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Rafael Taeho Han,1,2 Sewon Kim,3 Kyungmin Choi,1,2 Hyeonseok Jwa,1,2 JaeHee Lee,1,2 Hye Young Kim,1,2 Hee Jin Kim,4 Hang-Rae Kim,5 Seung Keun Back,6 Heung Sik Na1,2 1Neuroscience Research Institute, 2Department of Physiology, 3Department of Microbiology, College of Medicine, Korea University, Seoul, 4Division of Biological Science and Technology, Science and Technology College, Yonsei University Wonju Campus, Wonju, 5Department of Anatomy, College of Medicine, Seoul National University, Seoul, 6Department of Pharmaceutics and Biotechnology, College of Medical Engineering, Konyang University, Chungnam, South Korea Abstract: Recent studies have shown that approximately 70% of patients with severe atopic dermatitis (AD) develop asthma. Development of AD in infancy and subsequent other atopic diseases such as asthma in childhood is referred to as atopic march. However, a causal link between the diseases of atopic march has remained largely unaddressed, possibly due to lack of a proper animal model. Recently, we developed an AD rat model showing chronically relapsing dermatitis and scratching behaviors induced by neonatal capsaicin treatment. Here, we investigated whether our model also showed asthmatic changes, with the aim of expanding our AD model into an atopic march model. First, we confirmed that capsaicin treatment (50 mg/kg within 24 h after birth) induced dermatitis and scratching behaviors until 6 weeks of age. After that, the mRNA expression of Th1 and Th2 cytokines, such as IFN-γ and TNF-α, and IL-4, IL-5, and IL-13, respectively, was quantified with quantitative real-time polymerase chain reaction in the skin and the lungs. The number of total cells and eosinophils was counted in bronchoalveolar lavage (BAL) fluid. The levels of IgE in the serum and BAL fluid were determined with enzyme-linked immunosorbent assay. Paraffin-embedded sections (4 μm) were stained with hematoxylin/eosin to analyze the morphology of the lung and the airway. Airway responsiveness was measured in terms of airway resistance and compliance using the flexiVent system. In the capsaicin-treated rats, persistent dermatitis developed, and scratching behaviors increased over several weeks. The levels of IgE in the serum and BAL fluid as well as the mRNA expression of Th2 cytokines, including IL-4, IL-5, and IL-13, in both the skin and the lungs were elevated, and the number of eosinophils in the BAL fluid was also increased in the capsaicin-treated rats compared to control rats. Morphological analysis of the airway revealed smooth muscle hypertrophy and extensive mucus plug in the capsaicin-treated rats. Functional studies demonstrated an increment of the airway resistance and a decrement of lung compliance in the capsaicin-treated rats compared to control rats. Taken together, our findings suggested that neonatal capsaicin treatment induced asthma-like airway inflammation and responses in juvenile rats. Keywords: atopic march, scratching, cytokines, eosinophils, BAL fluid, pruritus, flexiVent, airway hypertrophy and remodelling

Jung-Ryul Kim,1 Hye In Woo,2 Mi-Ryung Chun,3 Shinn-Won Lim,4 Hae Deun Kim,5 Han Sung Na,5 Myeon Woo Chung,5 Woojae Myung,6 Soo-Youn Lee,1,3 Doh Kwan Kim6 1Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Seoul, 2Department of Laboratory Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, 3Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 4Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Seoul, 5Clinical Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Osong, Chungcheongbuk-do, 6Department of Psychiatry, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Purpose: This study investigated population pharmacokinetics of paroxetine, and then performed an integrated analysis of exposure and clinical outcome using population pharmacokinetic parameter estimates in depressed patients treated with paroxetine. Patients and methods: A total of 271 therapeutic drug monitoring (TDM) data were retrospectively collected from 127 psychiatric outpatients. A population nonlinear mixed-effects modeling approach was used to describe serum concentrations of paroxetine. For 83 patients with major depressive disorder, the treatment response rate and the incidence of adverse drug reaction (ADR) were characterized by logistic regression using daily dose or area under the concentration–time curve (AUC) estimated from the final model as a potential exposure predictor. Results: One compartment model was developed. The apparent clearance of paroxetine was affected by age as well as daily dose administered at steady-state. Overall treatment response rate was 72%, and the incidence of ADR was 30%. The logistic regression showed that exposure predictors were not associated with treatment response or ADR in the range of dose commonly used in routine practice. However, the incidence of ADR increased with the increase of daily dose or AUC for the patients with multiple concentrations. Conclusion: In depressed patients treated with paroxetine, TDM may be of limited value for individualization of treatment. Keywords: exposure–outcome relationship, paroxetine, therapeutic drug monitoring, population pharmacokinetics, NONMEM

Streptococcus mutans, a major etiological agent of dental caries, frequently causes systemic disease, such as subacute bacterial endocarditis, if it enters the bloodstream. In this study, the production pathways of the proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), induced by S. mutans in mouse macrophage were examined using a quantitative real-time polymerase chain reaction and an enzyme-linked immunosorbent assay. The S. mutans stimulated the expression of TNF-α and IL-1β mRNA at a multiplicity of infection of 1 : 100, which increased at 2 and 4 h, respectively, to 24 h. It also induced the production of high levels of the TNF-α and IL-1β proteins, which increased at 2 h and reached a peak at 4 and 24 h, respectively. Nuclear factor-κB (NF-κB) was activated and reached a maximum level 30 min after the S. mutans treatment. The expression of TNF-α and IL-1β mRNA and protein was suppressed by the treatment with pyrrolidine dithiocarbamate, an NF-κB inhibitor. The S. mutans-induced TNF-α expression was suppressed by the presence of SB203580, a p38 mitogen-activated protein (MAP) kinase inhibitor, or SP600125, a Jun N-terminal kinase (JNK) MAP kinase inhibitor. On the other hand, IL-1β expression was inhibited by extracellular signal-regulated kinase (ERK)/p38/JNK MAP kinase inhibitor pretreatment. In addition, TNF-α production was suppressed more in the Toll-like receptor 2(-/-) (TLR2(-/-)) macrophages than in the TLR4(-/-) macrophages, whereas IL-1β production was suppressed more in the TLR4(-/-) macrophages than in the TLR2(-/-) macrophages. These results show that S. mutans stimulates the production of TNF-α and IL-1β in the mouse macrophage cell line, RAW 264.7, by activating ERK/p38/JNK, and NF-κB through TLR2 and TLR4, respectively. [ABSTRACT FROM AUTHOR]

This randomised controlled study assessed whether continuous positive airway pressure (CPAP) of 10 cmH2O during cardiopulmonary bypass improves post-bypass oxygenation in children compared with no CPAP during bypass. We studied children with a ventricular septal defect. CPAP of 10 cmH2O was applied during bypass in the CPAP group (n=24), whereas the lungs were left deflated in the control group (n=20). In both groups, an alveolar recruitment maneuver was performed by applying positive pressure of 30 to 40 cmH2O for five seconds before weaning from bypass. Postoperative ventilation had the peak inflation pressure set to produce an expired tidal volume of 8 ml/kg with positive end expiratory pressure of 5 cmH2O. Arterial blood gas and haemodynamic measurements were performed at skin incision, five minutes after weaning from bypass, five minutes after chest closure and four hours after arrival in the intensive care unit. In four children CPAP was discontinued because it adversely affected the operating field. There was no difference in demographic characteristics, haemodynamic data, bypass time and operation time. No difference was observed between the groups with respect to pH, PaO2, P(A-a) DO2, PaCO2, and ETCO2 at each time. Variability in the data was greater than expected, leading to a decrease in the expected power of the study. CPAP at 10 cmH2O during bypass was not found to improve the post-bypass oxygenation as compared with leaving the lung deflated during bypass in children undergoing ventricular septal defect repair who had an alveolar recruitment maneuver at the end of bypass. [ABSTRACT FROM AUTHOR]

Background: The GlideScope intubating device has been reported to provide a comparable or superior laryngoscopic view compared with direct laryngoscopy in adults. This study compared the use of the GlideScope with direct laryngoscopy for the laryngoscopic view and intubation time in children.Methods: The laryngoscopic view in 203 children was scored using both the Macintosh laryngoscope and the GlideScope using Cormack and Lehane (C&L) grades. After scoring each laryngoscopic view with and without BURP, the patients were randomly allocated to two groups. The trachea was intubated using direct laryngoscopy (Group DL, n=100) or the GlideScope (Group GS, n=103). We compared C&L grades for the two views in the same patient, and also the time to intubate for each group.Results: The GlideScope improved the view without BURP in the patients with C&L grade 2 (16/26, P<0.01) and with C&L grades 3 and 4 (7/11, P<0.05). The view with BURP was also improved by the GlideScope in C&L grade 2 (4/9, P<0.05) and with C&L grades 3 and 4 (4/5, P=0.059). The mean time for tracheal intubation was 36.0 (17.9) s in the GS group and 23.8 (13.9) s in the DL group (P<0.001).Conclusions: In children, the GlideScope provided a laryngoscopic view equal to or better than that of direct laryngoscopy but required a longer time for intubation. [ABSTRACT FROM AUTHOR]

Objective: Osteoarthritis (OA) is a degenerative joint disease caused by the breakdown of joint cartilage and adjacent bone. Joint injury, being overweight, differences in leg length, high levels of joint stress, abnormal joint or limb development, and inherited factors have been implicated in the etiology of OA. In addition to physical damage to the joint, a role for inflammatory processes has been identified as well. Small heterodimer partner-interacting leucine zipper protein (SMILE) regulates transcription and many cellular functions. Among the proteins activated by SMILE is the peroxisome proliferator-activated receptor (PPAR) γ, which mediates the activities of CD4 + T helper cells, including Th1, Th2, and Th17, as well as Treg cells. PPAR-γ binds to STAT3 to inhibit its transcription, thereby suppressing the expression of the NF-κB pathway, and in turn, the expression of the inflammatory cytokines interferon (IFN), interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, which are sub-signals of STAT3 and NF-κB., Methods: OA was induced in control C57BL/6 mice and in C57BL/6-derived SMILE-overexpressing transgenic (SMILE Tg) mice. The protein expression levels in the joint and spleen tissues were analyzed by immunohistochemistry and immunofluorescence images. In addition, flow cytometry was performed for detecting changes of the changes of immune cells., Results: Less cartilage damage and significantly reduced levels of OA biomarkers (MMP13, TIMP3 and MCP-1) were observed in SMILE Tg mice. Immunohistochemistry performed to identify the signaling pathway involved in the link between SMILE expression and OA revealed decreased levels of IL-1β, IL-6, TNF-α, and phosphorylated AMPK in synovial tissues as well as a significant decrease in phosphorylated STAT3 in both cartilage and synovium. Changes in systemic immune cells were investigated via flow cytometry to analyze splenocytes isolated from control and SMILE Tg mice. SMILE Tg mice had elevated proportions of CD4 + IL-4 + cells (Th2) and CD4 + CD25 + Foxp3 + cells (Treg) and a notable decrease in CD4 + IL-17 + cells (Th17)., Conclusion: Our results show that overexpressed SMILE attenuates the symptoms of OA, by increasing AMPK signaling and decreasing STAT3, thus reducing the levels of inflammatory immune cells., Competing Interests: Declarations Ethics approval and consent to participate The study protocol involving human participants was approved by the Institutional Review Board of Seoul St. Mary’s Hospital. All patients/participants provided written informed consent to participate in this study. The animal study protocol was approved by the Animal Research Ethics Committee of the Catholic University of Korea (IACUC approval numbers: 2020-0306-02 and 2021-0010-01). Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Porphyromonase gingivalis (P. gingivalis) is a type of bacteria that causes periodontitis, which is strongly correlated with systemic diseases such as diabetes. However, the effect of hyperglycemia on periodontitis are unclear. The present study examined the effects of high glucose levels on the response to P. gingivalis infection., Results: The expression of P. gingivalis-induced interleukin-1β (IL-1β) and inflammasomes increased as the glucose concentration increased. High glucose conditions suppressed P. gingivalis-induced autophagy in human acute monocytic leukemia cell line (THP-1) macrophages. Zingerone increased autophagy and alleviated P. gingivalis-induced inflammatory response in THP-1 macrophages under high glucose conditions. In addition, P. gingivalis- induced inflammation in bone marrow-derived macrophages of diabetic mice was higher than in wild-type mice, but a zingerone treatment decreased the levels. Alveolar bone loss due to a P. gingivalis infection was significantly higher in diabetic mice than in wild-type mice., Conclusions: High-glucose conditions aggravated the inflammatory response to P. gingivalis infection by suppressing of autophagy, suggesting that autophagy induction could potentially to treat periodontitis in diabetes. Zingerone has potential use as a treatment for periodontal inflammation induced by P. gingivalis in diabetes patients., (© 2024. The Author(s).)

Background: Benzodiazepines reduce postoperative nausea and vomiting (PONV); however, conflicting results have been reported regarding the use of remimazolam, a novel benzodiazepine., Objective: This meta-analysis examines whether remimazolam reduces PONV incidence compared with propofol or volatile agents used in general anesthesia., Material and Methods: Electronic databases, including PubMed, EMBASE, CENTRAL, and Web of Science, were searched on 31 July 2023. The primary outcome was the incidence of PONV. Secondary outcomes included PONV severity, rescue antiemetic use, amounts of remifentanil used, and participant satisfaction scores. Odds ratios (OR) and mean differences (MD) with 95% confidence intervals (CI) were calculated using a random-effects model. The risk of bias (RoB) was assessed using the Cochrane RoB2 tool., Results: A total of 1514 adult patients from 11 randomized controlled trials were included. The incidences of PONV in the remimazolam and control groups were 16.1% and 16.5%, respectively. Remimazolam did not increase the incidence of PONV (OR 0.62; 95% CI, 0.37-1.04; p = 0.0676; I 2  = 48%). Subgroup analysis showed a significant reduction in PONV with remimazolam vs. volatile agents (OR 0.25; 95% CI, 0.13-0.47; P = 0.0000; I 2  = 0%) but not vs. propofol (OR 1.04; 95% CI, 0.70-1.56; p = 0.8332; I 2  = 0%). More remifentanil was used in the remimazolam group vs. the volatile group, with no significant difference between remimazolam and propofol groups. Participant satisfaction scores were higher with remimazolam., Conclusion: Remimazolam did not increase PONV risk compared to propofol and reduced PONV incidence compared to volatile agents, with higher participant satisfaction. To validate the present findings, further well-planned large clinical trials are required., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Neuroinflammation is postulated as a potential mechanism underlying postoperative delirium. This study aimed to investigate the impact of non-steroidal anti-inflammatory drug (NSAID) use on postoperative delirium., Methods: We conducted a literature search in electronic databases, including PubMed, EMBASE, CENTRAL, and Web of Science, to identify eligible randomized controlled studies. The primary outcome was the incidence of postoperative delirium, and the secondary outcomes included pain scores and the amounts of opioid used at 24 h postoperatively. We estimated the effect size through calculating the odds ratios (ORs) or mean differences (MDs) with 95% CIs, as appropriate., Results: In the analysis of eight studies involving 1,238 participants, the incidence of postoperative delirium was 11% and 19% in the NSAID and control groups, respectively, with a significant reduction in the NSAID group (OR: 0.54, 95% CI [0.38, 0.7], P = 0.0001, I2 = 0%). NSAID use had a significant effect on postoperative pain reduction (MD: -0.75, 95% CI [-1.37, -0.13], P = 0.0172, I2 = 88%). Significant lower postoperative opioid consumption was observed in the NSAID group (MD: -2.88, 95% CI [-3.54, -2.22], P = 0.0000; I2 = 0%)., Conclusions: NSAID administration reduced the incidence of postoperative delirium, severity of pain, and opioid dose used.

Objective . This study evaluated the predictive performance of a deep learning approach to predict stroke volume variation (SVV) from central venous pressure (CVP) waveforms. Approach . Long short-term memory (LSTM) and the feed-forward neural network were sequenced to predict SVV using CVP waveforms obtained from the VitalDB database, an open-source registry. The input for the LSTM consisted of 10 s CVP waveforms sampled at 2 s intervals throughout the anesthesia duration. Inputs of the feed-forward network were the outputs of LSTM and demographic data such as age, sex, weight, and height. The final output of the feed-forward network was the SVV. The performance of SVV predicted by the deep learning model was compared to SVV estimated derived from arterial pulse waveform analysis using a commercialized model, EV1000. Main results . The model hyperparameters consisted of 12 memory cells in the LSTM layer and 32 nodes in the hidden layer of the feed-forward network. A total of 224 cases comprising 1717 978 CVP waveforms and EV1000/SVV data were used to construct and test the deep learning models. The concordance correlation coefficient between estimated SVV from the deep learning model were 0.993 (95% confidence interval, 0.992-0.993) for SVV measured by EV1000. Significance . Using a deep learning approach, CVP waveforms can accurately approximate SVV values close to those estimated using commercial arterial pulse waveform analysis., (© 2024 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, abnormal inflammation, and fibrosis of the skin and internal organs, notably the skin and lungs, significantly impairing quality of life. There is currently no cure for SSc, and its etiology remains largely unknown, presenting a primary barrier to effective treatment. We investigated the role of interleukin-21 (IL-21) in the pathogenesis of SSc., Methods: We assessed the expression levels of fibrosis-related genes in human dermal fibroblasts exposed to IL-21 and TGF beta. We also induced SSc in wild-type C57BL/6 mice and IL-21 knockout (KO) mice with a C57BL/6 background using bleomycin (Bleomycin). Histological analyses were conducted on skin and lung tissues from these mice. The distribution and expression levels of fibrosis-related proteins in the tissues were examined via immunohistochemistry and quantitative real-time PCR. Furthermore, we measured the frequency of Th1, Th2, and Th17 cells among splenocytes through flow cytometry., Results: IL-21 activation led to STAT3 phosphorylation more than TGF beta in dermal fibroblasts. In IL-21 KO mice with BLM-induced SSc, skin thickness and lung fibrosis were reduced. The absence of IL-21 in these mice resulted in suppressed expression of fibrosis-related genes, including Col1a1, Col1a2, Col3a1, CTGF, α-SMA, STAT3, and TGFβ, in the skin and lungs. It also led to a decreased frequency of Th1, Th2, and Th17 cells, as well as a lower Th17/Treg ratio among splenocytes, factors known to contribute to the development of SSc., Conclusions: IL-21 contributes to the development of SSc by promoting the expression of fibrosis-related genes and modulating the levels of CD4+ T cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background/Objectives : Neuromuscular blocking agents (NMBAs) are not usually necessary during the induction of general anesthesia in patients using supraglottic airway (SGA) devices. In this study, we assessed the incidences of rocuronium use in adult patients undergoing general anesthesia using SGA devices. Methods : From September 2022 to August 2023, the medical records of adult patients (≥19 years) who underwent orthopedic surgery using SGA devices were retrospectively investigated. The incidences of rocuronium use during anesthetic induction were analyzed according to the anesthetic induction drug. The association of rocuronium use during anesthesia was analyzed in terms of demographic (age, sex, height, and weight), surgical (surgical time), and anesthetic factors (premedication, anesthetic agent, anesthetic time). Results : In total, 321 patients were enrolled. The incidence rate of rocuronium use during anesthetic induction was 28.3%. In the subgroup analysis, patients receiving total intravenous anesthesia (TIVA) with propofol (PPF) and remifentanil showed a markedly lower incidence (14.4%) than the other anesthetic groups. Premedication or short anesthetic duration was associated with lower incidences of rocuronium use. Demographic and other anesthetic factors did not seem to affect the incidences of rocuronium use during anesthesia. Conclusions : The incidence of rocuronium use during anesthetic induction with SGA devices was significantly lower with the PPF-TIVA compared to that using remimazolam-TIVA or inhalational anesthesia. Premedication with midazolam and shorter operation times were associated with a significantly lower incidence of rocuronium use.

Background: Although cerebral palsy is a risk factor for aspiration, there is insufficient research on residual gastric volume after preoperative fasting in children with cerebral palsy. We evaluated the incidence of a full stomach by ultrasound assessment of the gastric volume in children with cerebral palsy who underwent orthopedic surgery after preoperative fasting., Methods: The patients fasted for 8 h for solid foods and 2 h for clear liquids. We obtained the gastric antral cross-sectional area using ultrasound in the semi-recumbent and right lateral decubitus positions. A calculated stomach volume > 1.5 mL.kg -1 was considered as full, which poses a high aspiration risk. The primary outcome was the incidence of full stomach, and the secondary outcomes were the qualitative gastric volume, correlation of disease severity categorized according to the Gross Motor Function Classification System with the residual gastric volume, gastric volume per body weight, and qualitative gastric volume., Results: Thirty-seven pediatric patients with cerebral palsy, scheduled for elective orthopedic surgery, were included for analysis. Full-stomach status was observed in none, and the gastric volume per body weight was 0.5 (0.4-0.7) mL.kg -1 . No significant differences were observed in the residual gastric volume (p = 0.114), gastric volume per body weight (p = 0.117), or qualitative grade of gastric volume (p = 0.642) in relation to disease severities., Conclusion: Children with cerebral palsy who fasted preoperatively had empty or nearly empty stomachs. Further studies are required to determine the optimal fasting duration for such children., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2024 Sociedade Brasileira de Anestesiologia. Published by Elsevier España S.L.U. All rights reserved.)

Background: The lack of association between serum testosterone levels and symptoms suggestive of hypogonadism is a significant barrier in the determination of late-onset hypogonadism (LOH) in men. This study explored whether testosterone levels increase after morning awakening, likewise the cortisol awakening response (CAR) in the hypothalamic-pituitary-adrenal (HPA) axis, and whether testosterone levels during the post-awakening period are associated with age and symptoms suggestive of late-onset hypogonadism (LOH) in men., Methods: Testosterone and cortisol levels were determined in saliva samples collected immediately upon awakening and 30 and 60 min after awakening, and scores of the Aging Males' Symptoms (AMS) questionnaire were obtained from 225 healthy adult men., Results: A typical CAR (an increase in cortisol level ≥ 2.5 nmol/L above individual baseline) was observed in 155 participants (the subgroup exhibiting typical CAR). In the subgroup exhibiting CAR, testosterone levels sharply increased during the post-awakening period, showing a significant negative correlation with age, total AMS score, and the scores of 11 items on the somatic, psychological, and sexual AMS subscales. Of these items, three sexual items (AMS items #15-17) were correlated with age. Meanwhile, there was no notable increase in testosterone levels and no significant correlation of testosterone levels with age and AMS score in the subgroup exhibiting no typical CAR ( n  = 70)., Conclusions: The results indicate that the hypothalamus-pituitary-gonad (HPG) axis responds to morning awakening, and determining testosterone levels during the post-awakening period in men with typical CAR may be useful for assessing HPG axis function and LOH.

Background: In this study, we aimed to investigate whether opioid-sparing anesthesia (OSA) reduces postoperative nausea and vomiting (PONV) in patients undergoing laparoscopic gynecological surgery., Methods: Adult patients undergoing elective laparoscopic gynecological surgery were randomly assigned to either the opioid-using anesthesia (OUA) or the OSA groups. In the OUA group, remifentanil was administered as an opioid during general anesthesia. In the OSA group, apart from a single dose of 5 μg/kg of alfentanil for tracheal intubation, no other opioids were used. In both groups, a multimodal intravenous non-opioid analgesic regimen was used preferentially in the post-anesthesia care unit (PACU). The primary outcome was the incidence of PONV, assessed by symptoms until the postoperative day (POD) 1., Results: A total of 120 patients were included in this study. The incidence of nausea in the PACU was significantly lower in the OSA group compared to in the OUA group (31.7% in the OSA group vs. 51.7% in the OUA group, P = 0.026). Pain scores and the incidence of opioid analgesic administration were lower in the OSA group during PACU stay, resulting in a significantly lower number of patients requiring rescue opioid analgesics (3.3% vs. 18.3%, P = 0.008). There were no significant differences in intraoperative vital signs, hemodynamic interventions, or duration of PACU and hospital stay between the two groups., Conclusions: OSA significantly reduced postoperative nausea, pain scores, and the need for rescue analgesics in the PACU without increasing hemodynamic instability in patients undergoing laparoscopic gynecological surgery.

Population aging around the world is rapidly progressing; as a result, cognitive decline developing into dementia is becoming a social problem. There is no drug that can cure dementia, and though drugs that alleviate the symptoms of dementia have been developed, they also have side effects. Therefore, we conducted a study on improving cognitive function using natural products that have secured safety. We confirmed the effect of an extract of Scrophularia buergeriana on scopolamine-induced cognitive impairment through mouse behavioral experiments, and we observed metabolic changes in the cortex and hippocampus via brain tissue dissection after the behavioral experiment. Mitigating effects of S. buergeriana on cognitive impairment caused by scopolamine were observed in passive avoidance and Morris water maze tests. A metabolic analysis revealed biomarkers related to the alleviating effect of cognitive impairment. Niacinamide, tyrosine, uridine, and valine in the cortex and GABA, choline, creatine, formate, fumarate, hypoxanthine, leucine, myo-inositol, pyroglutamate, and taurine in the hippocampus were identified as biomarker candidates for recovering cognitive impairment. In addition to behavioral experiments, this metabolomics study using specific regions of the brain may be helpful in understanding the effects of cognitive improvement., (© 2024. The Author(s).)

(1) Background : Peptides are appealing as pharmacological materials because they are easily produced, safe, and tolerable. Despite increasing gum-care awareness, periodontitis is still prevalent and is influenced by factors like high sugar consumption, smoking, and aging. Porphyromonas gingivalis is considered a major etiologic agent of periodontitis and activates the NLR family pyrin domain containing 3 (NLRP3) but is absent in melanoma 2 (AIM2) inflammasomes, resulting in pro-inflammatory cytokine release. (2) Methods : We examined the anti-inflammatory effects of 18 peptides derived from human stromal cell-derived factor-1 (SDF-1) on THP-1 macrophages. Inflammation was induced by P. gingivalis , and the anti-inflammatory effects were analyzed using molecular biological techniques. In a mouse periodontitis model, alveolar bone resorption was assessed using micro-CT. (3) Results : Of the 18 SDF-1-derived peptides, S10 notably reduced IL-1β and TNF-α secretion. S10 also diminished the P. gingivalis -induced expression of NLRP3, AIM2, ASC (apoptosis-associated speck-like protein), caspase-1, and IL-1β. Furthermore, S10 attenuated the enhanced TLR (toll-like receptor) signaling pathway and decreased the phosphorylation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). In addition, S10 mitigated alveolar bone loss in our P. gingivalis -induced mouse model of periodontitis. (4) Conclusions : S10 suppressed TLR/NF-κB/NLRP3 inflammasome signaling and the AIM2 inflammasome in our P. gingivalis -induced murine periodontitis model, which suggests that it has potential use as a therapeutic treatment for periodontitis.

Background: The anti-oxidative, anti-inflammatory, and anti-apoptotic effects of erythropoietin may provide neuroprotective effects. Erythropoietin also modulates autophagy signaling that may play a role in anesthesia-induced neurotoxicity (AIN). Herein, we investigated whether AIN can be attenuated by the neuroprotective effect of erythropoietin in the Caenorhabditis elegans (C. elegans)., Methods: Synchronized worms were divided into the control, Iso, EPO, and EPO-Iso groups. The chemotaxis index (CI) was evaluated when they reached the young adult stage. The lgg-1::GFP-positive puncta per seam cell were used to determine the autophagic events. The erythropoietin-mediated pathway of autophagy was determined by measuring the genetic expression level of let-363, bec-1, atg-7, atg-5, and lgg-3., Results: Increased lgg-1::GFP puncta were observed in the Iso, EPO, and EPO-Iso groups. In the Iso group, only the let-363 level decreased significantly as compared to that in the control group (P = 0.009). bec-1 (P < 0.001), atg-5 (P = 0.012), and lgg-3 (P < 0.001) were expressed significantly more in the EPO-Iso group than in the Iso groups. Repeated isoflurane exposure during development decreased the CI. Erythropoietin could restore the decreased CI by isoflurane significantly in the EPO-Iso group., Conclusions: Erythropoietin showed neuroprotective effects against AIN and modulated the autophagic pathway in C. elegans. This experimental evidence of erythropoietin-related neuroprotection against AIN may be correlated with the induced autophagic degradation process that was sufficient for handling enhanced autophagy induction in erythropoietin-treated worms.

Objective: Next generation sequencing is commonly used to characterize the microbiome structure. MiSeq is most commonly used to analyze the microbiome due to its relatively long read length. Illumina also introduced the 250 × 2 chip for NovaSeq. The purpose of this study was to compare the performance of MiSeq and NovaSeq in the context of oral microbiome study., Methods: Total read count, read quality score, relative bacterial abundance, community diversity, and correlation between two platforms were analyzed. Phylogenetic trees were analyzed for Streptococcus and periodontopathogens., Results: NovaSeq produced significantly more read counts and assigned more operational taxonomic units (OTUs) compared to MiSeq. Community diversity was similar between MiSeq and NovaSeq. NovaSeq were able to detect more unique OTUs compared to MiSeq. When phylogenetic trees were constructed for Streptococcus and periodontopathogens, both platforms detected OTUs for most of the clades., Conclusion: Taken together, while both MiSeq and NovaSeq platforms effectively characterize the oral microbiome, NovaSeq outperformed MiSeq in terms of read counts and detection of unique OTUs, highlighting its potential as a valuable tool for large scale oral microbiome studies., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Recent studies have begun exploring the potential involvement of microbiota in the pathogenesis of oral lichen planus (OLP), yet comprehensive investigations remain limited. Hence, this study aimed to compare the microbial profiles in saliva samples obtained from patients with OLP against those from healthy controls (HC), along with a comparison between erosive (E) and non-erosive (NE) OLP patients. Saliva samples were collected from 60 OLP patients (E: n = 25, NE: n = 35) and 30 HC individuals. Analysis revealed no significant differences in alpha diversity, as assessed by the Chao1 and Shannon index, across the three groups. However, Bray-Curtis distance analysis indicated a significant disparity in microbiome composition distribution between HC and E-OLP, as well as HC and NE-OLP groups. The six most abundant phyla observed across the groups were Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, Fusobacteria, and Saccharibacteria (TM7). Notably, OLP groups exhibited a higher prevalence of Bacteroidetes. Prevotella emerged as the predominant genus in the OLP groups, while Capnocytophaga showed a relatively higher prevalence in E-OLP compared to NE-OLP. This study's findings indicate a notable difference in microbiota composition between HC and patients with OLP. Additionally, differences in the microbiome were identified between the E-OLP and NE-OLP groups. The increase in the proportion of certain bacterial species in the oral microbiome suggests that they may exacerbate the inflammatory response and act as antigens for OLP.

Osteoarthritis (OA) involves cartilage degeneration, thereby causing inflammation and pain. Cardiovascular diseases, such as dyslipidemia, are risk factors for OA; however, the mechanism is unclear. We investigated the effect of dyslipidemia on the development of OA. Treatment of cartilage cells with low-density lipoprotein (LDL) enhanced abnormal autophagy but suppressed normal autophagy and reduced the activity of transcription factor EB (TFEB), which is important for the function of lysosomes. Treatment of LDL-exposed chondrocytes with rapamycin, which activates TFEB, restored normal autophagy. Also, LDL enhanced the inflammatory death of chondrocytes, an effect reversed by rapamycin. In an animal model of hyperlipidemia-associated OA, dyslipidemia accelerated the development of OA, an effect reversed by treatment with a statin, an anti-dyslipidemia drug, or rapamycin, which activates TFEB. Dyslipidemia reduced the autophagic flux and induced necroptosis in the cartilage tissue of patients with OA. The levels of triglycerides, LDL, and total cholesterol were increased in patients with OA compared to those without OA. The C-reactive protein level of patients with dyslipidemia was higher than that of those without dyslipidemia after total knee replacement arthroplasty. In conclusion, oxidized LDL, an important risk factor of dyslipidemia, inhibited the activity of TFEB and reduced the autophagic flux, thereby inducing necroptosis in chondrocytes., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interest., (Copyright © 2024. The Korean Association of Immunologists.)

Background: Few studies have evaluated the use of automated artificial intelligence (AI)-based pain recognition in postoperative settings or the correlation with pain intensity. In this study, various machine learning (ML)-based models using facial expressions, the analgesia nociception index (ANI), and vital signs were developed to predict postoperative pain intensity, and their performances for predicting severe postoperative pain were compared., Methods: In total, 155 facial expressions from patients who underwent gastrectomy were recorded postoperatively; one blinded anesthesiologist simultaneously recorded the ANI score, vital signs, and patient self-assessed pain intensity based on the 11-point numerical rating scale (NRS). The ML models' area under the receiver operating characteristic curves (AUROCs) were calculated and compared using DeLong's test., Results: ML models were constructed using facial expressions, ANI, vital signs, and different combinations of the three datasets. The ML model constructed using facial expressions best predicted an NRS ≥ 7 (AUROC 0.93) followed by the ML model combining facial expressions and vital signs (AUROC 0.84) in the test-set. ML models constructed using combined physiological signals (vital signs, ANI) performed better than models based on individual parameters for predicting NRS ≥ 7, although the AUROCs were inferior to those of the ML model based on facial expressions (all P < 0.050). Among these parameters, absolute and relative ANI had the worst AUROCs (0.69 and 0.68, respectively) for predicting NRS ≥ 7., Conclusions: The ML model constructed using facial expressions best predicted severe postoperative pain (NRS ≥ 7) and outperformed models constructed from physiological signals.

Purpose: This study aimed to assess whether an artificial intelligence model based on facial expressions can accurately predict significant postoperative pain., Methods: A total of 155 facial expressions from patients who underwent gastric cancer surgery were analyzed to extract facial action units (AUs), gaze, landmarks, and positions. These features were used to construct various machine learning (ML) models, designed to predict significant postoperative pain intensity (NRS ≥ 7) from less significant pain (NRS < 7). Significant AUs predictive of NRS ≥ 7 were determined and compared to AUs known to be associated with pain in awake patients. The area under the receiver operating characteristic curves (AUROCs) of the ML models was calculated and compared using DeLong's test., Results: AU17 (chin raising) and AU20 (lip stretching) were found to be associated with NRS ≥ 7 (both P ≤ 0.004). AUs known to be associated with pain in awake patients did not show an association with pain in postoperative patients. An ML model based on AU17 and AU20 demonstrated an AUROC of 0.62 for NRS ≥ 7, which was inferior to a model based on all AUs (AUROC = 0.81, P = 0.006). Among facial features, head position and facial landmarks proved to be better predictors of NRS ≥ 7 (AUROC, 0.85-0.96) than AUs. A merged ML model that utilized gaze and eye landmarks, as well as head position and facial landmarks, exhibited the best performance (AUROC, 0.90) in predicting significant postoperative pain., Conclusion: ML models using facial expressions can accurately predict the presence of significant postoperative pain and have the potential to screen patients in need of rescue analgesia., Trial Registration Number: This study was registered at ClinicalTrials.gov (NCT05477303; date: June 17, 2022)., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: We assessed the effectiveness and safety of using intravesical onabotulinumtoxinA (onabotA; BOTOX) injection with a low dose (75 units) for treating urinary storage symptoms in patients with detrusor overactivity with detrusor underactivity (DODU) compared to using the standard 100 units of onabotA in patients with overactive bladder (OAB)., Methods: This ambidirectional study included 121 female patients who received intravesical onabotA injections at our hospitals. A total of 87 patients with OAB and 34 patients with DODU were reviewed using a 3-day voiding diary, uroflowmetry, and questionnaires including the International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score, and Patient Perception of Bladder Condition. Patients were evaluated at baseline, within 2 weeks of treatment, and beyond 3 months after treatment., Results: Questionnaire scores of the DODU group demonstrated significant improvement in the short term, with a subsequent decline, but an overall improvement compared to baseline in the long term. Notably, the DODU group exhibited enhanced IPSS voiding scores after the treatment. In the OAB group, most questionnaire scores, excluding the IPSS voiding score, showed significant posttreatment improvement, which was sustained to some extent in the long term. Voiding diary parameters related to storage symptoms were enhanced in both groups. The maximum and mean flow rates decreased in the OAB group but increased in the DODU group, particularly in the short term (P=0.000). The postvoid residual volume increased in both groups after posttreatment, with a mitigated change in the long term. Safety assessments revealed manageable adverse events in both groups with comparable frequencies., Conclusion: Low-dose intravesical onabotA for DODU demonstrated a relatively shorter duration of efficacy than OAB. Nonetheless, the treatment improved both storage and voiding symptoms in patients with DODU without significant adverse effects.

Background: A combination of opioids and adjunctive drugs can be used for intravenous patient-controlled analgesia (PCA) to minimize opioid-related side effects. We investigated whether two different analgesics administered separately via a dual-chamber PCA have fewer side effects with adequate analgesia than a single fentanyl PCA in gynecologic pelviscopic surgery., Methods: This prospective, double-blind, randomized, and controlled study included 68 patients who underwent pelviscopic gynecological surgery. Patients were allocated to either the dual (ketorolac and fentanyl delivered by a dual-chamber PCA) or the single (fentanyl alone) group. Postoperative nausea and vomiting (PONV) and analgesic quality were compared between the two groups at 2, 6, 12, and 24 h postoperatively., Results: The dual group showed a significantly lower incidence of PONV during postoperative 2-6 h (P = 0.011) and 6-12 h (P = 0.009). Finally, only two patients (5.7%) in the dual group and 18 (54.5%) in the single group experienced PONV during the entire postoperative 24 h and could not maintain intravenous PCA (odds ratio: 0.056, 95% CI [0.007, 0.229], P < 0.001). Despite the administration of less fentanyl via intravenous PCA during the postoperative 24 h in the dual group than in the single group (66.0 ± 77.8 vs. 383.6 ± 70.1 μg, P < 0.001), postoperative pain had no significant intergroup difference., Conclusions: Two different analgesics, continuous ketorolac and intermittent fentanyl bolus, administered via dual-chamber intravenous PCA, showed fewer side effects with adequate analgesia than conventional intravenous fentanyl PCA in gynecologic patients undergoing pelviscopic surgery.

Background and Objectives: Spinal anesthesia is widely used in various types of surgery. However, several complications can occur afterward. This study aimed to identify differences in the incidence of anesthesia-related complications according to the approach methods (midline versus paramedian) for landmark-based spinal anesthesia. Materials and Methods: We searched electronic databases, including PubMed, EMBASE, CENTRAL, Scopus, and Web of Science, for eligible randomized controlled trials. The primary outcome was post-dural puncture headache (PDPH) incidence, and secondary outcomes were low back pain (LBP) incidence and success rate in the first trial of spinal anesthesia. We estimated the odds ratio (OR) with 95% confidence intervals (CI) using a random-effects model. Results: In total, 2280 patients from 13 randomized controlled trials were included in the final analysis. The incidence rates of PDPH were 5.9% and 10.4% in the paramedian and midline approach groups, respectively. The pooled effect size revealed that the incidence of PDPH (OR: 0.43, 95% CI [0.22-0.83]; p = 0.01; I 2 = 53%) and LBP (OR: 0.27, 95% CI [0.16-0.44]; p < 0.001; I 2 = 16%) decreased, and the success rate in the first attempt was higher (OR: 2.30, 95% CI [1.36-3.87]; p = 0.002; I 2 = 35%) with the paramedian than with the midline approach. Conclusions: Paramedian spinal anesthesia reduced PDPH and LBP and increased the success rate of the first attempt.

Background: Remimazolam, a new benzodiazepine, is known for its quick onset of effects and recovery time. Recently, it has been licensed for general anesthesia and sedation in Korea and its use is increasing in other countries. However, less is known about its effect on postoperative recovery. We used a patient-reported outcome questionnaire to examine the effect of remimazolam on postoperative recovery., Methods: Patients who underwent hysteroscopy on day surgery basis were administered an induction dose of remimazolam 6 mg/kg/h followed by a maintenance dose of 1-2 mg/kg/h. After surgery, the translated Korean version of 15-item Quality of Recovery scale (QoR-15K) including post-discharge nausea and vomiting (PDNV) and/or pain, was surveyed 24 h after surgery to evaluate patient recovery., Results: Total of 38 patients were enrolled in this prospective, observational study. All patients successfully completed QoR-15K. Only one patient scored low for moderate pain and PDNV. On average, patients scored 9 and above for all QoR-15K items except for moderate pain (8.66 ± 1.68). When QoR-15K items were grouped into dimensions, all dimensions scored an average of 9 or higher on a 10-point scale. In addition, 19 out of 38 patients gave score range of 148 to 150 out of possible 150., Conclusions: Psychometric evaluation based on postoperative QoR-15K among patients receiving remimazolam shows satisfactory patient recovery profiles without significant pain or PDNV. Considering its effectiveness and safety, remimazolam could be one of useful agents for general anesthesia of day surgery in terms of postoperative recovery.

Aim: Periodontitis is caused by dysbiosis of oral microbes and is associated with increased cognitive decline in Alzheimer's disease (AD), and recently, a potential functional link was proposed between oral microbes and AD. We compared the oral microbiomes of patients with or without AD to evaluate the association between oral microbes and AD in periodontitis., Materials and Methods: Periodontitis patients with AD (n = 15) and cognitively unimpaired periodontitis patients (CU) (n = 14) were recruited for this study. Each patient underwent an oral examination and neuropsychological evaluation. Buccal, supragingival and subgingival plaque samples were collected, and microbiomes were analysed by next-generation sequencing. Alpha diversity, beta diversity, linear discriminant analysis effect size, analysis of variance-like differential expression analysis and network analysis were used to compare group oral microbiomes., Results: All 29 participants had moderate to severe periodontitis. Group buccal and supragingival samples were indistinguishable, but subgingival samples demonstrated significant alpha and beta diversity differences. Differential analysis showed subgingival samples of the AD group had higher prevalence of Atopobium rimae, Dialister pneumosintes, Olsenella sp. HMT 807, Saccharibacteria (TM7) sp. HMT 348 and several species of Prevotella than the CU group. Furthermore, subgingival microbiome network analysis revealed a distinct, closely connected network in the AD group comprised of various Prevotella spp. and several anaerobic bacteria., Conclusions: A unique microbial composition was discovered in the subgingival region in the AD group. Specifically, potential periodontal pathogens were found to be more prevalent in the subgingival plaque samples of the AD group. These bacteria may possess a potential to worsen periodontitis and other systemic diseases. We recommend that AD patients receive regular, careful dental check-ups to ensure proper oral hygiene management., (© 2023 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Background: This study assessed the postoperative analgesic efficacy and safety of the quadratus lumborum block (QLB) in pediatric patients., Methods: Electronic databases were searched for studies comparing the QLB to conventional analgesic techniques in pediatric patients. The primary outcome was the need for rescue analgesia 12 and 24 hours after surgery. Secondary outcomes covered the Face-Legs-Activity-Cry-Consolability Scale (FLACC) scores at various time points; parental satisfaction; time to the first rescue analgesia; hospitalization time; block execution time; block failure rates, and adverse events., Results: Sixteen randomized controlled trials were analyzed involving 1,061 patients. The QLB significantly reduced the need for rescue analgesia both at 12 and 24 hours after surgery (12 hours, relative risk [RR]: 0.45; 95% confidence interval [CI]: 0.01, 0.88; 24 hours, RR: 0.51; 95% CI: 0.31, 0.70). In case of 24 hours after surgery, type 1 QLB significantly reduced the need for rescue analgesia (RR: 0.56; 95% CI: 0.36, 0.76). The QLB also exhibited lower FLACC scores at 1 hour (standardized mean difference [SMD]: -0.87; 95% CI: -1.56, -0.18) and 6 hours (SMD: -1.27; 95% CI: -2.33, -0.21) following surgery when compared to non-QLB. Among QLBs, type 2 QLB significantly extended the time until the first rescue analgesia (SMD: 1.25; 95% CI: 0.84, 1.67). No significant differences were observed in terms of parental satisfaction, hospitalization time, block execution time, block failure, or adverse events between QLB and non-QLB groups., Conclusions: The QLB provides non-inferior analgesic efficacy and safety to conventional methods in pediatric patients.

Background: Coronavirus disease 2019 (COVID-19) induces a dysfunctional immune response, inflammation, autoantibody production, and coagulopathy, which are symptoms that bear resemblance to those of autoimmune diseases, including systemic sclerosis (SSc)., Methods: While there is a single case report suggesting an association between COVID-19 and SSc, the effects of COVID-19 on SSc are not yet fully understood. Human embryonic kidney 293 (HEK293) cells were transfected with the SARS-CoV-2 spike protein gene, in the presence of TGF-β. The expression levels of fibrosis-related proteins were measured via Western blotting. A bleomycin (BLM)-induced SSc mouse model was employed, wherein mice were injected with the gene encoding the SARS-CoV-2 spike protein and the ACE2 receptor. The levels of fibrosis, autoantibodies, thrombotic factors, and inflammatory cytokines in tissues and serum were analyzed., Results: In vitro, the expression levels of fibrosis marker proteins were elevated in the spike protein group compared to the control group. In vivo, the skin thickness of SSc mice increased following exposure to the SARS-CoV-2 spike protein. Furthermore, the levels of autoantibodies and thrombotic factors, such as anti-phospholipid antibodies (APLA), were significantly increased in the presence of the protein. Flow cytometry analysis revealed increased expression of the proinflammatory cytokine IL-17 in the skin, lungs, and blood. Moreover, tissue fibrosis and levels of inflammatory cytokines in skin and lung tissues were markedly escalated in SSc mice subjected to the protein., Conclusion: COVID-19 may accelerate the development and progression of SSc by intensifying fibrosis through the upregulation of inflammation, autoantibody production, and thrombosis., (© 2023. The Author(s).)

Regional nerve blocks (NBs) mitigate the occurrence of postoperative cognitive dysfunction (POCD) and postoperative delirium (POD) in adult patients undergoing thoracic surgery. This study aimed to determine the exact effect of NBs on POCD and POD. Electronic databases, including PubMed, EMBASE, CINAHL, Scopus, and Web of Science, were searched for studies. The primary outcome was the incidence of POD or POCD. The secondary outcome was pain scores assessed 24 and 48 h postoperatively. We calculated the log odds ratio (LOR) and standardized mean difference (SMD) with 95% confidence intervals (CIs). The LOR was converted to an odds ratio (OR). In the analysis of 1010 patients from seven randomized controlled trials, POD and POCD rates were 14.1% and 16.7%, respectively, in the NB group, and higher, at 27.3% and 35.2%, in the control group. NBs reduced the incidence of POD (OR, 0.44; 95%CI 0.30 to 0.64; p < 0.001; I 2 = 0.00%) and POCD (OR, 0.43; 95%CI 0.24 to 0.76; p < 0.001; I 2 = 0.00%). NBs reduced pain scores at 24 h (SMD, -2.60; 95%CI -3.90 to -1.30, p < 0.001; I 2 = 97.68%) and 48 h (SMD, -1.80; 95%CI -3.18 to -0.41, p = 0.01; I 2 = 98.14%) postoperatively. NBs mitigated the occurrence of POD and POCD in adult patients after thoracic surgery., Competing Interests: The authors declare no conflicts of interest.

Recent advances in genomic technologies have enabled more in-depth study of the oral microbiome. In this study, we compared the amplicons generated by primers targeting different sites of the 16S rRNA gene found in the Human Oral Microbiome Database (HOMD). Six sets of primer targeting V1-V2, V1-V3, V3-V4, V4-V5, V5-V7 and V6-V8 regions of 16S rRNA were tested via in silico simulation. Primers targeting the V1-V2, V3-V4, and V4-V5 regions generated more than 90% of the original input sequences. Primers targeting the V1-V2 and V1-V3 regions exhibited a low number of mismatches and unclassified sequences at the taxonomic level, but there were notable discrepancies at the species level. Phylogenetic tree comparisons showed primers targeting the V1-V2 and V3-V4 regions showed performances similar to primers targeting the whole 16s RNA region in terms of separating total oral microbiomes and periodontopathogens. In an analysis of clinical oral samples, V1-V2 primers showed superior performance for identifying more taxa and had better resolution sensitivity for Streptococcus than V3-V4 primers. In conclusion, primers targeting the V1-V2 region of 16S rRNA showed the best performance for oral microbiome studies. In addition, the study demonstrates the need for careful PCR primer selections.

Keloid disorder is an abnormal fibroproliferative reaction that can occur on any area of skin, and it can impair the quality of life of affected individuals. To investigate the pathogenesis and develop a treatment strategy, a preclinical animal model of keloid disorder is needed. However, keloid disorder is unique to humans, and the development of an animal model of keloid disorder is highly problematic. We developed the patient-derived keloid xenograft (PDKX), which is a humanized mouse model, and compared it to the traditional mouse xenograft model (transplantation of only keloid lesions). To establish the PDKX model, peripheral mononuclear cells (PBMCs) from ten keloid patients or five healthy control subjects were injected into NOD/SCID/IL-2Rγnull mice, and their keloid lesions were grafted onto the back after the engraftment of immune cells (transplantation of keloid lesions and KP PBMCs or HC PBMCs). Four weeks after surgery, the grafted keloid lesion was subjected to histologic evaluation. Compared to the traditional model, neotissue formed along the margin of the grafted skin, and lymphocyte infiltration and collagen synthesis were significantly elevated in the PDKX model. The neotissue sites resembled the margin areas of keloids in several respects. In detail, the levels of human Th17 cells, IL-17, HIF-1a, and chemokines were significantly elevated in the neotissue of the PDKX model. Furthermore, the weight of the keloid lesion was increased significantly in the PDKX model, which was due to the proinflammatory microenvironment of the keloid lesion. We confirmed that our patient-derived keloid xenograft (PDKX) model mimicked keloid disorder by recapitulating the in vivo microenvironment. This model will contribute to the investigation of cellular mechanisms and therapeutic treatments for keloid disorders., (© 2023. The Author(s).)