health. These clinical practice guidelines comprise 15 key questions covering various topics related to the following: the sedation providers; medications and equipment available; appropriate patient selection; anesthesiologist referrals for high-risk patients; pre-sedation fasting; comparison of representative drugs used in adult and pediatric patients; respiratory system, cardiovascular system, and sedation depth monitoring during sedation; management of respiratory complications during pediatric sedation; and discharge criteria. The recommendations in these clinical practice guidelines were systematically developed to assist providers and patients in sedation-related decision making for diagnostic and therapeutic examinations or procedures. Depending on the characteristics of primary, secondary, and tertiary care institutions as well as the clinical needs and limitations, sedation providers at each medical institution may choose to apply the recommendations as they are, modify them appropriately, or reject them completely.

Microorganisms play important roles in obesity; however, the role of the gut microbiomes in obesity is controversial because of the inconsistent findings. This study investigated the gut microbiome communities in obese and lean groups of captive healthy cynomolgus monkeys reared under strict identical environmental conditions, including their diet. No significant differences in the relative abundance of Firmicutes, Bacteroidetes and Prevotella were observed between the obese and lean groups, but a significant difference in Spirochetes (p < 0.05) was noted. Microbial diversity and richness were similar, but highly variable results in microbial composition, diversity, and richness were observed in individuals, irrespective of their state of obesity. Distinct clustering between the groups was not observed by principal coordinate analysis using an unweighted pair group method. Higher sharedness values (95.81% ± 2.28% at the genus level, and 79.54% ± 5.88% at the species level) were identified among individual monkeys. This paper reports the association between the gut microbiome and obesity in captive non-human primate models reared under controlled environments. The relative proportion of Firmicutes and Bacteroidetes as well as the microbial diversity known to affect obesity were similar in the obese and lean groups of monkeys reared under identical conditions. Therefore, obesity-associated microbial changes reported previously appear to be associated directly with environmental factors, particularly diet, rather than obesity.
Bacteroidetes ; Diet ; Environment, Controlled ; Firmicutes ; Gastrointestinal Microbiome ; Haplorhini ; Macaca fascicularis ; Methods ; Microbiota ; Obesity ; Prevotella ; Primates ; Spirochaetales

BACKGROUND: Considering the functional role of red blood cells (RBC) in maintaining oxygen supply to tissues, RBC transfusion can be a life-saving intervention in situations of severe bleeding or anemia. RBC transfusion is often inevitable to address intraoperative massive bleeding; it is a key component in safe perioperative patient management. Unlike general medical resources, packed RBCs (pRBCs) have limited availability because their supply relies entirely on voluntary donations. Additionally, excessive utilization of pRBCs may aggravate prognosis or increase the risk of developing infectious diseases. Appropriate perioperative RBC transfusion is, therefore, crucial for the management of patient safety and medical resource conservation. These concerns motivated us to develop the present clinical practice guideline for evidence-based efficient and safe perioperative RBC transfusion management considering the current clinical landscape. METHODS: This guideline was obtained after the revision and refinement of exemplary clinical practice guidelines developed in advanced countries. This was followed by rigorous evidence-based reassessment considering the healthcare environment of the country. RESULTS: This guideline covers all important aspects of perioperative RBC transfusion, such as preoperative anemia management, appropriate RBC storage period, and leukoreduction (removal of white blood cells using filters), reversal of perioperative bleeding tendency, strategies for perioperative RBC transfusion, appropriate blood management protocols, efforts to reduce blood transfusion requirements, and patient monitoring during a perioperative transfusion. CONCLUSIONS: This guideline will aid decisions related to RBC transfusion in healthcare settings and minimize patient risk associated with unnecessary pRBC transfusion.
Anemia ; Blood Transfusion ; Communicable Diseases ; Delivery of Health Care ; Erythrocyte Transfusion ; Erythrocytes ; Hemorrhage ; Humans ; Leukocytes ; Monitoring, Physiologic ; Oxygen ; Patient Safety ; Prognosis

Mitochondria continuously fuse and divide to maintain homeostasis. An impairment in the balance between the fusion and fission processes can trigger mitochondrial dysfunction. Accumulating evidence suggests that mitochondrial dysfunction is related to neurodegenerative diseases such as Parkinson's disease (PD), with excessive mitochondrial fission in dopaminergic neurons being one of the pathological mechanisms of PD. Here, we investigated the balance between mitochondrial fusion and fission in the substantia nigra of a non-human primate model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. We found that MPTP induced shorter and abnormally distributed mitochondria. This phenomenon was accompanied by the activation of dynamin-related protein 1 (Drp1), a mitochondrial fission protein, through increased phosphorylation at S616. Thereafter, we assessed for activation of the components of the cyclin-dependent kinase 5 (CDK5) and extracellular signal-regulated kinase (ERK) signaling cascades, which are known regulators of Drp1(S616) phosphorylation. MPTP induced an increase in p25 and p35, which are required for CDK5 activation. Together, these findings suggest that the phosphorylation of Drp1(S616) by CDK5 is involved in mitochondrial fission in the substantia nigra of a non-human primate model of MPTP-induced PD.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Cyclin-Dependent Kinase 5 ; Cyclin-Dependent Kinases ; Dopaminergic Neurons ; Homeostasis ; Mitochondria ; Mitochondrial Dynamics ; Neurodegenerative Diseases ; Parkinson Disease ; Phosphorylation ; Phosphotransferases ; Primates ; Substantia Nigra

The function of microglia/macrophages after ischemic stroke is poorly understood. This study examines the role of microglia/macrophages in the focal infarct area after transient middle cerebral artery occlusion (MCAO) in rhesus monkeys. We measured infarct volume and neurological function by magnetic resonance imaging (MRI) and non-human primate stroke scale (NHPSS), respectively, to assess temporal changes following MCAO. Activated phagocytic microglia/macrophages were examined by immunohistochemistry in post-mortem brains (n=6 MCAO, n=2 controls) at 3 and 24 hours (acute stage), 2 and 4 weeks (subacute stage), and 4, and 20 months (chronic stage) following MCAO. We found that the infarct volume progressively decreased between 1 and 4 weeks following MCAO, in parallel with the neurological recovery. Greater presence of cluster of differentiation 68 (CD68)-expressing microglia/macrophages was detected in the infarct lesion in the subacute and chronic stage, compared to the acute stage. Surprisingly, 98~99% of transforming growth factor beta (TGFβ) was found colocalized with CD68-expressing cells. CD68-expressing microglia/macrophages, rather than CD206⁺ cells, may exert anti-inflammatory effects by secreting TGFβ after the subacute stage of ischemic stroke. CD68⁺ microglia/macrophages can therefore be used as a potential therapeutic target.
Brain ; Haplorhini ; Immunohistochemistry ; Infarction, Middle Cerebral Artery ; Inflammation ; Macaca mulatta ; Magnetic Resonance Imaging ; Microglia ; Middle Cerebral Artery ; Primates ; Stroke ; Transforming Growth Factor beta

BACKGROUND: Patients with acute myocardial infarction (AMI) have worse clinical outcomes than those with stable coronary artery disease despite revascularization. Non-culprit lesions of AMI also involve more adverse cardiovascular events. This study aimed to investigate the influence of AMI on endothelial function, neointimal progression, and inflammation in target and non-target vessels. METHODS: In castrated male pigs, AMI was induced by balloon occlusion and reperfusion into the left anterior descending artery (LAD). Everolimus-eluting stents (EES) were implanted in the LAD and left circumflex (LCX) artery 2 days after AMI induction. In the control group, EES were implanted in the LAD and LCX in a similar fashion without AMI induction. Endothelial function was assessed using acetylcholine infusion before enrollment, after the AMI or sham operation, and at 1 month follow-up. A histological examination was conducted 1 month after stenting. RESULTS: A total of 10 pigs implanted with 20 EES in the LAD and LCX were included. Significant paradoxical vasoconstriction was assessed after acetylcholine challenge in the AMI group compared with the control group. In the histologic analysis, the AMI group showed a larger neointimal area and larger area of stenosis than the control group after EES implantation. Peri-strut inflammation and fibrin formation were significant in the AMI group without differences in injury score. The non-target vessel of the AMI also showed similar findings to the target vessel compared with the control group. CONCLUSION: In the pig model, AMI events induced endothelial dysfunction, inflammation, and neointimal progression in the target and non-target vessels.
Acetylcholine ; Arteries ; Balloon Occlusion ; Constriction, Pathologic ; Coronary Artery Disease ; Drug-Eluting Stents ; Endothelium ; Fibrin ; Follow-Up Studies ; Humans ; Inflammation ; Male ; Myocardial Infarction ; Reperfusion ; Stents ; Swine ; Vasoconstriction

BACKGROUND: Considering the functional role of red blood cells (RBC) in maintaining oxygen supply to tissues, RBC transfusion can be a life-saving intervention in situations of severe bleeding or anemia. RBC transfusion is often inevitable to address intraoperative massive bleeding; it is a key component in safe perioperative patient management. Unlike general medical resources, packed RBCs (pRBCs) have limited availability because their supply relies entirely on voluntary donations. Additionally, excessive utilization of pRBCs may aggravate prognosis or increase the risk of developing infectious diseases. Appropriate perioperative RBC transfusion is, therefore, crucial for the management of patient safety and medical resource conservation. These concerns motivated us to develop the present clinical practice guideline for evidence-based efficient and safe perioperative RBC transfusion management considering the current clinical landscape. METHODS: This guideline was obtained after the revision and refinement of exemplary clinical practice guidelines developed in advanced countries. This was followed by rigorous evidence-based reassessment considering the healthcare environment of the country. RESULTS: This guideline covers all important aspects of perioperative RBC transfusion, such as preoperative anemia management, appropriate RBC storage period, and leukoreduction (removal of white blood cells using filters), reversal of perioperative bleeding tendency, strategies for perioperative RBC transfusion, appropriate blood management protocols, efforts to reduce blood transfusion requirements, and patient monitoring during a perioperative transfusion. CONCLUSIONS This guideline will aid decisions related to RBC transfusion in healthcare settings and minimize patient risk associated with unnecessary pRBC transfusion.

Nonhuman primate models are valuable in biomedical research. However, reference data for clinical pathology parameters in cynomolgus and rhesus monkeys are limited. In the present study, we established hematologic and biochemical reference intervals for healthy cynomolgus and rhesus monkeys anesthetized with ketamine hydrochloride. A total of 142 cynomolgus monkeys (28 males and 114 females) and 42 rhesus monkeys (22 males and 20 females) were selected and analyzed in order to examine reference intervals of 20 hematological and 16 biochemical parameters. The effects of sex were also investigated. Reference intervals for hematological and biochemical parameters were separately established by species (cynomolgus and rhesus) and sex (male and female). No sex-related differences were determined in erythrocyte-related parameters for cynomolgus and rhesus monkey housed in indoor laboratory conditions. Alkaline phosphatase and gamma glutamyltransferase were significantly lower in females than males in both cynomolgus and rhesus monkeys aged 48–96 months. The reference values for hematological and biochemical parameters established herein might provide valuable information for researchers using cynomolgus and rhesus monkeys in experimental conditions for biomedical studies.

Gangliosides are ubiquitous components of the membranes of mammalian cells that are thought to play important roles in various cell functions such as cell-cell interaction, cell adhesion, cell differentiation, growth control, and signaling. However, the role that gangliosides play in the immune rejection response after xenotransplantation is not yet clearly understood. In this study, the regulatory effects of human leukocytes on ganglioside expression in primary cultured micro-pig aortic endothelial cells (PAECs) were investigated. To determine the impact of human leukocytes on the expression of gangliosides in PAECs, we performed high-performance thin layer chromatography (HPTLC) in PAECs incubated with FBS, FBS containing human leukocytes, human serum containing human leukocytes, and FBS containing TNF-alpha. Both HPTLC and immunohistochemistry analyses revealed that PAECs incubated with FBS predominantly express the gangliosides GM3, GM1, and GD3. However, the expression of GM1 significantly decreased in PAECs incubated for 5 h with TNF-alpha (10 ng/mL), 10% human serum containing human leukocytes, and 10% FBS containing human leukocytes. Taken together, these results suggest that human leukocytes induced changes in the expression profile of ganglioside GM1 similar to those seen upon treatment of PAECs with TNF-alpha. This finding may be relevant for designing future therapeutic strategies intended to prolong xenograft survival.
Cell Adhesion ; Cell Communication ; Chromatography, Thin Layer ; Endothelial Cells ; Gangliosides ; Humans ; Immunohistochemistry ; Leukocytes ; Membranes ; Rejection (Psychology) ; Transplantation, Heterologous ; Tumor Necrosis Factor-alpha

PURPOSE: Abnormal expression of E-cadherin has been shown to play a role in the progression and the metastasis of tumors. We investigated the correlation between the expressions of E-cadherin and the clinicopathologic factors and survival in pT2 gastric adenocarcinomas. METHODS: We examined formalin-fixed, paraffin-embedded archival tissues from 100 surgically resected gastric adeno-carcinomas with pT2 lesion. Tissue preparations were stained with Zymed's monoclonal mouse anti-E-cadherin (clone: 4A2C7). We analyzed the correlation between the expressions of E-cadherin and clinicopathologic factors. RESULTS: Normal gastric mucosa was immunoreactive with anti-E-cadherin antibody. Among the 100 tumors examined, 73 tumors showed expression of E-cadherin. The gender, age, size, depth of invasion, lymph node metastasis, stage (UICC), lymphatic invasion, vascular invasion were not related with E-cadherin expression but Lauren classification and histologic type were strongly correlated with E-cadherin expression (P=0.000, P=0.006). Though patients with dec-rea-sed expression of E-cadherin showed a poorer median survival than normal expression (43.85+/-23.95 months vs. 61.27+/-33.47 months), expression of E-cadherin was not related with survival rate (P=0.668). CONCLUSION: In patients with gastric cancer, expressions of E-cadherin correlated with histologic type and Lauren classi-fication but not with survival.
Adenocarcinoma ; Animals ; Cadherins* ; Classification ; Gastric Mucosa ; Humans ; Immunohistochemistry ; Lymph Nodes ; Mice ; Neoplasm Metastasis ; Stomach Neoplasms* ; Survival Rate