Phenylacetic acid, an anti-vaginitis metabolite produced by the vaginal symbiotic bacterium Chryseobacterium gleum.

The human microbiome contains genetic information that regulates metabolic processes in response to host health and disease. While acidic vaginal pH is maintained in normal conditions, the pH level increases in infectious vaginitis. We propose that this change in the vaginal environment triggers the biosynthesis of anti-vaginitis metabolites. Gene expression levels of Chryseobacterium gleum, a vaginal symbiotic bacterium, were found to be affected by pH changes. The distinctive difference in the metabolic profiles between two C. gleum cultures incubated under acidic and neutral pH conditions was suggested to be an anti-vaginitis molecule, which was identified as phenylacetic acid (PAA) by spectroscopic data analysis. The antimicrobial activity of PAA was evaluated in vitro, showing greater toxicity toward Gardnerella vaginalis and Candida albicans, two major vaginal pathogens, relative to commensal Lactobacillus spp. The activation of myeloperoxidase, prostaglandin E2, and nuclear factor-κB, and the expression of cyclooxygenase-2 were reduced by an intravaginal administration of PAA in the vaginitis mouse model. In addition, PAA displayed the downregulation of mast cell activation. Therefore, PAA was suggested to be a messenger molecule that mediates interactions between the human microbiome and vaginal health.

Shift schedules and circadian preferences: the association with sleep and mood.

Object: We explored the circadian preferences of non-shift workers (non-SWs) and various types of shift workers (SWs), and the associations of these preferences with sleep and mood. Methods: In total, 4,561 SWs (2,419 women and 2,142 men aged 37.00 ± 9.80 years) and 2,093 non-SWs (1,094 women and 999 men aged 37.80 ± 9.73 years) completed an online survey. Of all SWs, 2,415 (1,079 women and 1,336 men aged 37.77 ± 9.96 years) reported regularly rotating or fixed schedules ("regular SWs"), and 2,146 (1,340 women and 806 men aged 36.12 ± 9.64 years) had irregular schedules ("irregular SWs"). Of the regular SWs, 2,040 had regularly rotating schedules, 212 had fixed evening schedules, and 163 had fixed night schedules. All participants completed the Morningness-Eveningness Questionnaire (MEQ) exploring circadian preferences, the short form of the Center for Epidemiological Studies-Depression Scale (CES-D) evaluating depression, the Insomnia Severity Index (ISI), and the Epworth Sleepiness Scale (ESS). Results: Compared to non-SWs, SWs had lower MEQ scores, i.e., more eveningness, after controlling for age, gender, income, occupation, and weekly work hours (F = 87.97, p < 0.001). Irregular SWs had lower MEQ scores than regular SWs (F = 50.89, p < 0.001). Among regular SWs, the MEQ scores of fixed evening and fixed night SWs were lower than those of regularly rotating SWs (F = 22.42, p < 0.001). An association between the MEQ and ESS scores was apparent in non-SWs (r = -0.85, p < 0.001) but not in SWs (r = 0.001, p = 0.92). Conclusion: SWs exhibited more eveningness than non-SWs; eveningness was particularly prominent in SWs with irregular or fixed evening/night shifts. Eveningness was associated with sleepiness only in non-SWs, but not in SWs.

Advancements and turning point of artificial intelligence in ophthalmology: A comprehensive analysis of research trends and collaborative networks.

Artificial intelligence (AI) has emerged as a transformative force with great potential in various fields, including healthcare. In recent years, AI has garnered significant attention due to its potential to revolutionise ophthalmology, leading to advancements in patient care such as disease detection, diagnosis, treatment and monitoring of disease progression. This study presents a comprehensive analysis of the research trends and collaborative networks at the intersection of AI and ophthalmology. In this study, we conducted an extensive search of the Web of Science Core Collection to identify articles related to 'artificial intelligence' in ophthalmology published from 1968 to 2023. We performed co-occurrence keywords and co-authorship network analyses using VOSviewer software to explore the relationships between keywords and country collaboration. We found a remarkable surge in articles applying AI in ophthalmology after 2017, marking a turning point in the integration of AI within the medical field. The primary application of AI shifted towards the diagnosis of ocular disease, which was particularly evident through keywords such as glaucoma, diabetic retinopathy and age-related macular degeneration. Analysis of the collaboration networks of countries revealed a global expansion of ophthalmology-related AI research. This study provides valuable insights into the evolving landscape of AI integration in ophthalmology, indicating its growing potential for enhancing disease detection, diagnosis, treatment planning and monitoring of disease progression. In order to translate AI technologies into clinical practice effectively, it is imperative to comprehend the evolving research trends and advancements at the intersection of AI and ophthalmology.

Molecular basis for SOX2-dependent regulation of super-enhancer activity.

Pioneer transcription factors (TFs) like SOX2 are vital for stemness and cancer through enhancing gene expression within transcriptional condensates formed with coactivators, RNAs and mediators on super-enhancers (SEs). Despite their importance, how these factors work together for transcriptional condensation and activation remains unclear. SOX2, a pioneer TF found in SEs of pluripotent and cancer stem cells, initiates SE-mediated transcription by binding to nucleosomes, though the mechanism isn't fully understood. To address SOX2's role in SEs, we identified mSE078 as a model SOX2-enriched SE and p300 as a coactivator through bioinformatic analysis. In vitro and cell assays showed SOX2 forms condensates with p300 and SOX2-binding motifs in mSE078. We further proved that SOX2 condensation is highly correlated with mSE078's enhancer activity in cells. Moreover, we successfully demonstrated that p300 not only elevated transcriptional activity but also triggered chromatin acetylation via its direct interaction with SOX2 within these transcriptional condensates. Finally, our validation of SOX2-enriched SEs showcased their contribution to target gene expression in both stem cells and cancer cells. In its entirety, this study imparts valuable mechanistic insights into the collaborative interplay of SOX2 and its coactivator p300, shedding light on the regulation of transcriptional condensation and activation within SOX2-enriched SEs.

A Bibliometric Analysis of Myopia Research in East Asia in the 21st Century: The Socio-Economic Status and Quantitative Analysis.

The purpose of this study is to assess the quantity and quality of myopia related articles from 2001 to 2021 using bibliometric methods. The number of published articles and citations, the correlation analysis between gross domestic product (GDP) and annual publication number and citations was investigated. The proportion of myopia articles from East Asia accounted for 55.28% in 2021. The researchers from China published the most articles on myopia during 2001 to 2021, followed by Japan and South Korea. The annual number of articles and citations from China and South Korea showed an exponential increase with strong positive correlation with GDP. All 3 countries in East Asia are mainly researching refractive surgery, prevalence, and glaucoma, and research on children's myopia is particularly active in China, and in Japan. The researchers from East Asia published more than half of articles on myopia since 2019, in order of China, Japan, and South Korea. The annual number of articles and citations from China and South Korea showed an exponential increase with strong positive correlation with GDP whereas those from Japan did not. All 3 countries are mainly researching refractive surgery, and glaucoma, and research on children's myopia is particularly active in China, and in Japan.

The Ionization of Polymeric Materials Accelerates Protein Deposition on Hydrogel Contact Lens Material.

Contact lens materials include polymers that are ionized in the ocular pH condition and are susceptible to protein deposition due to their surface characteristics. Herein, we investigated the effect of the electrostatic state of the contact lens material and protein on protein deposition level using hen egg white lysozyme (HEWL) and bovine serum albumin (BSA) as model proteins and etafilcon A and hilafilcon B as model contact lens materials. Only HEWL deposition on etafilcon A showed a statistically significant pH-dependency (p < 0.05); protein deposition increased with pH. HEWL showed a positive zeta potential at acidic pH, while BSA showed a negative zeta potential at basic pH. Only etafilcon A showed a statistically significant pH-dependent point of zero charge (PZC) (p < 0.05), implying that its surface charge became more negative under basic conditions. This pH-dependency of etafilcon A is attributed to the pH-responsive degree of ionization of its constituent methacrylic acid (MAA). The presence of MAA and its degree of ionization could accelerate protein deposition; more HEWL deposited as pH increased despite the weak positive surface charge of HEWL. The highly negatively charged etafilcon A surface attracted HEWL, even overwhelming weak positive charge of HEWL, increasing the deposition with pH.

The pH-induced physical properties of ionic contact lens material.

The degree of protonation of contact lens materials is affected by the surrounding pH environment, due to the different pKa values. The swelling of ionic contact lenses is generally controlled by these factors which determines physical properties of contact lenses. The purpose of this study was to evaluate the pH dependence of the physical properties of contact lenses. The ionic etafilcon A and non-ionic hilafilcon B contact lenses were used in this study. The diameter, refractive power, equilibrium water content (EWC), and the amounts of freezable-free water (Wff), freezable-bound water (Wfb) and non-freezable water (Wnf) in the contact lens at each pH condition were measured. The diameter, refractive power and EWC of etafilcon A decreased with decreasing pH below 7.0 or 7.4, whereas hilafilcon B showed relatively constant values. The quantity of Wfb tended to increase with increasing pH, showing a relatively constant value above 7.0, whereas Wnf decreased. Hilafilcon B did not show changes in EWC and specific trends in Wfb and Wnf. The significant change of etafilcon A at more acidic condition is derived from the presence of methacrylic acid (MA) which makes it vulnerable to pH. Additionally, though the EWC is composed of various states of water, (i) various states of water could response to surrounding environment in different way with EWC and (ii) Wfb could be the crucial factor that determines physical properties of contact lens.

A method for early diagnosis of lung cancer from tumor originated DNA fragments using plasma cfDNA methylome and fragmentome profiles.

Early detection is critical for minimizing mortality from cancer. Plasma cell-free DNA (cfDNA) contains the signatures of tumor DNA, allowing us to quantify the signature and diagnose early-stage tumors. Here, we report a novel tumor fragment quantification method, TOF (Tumor Originated Fragment) for the diagnosis of lung cancer by quantifying and analyzing both the plasma cfDNA methylation patterns and fragmentomic signatures. TOF utilizes the amount of ctDNA predicted from the methylation density information of each cfDNA read mapped on 6243 lung-tumor-specific CpG markers. The 6243 tumor-specific markers were derived from lung tumor tissues by comparing them with corresponding normal tissues and healthy blood from public methylation data. TOF also utilizes two cfDNA fragmentomic signatures: 1) the short fragment ratio, and 2) the 5' end-motif profile. We used 298 plasma samples to analyze cfDNA signatures using enzymatic methyl-sequencing data from 201 lung cancer patients and 97 healthy controls. The TOF score showed 0.98 of the area under the curve in correctly classifying lung cancer from normal samples. The TOF score resolution was high enough to clearly differentiate even the early-stage non-small cell lung cancer patients from the healthy controls. The same was true for small cell lung cancer patients.

CCL2 overexpression is associated with paclitaxel resistance in ovarian cancer cells via autocrine signaling and macrophage recruitment.

Tumor cells can secret various cytokines and chemokines, which affect the tumor cells themselves and the neighboring cells. Here, we observed that human ovarian cancer (OC) cells developed resistance to paclitaxel treatment following culture with the conditioned medium (CM) derived from paclitaxel-resistant OC (OCTR) cells. A cytokine array revealed that both OCTR cells secreted large amounts of CC chemokine ligand 2 (CCL2). CCL2 and its receptor, CCR2, were overexpressed in OCTR cells. CCL2 expression was associated with worse progression-free survival in patients with ovarian cancer. The inhibition of the CCL2/CCR2 axis suppressed the chemoresistance induced by OCTR-CM. The enhanced expression and production of CCL2 in OC cells were mediated via the NF-κB pathway, and stimulated the activation of the PI3K/Akt pathway, which resulted in the development of paclitaxel resistance in OC cells. Additionally, the OCTR cells significantly increased the migration of macrophages, which was also associated with the overproduction of CCL2 in chemoresistant cancer cells. The macrophages stimulated by OCTR cells expressed high levels of markers of M2 phenotype, and their CM significantly decreased the paclitaxel responsiveness of OC cells. The administration of a CCR2 inhibitor to a murine model significantly improved the paclitaxel sensitivity. These data suggested that apart from inducing chemoresistance in OC cells by acting as an autocrine factor, CCL2 also functions as a chemokine that induces the chemotaxis of macrophages, which may contribute to chemoresistance. Therefore, targeting the CCL2/CCR2 signaling axis may improve the therapeutic response of patients with ovarian cancer to paclitaxel.

Citromycin Isolated from the Antarctic Marine-Derived Fungi, Sporothrix sp., Inhibits Ovarian Cancer Cell Invasion via Suppression of ERK Signaling.

Recently, microorganisms and their metabolites in the Antarctic marine environment have attracted attention as useful sources for novel therapeutics, including anticancer drugs. Here, we investigated the effects of citromycin, isolated from the Antarctic marine-derived fungus, Sporothrix sp., on human ovarian cancer cells. Citromycin inhibited the migration and invasion of human ovarian cancer SKOV3 and A2780 cells, but had no cytotoxic activity against them. Additionally, it inhibited the expression of epithelial-mesenchymal transition (EMT) markers and the activation of matrix metalloproteinase (MMP)-2 and MMP9. Moreover, extracellular signal-regulated kinase (ERK)-1/2 signaling was inhibited after citromycin treatment, and the ectopic expression of ERK negated the anti-invasive activity of citromycin. Our findings suggest that citromycin inhibits the migration and invasion of human ovarian cancer cells by downregulating the expression levels of EMT markers and MMP-2/9 via inhibition of the ERK1/2 pathway.

The Anti-Endometriotic Effect of Cyperi Rhizoma Extract, Inhibiting Cell Adhesion and the Expression of Pain-Related Factors through Akt and NF-kB Pathways.

Rhizomes of Cyperus rotundus have been widely used as a traditional medicine in Asia for the treatment of gynecological diseases. However, there is no scientific evidence demonstrating the effect of C. rotundus rhizomes on endometriosis, which is characterized by the adhesion of endometrial tissues outside the uterus, resulting in chronic and severe pelvic pain. The aim of this study was to investigate the effects of Cyperi rhizoma extract (CRE) on cell adhesion and the expression of pain-related factors (neurotrophins) in endometriotic cells, and to elucidate the underlying molecular mechanisms. CRE inhibited the adhesion of human endometriotic 12Z cells to peritoneal mesothelial Met5A cells using by adhesion assays. The mRNA expression of adhesion molecules [P-cadherin and matrix metalloproteinase (MMP)-2] was downregulated by CRE treatment. In addition, CRE significantly inhibited the mRNA expression of neurotrophins (BDNF, NGF, NT-3 and NT-4/5) in 12Z cells. Moreover, Akt overexpression markedly neutralized the inhibition of cell adhesion by CRE and expression of neurotrophins in 12Z cells. Furthermore, it was found that CRE suppressed NF-kB activation through the Akt pathway. These data suggest that CRE exerts anti-endometriotic activities by the inhibition of cell adhesion and neurotrophin expression, through the negative regulation of the Akt and NF-kB pathways in endometriotic cells.

LT1, an ONT long-read-based assembly scaffolded with Hi-C data and polished with short reads.

We present LT1, the first high-quality human reference genome from the Baltic States. LT1 is a female de novo human reference genome assembly, constructed using 57× nanopore long reads and polished using 47× short paired-end reads. We utilized 72 GB of Hi-C chromosomal mapping data for scaffolding, to maximize assembly contiguity and accuracy. The contig assembly of LT1 was 2.73 Gbp in length, comprising 4490 contigs with an NG50 value of 12.0 Mbp. After scaffolding with Hi-C data and manual curation, the final assembly has an NG50 value of 137 Mbp and 4699 scaffolds. Assessment of gene prediction quality using Benchmarking Universal Single-Copy Orthologs (BUSCO) identified 89.3% of the single-copy orthologous genes included in the benchmark. Detailed characterization of LT1 suggests it has 73,744 predicted transcripts, 4.2 million autosomal SNPs, 974,616 short indels, and 12,079 large structural variants. These data may be used as a benchmark for further in-depth genomic analyses of Baltic populations.

Model-Informed Drug Development in Pediatric Dose Selection.

Model-informed drug development (MIDD) has been a powerful and efficient tool applied widely in pediatric drug development due to its ability to integrate and leverage existing knowledge from different sources to narrow knowledge gaps. The dose selection is the most common MIDD application in regulatory submission related to pediatric drug development. This article aims to give an overview of the 3 broad categories of use of MIDD in pediatric dose selection: leveraging from adults to pediatric patients, leveraging from animals to pediatric patients, and integrating mechanism in infants and neonates. Population pharmacokinetic analyses with allometric scaling can reasonably predict the clearance in pediatric patients aged >5 years. A mechanistic-based approach, such as physiologically based pharmacokinetic accounting for ontogeny, or an allometric model with age-dependent exponent, can be applied to select the dose in pediatric patients aged ≤2 years. The exposure-response relationship from adults or from other drugs in the same class may be useful in aiding the pediatric dose selection and benefit-risk assessment. Increasing application and understanding of use of MIDD have contributed greatly to several policy developments in the pediatric field. With the increasing efforts of MIDD under the Prescription Drug User Fee Act VI, bigger impacts of MIDD approaches in pediatric dose selection can be expected. Due to the complexity of model-based analyses, early engagement between drug developers and regulatory agencies to discuss MIDD issues is highly encouraged, as it is expected to increase the efficiency and reduce the uncertainty.

Binding affinity of benzalkonium chloride on contact lens surfaces and the effects on their physical properties.

Benzalkonium chloride (BKC) is a cationic surfactant used as a component in ophthalmic eye drops. The effects of BKC on the eye and the simple binding of BKC on the contact lens surface have been reported in other studies. However, the exact value of the BKC binding affinity on the contact lens surfaces and its effects on the physical properties of contact lenses have not been studied. Here, the binding affinity of BKC toward two types of contact lenses, those with the wetting agent polyvinylpyrrolidone (PVP) and those without, was calculated. In addition, the refractive power, UV-vis transmittance, contact angle, water content, base curve, and diameter of the contact lenses after treatment with BKC were examined to evaluate the effects of its adsorption on the contact lens. We found that the maximum amount of adsorbed BKC was 2.88 mM for the contact lens without PVP whereas it was 2.32 mM for that with PVP. In contrast, the BKC binding affinities were similar. Crucially, the physical properties of the contact lens changed significantly because of the adsorption of BKC. Although BKC is a widely used preservative, our results suggest that use of PVP-containing contact lenses reduces BKC adsorption and discomfort.

Reduced Levels of Intestinal Neuropeptides and Neurotrophins in Neurotoxin-Induced Parkinson Disease Mouse Models.

Intestinal neuropeptides and neurotrophins as endocrine messengers play a key role in the bidirectional gut-brain interaction both in health and disease status. Their alterations in several neurological disorders have been reported, but whether a remarkable change occurs in Parkinson disease (PD) remains unexplored. In this study, we aimed to investigate the levels of 13 neuropeptides and 4 neurotrophins in the intestine of neurotoxin-induced PD mice. The PD mice were obtained by chronic injection of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) or MPTP/probenecid (MPTP/p). The levels of mRNA and protein expression in mouse intestines were measured by using real-time reverse transcription polymerase chain reaction and Western blotting, respectively. We found that the mRNA expression of 2 neuropeptides (cholecystokinin [CCK] and dynorphin A [Dyn A]) and 2 neurotrophins (brain-derived neurotrophic factor [BDNF] and neurotrophin-5) was significantly decreased in the colon of MPTP group compared to the vehicle-treated group. The protein levels of CCK, Dyn A, and BDNF were reduced in the colon of MPTP- or MPTP/p-treated mice compared to those of the vehicle-treated group. These data suggest that the intestinal expression of CCK, Dyn A, and BDNF was significantly reduced in PD animal models, and may play a role in the gut-brain axis in PD.

Time-Dependent Anti-Demineralization Effect of Silver Diamine Fluoride.

This study compared the demineralization resistance of teeth treated with silver diamine fluoride (SDF) to that treated with fluoride varnish. A total of 105 healthy bovine incisors were divided into control, fluoride varnish, and SDF groups. The enamel surface density change was then measured by micro-computed tomography (micro-CT) at three depths. The demineralized zone volume was measured on 3D micro-CT images to evaluate the total demineralization rate. The enamel surface morphology was assessed by scanning electron microscope. The enamel density had continuously decreased while demineralization increased in the control and fluoride varnish groups. The enamel density had increased in the SDF group till the 7th day of demineralization treatment and decreased thereafter. However, the decrease in the SDF group was less severe than that in the other groups (p < 0.05). The demineralized enamel volume had increased through treatment and was the highest in the control group, followed by the fluoride varnish and SDF group. The enamel surface morphology was the roughest and most irregular in the control group, followed by the fluoride varnish group and SDF groups.

Longevity effects of hispidol in Caenorhabditis elegans.

In this study, we investigated the longevity effects of hispidol, a 6,4'-dihydroxyaurone, using the Caenorhabditis elegans model system. Our lifespan assay data revealed that hispidol could prolong the lifespan of wild-type worms under normal culture condition. Moreover, hispidol increased the survival rate of the worms against a heat stress condition through up-regulated expressions of HSP-16.2. Similarly, hispidol protected worms from paraquat-induced oxidative stress. We also found that the hispidol elevated the activities of antioxidant enzymes, thereby attenuating the generation of intracellular reactive oxygen species. These results suggest that the enhancement of lifespan and stress resistance by the hispidol treatment might be attributed to its strong in vivo antioxidant capacity and regulation of stress proteins. Further tests on the aging-related factors revealed that hispidol could regulate the speed of pharyngeal pumping, indicating the association of dietary restriction with the hispidol-mediated longevity. However, there were no significant alterations in the body length of the worms between the groups. We then investigated the effects of hispidol on body movement and lipofuscin accumulation in aged worms. Interestingly, these healthspan parameters were strongly improved by the hispidol treatment. Our genetic studies showed no significant change in the lifespan of the daf-16 null mutants by hispidol supplementation. In addition, enhanced nuclear translocation of DAF-16 was observed in the hispidol-fed DAF-16::GFP fused transgenic mutants, suggesting the requirement of DAF-16/FOXO activation for the longevity effect of hispidol.

Anti-inflammatory effects of dexmedetomidine on human amnion-derived WISH cells.

Background: To maintain the normal pregnancy, suppression of inflammatory signaling pathway is a crucial physiologic response. Dexmedetomidine has been used for labor analgesia or supplement of inadequate regional analgesia during delivery. And it has been reported that dexmedetomidine has an anti-inflammatory effect. In this study, we examined the influence of dexmedetomidine on the expression of cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) and inflammatory cytokines in lipopolysaccharide (LPS)-stimulated human amnion-derived WISH cells. In addition, we evaluated the association of mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathway in anti-inflammatory effect of dexmedetomidine. Methods: Human amnion-derived WISH cells were pretreated with various concentrations of dexmedetomidine (0.001-1 µg/ml) for 1 h and after then treated with LPS (1 µg/ml) for 24 h. MTT assay was conducted to evaluate the cytotoxicity. Nitric oxide (NO) production was analyzed using Griess-reaction microassay. RT-PCR was performed for analysis of mRNA expressions of COX-2, PGE2, tumor necrosis factor (TNF)-α and interlukin (IL)-1ß. Protein expressions of COX-2, PGE2, p38 and NF-κB were analyzed by western blotting. Results: LPS and dexmedetomidine had no cytotoxic effect on WISH cells. There was no difference in NO production after dexmedetomidine pretreatment. The mRNA and protein expressions of COX-2 and PGE2 were decreased by dexmedetomidine pretreatment in LPS-treated WISH cells. Dexmedetomidine also attenuated the LPS-induced mRNA expression of TNF-α and IL-1ß. The activation of p38 and NF-κB was suppressed by dexmedetomidine pretreatment in LPS-treated WISH cells. Conclusion: We demonstrated that dexmedetomidine pretreatment suppressed the expressions of inflammatory mediators increased by LPS. In addition, this study suggests that anti-inflammatory effect of dexmedetomidine on WISH cells was mediated by the inhibitions of p38 and NF-κB activation.

Optimal effect-site concentration of remifentanil to prevent hemodynamic changes during nasotracheal intubation using a video laryngoscope.

BACKGROUND: Nasotracheal intubation is the most commonly used method to secure the field of view when performing surgery on the oral cavity or neck. Like orotracheal intubation, nasotracheal intubation uses a laryngoscope. Hemodynamic change occurs due to the stimulation of the sympathetic nervous system. Recently, video laryngoscope with a camera attached to the end of the direct laryngoscope blade has been used to minimize this change. In this study, we investigated the optimal effect-site concentration (Ce) of remifentanil for minimizing hemodynamic responses during nasotracheal intubation with a video laryngoscope. METHODS: Twenty-one patients, aged between 19 and 60 years old, scheduled for elective surgery were included in this study. Anesthesia was induced by slowly injecting propofol. At the same time, remifentanil infusion was initiated at 3.0 ng/ml via target-controlled infusion (TCI). When remifentanil attained the preset Ce, nasotracheal intubation was performed using a video laryngoscope. The patient's blood pressure and heart rate were checked pre-induction, right before and after intubation, and 1 min after intubation. Hemodynamic stability was defined as an increase in systolic blood pressure and heart rate by 20% before and after nasotracheal intubation. The response of each patient determined the Ce of remifentanil for the next patient at an interval of 0.3 ng/ml. RESULTS: The Ce of remifentanil administered ranged from 2.4 to 3.6 ng/ml for the patients evaluated. The estimated optimal effective effect-site concentrations of remifentanil were 3.22 and 4.25 ng/ml, that were associated with a 50% and 95% probability of maintaining hemodynamic stability, respectively. CONCLUSION: Nasotracheal intubation using a video laryngoscope can be successfully performed in a hemodynamically stable state by using the optimal remifentanil effect-site concentration (Ce50 , 3.22 ng/ml; Ce95 , 4.25 ng/ml).

Neurotoxicity of local anesthetics in dentistry.

During dental treatment, a dentist usually applies the local anesthesia. Therefore, all dentists should have expertise in local anesthesia and anesthetics. Local anesthetics have a neurotoxic effect at clinically relevant concentrations. Many studies have investigated the mechanism of neurotoxicity of local anesthetics but the precise mechanism of local anesthetic-induced neurotoxicity is still unclear. In addition, it is difficult to demonstrate the direct neurotoxic effect of local anesthetics because perioperative nerve damage is influenced by various factors, such as the anesthetic, the patient, and surgical risk factors. This review summarizes knowledge about the pharmacology of local anesthetics, nerve anatomy, and the incidence, risk factors, and possible cellular mechanisms of local anesthetic-induced neurotoxicity.