Young small extracellular vesicles rejuvenate replicative senescence by remodeling Drp1 translocation-mediated mitochondrial dynamics.

BACKGROUND: Human mesenchymal stem cells have attracted interest in regenerative medicine and are being tested in many clinical trials. In vitro expansion is necessary to provide clinical-grade quantities of mesenchymal stem cells; however, it has been reported to cause replicative senescence and undefined dysfunction in mesenchymal stem cells. Quality control assessments of in vitro expansion have rarely been addressed in ongoing trials. Young small extracellular vesicles from the remnant pulp of human exfoliated deciduous teeth stem cells have demonstrated therapeutic potential for diverse diseases. However, it is still unclear whether young small extracellular vesicles can reverse senescence-related declines. RESULTS: We demonstrated that mitochondrial structural disruption precedes cellular dysfunction during bone marrow-derived mesenchymal stem cell replication, indicating mitochondrial parameters as quality assessment indicators of mesenchymal stem cells. Dynamin-related protein 1-mediated mitochondrial dynamism is an upstream regulator of replicative senescence-induced dysfunction in bone marrow-derived mesenchymal stem cells. We observed that the application of young small extracellular vesicles could rescue the pluripotency dissolution, immunoregulatory capacities, and therapeutic effects of replicative senescent bone marrow-derived mesenchymal stem cells. Mechanistically, young small extracellular vesicles could promote Dynamin-related protein 1 translocation from the cytoplasm to the mitochondria and remodel mitochondrial disruption during replication history. CONCLUSIONS: Our findings show that Dynamin-related protein 1-mediated mitochondrial disruption is associated with the replication history of bone marrow-derived mesenchymal stem cells. Young small extracellular vesicles from human exfoliated deciduous teeth stem cells alleviate replicative senescence by promoting Dynamin-related protein 1 translocation onto the mitochondria, providing evidence for a potential rejuvenation strategy.

Combined toxic effects of polyethylene microplastics and lambda-cyhalothrin on gut of zebrafish (Danio rerio).

Microplastics (MPs), which are prevalent and increasingly accumulating in aquatic environments. Other pollutants coexist with MPs in the water, such as pesticides, and may be carried or transferred to aquatic organisms, posing unpredictable ecological risks. This study sought to assess the adsorption of lambda-cyhalothrin (LCT) by virgin and aged polyethylene MPs (VPE and APE, respectively), and to examine their influence on LCT's toxicity in zebrafish, specifically regarding acute toxicity, oxidative stress, gut microbiota and immunity. The adsorption results showed that VPE and APE could adsorb LCT, with adsorption capacities of 34.4 mg∙g-1 and 39.0 mg∙g-1, respectively. Compared with LCT exposure alone, VPE and APE increased the acute toxicity of LCT to zebrafish. Additionally, exposure to LCT and PE-MPs alone can induce oxidative stress in the zebrafish gut, while combined exposure can exacerbate the oxidative stress response and intensify intestinal lipid peroxidation. Moreover, exposure to LCT or PE-MPs alone promotes inflammation, and combined exposure leads to downregulation of the myd88-nf-κb related gene expression, thus impacting intestinal immunity. Furthermore, exposure to APE increased LCT toxicity to zebrafish more than VPE. Meanwhile, exposure to PE-MPs and LCT alone or in combination has the potential to affect gut microbiota function and alter the abundance and diversity of the zebrafish gut flora. Collectively, the presence of PE-MPs may affect the toxicity of pesticides in zebrafish. The findings emphasize the importance of studying the interaction between MPs and pesticides in the aquatic environment.

Fat mass and obesity-associated protein (FTO) affects midpalatal suture bone remodeling during rapid maxillary expansion.

BACKGROUND: The fat mass and obesity-associated protein (FTO) is an RNA demethylase that contributes to several physiological processes. Nonetheless, the impact of FTO on bone remodeling in the midpalatal suture while undergoing rapid maxillary expansion (RME) remains unclear. METHODS: First, to explore the expression of FTO in the midpalatal suture during RME, six rats were randomly divided into two groups: Expansion group and Sham group (springs without being activated). Then, suture mesenchymal stem cells (SuSCs) were isolated as in vitro model. The expression of FTO was knocked down by small interfering RNA to study the effect of FTO on the osteogenic differentiation of SuSCs. Finally, to evaluate the function of FTO in the process of bone remodeling in the midpalatal suture, ten rats were randomly divided into two groups: FB23-2 group (10 µM, a small molecule inhibitor of FTO) and DMSO group (control). RESULTS: Increased arch width and higher expression of OCN and FTO in the midpalatal area were observed in expansion group (P < .05). In the in vitro model, the mRNA expression levels of Runx2, Bmp2, Col1a1, Spp1, and Tnfrsf11b were decreased (P < .05) upon knocking down FTO. Additionally, the protein levels of RUNX2 and OPN were also decreased (P < 0.05). Adding FB23-2, a small-molecule inhibitor targeting FTO, to the medium of SuSCs caused a decrease in the mRNA expression levels of Runx2, Bmp2, Col1a1, Spp1, and Tnfrsf11b (P < 0.05). There was a statistically significant difference in evaluating the expression of OCN and OPN on the palatal suture between the FB23-2 and DMSO groups (P < .05). LIMITATION: The molecular mechanisms by which FTO regulates SuSCs osteogenesis remain to be elucidated. The FTO conditional knock out mouse model can be established to further elucidate the role of FTO during RME. CONCLUSION: FTO contributes to the osteogenic differentiation of SuSCs and plays a promoting role in midpalatal suture bone remodeling during the RME.

Efficacy and safety of a nanoparticle therapeutic vaccine in patients with chronic hepatitis B: A randomized clinical trial.

BACKGROUND AND AIM: HBV DNA can be reduced using antiviral drugs in patients with chronic hepatitis B (CHB); however, the rate of HBeAg seroconversion remains low. A clinical trial was conducted to assess the efficacy and safety of a de novo designed liposome-based nanoparticle lipopeptide vaccine, εPA-44, for CHB. APPROACH AND RESULTS: A two-stage phase 2 trial, which included a 76-week, randomized, double-blind, placebo-controlled trial (stage 1) and a 68-week open-label extension (stage 2), was conducted in 15 centers across China (Clinicaltrials.gov No. NCT00869778). In stage 1, 360 human leukocyte antigen A2 (HLA-A2)-positive and HBeAg-positive patients were randomly and equally distributed to receive six subcutaneous injections of 600 µg or 900 µg εPA-44 or placebo at week 0, 4, 8, 12, 20, and 28. In stage 2, 183 patients received extended 900 µg εPA-44, and 26 patients were observed for relapse without further treatment. The primary endpoint was the percentage of patients with HBeAg seroconversion at week 76. At week 76, patients receiving 900 µg εPA-44 achieved significantly higher HBeAg seroconversion rate (38.8%) versus placebo (20.2%) (95% CI, 6.9-29.6%; p = 0.002). With a combined endpoint of HBeAg seroconversion, alanine aminotransferase normalization and HBV DNA < 2,000 IU/mL, both 900 µg (18.1%) and 600 µg (14.3%), resulted in significantly higher rate versus placebo (5.0%) (p = 0.002 and p = 0.02, respectively) at week 76. In stage 2, none (0 of 20) of 900 µg εPA-44-treated patients experienced serologic relapse. The safety profile of εPA-44 was comparable to that of placebo. CONCLUSIONS: Among HLA-A2-positive patients with progressive CHB, a finite duration of 900 µg εPA-44 monotherapy resulted in significantly higher HBeAg seroconversion rate than placebo and sustained off-treatment effect. A phase 3 trial is ongoing (ChiCTR2100043708).

Obstructive sleep apnea-related knowledge, attitude, experience, and behaviors among orthodontic professionals: a survey.

PURPOSE: To assess obstructive sleep apnea (OSA)-related experience, knowledge, attitude, and behaviors among orthodontic professionals in China and identify factors associated with their knowledge levels, attitude toward referring, and self-confidence in the management of patients with OSA. METHODS: An online cross-sectional survey was conducted using a 31-item questionnaire developed with a professional online survey tool ( www.wjx.cn ) and distributed via WeChat (Tencent, Shenzhen, China). Data were collected between January 16 and 23, 2022 and analyzed using the chi-square test, Fisher's exact test, and multivariate generalized estimation equations. RESULTS: A total of 1760 professionals responded to the survey, and responses to 1611 questionnaires were valid. The average score of correct answers to the 15 OSA knowledge questions was 12.1 ± 2.0. Most of the professionals agreed that it was necessary to identify patients who might have OSA in practice. The top three sources for gaining knowledge of OSA according to the survey were classrooms and textbooks (76.3%), medical lectures (75.7%), and academic conferences (73.2%). The level of knowledge was significantly correlated with self-confidence in treatment (P < 0.001) and willingness to refer patients to otolaryngologists or clinicians of related disciplines (P < 0.001). CONCLUSIONS: Most orthodontic professionals agreed that there was a need to identify patients with OSA and learn further about related problems. Treatment confidence and willingness of professionals to refer patients were related to the level of OSA knowledge. These findings suggest that promotion of OSA-related education may help improve the care of patients with OSA.

The knowledge, experience, and attitude on artificial intelligence-assisted cephalometric analysis: Survey of orthodontists and orthodontic students.

INTRODUCTION: Artificial intelligence (AI) developed rapidly in orthodontics, and AI-based cephalometric applications have been adopted. This study aimed to assess AI-assisted cephalometric technologies related knowledge, experience, and attitude among orthodontists and orthodontic students; describe their subject view of the applications and related technologies in orthodontics; and identify associated factors. METHODS: An online cross-sectional survey based on a professional tool (www.wjx.cn) was performed from October 11-17, 2022. Participants were recruited with a purposive and snowball sampling approach. Data was collected and analyzed with descriptive statistics, chi-square tests, and multivariable generalized estimating equations. RESULTS: Four hundred eighty valid questionnaires were collected and analyzed; 68.8% of the respondents agreed that AI-based cephalometric applications would replace manual and semiautomatic approaches. Practitioners using AI-assisted applications (87.5%) spent less time in cephalometric analysis than the other groups using other approaches, and 349 (72.7%) respondents considered AI-based applications could assist in obtaining more accurate analysis results. Lectures and training programs (56.0%) were the main sources of respondents' knowledge about AI. Knowledge level was associated with experience in AI-related clinical or scientific projects (P <0.001). Most respondents (88.8%) were interested in future AI applications in orthodontics. CONCLUSIONS: Respondents are optimistic about the future of AI in orthodontics. AI-assisted cephalometric applications were believed to make clinical diagnostic analysis more convenient and straightforward for practitioners and even replace manual and semiautomatic approaches. The education and promotion of AI should be strengthened to elevate orthodontists' understanding.

The dental and craniofacial characteristics among children with obstructive sleep apnoea: a systematic review and meta-analysis.

BACKGROUND: Paediatric obstructive sleep apnoea (OSA) is a sleep breathing disorder which may have dramatic effects on childhood behaviour, neurodevelopment, metabolism, and overall health in children. Malocclusion and craniofacial morphology may be related to paediatric OSA, and therefore provide information for clinicians to recognize, evaluate and treat patients with this sleeping disorder. OBJECTIVE: The aim of this systematic review was to summarize evidence regarding the association between paediatric OSA and children's dental and craniofacial characteristics. SEARCH METHODS: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched from inception to 1 June 2022. SELECTION CRITERIA: Cross-sectional studies, comparing dental or craniofacial characteristics using clinical dental examinations or radiographic findings between OSA children (less than 18 year, diagnosed with overnight polysomnography) and healthy children, were included. DATA COLLECTION AND ANALYSIS: The Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies was used to assess the quality of included studies. RevMan software was used for performing the Meta-analyses. RESULTS: Sixteen studies were included. Meta-analyses showed that the overjet (MD = 0.86, 95% CI: 0.20 to 1.51; P = 0.01), the saggital skeletal jaw discrepancy (ANB; MD = 1.78, 95% CI: 1.04 to 2.52; P < 0.00001) and mandibular plane angle (FH-MP; MD = 3.65, 95% CI: 2.45 to 4.85; P < 0.00001) were greater in OSA-affected children. In contrast, the upper molar arch width (upper first deciduous molar width; MD = -1.86, 95% CI: -3.52 to -0.20; P = 0.03), (Upper second deciduous molar width; MD = -1.06, 95% CI: -1.88 to -0.24; P = 0.01), SNB (MD = -2.10, 95% CI: -3.11 to -1.09; P < 0.0001), and maxillary length (ANS-PNS; MD = -1.62, 95% CI: -2.66 to -0.58; P = 0.002) were smaller in the OSA group. CONCLUSIONS: This review shows that OSA-affected children tend to present with mandibular retroposition or retrognathia, increased mandibular plane angle and excess anterior overjet. However, these findings need to be viewed with caution as the corresponding differences may not be significant clinically. REGISTRATION: PROSPERO (CRD42020162274).

Role of the tonsil-oropharynx ratio on lateral cephalograms in assessing tonsillar hypertrophy in children seeking orthodontic treatment.

OBJECTIVES: To analyze the diagnostic value of the tonsil-oropharynx (T/O) ratio on lateral cephalograms for evaluating tonsillar hypertrophy (TH). METHODS: A cross-sectional study was performed on 185 consecutive children (101 males, 84 females; mean age 7.3 ± 1.4 years) seeking orthodontic treatment. The T/O ratios on lateral cephalograms were calculated following Baroni et al.'s method. Tonsil sizes were clinically determined according to the Brodsky grading scale. Spearman correlation coefficients between the T/O ratio and clinical tonsil size were calculated with the total sample and subgroups and then compared between subgroups. Diagnostic value was analyzed using the receiver operating characteristic (ROC) curve, sensitivity, specificity, positive and negative predictive values, and accuracy. RESULTS: There was a strong correlation between the T/O ratio and clinical tonsil size in children (ρ = 0.73; P < 0.001). A significantly higher correlation coefficient was found in the Class III children. The ROC curve revealed an area under the curve of 0.90 (95% CI, 0.86-0.94; P < 0.001). The optimal cutoff value of the T/O ratio for predicting TH was 0.58, with a sensitivity of 98.7% and specificity of 64.2%. Employing the cutoff value of 0.5, the sensitivity was 100% and the specificity was 45.9%. CONCLUSIONS: Measurement of the T/O ratio on lateral cephalograms may be helpful to initial screening in children for TH. Practitioners may combine the clinical examination of tonsil size with the cephalometric findings for a more comprehensive evaluation.

THE USE OF DENTAL PATIENT-REPORTED OUTCOMES AMONG RANDOMIZED CONTROLLED TRIALS IN ORTHODONTICS: A METHODOLOGICAL STUDY.

OBJECTIVE: To identify and summarize the use and characteristics of dental patient-reported outcomes (dPROs) and dental patient-reported outcome measures (dPROMs) within randomized controlled trials (RCTs) published in 5 leading orthodontic journals. METHODS: A manual search was conducted to identify intervention (therapeutic or preventive) related RCTs published in selected journals between 2015 and 2021. Two authors extracted the characteristics of each included trial, as well as all outcomes and outcome measures used in these trials independently and in duplicate. Thereafter, the use of dPROs and dPROMs was identified and summarized. We classified all dPROs into 2 general types (oral health-related quality of life [OHRQoL] and others) and dPROMs into 3 categories (single-item questionnaires, generic multiple-item questionnaires, and specific multiple-item questionnaires). We also identified whether these dPROMs assessed 4 dimensions of OHRQoL (Oral Function, Orofacial Pain, Orofacial Appearance, and Psychosocial Impact). RESULTS: From 4631 examined articles, a total of 315 RCTs were included, of which 76 (24.1%) used dPROs and dPROMs. Eight different dPROs (OHRQoL, patients' satisfaction with treatment, difficulty, compliance, preference, efficacy, duration, and unwanted events) and 34 different dPROMs (including 13 single-item questionnaires, 7 generic multiple-item questionnaires, and 14 specific multiple-item questionnaires) were identified in these trials. OHRQoL was the most commonly used dPRO (n = 71; 93.4%), followed by patients' satisfaction with treatment (n = 10; 13.2%), patient-reported difficulty (n = 5; 6.6%), and patient-reported compliance (n = 4, 5.3%). The 4 most frequently used dPROMs were pain measured with 10 mm Visual Analogue Scale (n = 20; 24.1%), pain measured with Numerical Rating Scale (n = 11; 13.3%), the Feldmann's Questionnaire (2007) (n = 6; 7.2%), and the Oral Health Impact Profile 14 (n = 5; 6.0%). CONCLUSION: Only about one-fourth of RCTs published in leading orthodontic journals can reflect patients' perspectives. OHRQoL was the most commonly used dPRO in these trials. Substantial heterogeneity exists among dPROMs used for OHRQoL assessment. Efforts are needed from researchers, reviewers, editors and other stakeholders to promote the wide and standardized use of dPROs in orthodontic research.

THE REPORTING QUALITY OF SYSTEMATIC REVIEW ABSTRACTS IN LEADING GENERAL DENTAL JOURNALS: A METHODOLOGICAL STUDY.

OBJECTIVE: To assess the reporting quality of systematic review (SR) abstracts published in leading general dental journals according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Abstracts (PRISMA-A) guidelines, and to identify factors associated with overall reporting quality. METHODS: We identified SR abstracts published in 10 leading general dental journals and assessed their reporting quality. For each abstract, an overall reporting score (ORS, range: 0-13) was calculated. Risk ratio (RR) was calculated to compare the reporting quality of abstracts in Pre-PRISMA (2011-2012) and Post-PRISMA (2017-2018) periods. Univariable and multivariable linear regression analyses were performed to identify factors associated with reporting quality. RESULTS: A total of 104 eligible abstracts were included. The mean ORS was 5.59 (SD = 1.48) and 6.97 (1.74) respectively in the Pre- and Post-PRISMA abstracts, with statistically significant difference (mean difference = 1.38; 95% CI: 0.70, 2.05). Reporting of the exact P-value (B = 1.22; 95% CI: 0.45, 1.99) was a significant predictor of higher reporting quality. CONCLUSION: The reporting quality of SR abstracts published in leading general dental journals improved after the release of PRISMA-A guidelines, but is still suboptimal. Relevant stakeholders need to work together to enhance the reporting quality of SR abstracts in dentistry.

DNA Computation-Modulated Self-Assembly of Stimuli-Responsive Plasmonic Nanogap Antennas for Correlated Multiplexed Molecular Imaging.

Nanogap antennas with strong electromagnetic fields of the "hot spot" in the gap region of two adjacent particles that can significantly improve the optical properties of fluorophores hold great potential for ultrasensitive bioanalysis. Herein, a DNA computation-mediated self-assembly of Au NBP dimer-based plasmonic nanogap antennas was designed for imaging of intracellular correlated dual disease biomarkers. It is worth noting that with the benefit from the electromagnetic fields of the "hot spot" in the gap region and strand displacement amplification, the fluorescence intensity can be enhanced ∼14.7-fold by Au NBP dimer-based plasmonic nanogap antennas. In addition, the AND-gate sensing mechanism was confirmed through monitoring the response of three designed nAP-PH1, m-PH1, and PH1 probes, the fluorescence recovery in different cell lines (Hela and L02), and inhibitor-treated cells, respectively. Furthermore, thanks to the "dual keys" activation design, such an "AND-gate" sensing manner can be used for ultrasensitive correlated multiplexed molecular imaging, demonstrating its feasible prospect in correlated multiplexed molecular imaging.

CNTs-CaP/chitosan-coated AZ91D magnesium alloy extract promoted rat dorsal root ganglia neuron growth via activating ERK signalling pathway.

Increasing attention has been paid on the application of biodegradable materials such as magnesium and its alloys in neuron repair. AZ91D magnesium alloy coated with carbon nanotubes (CNTs) and/or calcium phosphate (CaP)/chitosan (CS) was fabricated in this study. To evaluate the bioactivity of these AZ91D-based composites, the extracts were prepared by immersing samples in modified simulated body fluid (m-SBF) for 0, 2, 8, 16, 24, 34, 44, 60, or 90 days. Immunofluorescence staining for neuronal class III ß-tubulin (TUJ1) revealed that both CNTs-CaP/CS-AZ91D and CaP/CS-AZ91D extracts promoted axon outgrowth of dorsal root ganglia (DRG) neurons, accompanied with increased expression of phosphorylated focal adhesion kinase (p-FAK) and growth associated protein-43 (GAP-43). Besides, the extracts increased the expression and the release of neurotrophic factors including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). ERK signalling was activated in DRG neurons after treating with either CNTs-CaP/CS-AZ91D or CaP/CS-AZ91D extracts, and its inhibition with U0126 counteracted the beneficial effects of these extracts on DRG neuron. Overall, the extracts from these AZ91D-based composites might promote DRG neuron growth via activating ERK signalling pathway. Notably, CNTs-CaP/CS-AZ91D extracts showed a better promoting effect on neuron growth than CaP/CS-AZ91D. Assessment of ion elements showed that the addition of CNTs coating enhanced magnesium corrosion resistance and reduced the deposition of calcium and phosphorus on the surface of CaP/CS-AZ91D alloy. These findings demonstrate that CNTs-CaP/CS-AZ91D likely provide a more suitable environment for neuron growth, which suggests a potential implantable biomaterial for the treatment of nerve injury. SIGNIFICANCE: AZ91D magnesium alloy coated with carbon nanotubes (CNTs) and/or calcium phosphate (CaP)/chitosan (CS) was fabricated and their immersion extracts were prepared using modified simulated body fluid in this study. Both extracts from CNTs-CaP/CS and CaP/CS-coated AZ91D magnesium alloy promotes rat dorsal root ganglia (DRG) neuron growth via activating ERK signalling pathway. Notably, the addition of CNTs improves the performance of CaP/CS-AZ91D. For the first time, our research demonstrates that CNTs-CaP/CS-AZ91D likely provide a suitable environment for neuron growth, suggesting these AZ91D-based composites as potential implantable biomaterials for the treatment of nerve injury.

Rapid maxillary expansion may increase the upper airway volume of growing patients with maxillary transverse deficiency.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Niu X, Di Carlo G, Cornelis MA, Cattaneo PM. Three-dimensional analyses of short- and long-term effects of rapid maxillary expansion on nasal cavity and upper airway: A systematic review and meta-analysis. Orthod Craniofac Res. 2020 Aug;23(3):250-276. doi: 10.1111/ocr.12378. Epub 2020 May 5. PMID: 32248642. SOURCE OF FUNDING: China Scholar Council TYPE OF STUDY/DESIGN: Systematic review with meta-analysis.

Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia.

BACKGROUND: Ventilator-associated pneumonia (VAP) is defined as pneumonia developing in people who have received mechanical ventilation for at least 48 hours. VAP is a potentially serious complication in these patients who are already critically ill. Oral hygiene care (OHC), using either a mouthrinse, gel, swab, toothbrush, or combination, together with suction of secretions, may reduce the risk of VAP in these patients. OBJECTIVES: To assess the effects of oral hygiene care (OHC) on incidence of ventilator-associated pneumonia in critically ill patients receiving mechanical ventilation in hospital intensive care units (ICUs). SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 25 February 2020), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2020, Issue 1), MEDLINE Ovid (1946 to 25 February 2020), Embase Ovid (1980 to 25 February 2020), LILACS BIREME Virtual Health Library (1982 to 25 February 2020) and CINAHL EBSCO (1937 to 25 February 2020). We also searched the VIP Database (January 2012 to 8 March 2020). The US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: We included randomised controlled trials (RCTs) evaluating the effects of OHC (mouthrinse, gel, swab, toothbrush or combination) in critically ill patients receiving mechanical ventilation for at least 48 hours. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed search results, extracted data and assessed risk of bias in included studies. We contacted study authors for additional information. We reported risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, using the random-effects model of meta-analysis when data from four or more trials were combined. MAIN RESULTS: We included 40 RCTs (5675 participants), which were conducted in various countries including China, USA, Brazil and Iran. We categorised these RCTs into five main comparisons: chlorhexidine (CHX) mouthrinse or gel versus placebo/usual care; CHX mouthrinse versus other oral care agents; toothbrushing (± antiseptics) versus no toothbrushing (± antiseptics); powered versus manual toothbrushing; and comparisons of other oral care agents used in OHC (other oral care agents versus placebo/usual care, or head-to-head comparisons between other oral care agents). We assessed the overall risk of bias as high in 31 trials and low in two, with the rest being unclear. Moderate-certainty evidence from 13 RCTs (1206 participants, 92% adults) shows that CHX mouthrinse or gel, as part of OHC, probably reduces the incidence of VAP compared to placebo or usual care from 26% to about 18% (RR 0.67, 95% confidence intervals (CI) 0.47 to 0.97; P = 0.03; I2 = 66%). This is equivalent to a number needed to treat for an additional beneficial outcome (NNTB) of 12 (95% CI 7 to 128), i.e. providing OHC including CHX for 12 ventilated patients in intensive care would prevent one patient developing VAP. There was no evidence of a difference between interventions for the outcomes of mortality (RR 1.03, 95% CI 0.80 to 1.33; P = 0.86, I2 = 0%; 9 RCTs, 944 participants; moderate-certainty evidence), duration of mechanical ventilation (MD -1.10 days, 95% CI -3.20 to 1.00 days; P = 0.30, I2 = 74%; 4 RCTs, 594 participants; very low-certainty evidence) or duration of intensive care unit (ICU) stay (MD -0.89 days, 95% CI -3.59 to 1.82 days; P = 0.52, I2 = 69%; 5 RCTs, 627 participants; low-certainty evidence). Most studies did not mention adverse effects. One study reported adverse effects, which were mild, with similar frequency in CHX and control groups and one study reported there were no adverse effects. Toothbrushing (± antiseptics) may reduce the incidence of VAP (RR 0.61, 95% CI 0.41 to 0.91; P = 0.01, I2 = 40%; 5 RCTs, 910 participants; low-certainty evidence) compared to OHC without toothbrushing (± antiseptics). There is also some evidence that toothbrushing may reduce the duration of ICU stay (MD -1.89 days, 95% CI -3.52 to -0.27 days; P = 0.02, I2 = 0%; 3 RCTs, 749 participants), but this is very low certainty. Low-certainty evidence did not show a reduction in mortality (RR 0.84, 95% CI 0.67 to 1.05; P = 0.12, I2 = 0%; 5 RCTs, 910 participants) or duration of mechanical ventilation (MD -0.43, 95% CI -1.17 to 0.30; P = 0.25, I2 = 46%; 4 RCTs, 810 participants). AUTHORS' CONCLUSIONS: Chlorhexidine mouthwash or gel, as part of OHC, probably reduces the incidence of developing ventilator-associated pneumonia (VAP) in critically ill patients from 26% to about 18%, when compared to placebo or usual care. We did not find a difference in mortality, duration of mechanical ventilation or duration of stay in the intensive care unit, although the evidence was low certainty. OHC including both antiseptics and toothbrushing may be more effective than OHC with antiseptics alone to reduce the incidence of VAP and the length of ICU stay, but, again, the evidence is low certainty. There is insufficient evidence to determine whether any of the interventions evaluated in the studies are associated with adverse effects.

Effects of Maxillary Skeletal Expansion on Upper Airway Airflow: A Computational Fluid Dynamics Analysis.

The effect of maxillary skeletal expansion (MSE) on upper airway in adolescent patients is not clear. The purpose of this study was to determine the upper airway airflow with MSE treatment using computational fluid dynamics analysis. Three-dimensional upper airway finite element models fabricated from cone beam computed tomography images were obtained before and after treatment in an adolescent patient with maxillary constriction. Turbulent analyses were applied. The nasal cavity (NC) was divided into 6 planes along the y-axis and the pharynx was divided into 7 planes in the z-axis. Changes in cross-sectional area, airflow velocity, pressure, and total resistance at maximum expiration and maximum inspiration were determined at each plane after MSE treatment. The greatest increase in area occurred in the oropharynx which was around 40.65%. The average increase in area was 7.42% in the NC and 22.04% in the pharynx. The middle part of pharynx showed the greatest increase of 212.81 mm and 217.99 mm or 36.58% and 40.66%, respectively. During both inspiration and expiration, airflow pressure decreased in both the NC and pharynx, which ranged from -11.34% to -23.68%. In the NC, the average velocity decrease was -0.18 m/s at maximum expiration (ME) and -0.13 m/s at maximum inspiration (MI). In the pharynx, the average velocity decrease was -0.07 m/s for both ME and MI. These results suggest that treatment of maxillary constriction using MSE appliance may show positive effects in improvement of upper airway cross-sectional areas and reduction of upper airway resistance and velocity.

Alternate Rapid Maxillary Expansion and Constriction (Alt-RAMEC) May Be More Effective Than Rapid Maxillary Expansion Alone for Protraction Facial Mask Treatment.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: The effectiveness of Alt-RAMEC combined with maxillary protraction in the treatment of patients with a class III malocclusion: a systematic review and meta-analysis, Mohammed Almuzian, Elise McConnell, M. Ali Darendeliler, Fahad Alharbi & Hisham Mohammed. J Orthod 2018;45(4);250-9. SOURCE OF FUNDING: No financial support was reported. TYPE OF STUDY/DESIGN: Systematic review.

Exfoliation and Sensitization of 2D Carbon Nitride for Photoelectrochemical Biosensing under Red Light.

Two-dimensional carbon nitride (CN) has drawn increasing attention as a conjugated metal-free polymer for photoelectrochemical (PEC) biosensing. However, CN only absorbs ultraviolet and very limited visible light (λ<460 nm), which poses potential risks for biomolecules and also cannot pass through tissue for in vivo detection. Herein, simultaneous exfoliation and functionalization of CN nanosheets (CNNS) with copper phthalocyanine (TsCuPc) simply by mechanical milling, thanks to the delicate π-π interaction between them, is reported. Moreover, due to energy-level matching, an effective donor-acceptor (D-A) interaction with much-improved photocurrent under irradiation with red light (λ>630 nm) was observed for the as-prepared CNNS-TsCuPc. As an example, dopamine in blood was detected by using red light by a CNNS-TsCuPc photoelectrode with uncompromised linear range and detection limit, as well high selectivity. As one of the few successful demonstrations of red-light-responsive PEC sensing systems, this work takes a first step toward future in vivo applications by enriching the optoelectronic properties of CN with task-specific antenna molecules via D-A interaction.

Synthesis of a magnetic polystyrene-based cation-exchange resin and its utilization for the efficient removal of cadmium (II).

A magnetic cation-exchange resin (MCER) was prepared by copolymerization of oleic acid-grafted magnetite with styrene, divinylbenzene (DVB), and triallylisocyanurate (TAIC) for removing Cd(II) from wastewater. A non-magnetic cation-exchange polystyrene resin (CEPR) was also prepared as a reference. Structural and morphological analyses revealed that the MCER and CEPR were mesoporous microspheres; the MCER contained about 25% Fe3O4. The influence of temperature, pH, contact time, and the initial concentration of Cd(II) on the adsorption of Cd(II) was investigated. The maximum adsorption capacity of the MCER reached 88.56 mg/g, which was achieved at 343 K using a Cd(II) initial concentration of 200 mg/L. The adsorption processes attained equilibrium within 120 min for the MCER and 300 min for the CEPR, and were well described by a pseudo-second-order kinetic model. Furthermore, the equilibrium adsorption data fitted the Freundlich isotherm model better than the Langmuir model. The superior magnetic response and regeneration of the MCER make it a good candidate as an adsorbent for removing Cd(II) from wastewater.

Real-Time Discrimination and Versatile Profiling of Spontaneous Reactive Oxygen Species in Living Organisms with a Single Fluorescent Probe.

Fluorescent probes are powerful tools for the investigations of reactive oxygen species (ROS) in living organisms by visualization and imaging. However, the multiparallel assays of several ROS with multiple probes are often limited by the available number of spectrally nonoverlapping chromophores together with large invasive effects and discrepant biological locations. Meanwhile, the spontaneous ROS profilings in various living organs/tissues are also limited by the penetration capability of probes across different biological barriers and the stability in reactive in vivo environments. Here, we report a single fluorescent probe to achieve the effective discrimination and profiling of hydroxyl radicals (•OH) and hypochlorous acid (HClO) in living organisms. The probe is constructed by chemically grafting an additional five-membered heterocyclic ring and a lateral triethylene glycol chain to a fluorescein mother, which does not only turn off the fluorescence of fluorescein, but also create the dual reactive sites to ROS and the penetration capability in passing through various biological barriers. The reactions of probe with •OH and HClO simultaneously result in cyan and green emissions, respectively, providing the real-time discrimination and quantitative analysis of the two ROS in cellular mitochondria. Surprisingly, the accumulation of probes in the intestine and liver of a normal-state zebrafish and the transfer pathway from intestine-to-blood-to-organ/tissue-to-kidney-to-excretion clearly present the profiling of spontaneous •OH and HClO in these metabolic organs. In particular, the stress generation of •OH at the fresh wound of zebrafish is successfully visualized for the first time, in spite of its extremely short lifetime.

Highly Sensitive CO2-Responsive Polymeric Microgels That Respond Within Seconds.

In this work, polymeric microgels with swift response to CO2 are synthesized by polymerization of tertiary-amine containing methacrylate monomers (N,N-diethylaminoethyl methacrylate, DEAEMA) and polyethylene glycol monomethyl ether acrylate (PEGMA) as stabilizers. The obtained microgels are stable but very sensitive to CO2, which can rapidly swell and further collapse within 5 s upon bubbling of CO2, or within minutes in an atmosphere of gaseous CO2. The protonation of the tertiary amine groups in the presence of CO2 induces sensitive swelling and further irreversible collapse of the microgels due to the internal charge repulsion and relatively low cross-linking density in the core area of microgels. This rapid response to CO2 may find further applications in the fields of sensitive detection or responsive loading and release upon CO2 stimulus.