50% efficacy dose of intravenous lidocaine in supressing sufentanil-induced cough in children: a randomised controlled trial.

BACKGROUND: Opioids such as sufentanil are used as anaesthetics due to their rapid action and superior analgesic effect. However, sufentanil induces a huge cough in paediatric patients. In contrast, intravenous (IV) lidocaine suppresses opioid-induced cough in children, but its use is limited due to anaesthetists' concern about its toxicity. Therefore, this study aimed to evaluate the effect of dose-dependent IV lidocaine on sufentanil-induced cough (SIC) in paediatric patients. METHODS: A total of 188 patients aged 3-12 years scheduled for elective tonsillectomy with or without adenoidectomy were enrolled and divided into four groups depending on different dose of lidocaine: A (0 mg.kg-1), B (1 mg.kg-1), C (1.5 mg.kg-1), and D (2 mg.kg-1). The primary outcome was the SIC grade observed during the induction of general anaesthesia. The secondary outcomes were the incidence of SIC, mean arterial pressure, and heart rate at T0, T1, T2, T3, T4, and T5. RESULTS: The SIC grade was significantly different between groups A and D (P = 0.04) and between groups B and D (P = 0.03). Moreover, the incidence of SIC in groups A, B, C, and D was 81%, 87%, 68%, and 64%, respectively, and the difference between groups B and C (P = 0.03) and between groups B and D (P = 0.0083) was statistically significant. No statistical differences were observed in the hemodynamic parameters between the groups. The incidence of severe cough was statistically different between group D and group A (P < 0.0001), between group D and group B (P < 0.0001), and between group D and group C (P < 0.0001) respectively. CONCLUSIONS: Lidocaine suppresses SIC in a dose-dependent manner without severe adverse events. IV lidocaine can be used in paediatric patients safely and efficiently, and the median effective dose was 1.75 mg/kg. TRIAL REGISTRATION: This study was approved by the Institutional Review Board of Yichang Central People's Hospital (HEC-KYJJ-2020-038-02), The trial was registered at www.chictr.org.cn (ChiCTR2100053006).

Effect of endoscopic therapy and drug therapy on prognosis and rebleeding in patients with esophagogastric variceal bleeding.

Esophagogastric variceal bleeding (EVB) is one of the common digestive system emergencies with poor prognosis and high rate of rebleeding after treatment. To explore the effects of endoscopic therapy and drug therapy on the prognosis and rebleeding of patients with EVB, and then select better treatment methods to effectively improve the prognosis. From January 2013 to December 2022, 965 patients with EVB who were hospitalized in gastroenterology Department of the 940 Hospital of Joint Logistic Support Forces of PLA were retrospectively analyzed. Patients were divided into endoscopic treatment group (ET, n = 586) and drug treatment group (DT, n = 379). Propensity score matching (PSM) analysis was performed in both groups, and the general information, efficacy and length of hospital stay were recorded. The patients were followed up for 3 months after bleeding control to determine whether rebleeding occurred. There were 286 cases in each group after PSM. Compared with DT group, ET had higher treatment success rate (P < 0.001), lower rebleeding rate (P < 0.001), lower mortality rate within 3 months, and no significant difference in total hospital stay (P > 0.05). Compared with drug therapy, endoscopic treatment of EVB has short-term efficacy advantages, and can effectively reduce the incidence of rebleeding and mortality within 3 months.

DDX6 is involved in the pathogenesis of inflammatory diseases via NF-κB activation.

The IL-6 amplifier was originally discovered as a mechanism for the enhanced activation of NF-κB in non-immune cells. In the IL-6 amplifier, IL-6-STAT3 and NF-κB stimulation is followed by an excessive production of IL-6, chemokines, and growth factors to develop chronic inflammation preceding the development of inflammatory diseases. Previously, using a shRNA-mediated genome-wide screening, we found that DEAD-Box Helicase 6 (DDX6) is a candidate positive regulator of the amplifier. Here, we investigate whether DDX6 is involved in the pathogenesis of inflammatory diseases via the IL-6 amplifier. We found that DDX6-silencing in non-immune cells suppressed the NF-κB pathway and inhibited activation of the IL-6 amplifier, while the forced expression of DDX6 enhanced NF-κB promoter activity independent of the RNA helicase activity of DDX6. The imiquimod-mediated dermatitis model was suppressed by the siRNA-mediated gene downregulation of DDX6. Furthermore, silencing DDX6 significantly reduced the TNF-α-induced phosphorylation of p65/RelA and IκBα, nuclear localization of p65, and the protein levels of IκBα. Mechanistically, DDX6 is strongly associated with p65 and IκBα, but not TRADD, RIP, or TRAF2, suggesting a novel function of DDX6 as an adaptor protein in the NF-κB pathway. Thus, our findings demonstrate a possible role of DDX6 beyond RNA metabolism and suggest DDX6 is a therapeutic target for inflammatory diseases.

Neutrophil extracellular traps in central nervous system (CNS) diseases.

Excessive induction of inflammatory and immune responses is widely considered as one of vital factors contributing to the pathogenesis and progression of central nervous system (CNS) diseases. Neutrophils are well-studied members of inflammatory and immune cell family, contributing to the innate and adaptive immunity. Neutrophil-released neutrophil extracellular traps (NETs) play an important role in the regulation of various kinds of diseases, including CNS diseases. In this review, current knowledge on the biological features of NETs will be introduced. In addition, the role of NETs in several popular and well-studied CNS diseases including cerebral stroke, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis (ALS), and neurological cancers will be described and discussed through the reviewing of previous related studies.

Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways.

Current treatments for neurodegenerative diseases and neural injuries face major challenges, primarily due to the diminished regenerative capacity of neurons in the mammalian CNS as they mature. Here, we investigated the role of Ezh2, a histone methyltransferase, in regulating mammalian axon regeneration. We found that Ezh2 declined in the mouse nervous system during maturation but was upregulated in adult dorsal root ganglion neurons following peripheral nerve injury to facilitate spontaneous axon regeneration. In addition, overexpression of Ezh2 in retinal ganglion cells in the CNS promoted optic nerve regeneration via both histone methylation-dependent and -independent mechanisms. Further investigation revealed that Ezh2 fostered axon regeneration by orchestrating the transcriptional silencing of genes governing synaptic function and those inhibiting axon regeneration, while concurrently activating various factors that support axon regeneration. Notably, we demonstrated that GABA transporter 2, encoded by Slc6a13, acted downstream of Ezh2 to control axon regeneration. Overall, our study underscores the potential of modulating chromatin accessibility as a promising strategy for promoting CNS axon regeneration.

Traditional Chinese medicine for smoking cessation: An umbrella review of systematic reviews and meta-analysis of randomized controlled trials.

INTRODUCTION: Traditional Chinese medicine (TCM) may have special advantages in facilitating smoking cessation, but consensus on effectiveness is lacking. We aim to comprehensively review, update, and refine current evidence on TCM effectiveness and safety. METHODS: Nine databases were searched from their inception up to 28 February 2023. Systematic reviews (SRs) and meta-analysis of TCM for smoking cessation were identified and retrieved. Additional databases and hand searches of RCTs from included SRs were performed for data pooling. Cochrane ROB tools and AMSTAR-2 were used to evaluate the methodological quality of RCTs and SRs, respectively. RCT data are presented as relative risks (RR) or mean differences (MD) with 95% confidence intervals (CI) using RevMan 5.4. RESULTS: Thirteen SRs involving 265 studies with 33081 participants were included. Among these 265 studies, 157 were duplicates (58.36%) and 52 were non-RCTs (19.62%). Combined with the remaining 56 RCTs identified through hand searches, 88 RCTs involving 12434 participants were finally included for data synthesis. All the SRs focused on acupoint stimulation, and the majority were of low or very low quality. The methodological quality of RCTs was either unclear or high risk. For continuous abstinence rate, TCM external interventions were better than placebo in 6 months to 1 year (RR=1.60; 95% CI: 1.14-2.25; I2=27%; n=5533 participants). Compared with placebo, TCM external application was effective in reducing nicotine withdrawal symptoms, and the effect was gradually stable and obvious in the fourth week (MD= -4.46; 95% CI: -5.43 - -3.49; n=165 participants). Twelve RCTs reported adverse events as outcome indicators for safety evaluation, and no serious adverse events occurred. CONCLUSIONS: Despite the methodological limitations of the original studies, our review suggests that TCM intervention shows potential effectiveness on the continuous abstinence rate. Extending the intervention time can enhance the effect of TCM on nicotine withdrawal symptoms. Referred to adverse events, more data for safety evaluation are required.

Structural and signaling mechanisms of TAAR1 enabled preferential agonist design.

Trace amine-associated receptor 1 (TAAR1) senses a spectrum of endogenous amine-containing metabolites (EAMs) to mediate diverse psychological functions and is useful for schizophrenia treatment without the side effects of catalepsy. Here, we systematically profiled the signaling properties of TAAR1 activation and present nine structures of TAAR1-Gs/Gq in complex with EAMs, clinical drugs, and synthetic compounds. These structures not only revealed the primary amine recognition pocket (PARP) harboring the conserved acidic D3.32 for conserved amine recognition and "twin" toggle switch for receptor activation but also elucidated that targeting specific residues in the second binding pocket (SBP) allowed modulation of signaling preference. In addition to traditional drug-induced Gs signaling, Gq activation by EAM or synthetic compounds is beneficial to schizophrenia treatment. Our results provided a structural and signaling framework for molecular recognition by TAAR1, which afforded structural templates and signal clues for TAAR1-targeted candidate compounds design.

Identification of 8 Rare Deleterious Variants in ADAMTS13 by Next-generation Sequencing in a Chinese Population with Thrombotic Thrombocytopenic Purpura.

OBJECTIVE: Thrombotic thrombocytopenic purpura (TTP) is a rare and fatal disease caused by a severe deficiency in the metalloprotease ADAMTS13 and is characterized by thrombotic microangiopathy. The present study aimed to investigate the genes and variants associated with TTP in a Chinese population. METHODS: Target sequencing was performed on 220 genes related to complements, coagulation factors, platelets, fibrinolytic, endothelial, inflammatory, and anticoagulation systems in 207 TTP patients and 574 controls. Subsequently, logistic regression analysis was carried out to identify the TTP-associated genes based on the counts of rare deleterious variants in the region of a certain gene. Moreover, the associations between common variants and TTP were also investigated. RESULTS: ADAMTS13 was the only TTP-associated gene (OR = 3.77; 95% CI: 1.82-7.81; P=3.6×10È¡4) containing rare deleterious variants in TTP patients. Among these 8 variants, 5 novel rare variants that might contribute to TTP were identified, including rs200594025, rs782492477, c.T1928G (p.I643S), c.3336_3361del (p.Q1114Afs*20), and c.3469_3470del (p.A1158Sfs*17). No common variants associated with TTP were identified under the stringent criteria of correction for multiple testing. CONCLUSION: ADAMTS13 is the primary gene related to TTP. The genetic variants associated with the occurrence of TTP were slightly different between the Chinese and European populations.

Experimental and theoretical studies on inhibition against tyrosinase activity and melanin biosynthesis by antioxidant ergothioneine.

Ergothioneine, a natural derivative of histidine with a thiol/thine tautomeric structure, exhibits exceptional antioxidant properties and inhibition activities on tyrosinase. In this study, enzyme kinetics experiments and chromatographic spectral analysis revealed that ergothioneine inhibited tyrosinase in a reversible and non-competitive manner, with an inhibition constant of 0.554 mg/mL (2.41 mM). As the concentration of ergothioneine increased, the extremely flexible loop structure of tyrosinase extended from 40.1 % to 41.0 %, effectively covering the active center or binding site. Theoretical molecular docking simulation results show that ergothioneine forms complexes with tyrosinase through hydrogen bonding and salt bridges in the active center of Cu ions. Additionally, it was observed that ergothioneine's antioxidant had a stronger reducing impact on dopaquinone, an intermediate in melanin production, than the effect of ascorbic acid at an equivalent concentration (0.5 mg/mL). Ergothioneine reduced the intracellular reactive oxygen species to lower levels than the control group without UVA radiation and regulated the proliferation and differentiation in B16-F10 melanocytes. Clinical trials have shown that a 0.1 % concentration of ergothioneine can effectively suppress melanin production in irradiated skin. The significant reduction in melanin index and an increase in the individual type angle (ITA°) degree were measured after 4 weeks. These results collectively suggest that ergothioneine may be a promising inhibitor of natural antioxidant tyrosinase. Furthermore, due to its safety and efficacy, ergothioneine could be considered one of the bioactive substances for further study on diseases related to melanin production and tyrosinase activity which is of great significance for the cosmetics, medicine and food industries.

ED95 of remimazolam in nasal administration for attenuating preoperative anxiety in children.

Background: Preoperative anxiety often prevails in children at higher levels than adults, which is a common impediment for surgeons and anesthesiologists. It is of great necessity to explore an appropriate medication to improve this situation. Remimazolam, a type of benzodiazepine drug, has been indicated for the induction and maintenance of procedural sedation in adults since 2020. To date, rare studies were reported to investigate the effect of remimazolam on children. In this study, we investigated the safety and efficacy of intranasal drops of remimazolam and tried to determine the 95% effective dose (ED95) of remimazolam in single intranasal administration in attenuating preoperative anxiety in children. Methods: In this study, 114 children were enrolled who underwent laparoscopic high-level inguinal hernia ligation between January 2021 and December 2022 and were divided into an early childhood children group and a pre-school children group. The biased coin design (BCD) was used to determine the target doses. A positive response was defined as the effective relief of preoperative anxiety (modified Yale Preoperative Anxiety Scale, mYPAS < 30). The initial nasal dose of remimazolam was 0.5 mg·kg-1 in the two groups. An increment or decrement of 0.1 mg·kg-1 was applied depending on the sedative responses. Isotonic regression and bootstrapping methods were used to calculate the ED95 and 95% confidence intervals (CIs), respectively. Results: A total of 80 children completed the study, including 40 in the early childhood group and 40 in the pre-school children group. As statistical analysis indicated, the ED95 of a single intranasal infusion of remimazolam for the relief of preoperative anxiety is 1.57 mg·kg-1 (95% CI: 1.45-1.59 mg·kg-1) in early childhood children and 1.09 mg·kg-1 (95% CI: 0.99-1.11 mg·kg-1) in pre-school children, and the CIs did not overlap each other. Conclusion: Remimazolam is an effective medication to relieve preoperative anxiety in children. Moreover, the ED95 of single nasal administration of remimazolam for effective relief of preoperative anxiety was 1.57 and 1.09 mg·kg-1 in early childhood children and pre-school children, respectively.

An inflammatory bowel disease-associated SNP increases local thyroglobulin expression to develop inflammation in miniature dachshunds.

Inflammatory colorectal polyp (ICRP) in miniature dachshunds (MDs) is a chronic inflammatory bowel disease (IBD) characterized by granulomatous inflammation that consists of neutrophil infiltration and goblet cell hyperplasia in the colon. Recently, we identified five MD-associated single-nucleotide polymorphisms (SNPs), namely PLG, TCOF1, TG, COL9A2, and COL4A4, by whole-exome sequencing. Here, we investigated whether TG c.4567C>T (p.R1523W) is associated with the ICRP pathology. We found that the frequency of the T/T SNP risk allele was significantly increased in MDs with ICRP. In vitro experiments showed that TG expression in non-immune cells was increased by inducing the IL-6 amplifier with IL-6 and TNF-α. On the other hand, a deficiency of TG suppressed the IL-6 amplifier. Moreover, recombinant TG treatment enhanced the activation of the IL-6 amplifier, suggesting that TG is both a positive regulator and a target of the IL-6 amplifier. We also found that TG expression together with two NF-κB targets, IL6 and CCL2, was increased in colon samples isolated from MDs with the T/T risk allele compared to those with the C/C non-risk allele, but serum TG was not increased. Cumulatively, these results suggest that the T/T SNP is an expression quantitative trait locus (eQTL) of TG mRNA in the colon, and local TG expression triggered by this SNP increases the risk of ICRP in MDs via the IL-6 amplifier. Therefore, TG c.4567C>T is a diagnostic target for ICRP in MDs, and TG-mediated IL-6 amplifier activation in the colon is a possible therapeutic target for ICRP.

Prevalence and risk factors for colonisation and infection with carbapenem-resistant Enterobacterales in intensive care units: A prospective multicentre study.

OBJECTIVES: This study aimed to investigate the prevalence and risk factors for carbapenem-resistant Enterobacterales colonisation/infection at admission and acquisition among patients admitted to the intensive care unit. RESEARCH METHODOLOGY/DESIGN: A prospective and multicentre study. SETTING: This study was conducted in 24 intensive care units in Anhui, China. MAIN OUTCOME MEASURES: Demographic and clinical data were collected, and rectal carbapenem-resistant Enterobacterales colonisation was detected by active screening. Multivariate logistic regression models were used to analyse factors associated with colonisation/infection with carbapenem-resistant Enterobacterales at admission and acquisition during the intensive care unit stay. RESULTS: There were 1133 intensive care unit patients included in this study. In total, 5.9% of patients with carbapenem-resistant Enterobacterales colonisation/infection at admission, and of which 56.7% were colonisations. Besides, 8.5% of patients acquired carbapenem-resistant Enterobacterales colonisation/infection during the intensive care stay, and of which 67.6% were colonisations. At admission, transfer from another hospital, admission to an intensive care unit within one year, colonisation/infection/epidemiological link with carbapenem-resistant Enterobacterales within one year, and exposure to any antibiotics within three months were risk factors for colonisation/infection with carbapenem-resistant Enterobacterales. During the intensive care stay, renal disease, an epidemiological link with carbapenem-resistant Enterobacterales, exposure to carbapenems and beta-lactams/beta-lactamase inhibitors, and intensive care stay of three weeks or longer were associated with acquisition. CONCLUSION: The prevalence of colonisation/infection with carbapenem-resistant Enterobacterales in intensive care units is of great concern and should be monitored systematically. Particularly for the 8.5% prevalence of carbapenem-resistant Enterobacterales acquisition during the intensive care stay needs enhanced infection prevention and control measures in these setting. Surveillance of colonisation/infection with carbapenem-resistant Enterobacterales at admission and during the patient's stay represents an early identification tool to prevent further transmission of carbapenem-resistant Enterobacterales. IMPLICATIONS FOR CLINICAL PRACTICE: Carbapenem-resistant Enterobacterales colonization screening at admission and during the patient's stay is an important tool to control carbapenem-resistant Enterobacterales spread in intensive care units.

Risk factors of infection among close contacts of COVID-19: A systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) was first detected in December 2019, and declared as a pandemic by the World Health Organization (WHO) on March 11, 2020. The current management of COVID-19 is based generally on supportive therapy and treatment to prevent respiratory failure. METHODS: PubMed, Web of Science, Embase, CNKI, and other databases were searched by computer, and relevant literature published from December 2019 to November 2022 on the influencing factors of infection in close contacts with novel coronavirus pneumonia was collected. Meta-analysis was carried out after literature screening, quality assessment, and data extraction. RESULTS: A total of 425 articles were retrieved and 11 were included. Meta-analysis showed that there were 6 risk factors, and the combined OR value and 95% CI of each influencing factor were 5.23 (3.20, 8.57) for family members, 1.63 (0.56, 4.77) for regular contact, 2.14 (0.62, 7.32) for the elderly, 0.58 (0.001569.89) for cohabitation, 1.97 (1.02, 3.82) for women and 0.75 (0.01, 54.07) for others. The Deeks' funnel diagram indicates that there is no potential publication bias among the included studies. CONCLUSION: Family members and gender differences are the risk factors of infection among close contacts, and it cannot be proved that there are differences in infection among frequent contact, advanced age, and living together.

Computer model of IL-6-dependent rheumatoid arthritis in F759 mice.

The interleukin-6 (IL-6) amplifier, which describes the simultaneous activation of signal transducer and activator of transcription 3 (STAT3) and NF-κb nuclear factor kappa B (NF-κB), in synovial fibroblasts causes the infiltration of immune cells into the joints of F759 mice. The result is a disease that resembles human rheumatoid arthritis. However, the kinetics and regulatory mechanisms of how augmented transcriptional activation by STAT3 and NF-κB leads to F759 arthritis is unknown. We here show that the STAT3-NF-κB complex is present in the cytoplasm and nucleus and accumulates around NF-κB binding sites of the IL-6 promoter region and established a computer model that shows IL-6 and IL-17 (interleukin 17) signaling promotes the formation of the STAT3-NF-κB complex followed by its binding on promoter regions of NF-κB target genes to accelerate inflammatory responses, including the production of IL-6, epiregulin, and C-C motif chemokine ligand 2 (CCL2), phenotypes consistent with in vitro experiments. The binding also promoted cell growth in the synovium and the recruitment of T helper 17 (Th17) cells and macrophages in the joints. Anti-IL-6 blocking antibody treatment inhibited inflammatory responses even at the late phase, but anti-IL-17 and anti-TNFα antibodies did not. However, anti-IL-17 antibody at the early phase showed inhibitory effects, suggesting that the IL-6 amplifier is dependent on IL-6 and IL-17 stimulation at the early phase, but only on IL-6 at the late phase. These findings demonstrate the molecular mechanism of F759 arthritis can be recapitulated in silico and identify a possible therapeutic strategy for IL-6 amplifier-dependent chronic inflammatory diseases.

GM-CSF Promotes the Survival of Peripheral-Derived Myeloid Cells in the Central Nervous System for Pain-Induced Relapse of Neuroinflammation.

We recently discovered a (to our knowledge) new neuroimmune interaction named the gateway reflex, in which the activation of specific neural circuits establishes immune cell gateways at specific vessel sites in organs, leading to the development of tissue-specific autoimmune diseases, including a multiple sclerosis (MS) mouse model, experimental autoimmune encephalomyelitis (EAE). We have reported that peripheral-derived myeloid cells, which are CD11b+MHC class II+ and accumulate in the fifth lumbar (L5) cord during the onset of a transfer model of EAE (tEAE), play a role in the pain-mediated relapse via the pain-gateway reflex. In this study, we investigated how these cells survive during the remission phase to cause the relapse. We show that peripheral-derived myeloid cells accumulated in the L5 cord after tEAE induction and survive more than other immune cells. These myeloid cells, which highly expressed GM-CSFRα with common ß chain molecules, grew in number and expressed more Bcl-xL after GM-CSF treatment but decreased in number by blockade of the GM-CSF pathway, which suppressed pain-mediated relapse of neuroinflammation. Therefore, GM-CSF is a survival factor for these cells. Moreover, these cells were colocalized with blood endothelial cells (BECs) around the L5 cord, and BECs expressed a high level of GM-CSF. Thus, GM-CSF from BECs may have an important role in the pain-mediated tEAE relapse caused by peripheral-derived myeloid cells in the CNS. Finally, we found that blockade of the GM-CSF pathway after pain induction suppressed EAE development. Therefore, GM-CSF suppression is a possible therapeutic approach in inflammatory CNS diseases with relapse, such as MS.

Safe and Effective Antioxidant: The Biological Mechanism and Potential Pathways of Ergothioneine in the Skin.

Ergothioneine, a sulfur-containing micromolecular histidine derivative, has attracted increasing attention from scholars since it was confirmed in the human body. In the human body, ergothioneine is transported and accumulated specifically through OCTN-1, especially in the mitochondria and nucleus, suggesting that it can target damaged cells and tissues as an antioxidant. It shows excellent antioxidant, anti-inflammatory effects, and anti-aging properties, and inhibits melanin production. It is a mega antioxidant that may participate in the antioxidant network system and promote the reducing glutathione regeneration cycle. This review summarizes studies on the antioxidant effects of ergothioneine on various free radicals in vitro to date and systematically introduces its biological activities and potential mechanisms, mostly in dermatology. Additionally, the application of ergothioneine in cosmetics is briefly summarized. Lastly, we propose some problems that require solutions to understand the mechanism of action of ergothioneine. We believe that ergothioneine has good prospects in the food and cosmetics industries, and can thus meet some needs of the health and beauty industry.

Dupuytren's contracture-associated SNPs increase SFRP4 expression in non-immune cells including fibroblasts to enhance inflammation development.

Dupuytren's contracture (DC) is an inflammatory fibrosis characterized by fibroproliferative disorders of the palmar aponeurosis, for which there is no effective treatment. Although several genome-wide association studies have identified risk alleles associated with DC, the functional linkage between these alleles and the pathogenesis remains elusive. We here focused on two single nucleotide polymorphisms (SNPs) associated with DC, rs16879765 and rs17171229, in secreted frizzled related protein 4 (SFRP4). We investigated the association of SRFP4 with the IL-6 amplifier, which amplifies the production of IL-6, growth factors and chemokines in non-immune cells and aggravates inflammatory diseases via NF-κB enhancement. Knockdown of SFRP4 suppressed activation of the IL-6 amplifier in vitro and in vivo, whereas the overexpression of SFRP4 induced the activation of NF-κB-mediated transcription activity. Mechanistically, SFRP4 induced NF-κB activation by directly binding to molecules of the ubiquitination SFC complex, such as IkBα and ßTrCP, followed by IkBα degradation. Furthermore, SFRP4 expression was significantly increased in fibroblasts derived from DC patients bearing the risk alleles. Consistently, fibroblasts with the risk alleles enhanced activation of the IL-6 amplifier. These findings indicate that the IL-6 amplifier is involved in the pathogenesis of DC, particularly in patients harboring the SFRP4 risk alleles. Therefore, SFRP4 is a potential therapeutic target for various inflammatory diseases and disorders, including DC.

The price of private dental services: results from a national representative survey of Ireland.

INTRODUCTION: Dental services in Ireland are delivered in a mixed public-private system but the majority of dental care is paid for out-of-pocket by individuals. Ireland is not unusual in the global context where public subsidisation for oral healthcare is limited in many countries. This is despite the fact that oral health plays an important role in well-being and despite international evidence on the negative impact of user fees on utilisation of beneficial healthcare. However, there has been little up-to-date assessment of the prices faced by individuals for a range of non-acute care services in Ireland, including dental care. This paper presents an up-to-date assessment of private dental prices in Ireland for a range of preventive, primary, and complex services based on a nationally representative survey. METHODS: The total sample size for the desk-based survey was 103, accounting for 6% of private dentists in Ireland, weighted to reflect the geographic distribution of dentists. Dentists were selected at random from the publicly available list of dentists participating in the Dental Treatment Benefit Scheme. The adult price of 10 different services covering core preventive, primary, and complex procedures were identified from public websites for the selected dental practices. RESULTS: Results showed that in addition to there being an uneven supply of dentists across the country, dental prices also vary with some notable variations by region and type of service. In particular, dental practices located in border counties, and those in rural areas typically show lower mean prices relative to non-border counties and urban areas. These factors need to be considered when planning how to reduce inequalities in access to oral health services in Ireland.