Progress in the Study of Temporomandibular Joint Lavage in Temporomandibular Joint Disorder.

With the continuous development and progress of medicine, there are many methods for the treatment of temporomandibular disorders, among which temporomandibular joint lavage is also constantly developed. In the past century, through the efforts of some scholars and clinical summary, the understanding of this disease has been deepened and broadened. At present, through continuous exploration of the treatment methods, the lavage is relatively mature, and has achieved good clinical results. In this paper, the application of temporomandibular joint lavage in the treatment of temporomandibular joint disorders, its treatment methods, treatment mechanism, the auxiliary of other drugs, indications, complications and so on were discussed.

Population Pharmacokinetic Modeling and Exposure-Efficacy and Body Weight-Response Analyses for Tezepelumab in Patients With Severe, Uncontrolled Asthma.

Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin. This analysis assessed the suitability of a fixed-dose regimen of tezepelumab 210 mg every 4 weeks (Q4W) in adults and adolescents with severe, uncontrolled asthma. A population pharmacokinetic model was developed using data from 1368 patients with asthma or healthy participants enrolled in 8 clinical studies (phases 1-3). Tezepelumab exposure-efficacy relationships were analyzed in the phase 3 NAVIGATOR study (NCT03347279), using asthma exacerbation rates over 52 weeks and changes in pre-bronchodilator forced expiratory volume in 1 s at week 52. Tezepelumab pharmacokinetics were well characterized by a 2-compartment linear disposition model with first-order absorption and elimination following subcutaneous and intravenous administration at 2.1-420 and 210-700 mg, respectively. There were no clinically relevant effects on tezepelumab pharmacokinetics from age (≥12 years), sex, race/ethnicity, renal or hepatic function, disease severity (inhaled corticosteroid dose level), concomitant asthma medication use, smoking history, or anti-drug antibodies. Body weight was the most influential covariate on tezepelumab exposure, but no meaningful differences in efficacy or safety were observed across body weight quartiles in patients with asthma who received tezepelumab 210 mg subcutaneously Q4W. There was no apparent relationship between tezepelumab exposure and efficacy at this dose regimen, suggesting that it is on the plateau of the exposure-response curve of tezepelumab. In conclusion, a fixed-dose regimen of tezepelumab 210 mg subcutaneously Q4W is appropriate for eligible adults and adolescents with severe, uncontrolled asthma.

Distress tolerance as a mechanism of mindfulness for depression and anxiety: Cross-sectional and diary evidence

Background: Both trait and state mindfulness are associated with less depression and anxiety, but the mechanisms remain unknown. Distress tolerance, an important transdiagnostic factor of emotional disorders, may mediate the relationship between mindfulness and depression/anxiety. Method: Study 1 examined the mediation model at the between-person level in a large cross-sectional sample (n = 905). In Study 2, a daily diary study (n = 110) was conducted to examine within-person changes. Participants were invited to complete daily diaries measuring daily mindfulness, distress tolerance, depression and anxiety for 14 consecutive days. Results: In Study 1, results of simple mediation analyses indicated that distress tolerance mediated the relationship between mindfulness and depression/anxiety at the between-person level. In Study 2, results of multilevel mediation analyses indicated that, in both the concurrent model and time-lagged model, daily distress tolerance mediated the effects of daily mindfulness on daily depression/anxiety at both the within- and between-person level. Conclusions: Distress tolerance is a mechanism underlying the relationship between mindfulness and depression/anxiety. Individuals with high or fluctuating depression and anxiety may benefit from short-term or long-term mindfulness training to increase distress tolerance. (AU)

Children's Dental Fear: Occurrence Mechanism and Prevention Guidance.

Children's dental fear (CDF) has become one of the main reasons affecting the quality of dental treatment. In order to reduce the incidence of CDF in China before and after children's dental visits, this review applies literature analysis and empirical summary methods to analyze and summarize academic discussions on this topic, including occurrence mechanism, prevention guidance, and the conclusion that the occurrence and prevention of CDF is closely related with children's internal characteristics and external influences. In the end, we propose a breakthrough of combining the CFSS-DS scale and three-grade prevention theory together in the future to provide new ideas and hypotheses for the prevention of CDF.

Distress tolerance as a mechanism of mindfulness for depression and anxiety: Cross-sectional and diary evidence.

Background: Both trait and state mindfulness are associated with less depression and anxiety, but the mechanisms remain unknown. Distress tolerance, an important transdiagnostic factor of emotional disorders, may mediate the relationship between mindfulness and depression/anxiety. Method: Study 1 examined the mediation model at the between-person level in a large cross-sectional sample (n = 905). In Study 2, a daily diary study (n = 110) was conducted to examine within-person changes. Participants were invited to complete daily diaries measuring daily mindfulness, distress tolerance, depression and anxiety for 14 consecutive days. Results: In Study 1, results of simple mediation analyses indicated that distress tolerance mediated the relationship between mindfulness and depression/anxiety at the between-person level. In Study 2, results of multilevel mediation analyses indicated that, in both the concurrent model and time-lagged model, daily distress tolerance mediated the effects of daily mindfulness on daily depression/anxiety at both the within- and between-person level. Conclusions: Distress tolerance is a mechanism underlying the relationship between mindfulness and depression/anxiety. Individuals with high or fluctuating depression and anxiety may benefit from short-term or long-term mindfulness training to increase distress tolerance.

Effect of Cognitive Load on Anticipatory Postural Adjustment Latency and its Relationship with Pain-Related Dysfunction in Non-specific Chronic Low Back Pain: A Cross-Sectional Study.

INTRODUCTION: This study aimed to investigate the effect of cognitive load on anticipatory postural adjustment (APA) latency in patients with non-specific chronic low back pain (NCLBP) and its relationship with pain-related functional changes. METHODS: A cross-sectional study was conducted from December 15, 2022 to January 25, 2023. Participants were divided into a healthy control group (n = 29) and an NCLBP group (n = 29). Each group was assigned a single task of rapid arm raising and a dual task of rapid arm raising combined with a cognitive load. The cognitive load task was conducted using visual conflict. The APA latency for bilateral trunk muscles was observed using electromyography. The duration of electromyography recording in each task cycle was 28 s. Pain related-functional changes were evaluated using Roland-Morris Disability Questionnaire (RMDQ) before all tasks. RESULTS: The APA latency for the right multifidus was significantly delayed in the NCLBP group [25.38, 95% confidence interval (CI) 13.41-37.35] than in the healthy control group (- 5.80, 95% CI - 19.28 to 7.68) during dual task (p = 0.0416). The APA latency for the right multifidus (25.38, 95% CI 13.41-37.35) and transverse abdominis/internal oblique (29.15, 95% CI 18.81-39.50) were significantly delayed compared with on the left side in the NCLBP group during dual task (- 3.03, 95% CI - 15.18-9.13, p = 0.0220; 3.69, 95% CI - 6.81 to 14.18, p = 0.0363). The latency delay of the right and left multifidus APA in the NCLBP group under the dual-task was positively correlated with RMDQ scores (r = 0.5560, p = 0.0017; r = 0.4010, p = 0.0311). CONCLUSIONS: Cognitive load could induce APA delay in the right trunk muscles and co-activation pattern changes in bilateral trunk muscle APA in patients with NCLBP. The APA onset delay in multifidus is positively related to pain-related daily dysfunction. Trial Registration ChiCTR2300068580 (retrospectively registered in February 23, 2023).

The potential mediating role of anxiety sensitivity in the impact of mindfulness training on anxiety and depression severity and impairment: A randomized controlled trial.

The benefits of mindfulness-based interventions to alleviate anxiety and depression have been supported by many studies. Given the effectiveness of mindfulness-based interventions on anxiety and depression, the underlying mechanisms need to be explored. Using a randomized waitlist-controlled design, this study investigated whether anxiety sensitivity was a potential mechanism for the impact of mindfulness training on anxiety and depression. Participants with high psychological distress were randomly assigned to an eight-week mindfulness intervention (N = 35) or a wait-list control group (N = 34). Before and after the intervention or corresponding waitlist period, participants completed measures of anxiety and depression severity and impairment and anxiety sensitivity. Separate mixed ANOVA demonstrated significant group (intervention vs. control group) × time (pre- vs. post-test) interactions for anxiety sensitivity and overall anxiety severity and impairment and marginally significant interaction for overall depression severity and impairment. Moreover, simple mediation models showed that reductions of anxiety sensitivity from pre- to post-test mediated the impact of mindfulness training on changes in anxiety and depression severity and impairment. The findings suggest that anxiety sensitivity is a potential mechanism underlying the effect of mindfulness training on anxiety and depression, which provides a new perspective for the study of processes of change of mindfulness-based interventions.

Microenvironment Modulation of Metal-Organic Frameworks (MOFs) for Coordination Olefin Oligomerization and (co)Polymerization.

The majority of commercial polyolefins are produced by coordination polymerization using early or late transition metal catalysts. Molecular catalysts containing these transition metals (Ti, Zr, Cr, Ni, and Fe, etc.) are loaded on supports for controlled polymerization behavior and polymer morphology in slurry or gas phase processes. Within the last few years, metal-organic frameworks (MOFs), a class of unique porous crystalline materials constructed from metal ions/clusters and organic ligands, have been designed and utilized as excellent supports for heterogeneous polymerization catalysis whose high density and uniform distribution of active sites would benefit the modulations of molecular weight distributions of high-performance olefin oligomers and (co)polymers. Impressive efforts have been made to modulate the microenvironment surrounding the active centers at the atomic level for improved activities of MOFs-based catalysts and controlled selectivity of olefin insertion. This review aims to draw a comprehensive picture of MOFs for coordination olefin oligomerization and (co)polymerization in the past decades with respect to different transition metal active centers, various incorporation sites, and finally microenvironment modulation. In consideration of more efforts are needed to overcome challenges for further industrial and commercial application, a brief outlook is provided.

Plasmonic Nanostructures-Decorated ZIF-8-Derived Nanoporous Carbon for Surface-Enhanced Raman Scattering.

Surface-enhanced Raman scattering (SERS) is considered to be a highly sensitive platform for chemical and biological sensing. Recently, owing to their high porosity and large surface area, metal-organic frameworks (MOFs) have attracted considerable attention in sensing applications. Porous carbon nanostructures are promising SERS substrates due to their strong broadband charge-transfer resonance and reproducible fabrication. Furthermore, an extraordinarily large enhancement of the electromagnetic field enables plasmonic nanomaterials to be ideal SERS substrates. Here, we demonstrate the porous Au@Ag nanostructure-decorated MOF-derived nanoporous carbon (NPC) for highly efficient SERS sensing. Specifically, this plasmonic nanomaterial-NPC composite offers high Raman signal enhancement with the ability to detect the model Raman reporter 2-naphthalenethiol (2-NT) at picomolar concentration levels.

Population Pharmacokinetics of Cotadutide in Subjects with Type 2 Diabetes.

BACKGROUND AND OBJECTIVES: Cotadutide is a balanced dual glucagon-like peptide-1/glucagon receptor agonist under development for the treatment of nonalcoholic steatohepatitis and chronic kidney disease with type 2 diabetes. The objectives of the analysis were to characterize the population pharmacokinetics of cotadutide following daily subcutaneous injection in subjects with type 2 diabetes and to evaluate the effect of demographic and clinical variables of interest on cotadutide pharmacokinetics. METHODS: This study analyzed 8834 plasma concentrations of cotadutide from 759 subjects with type 2 diabetes who received daily subcutaneous doses from 20 to 600 µg from six clinical studies. The impact of covariates on cotadutide pharmacokinetics was quantified, and body weight effect on cotadutide exposure was further evaluated using a simulation approach. The model performance was evaluated through prediction-corrected visual predictive checks. RESULTS: A one-compartment model with first-order absorption and elimination described cotadutide pharmacokinetic data well. The mean values for cotadutide apparent clearance, apparent distribution volume, absorption rate constant, and half-life were 1.04 L/h (interindividual variability [IIV]: 26.5%), 18.7 L (IIV: 28.7%), 0.343 h-1 (IIV: 38.6%), and 12.9 h, respectively. Higher body weight, lower albumin, and higher alanine aminotransferase were associated with an increase in cotadutide clearance, while an increase in anti-drug antibody titers was associated with a decrease in cotadutide clearance. These statistically significant effects were not considered clinically significant and did not warrant dose adjustment. Effects of other tested baseline covariates (age, sex, body mass index, hemoglobin A1c, renal function, duration of diabetes) were not found to statistically significantly affect cotadutide pharmacokinetics. CONCLUSIONS: Cotadutide pharmacokinetics was adequately described by a one-compartment linear model with first-order absorption and elimination. Body weight-based dosing is not necessary for cotadutide based on the simulation using the final population pharmacokinetic modeling. This model will be used to evaluate exposure-response relationships for efficacy and safety in different indications that are being studied for cotadutide.

Interactions of N-hydroxyamphetamine with an iron porphyrin: A unique intramolecular H-bond probed by DFT calculations.

Hydroxylamine (NH2OH) and its N-substituted derivatives (RNHOH) are important biological intermediates in the global N cycle. Heme plays a central role in the binding and activation of these hydroxylamines. We report the crystal structures of N-hydroxyamphetamine (AmphNHOH) in complex with Fe and Co heme models. We demonstrate a previously unrecognized internal H-bond interaction between a hydroxylamine RNHO-H group and a porphyrin N-atom. We utilize density functional theoretical (DFT) calculations to show that the conformations with the internal H-bond represent global minima along the potential energy surfaces for both the Fe and Co heme models. A natural bond orbital (NBO) analysis reveals a donor π (porN=C) to acceptor σ* (O-H) interaction of 3.04 kcal/mol for Fe, accounting for 11% of the total heme-AmphNHOH interaction energy. Our DFT calculations with the parent Fe-NH2OH suggests that the presence of internal H-bonds between hydroxylamine (R/H)NHOH moieties and heme N-atoms may be more common than previously recognized.

A retrospective study of 12,538 internal conical connection implants focused on the long-term integrity of implant-abutment complexes.

OBJECTIVE: To evaluate the long-term integrity of implant-abutment complexes in implant systems with two internal conical angles. MATERIAL AND METHODS: 12,538 bone-level implants of two systems placed between January 2012 and December 2018 were retrospectively analyzed. Cumulative abutment/implant fracture rates in systems with larger (LA, 7.5°) and smaller (SA, 5.7°) internal conical angles were estimated using the Kaplan-Meier analysis and compared between groups. The association between implant systems and jammed abutment retrievability was evaluated by multivariable generalized estimating equation logistic regression modeling. RESULTS: For LA, the 8-year cumulative incident rate was 0.10% (95% confidence interval (CI): 0-0.24%) for implant fracture and 0.26% (95% CI: 0.11%-0.41%) for abutment fracture, demonstrating a significant difference in gender (p = .03), implant diameter (p = .01), jaw (p = .006), and antagonist tooth (p < .001). For SA, the 8-year cumulative incident rate was 0.38% (95% CI: 0-0.79%) for implant fracture and 2.62% (95% CI: 0.05%-5.13%) for abutment fracture, which was influenced by implant diameter (p < .001) and site (p = .03). The cumulative implant/abutment fracture rate was lower for LA implants, particularly for LA implant-supported single crowns (SCs) (p < .05). The abutment-retrieval success rate was 92.9% for LA and 57.1% for SA (p = .055). CONCLUSION: LA implants exhibited a lower incidence of fracture in abutment-implant complexes and a relatively higher retrievability success rate for jammed abutments.

To explore the active constituents of Sedum aizoon L in the treatment of coronary heart disease based on network pharmacology and molecular docking methodology.

Background: There is a lack of effective drugs for the treatment of coronary heart disease (CHD). Sedum aizoon L (SL) has multiple effects, and there is no report on CHD in SL at present. The aim of this study is to explore the mechanisms of action of SL in the treatment of CHD based on network pharmacology and molecular docking technology. Methods: The targets and active ingredients of SL were screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and CHD-related targets were obtained by searching GeneCards and DisGeNet databases. The intersection of LS active ingredient targets and CHD targets was used to construct a "drug-ingredient-disease-target" network using the Cytoscape software. The STRING database was used to construct a protein-protein interaction (PPI) network, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. Key targets and core active ingredients were selected and molecular docking was performed using the AutoDock software. Results: According to the predicted results, a total of 134 corresponding target genes for LS, 12 active components, 1,704 CHD-related targets, and 52 intersecting targets were obtained. GO function and KEGG pathway analysis showed that the key targets were involved with signal transducer and activator of transcription 3 (STAT3), tumor protein p53 (TP53), and vascular endothelial growth factor A (VEGFA). The molecular docking results showed that the key targets bound to the important active ingredients in a stable conformation. The core active ingredients of LS in the treatment of CHD were determined to be ursolic acid, myricetin, and beta-sitosterol. Conclusions: SL may act on targets such as STAT3, TP53, and VEGFA through tumor necrosis factor (TNF) signaling pathway, interleukin 17A (IL-17A) signaling pathway, AGE-RAGE signaling pathway in diabetic complications, and other related pathways, thereby playing a role in preventing and treating CHD.

Yixin Ningshen Tablet Alleviates Comorbidity of Myocardial Infarction and Depression by Enhancing Myocardial Energy Metabolism and Increasing Availability of Monoamine Neurotransmitter / 中国结合医学杂志

OBJECTIVE@#To investigate the therapeutic effect of Yixin Ningshen Tablet (YXNS) on comorbidity of myocardial infarction (MI) and depression in rats and explore the underlying mechanism.@*METHODS@#The Sprague-Dawley rats were randomly divided into 5 groups with 7 rats in each group according to their weights, including control, model, fluoxetine (FLXT, 10 mg/kg), low-dose YXNS (LYXNS, 100 mg/kg), and high-dose YXNS (HYXNS, 300 mg/kg) groups. All rats were pretreated with corresponding drugs for 12 weeks. The rat model of MI and depression was constructed by ligation of left anterior descending coronary artery and chronic mild stress stimulation. The echocardiography, sucrose preference test, open field test, and forced swim test were performed. Myocardial infarction (MI) area and myocardial apoptosis was also detected. Serum levels of interleukin (IL)-6, IL-1β, tumor necrosis factor-α (TNF-α), 5-hydroxytryptamine (5-HT), adrenocorticotrophic hormone (ACTH), corticosterone (CORT), and norepinephrine (NE) were determined by enzyme linked immunosorbent assay. The proteins of adenosine 5'-monophosphate -activated protein kinase (AMPK), p-AMPK, peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and nuclear respiratory factor 1 (NRF1) in heart were detected by Western blot analysis. The expression levels of TNF-α, IL-6, indoleamine 2,3-dioxygenase (IDO1), kynurenine 3-monooxygenase (KMO), and kynureninase (KYNU) in hippocampus were detected by real-time quantitative polymerase chain reaction.@*RESULTS@#Compared with the model group, the cardiac function of rats treated with YXNS improved significantly (P<0.01). Meanwhile, YXNS effectively reduced MI size and cardiomyocytes apoptosis of rats (P<0.01 or P<0.05), promoted AMPK phosphorylation, and increased PGC-1α protein expression (P<0.01 or P<0.05). HYXNS significantly increased locomotor activity of rats, decreased the levels of TNF-α, IL-6 and IL-1β, and increased the serum levels of 5-HT, NE, ACTH, and CORT (all P<0.05). Moreover, HYXNS decreased the mRNA expressions of IDO1, KMO and KYNU (P<0.05).@*CONCLUSIONS@#YXNS can relieve MI by enhancing myocardial energy metabolism. Meanwhile, YXNS can alleviate depression by resisting inflammation and increasing availability of monoamine neurotransmitters. It may be used as a potential drug to treat comorbidity of MI and depression.

Retrospective Study of Short Versus Standard Posterior Implants and Analysis of Implant Failure Risk Factors.

PURPOSE: To compare the clinical and radiographic outcomes of short implants (≤ 8 mm) vs standard implants (> 8 mm, < 10 mm) and to uncover risk factors influencing implant failure in short implants. MATERIALS AND METHODS: Short and standard implants were compared in the aspect of survival rates, biologic and mechanical complications, and marginal bone loss. To analyze risk factors of implant failure in short implants, several variables were taken into consideration, including sex, age, time interval, arch, implant brand, additional surgery, prosthesis material, restoration, smoking status, and crown-root ratio. RESULTS: Three hundred twenty-one short implants and 136 standard implants were retrospectively followed up from 12 to 104 months with an average of 40 months (3.33 years) in short implants and 34 months (2.83 years) in standard implants. The survival rates of short implants were 95.6% at the implant-based analysis and 94.9% at the patient-based analysis, and rates of 96.3% and 94.0%, respectively, were calculated for standard implants. No statistically significant differences were observed between short and standard implants with respect to survival rate, complications, or marginal bone loss. The failure rates were 4.2% for implants and 5.4% for patients in total implants with an average of 38 months (3.17 years). In analyzing risk factors of short implants for survival rate, single short implants resulted in a higher failure rate compared with splinted short implants, while no significant variable was found in standard implants. CONCLUSION: Short implants tend to be a reliable alternative in atrophic posterior regions. Splinted prostheses were more ideal for short implant restorations.

Dipetidyl peptidase-4 and transferrin receptor serve as prognostic biomarkers for acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is the most common hematological malignancy in adult patients. Ferroptosis-related signatures have been shown to act as regulators of the progression of multiple cancer types, but the role of ferroptosis in AML remains to be elucidated. We performed the present study to preliminarily investigate the roles of ferroptosis-related genes (FRGs) in AML. METHODS: The transcriptome data of AML patients was downloaded from The Cancer Genome Atlas (TCGA) and the transcriptome data of normal samples was obtained from the Genotype-Tissue Expression (GTEx) database. FRGs were selected via public articles. Expression levels of FRGs between AML and normal samples were analyzed. The prognostic model based on FRGs was constructed via lasso regression. The expression levels and prognostic role of FRGs were identified from the risk model. We also performed validation experiments to verify the expression levels of the final selected genes via immunohistochemistry, polymerase chain reaction (PCR), and RNA-seq. Finally, we explored the associations between immune infiltration, drug sensitivity, and the selected FRGs. RESULTS: The transcriptome data of 151 AML samples were retrieved from TCGA and 70 bone marrow normal samples were retrieved from the GTEx database. Additionally, 23 FRGs were collected from the published articles. There were 22 differentially expressed FRGs, and among them, dipetidyl peptidase-4 (DPP4) (P= 0.011, HR =1.504), GPX4 (P=0.055, HR =1.569), LPCAT3 (P<0.001, HR =2.243), SLC7A11 (P=0.012, HR =2.243), and transferrin receptor (TFRC) (P=0.029, 0.774) had a significant influence on the prognosis of AML patients via lasso regression. The area under the curve (AUC) values of the 1-, 3-, and 5-year receiver operating characteristic (ROC) curves of the FRG signatures indicated that this model is novel and effective method for predicting the prognosis of AML patients. DPP4 (P<0.001) was overexpressed while LPCAT3 (P<0.001), TFRC (P<0.001), GPX4 (P<0.001), and SLC7A11 (P<0.001) were downregulated, further validation experiment results indicated that DPP4 was significantly downregulated but TFRC was upregulated in AML samples. Dysregulation of DPP4 and TFRC influence numbers of chemotherapy regimens sensitivity. CONCLUSIONS: DPP4 and TFRC act as biomarkers for predicting and diagnosing AML, and their expression levels also have significant correlations with drug resistance in AML.

LEGACY: Phase 2a Trial to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamic Effects of the Anti-EL (Endothelial Lipase) Antibody MEDI5884 in Patients With Stable Coronary Artery Disease.

OBJECTIVE: Functional HDL (high-density lipoprotein) particles that facilitate cholesterol efflux may be cardioprotective. EL (endothelial lipase) hydrolyzes phospholipids promoting catabolism of HDL and subsequent renal excretion. MEDI5884 is a selective, humanized, monoclonal, EL-neutralizing antibody. We sought to determine the safety, pharmacokinetics, and pharmacodynamic effects of multiple doses of MEDI5884 in patients with stable coronary artery disease. Approach and Results: LEGACY was a phase 2a, double-blind, placebo-controlled, parallel-design trial that randomized 132 patients with stable coronary artery disease receiving high-intensity statin therapy to 3 monthly doses of 1 of 5 dose levels of MEDI5884 (50, 100, 200, 350, or 500 mg SC) or matching placebo. The primary end point was the safety and tolerability of MEDI5884 through the end of the study (day 151). Additional end points included change in HDL cholesterol and cholesterol efflux from baseline to day 91, hepatic uptake of cholesterol at day 91, changes in various other lipid parameters. The incidence of adverse events was similar between the placebo and MEDI5884 groups. In a dose-dependent manner, MEDI5884 increased HDL cholesterol up to 51.4% (P<0.0001) and global cholesterol efflux up to 26.2% ([95% CI, 14.3-38.0] P<0.0001). MEDI5884 increased HDL particle number up to 14.4%. At the highest dose tested, an increase in LDL (low-density lipoprotein) cholesterol up to 28.7% (P<0.0001) and apoB (apolipoprotein B) up to 13.1% (P=0.04) was observed with MEDI5884. However, at the potential target doses for future studies, there was no meaningful increase in LDL cholesterol or apoB. CONCLUSIONS: Inhibition of EL by MEDI5884 increases the quantity and quality of functional HDL in patients with stable coronary artery disease on high-intensity statin therapy without an adverse safety signal at the likely dose to be used. These data support further clinical investigation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03351738.

Zinc- and strontium- co-incorporated nanorods on titanium surfaces with favorable material property, osteogenesis, and enhanced antibacterial activity.

Early infection and peri-implantitis after implant restoration are major reasons for dental implant failure. Implant-associated infections are majorly attributed to biofilm formation. In this study, co-incorporated zinc- (Zn-) and strontium- (Sr-) nanorod coating on sandblasted and acid-etched (SLA) titanium (SLA-Zn/Sr) was fabricated by hydrothermal synthesis. It was aimed at promoting osteogenesis while inhibiting biofilm formation. The nanorod-like particles (φ 30-50 nm) were found to be evenly formed on SLA-Zn/Sr (Zn: 1.49 ± 0.16 wt%; Sr: 21.69 ± 2.74 wt%) that was composed of well-crystallized ZnTiO3 and SrTiO3 phases. With a sufficient interface bonding strength (42.00 ± 3.00 MPa), SLA-Zn/Sr enhanced the corrosion resistance property of titanium. Besides, SLA-Zn/Sr promoted the cellular initial adhesion, proliferation and osteogenic differentiation of rBMSCs in vitro while inhibiting the adhesion of Staphylococcus aureus and Porphyromonas gingivalis . In addition, through down-regulating icaA gene expression, this novel surface reduced the secretion of polysaccharide intercellular adhesion (reduced by 87.9% compared to SLActive) to suppress the S. aureus biofilm formation. We, therefore, propose a new chemical modification on titanium for multifunctional implant material development. Due to the Zn/Sr co-doping in coating, material properties, early osteogenic effect and antibacterial ability of titanium can be simultaneously enhanced, which has the potential to be applied in dental implantation in the future.

Comparative Evaluation of Endo-sinus Bone Augmentation After Osteotome Sinus Floor Elevation Without Grafting Using Two Radiographic Methods.

PURPOSE: Using panoramic radiograph and CBCT to compare the measurement errors of the residual bone height in the same site before implant placement in the posterior maxilla and endo-sinus bone gain after osteotome sinus floor elevation without grafting, and to evaluate endo-sinus bone augmentation before stage-two surgery with CBCT. Also, some related factors of new bone formation in the sinus were analyzed, such as small bone block elevated by osteotome at the implant apex intraoperatively. MATERIALS AND METHODS: Patients were enrolled in the retrospective study; dental implants were placed in the maxillary posterior region using osteotome sinus floor elevation without grafting. The panoramic radiograph and CBCT were taken preoperatively, immediate postoperatively, and before the stage-two surgery. Endo-sinus bone augmentation was evaluated. A generalized linear model was made to explore the related factors of endo-sinus bone gain. Also, some clinical indexes, such as sinus membrane perforation rate, implant success, and failure criteria were assessed. RESULTS: One hundred two dental implants were inserted in 91 patients. Preoperatively, the mean residual bone height was 8.53 ± 1.76 mm and 7.87 ± 1.45 mm measured using a panoramic radiograph and CBCT, respectively, with significant statistical differences (P < .05). Endo-sinus bone gains of 1.31 °æ 1.05 mm by panoramic radiograph and 1.80 ± 1.72 mm by CBCT were observed, with statistically significant differences (P < .05). The final endosinus bone gain was positively correlated with the implant protrusion length at baseline without any other relevant factors, such as elevated small bone block. CONCLUSION: Measurement errors could be relatively minimized when using CBCT. Using the osteotome sinus floor elevation technique without grafting, approximately 2 mm of endo-sinus bone could be acquired. The final endo-sinus bone gain was positively correlated with implant protrusion length at baseline. Small bone block elevated intraoperatively did not gain more endo-sinus bone.