Predicting completion of clinical trials in pregnant women: Cox proportional hazard and neural network models.

This study aimed to develop a model for predicting the completion of clinical trials involving pregnant women using the Cox proportional hazard model and neural network model (DeepSurv) and to compare the predictive performance of both methods. We collected data on 819 clinical trials performed on pregnant women and intervention studies using at least one drug as intervention from 2009 to 2018 from ClinicalTrials.gov. The Cox proportional hazard model and DeepSurv were used to develop models that predict clinical trial completion. The concordance index (C-index) was used to evaluate the predictive performance. The Cox proportional hazard model revealed that a sample size of n ≥ 329 (hazard ratio [HR] = 0.53), very high human development index (HDI) country (HR = 0.28), abortion (HR = 3.30), labor (HR = 2.16), and iron deficiency anemia (HR = 2.29) were significantly related to the probability of clinical trial completion (all p value < 0.01). The C-index of the model development dataset and test dataset were 0.72 and 0.73, respectively. DeepSurv model consisted of one hidden layer with 16 nodes. DeepSurv showed the C-index comparable to the Cox proportional hazard model. The C-index of the training dataset and test dataset were 0.76 and 0.72, respectively. Further a nomogram that calculate a probability of clinical trial completion at 1 year, 3 years, and 5 years was developed. Both the Cox proportional hazard model and DeepSurv yielded sufficient predicting performance. We hope that this study will contribute to the execution of future clinical trials in pregnant women.

Epigenetic mechanisms involved in the neuroprotective effect of scorpion extract in a Parkinson's disease murine model based on multi-omics approach.

OBJECTIVE: To investigate whether scorpion extract elicits a neuroprotective effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice models, and the genes associated with the therapeutic effects using RNA sequencing (seq) analysis. METHODS: This study investigated the changes in interaction between messenger ribonucleic acid (mRNA) expression and deoxyribonucleic acid (DNA) methylation related to the protective effects of scorpion extracts, in the substantia nigra (SN) region of a MPTP-induced Parkinson's disease (PD) model. RESULTS: In this model, scorpion extracts attenuated the motor impairment as demonstrated by the rotarod and open field tests. Scorpion extracts consistently attenuated the decrease of tyrosine hydroxylase (TH) positive neural cells in the SN and striatum of mice. We profiled genome- wide DNA methylation using Methyl-Seq and measured the transcriptome using RNA-Seq in murine SN in the following groups: vehicle-treated MPTP-induced PD mice and scorpion extract- treated MPTP-induced PD mice. In total, 13 479 differentially expressed genes were identified in association with the anti-PD effect of the scorpion extract, mainly in the promoter and coding regions. Among them, 47 were negatively correlated down- regulated genes. Nineteen genes out of 47 down- regulated genes were negatively correlated with the expression of the other 28 genes. Among these genes, SGSM1 was related to dopaminergic neu- rons including dopamine transporters, TH, dihy- droxyphenylalanine decarboxylase, and dopamine D2 receptor. CONCLUSION: This study provides insights into the anti-parkinsonian effects of scorpion extract and reveals the epigenetic targets in its therapeutic mechanism.

Removing bacteria from rough surface titanium discs with chlorhexidine and additional brushing with dentifrice.

OBJECTIVES: This in vitro study was conducted: (i) to evaluate the effect of using cotton pellets soaked with chlorhexidine (CHX) on titanium surface roughness; (ii) to assess the removal of Porphyromonas gingivalis (P. gingivalis) from resorbable blast material (RBM) titanium surfaces using CHX pellets; and (iii) to evaluate the effects of additional brushing on bacterial removal efficiency. MATERIALS AND METHODS: RBM titanium discs were treated with CHX-soaked cotton pellets, and change in surface roughness was measured using confocal microscopy. After the titanium discs were incubated with P. gingivalis for 2 days, the discs were cleaned with CHX pellets for 40 s. The quantity of remaining adherent bacteria was measured using crystal violet assay. Additional brushing was performed with dentifrice for a total of 40 s, and bacterial removal efficiency with brushing and dentifrice was evaluated using crystal violet assay and scanning electron microscopy. RESULTS: The changes in surface roughness after treatment were observed by confocal microscopy. Statistically significant decrease in surface roughness was seen in CHX 40-s group (p < 0.05). Cleaning with CHX-soaked pellets resulted in significant decrease in remaining adherent bacteria. Brushing the bacteria-incubated discs with dentifrice reduced adhering bacteria. There were fewer bacteria left on the CHX-pre-treated discs compared with the brushing-only group, but there were no significant differences when compared with the brushing-only group (p > 0.05). CONCLUSIONS: This study clearly showed that burnishing with CHX influenced the RBM titanium surface, and burnishing with CHX pellets and brushing with dentifrice were efficient in removing bacteria from the contaminated titanium surface.

Antimicrobial effectiveness of cetylpyridinium chloride and zinc chloride-containing mouthrinses on bacteria of halitosis and peri-implant disease.

PURPOSE: To clarify the antimicrobial efficacy of zinc chloride (ZnCl2) and cetylpyridinium chloride (CPC) by testing their impact on the growth of seven bacterial strains known to be involved in the pathophysiology of both peri-implant disease and halitosis-Staphylococcus aureus, Streptococcus mutans, Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, Treponema denticola, and Tannerella forsythia. MATERIALS AND METHODS: A time-response growth curve was obtained. Commercial mouthrinses with CPC, ZnCl2, or both were added to the media in a final concentration of 0.25% CPC, 2.5% ZnCl2, and 2.5% ZnCl2 with 0.25% CPC. RESULTS: Both CPC and ZnCl2 effectively inhibited the growth of almost all bacterial strains tested except T denticola. ZnCl2 was generally more effective in suppressing bacterial growth than CPC. ZnCl2 with CPC showed the greatest inhibitory activities on almost all strains of bacterial growth except for P gingivalis and T denticola, followed by ZnCl2, then CPC, thus suggesting the possibility of a synergistic effect of the two agents. P gingivalis exhibited a different pattern because ZnCl2 showed the most significant inhibitory effect. CPC did not show growth inhibitory effects on T denticola, but ZnCl2 did. CONCLUSION: Zinc and CPC effectively inhibit bacterial growth that causes both halitosis and peri-implant disease. The effect is even more powerful when applied in combination.

Differential effect of autoinducer 2 of Fusobacterium nucleatum on oral streptococci.

Autoinducer 2 (AI-2) is a quorum sensing molecule and plays an important role in dental biofilm formation, mediating interspecies communication and virulence expression of oral bacteria. Fusobacterium nucleatum connects early colonizing commensals and late colonizing periodontopathogens. F. nucleatum AI-2 and quorum sensing inhibitors (QSIs) can manipulate dental biofilm formation. In this study, we evaluated the effect of F. nucleatum AI-2 and QSIs on biofilm formation of Streptococcus gordonii and Streptococcus oralis, which are initial colonizers in dental biofilm. F. nucleatum AI-2 significantly enhanced biofilm growth of S. gordonii and attachment of F. nucleatum to preformed S. gordonii biofilms. By contrast, F. nucleatum AI-2 reduced biofilm growth of S. oralis and attachment of F. nucleatum to preformed S. oralis biofilms. The QSIs, (5Z)-4-bromo-5-(bromomethylene)-2(5H)-furanone and d-ribose, reversed the stimulatory and inhibitory effects of AI-2 on S. gordonii and S. oralis, respectively. In addition, co-culture using a two-compartment system showed that secreted molecules of F. nucleatum had the same effect on biofilm growth of the streptococci as AI-2. Our results demonstrate that early colonizing bacteria can influence the accretion of F. nucleatum, a secondary colonizer, which ultimately influences the binding of periodontopathogens.

Treatment with various ultrasonic scaler tips affects efficiency of brushing of SLA titanium discs.

PURPOSE: The dental implant surface will be colonized by bacteria once it is exposed to the oral cavity. It is necessary to keep the titanium surface clean to prevent peri-implant diseases. Mechanical instrumentation is widely used, but this may cause damage to the implant surfaces. There is limited information whether surface change resulting from instrumentation influences the adherence of bacteria to the implant surface or influences the ease of removal of bacteria from the titanium surface by daily brushing. Therefore, this in vitro study was performed (1) to evaluate removal of Porphyromonas gingivalis from sand-blasted and acid-etched (SLA) titanium discs after the discs were instrumented by various ultrasonic scaler tips or brushed with a toothbrush with dentifrice using crystal violet assay and scanning electron microscopy (SEM), and (2) to assess the change of surface roughness after the treated discs were brushed with a toothbrush with dentifrice. MATERIALS AND METHODS: SLA discs were treated with various ultrasonic scaler tips and a toothbrush. The titanium discs were incubated with P. gingivalis for 2 days after treatment (ultrasonic scales tips and brush) and then the disc surfaces were brushed for total of 40 seconds (20 seconds, two cycles) with a toothbrush with dentifrice. Differences in adhering bacteria were evaluated using crystal violet assay and SEM. Surface roughness of the treated discs after brushing with dentifrice was measured using confocal microscopy. RESULTS: The change of surface structure was observed after different treatment modalities. Removal of bacteria was increased with the longer time of brushing, and the ultrasonic metal tip group displayed a significantly lower number of bacteria after brushing when compared to other groups. CONCLUSIONS: Within the limits of this study, it may be suggested that when SLA surface is exposed to the oral cavity, it should firstly be treated with metal tips to smoothen the rough surface and thereby reduce attachment of bacteria and facilitate the removal of bacteria by daily oral hygiene procedures.

Autoinducer 2 of Fusobacterium nucleatum as a target molecule to inhibit biofilm formation of periodontopathogens.

Periodontitis is initiated by bacteria in subgingival biofilms, which are composed mostly of Gram-negative anaerobes. Autoinducer 2 (AI-2) is a universal quorum sensing (QS) molecule that mediates intergeneric signalling in multispecies bacterial communities and may induce biofilm formation. As Fusobacterium nucleatum is the major coaggregation bridge organism that links early colonising commensals and late pathogenic colonisers in dental biofilms via the accretion of periodontopathogens, we hypothesised that AI-2 of F. nucleatum contributes to this interspecies interaction, and interruption of this signalling could result in the inhibition of biofilm formation of periodontopathogens. To test this hypothesis, we evaluated the effect of partially purified F. nucleatum AI-2 on monospecies biofilm as well as mutualistic interactions between F. nucleatum and the so-called 'red complex' (Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia). Then we tested the effect of two QS inhibitors (QSIs), (5Z)-4-bromo-5-(bromomethylene)-2(5H)-furanone (furanone compound) and d-ribose, on AI-2-induced biofilm formation and coaggregation. F. nucleatum AI-2 remarkably induced biofilm growth of single and dual species and coaggregation between F. nucleatum and each species of the 'red complex', all of which were inhibited by the QSIs. F. nucleatum AI-2 induced the expression of the representative adhesion molecules of the periodontopathogens, which were inhibited by the QSIs. Our results demonstrate that F. nucleatum AI-2 plays an important role in inter- and intraspecies interactions between periodontopathogens via enhanced expression of adhesion molecules and may be a target for the inhibition of pathogenic dental biofilm formation.

In vitro analysis of the efficacy of ultrasonic scalers and a toothbrush for removing bacteria from resorbable blast material titanium disks.

BACKGROUND: A resorbable blast material (RBM) surface is reported to have a higher bone-to-implant contact percentage than machined surfaces, but modified surfaces with rougher textures have been shown to favor colonization by bacteria and development of peri-implantitis. Therefore, this in vitro study compares the effects of different instruments on surface roughness and removal of bacteria from RBM titanium implant disks. METHODS: RBM titanium disks were treated with various ultrasonic scaler tips and a toothbrush, and change in surface roughness was measured by confocal microscopy. The disks were incubated with bacteria, and instruments made of carbon or plastic, two metal ultrasonic scaler tips, or a toothbrush were used to remove the attached bacteria. The amount of remaining bacteria was evaluated using a crystal violet assay. RESULTS: The change in surface structure following different treatment modalities was analyzed by confocal microscopy. A statistically significant decrease in the arithmetic mean value of RBM surfaces (R(a)) was observed after treatment with an ultrasonic scaler with a metal tip. The use of a metal tip (rather than a carbon or plastic tip) and brushing with dentifrice was more efficient in removing bacteria from the contaminated titanium surface according to the crystal violet assay. CONCLUSION: Within the limits of this study, the use of a metal tip may be effective in removing bacteria from contaminated surfaces.

The effect of pretreating resorbable blast media titanium discs with an ultrasonic scaler or toothbrush on the bacterial removal efficiency of brushing.

PURPOSE: This in vitro study was performed to assess the adherence of Porphyromonas gingivalis to a resorbable blast media (RBM) titanium surface pretreated with an ultrasonic scaler or toothbrush and to evaluate the effects of the treatment of the RBM titanium discs on the bacterial removal efficiency of brushing by crystal violet assay and scanning electron microscopy. METHODS: RBM titanium discs were pretreated with one of several ultrasonic scaler tips or cleaned with a toothbrush. Then the titanium discs were incubated with P. gingivalis and the quantity of adherent bacteria was compared. The disc surfaces incubated with bacteria were brushed with a toothbrush with dentifrice. Bacteria remaining on the disc surfaces were quantified. RESULTS: A change in morphology of the surface of the RBM titanium discs after different treatments was noted. There were no significant differences in the adherence of bacteria on the pretreated discs according to the treatment modality. Pretreatment with various instruments did not produce significant differences in the bacterial removal efficiency of brushing with dentifrice. CONCLUSIONS: Within the limits of this study, various types of mechanical instrumentation were shown to cause mechanical changes on the RBM titanium surface but did not show a significant influence on the adherence of bacteria and removal efficiency of brushing.