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The alveolar bone is an essential consideration when planning treatment for patients with tooth agenesis. This study evaluated the changes in the alveolar bone and adjacent teeth in patients with a congenitally missing mandibular lateral incisor using cone-beam computed tomography.Twenty-three nonorthodontically treated adults with a unilateral congenitally missing mandibular lateral incisor were the missing group (M group). The control group (C group) consisted of 23 nonorthodontically treated adults with normal occlusion and no missing teeth. First, the difference in the arch perimeter between the groups was compared at the cementoenamel junction (CEJ) level and the root apex (RA) level. Next, the root divergence of the anterior teeth in the M group was observed. Finally, the alveolar bone thickness ratio was compared between the M and C groups at different vertical levels.The arch perimeter was significantly decreased in the M group at the CEJ and RA levels (P 0.05). Root divergence was observed adjacent to the missing site (P 0.0001). There were a reduction in total and cancellous cortical alveolar bone thickness (ABT) ratios at the 3-, 6-, and 9-mm positions (P 0.05). The buccal cortical ABT ratios decreased at the 3-and 6-mm positions. The lingual ABT ratio increased at the 9-mm position (P 0.05).The congenitally missing mandibular lateral incisor caused a reduction in the arch perimeter in the CEJ area and the RA area. The root divergences were observed in the teeth adjacent to the missing areas. A significant decrease in the buccal cortical bone and cancellous bone was observed in the missing area.

ObjectivesTo investigate the relationship between circummaxillary sutures and miniscrew-assisted rapid palatal expansion (MARPE) success in adult male patients and to evaluate the correlation between the width of the sutures and the maxilla expansion ratio.Materials and MethodsThis retrospective study comprised 40 adult male patients treated with MARPE divided into a separation group (N = 20, mean age, 21.9 years) consisting of subjects with midpalatal suture opening and a nonseparation group (N = 20, mean age, 21.7 years) consisting of subjects with no midpalatal suture opening. Cone-beam computed tomography images were obtained before MARPE expansion for both groups and after expansion for the separation group. Vertical and horizontal skeletal relationships, palate length, and widths of 10 circummaxillary sutures before expansion were compared. The correlation between maxilla expansion ratio (jackscrew expansion to maxillary expansion ratio) and circummaxillary suture widths was also analyzed in the separation group.ResultsThere were no significant differences in age, vertical and horizontal skeletal relationships, and palate length between the two groups. Zygomaticomaxillary, pterygomaxillary, midpalatal, and transverse palatine sutures showed significantly greater width in the separation group (P < .05). The zygomaticomaxillary suture showed the greatest difference (Δ = 0.36 mm) between the groups. The zygomaticomaxillary and pterygomaxillary sutures showed significant positive correlation with the maxilla expansion ratio (P < .01).ConclusionsIn adult male patients, greater circummaxillary suture widths before MARPE expansion, especially zygomaticomaxillary and pterygomaxillary sutures, resulted in a better chance of successful suture separation and more maxillary expansion.

Children with Down syndrome (DS) have distinct orofacial structures that predispose them to sleep-disordered breathing. The management options for obstructive sleep apnea include continuous positive airway pressure, adenotonsillectomy, mandibular advancement, and maxillary expansion. However, most of these treatment options are less effective or less viable for children with DS. Rapid maxillary expansion with a fixed orthodontic appliance is a viable alternative for DS patients because it separates the midpalatal suture and dilates the airway, regardless of the patient’s compliance. We present a case of a 15-year-old boy with DS and severe obstructive sleep apnea, which dramatically improved with rapid maxillary expansion and subsequent orthodontic treatment. Although only the short-term changes have been presented in this report, this case emphasizes the need for further discussions on the viability of rapid maxillary expansion for treating obstructive sleep apnea in children with DS. CITATION: Kim A, Cho HJ, Choi EK, Choi YJ. Improvement in obstructive sleep apnea in a child with Down syndrome with rapid palatal expansion. J Clin Sleep Med. 2022;18(7):1885–1888.

The objectives of this study were to compare the time-dependent changes in occlusal contact area (OCA) and bite force (BF) of the deviated and non-deviated sides in mandibular prognathic patients with mandibular asymmetry before and after orthognathic surgery and investigate the factors associated with the changes in OCA and BF on each side.The sample consisted of 67 patients (33 men and 34 women; age range 15-36 years) with facial asymmetry who underwent 2-jaw orthognathic surgery. OCA and BF were taken before presurgical orthodontic treatment, within 1 month before surgery, and 1 month, 3 months, 6 months, 1 year, and 2 years after surgery. OCA and BF were measured using the Dental Prescale System.The OCA and BF decreased gradually before surgery and increased after surgery on both sides. The OCA and BF were significantly greater on the deviated side than on the non-deviated side before surgery, and there was no difference after surgery. According to the linear mixed-effect model, only the changes in the mandibular plane angle had a significant effect on BF (There was a difference in the amount of the OCA and BF between the deviated and non-deviated sides before surgery. The change in mandibular plane angle affects the change, especially on the non-deviated side, during the observation period.

Many studies have investigated the transcriptome profiles of dental stem cells for regenerative medicine. However, such studies use bulk RNA and do not consider cell-level heterogeneity. Here, we investigated the characteristics and heterogeneity of human dental pulp stem cells (hDPSCs) and human periodontal ligament stem cells (hPDLSCs) at the single-cell level and examined the differences between them.hDPSCs and hPDLSCs were obtained from caries-free premolars (n = 2). Single-cell RNA sequencing of hDPSCs and hPDLSCs was performed using a Single Emulsion Systems (Dolomite Microfluidics, Royston, UK) droplet microfluidic device and the Illumina NextSeq550 system (Illumina, San Diego, CA). Data alignment was performed using STAR v2.4.0, and further analysis was performed using the Seurat, singleR, and clusterProfiler packages in R (R Foundation for Statistical Computing, Vienna, Austria).hDPSCs and hPDLSCs were separated into 3 clusters. hDPSCs mainly exhibited osteogenic and neurogenic cell populations. The main populations of hPDLSCs comprised osteogenic and myofibroblastic populations. hPDLSCs showed high "scores" for osteogenic gene expression, whereas hDPSCs had high neurogenic and endogenic scores.Single-cell RNA sequencing of hDPSCs and hPDLSCs revealed that the genes were expressed in specific clusters. The results of these analyses can be used as reference databases and valuable resources for further research in dental therapeutics.

Objectives: Masticatory function, including masticatory muscle activity and occlusal function, can be affected by craniofacial morphology. This study aimed to investigate the relationship between craniofacial morphology and masticatory function in participants who had completed orthodontic treatment at least two years before and had stable occlusion. Materials and Methods: Fourty-two healthy participants were prospectively enrolled and divided into three vertical cephalometric groups according to the mandibular plane angle. Masticatory muscle activity (MMA) in the masseter and anterior temporalis muscles was assessed using surface electromyography. The occlusal contact area and occlusal force (OF) were evaluated using the Dental Prescale System. Masticatory muscle efficiency was calculated by dividing MMA by OF. The craniofacial morphology was analyzed using a lateral cephalogram. The masticatory function was compared using one-way analysis of variance. Pearson correlations were used to assess the relationships between craniofacial morphology and masticatory function. Results: The hypodivergent group had the lowest MMA and the highest efficiencies in the masseter and anterior temporalis muscle (p < 0.05). MMA showed a positive relationship with mandibular plane angle, whereas the occlusal function demonstrated a negative relationship (p < 0.05). The anterior temporalis muscle activity negatively correlated with ramus height (p < 0.05). Conclusions: Vertical craniofacial morphology was related to masticatory function in participants with normal occlusion after orthodontic treatment. Participants with hypodivergent facial profiles may have low MMA and high occlusal function, resulting in good masticatory muscle efficiency. Clinical relevance: Vertical craniofacial morphology is an important factor to consider in orthodontic diagnosis and prosthetic treatment planning.

To evaluate changes in masticatory performance (MP) during the retention period after extraction and non-extraction treatment and compare it with MP in individuals with normal occlusion.Adult patients who had completed orthodontic fixed appliance treatment comprised the extraction and non-extraction treatment groups, and those with normal occlusion comprised the control group. Their mixing ability (MA), maximum bite force (MBF), and occlusal contact area (OCA) were recorded immediately after the fixed appliance was removed and at 1 month, 6 months, and 1 year post-treatment. The MA was measured via the two-color chewing gum MA test using ViewGum software, and the MBF and OCA were measured using Dental Prescale II system.MA immediately after orthodontic treatment was lower than that in the normal group but showed a time-dependent gradual increase during a 1-year retention period (P 0.01). The MA at 1 month post-treatment was not significantly different between the three groups (P 0.05). The MA revealed a significant correlation with the MBF and OCA (P 0.01).The MP immediately after orthodontic treatment was lower than that in the normal group but increased gradually, with levels comparable to those of the normal occlusion group at 1 month post-treatment. Further, extraction did not affect the recovery of the MP after orthodontic treatment.No other study has evaluated the changes in MP during the retention period after orthodontic treatment. The findings show that compared with MBF and OCA, the patients' MP improved faster to levels found in normal occlusion.

Orthodontic diagnosis is a comprehensive procedure that integrates various information obtained from the facial and occlusal structure as well as patient's individual needs. Hence it is not easy to imagine if the artificial intelligence(AI) would eventually replace the conventional diagnostic process. Nonetheless, recent advances in the machine learning and artificial intelligence have been applied to the cephalometric tracing and model analysis via automated image recognition, exhibiting relatively high reliability. Based on the cumulated experiences and research outcomes, orthodontic diagnostics have taken a small step towards an automated process. Considering that the orthodontic diagnosis starts from the recognition of the space discrepancy between the initial status and idealized occlusion, semi-automated three-dimensional visualized treatment objectives (VTO) may be established. This article covers the brief overview of the current status in machine learning especially focusing on the image recognition. Recent advances in the fabrication of three-dimensional VTO using surface landmarks and automated setup process is demonstrated. In the near future, a more clinically relevant VTO can be utilized using the imaginary center of resistance, to provide useful clues to the orthodontists in many of the borderline cases between extraction and non-extraction, and between surgery and non-surgery.

Objective This study aimed to evaluate the following null hypothesis: there are no differences in the morphology of the temporomandibular joint (TMJ) structures in relation to vertical and sagittal cephalometric patterns. Methods This retrospective study was performed with 131 participants showing no TMJ symptoms. The participants were divided into Class I, II, and III groups on the basis of their sagittal cephalometric relationships and into hyperdivergent, normodivergent, and hypodivergent groups on the basis of their vertical cephalometric relationships. The following measurements were performed using cone-beam computed tomography images and compared among the groups: condylar volume, condylar size (width, length, and height), fossa size (length and height), and condyle-to-fossa joint spaces at the anterior, superior, and posterior condylar poles. Results The null hypothesis was rejected. The Class III group showed larger values for condylar width, condylar height, and fossa height than the Class II group (p < 0.05). Condylar volume and superior joint space in the hyperdivergent group were significantly smaller than those in the other two vertical groups (p < 0.001), whereas fossa length and height were significantly larger in the hyperdivergent group than in the other groups (p < 0.01). The hypodivergent group showed a greater condylar width than the hyperdivergent group (p < 0.01). The sagittal and vertical cephalometric patterns showed statistically significant interactions for fossa length and height. Conclusions TMJ morphology differed across diverse skeletal cephalometric patterns. The fossa length and height were affected by the interactions of the vertical and sagittal skeletal patterns.

Background and Overview Orthodontic miniscrews have become popular tools for providing temporary anchorage during orthodontic treatment. Although they are easy to insert, damage to the periodontal ligament or dental root during insertion is an unfavorable iatrogenic complication. Root perforation during miniscrew insertion in human teeth has been reported in a few articles. In this article, the authors describe the spontaneous repair of an iatrogenic root perforation in a mandibular first molar that occurred during insertion of an orthodontic miniscrew in a young girl undergoing orthodontic treatment. Case Description A 15-year-old girl with malocclusion was undergoing orthodontic treatment when the mesial root of her mandibular right first molar was damaged by an orthodontic miniscrew. The miniscrew and corresponding bracket were immediately removed to avoid any unnecessary forces on the tooth. Because the pulp remained vital without any additional damage and infection for 6 months, orthodontic treatment was resumed and completed in 9 months without any pulp damage or unfavorable symptoms. Serial periapical radiographs and cone-beam computed tomographic images showed that the injured area was surrounded by reparative tissue without any apical lesion. Conclusions and Practical Implications The findings of this case suggest that immediate removal of unnecessary forces provides an environment for spontaneous repair in cases of iatrogenic root perforation by orthodontic miniscrews, even when the damage involves the pulp. If force stimulation is avoided for a certain period, which was 6 months in this case, it may be possible to complete the orthodontic treatment without unfavorable symptoms.

Accelerated tooth movement can be achieved using micro-osteoperforations (MOPs) to stimulate regeneration of the alveolar bone during minimally invasive surgical trauma. However, there is currently no standardized protocol and limited reports regarding the side effects of MOPs based on biological evidence. This study sought to evaluate the biological effects of the number of MOPs on orthodontic tooth movement (OTM) and the potential risk for root resorption. Male CD1 mice were divided into 4 groups based on the number of MOPs, as follows: Sham; 0MOP+OTM; 2MOP+OTM; and 4MOP+OTM groups. Tooth movement distance and the number of osteoclasts were higher whereas bone volume and trabecular number were lower in the 4MOP+OTM group compared to those of the 0MOP+OTM group. Immunofluorescent assay analysis indicated that the 4MOP+OTM group was positively associated with rapid cementum regeneration and periodontal ligament tissue formation. Our findings revealed that the MOP procedure affected tooth movement and did not significantly contribute to root resorption, whereas it may promote constitutive activation of cementogenesis.

Mandibular step osteotomy, performed for mandibular prognathism, is a difficult and time-consuming procedure. Virtual computer surgery and computer-aided designcomputer-aided manufacturing have demonstrated accurate results in orthognathic surgery, though not used for mandibular step osteotomy yet. In this study, the authors report the case of a 21-year-old man with severe mandibular prognathism, with a reverse overjet of 12 mm. Step osteotomy, a modified method of body osteotomy, was planned virtually and performed using 3-dimensional (3D) printed titanium surgical guides and osteosynthesis plates, using computer-aided designcomputer-aided manufacturing. At the 6-month postoperative follow-up, there were no notable complications, and normal healing was observed. Each segment was stably in place with the prefabricated plates. The proximal segments were not sagged medially or laterally. With 3D-printed surgical guides and osteosynthesis plates, intraoperative complications, such as injury to adjacent teeth and nerves, could be avoided. They also showed reasonable accuracy and helped reduce operative time and improve outcomes. Unlike surgical guides made of resin/polyamide, titanium surgical guides can be made thinner, which can reduce the extent of detachment. They also did not undergo any deterioration during the operation. Cutting guides and prefabricated plates using virtual surgical planning and 3D printing have many advantages, including reduced preoperative preparation time and operative time, reduced incidence of intraoperative complications, and improved outcomes. However, limitations still exist and further studies are required.

The miniscrew-assisted rapid palatal expander (MARPE) has extended not only skeletal effects with fewer dental changes and but also the age limit of nonsurgical maxillary expansion treatment. Amid its gaining popularity in clinical orthodontics, our current understanding of treatment effectiveness, efficiency, and stability needs to be reassessed. In this review article, the authors have attempted to evaluate MARPE from various aspects with a focus on recent studies.

Introduction The registration of cone-beam computed tomography (CBCT) images and digital dental models is required for the design and manufacturing of dental devices such as implant guides and surgical wafers. This study aims to register intraoral scan (IS) models and cast scan (CS) models onto CBCT images using 3-dimensional (3D) planning software and evaluate the registration accuracy according to scanning methods and 3D planning software. Methods The CBCT image of an artificial skull model with reference markers was taken. The CS model and the IS model were obtained from the same skull model, registered onto the CBCT image using 3D planning software packages providing manual registration (MR) function and point-based registration (PR) functions, and set as the experimental groups. After registration, shell to shell deviations and positional differences between the reference model and the experimental models were evaluated. Results The shell to shell deviations ranged from 0.03 to 0.18 mm. Deviations in both the maxilla and mandible were significantly different according to scanning methods and software packages. In the anteroposterior direction, the IS-MR and CS-MR groups showed significantly different positions. In the superoinferior direction, the MR and PR groups showed significantly different positions. Conclusions The registration using the PR function of the 3D planning software packages was significantly more accurate than the registration using the MR function. There was no significant difference between the registrations using the IS model and the CS model when using the PR functions.

This paper report on the significantly improved performance of InP/ZnSeS/ZnS quantum dot (QD) devices with multi-functional ligands. These quantum dots in which the monodentate ligand oleylamine is coordinated to the shell surface are reacted with the delocalized bipyridine bidentate ligand, where some oleylamine is replaced by bipyridine. The coordination of the delocalized bidentate bipyridine ligand results in many electronic property changes in the QD-LED (light emitting diode) device. 1H-NMR (nuclear magnetic resonance) and TGA (thermogravimetric analysis) data indicated that up to 60.6% of the native ligands were partially exchanged with the bipyridine lig-ands. Photoluminescence (PL) spectra before and after ligand substitution show a bathochromic shift of about 2.6 nm due to the electrical resonant properties of the bipyridine ligands. QD-LED devices were fabricated using QDs with substituted bipyridine ligand, and significant improvements in the device properties were observed. Here, we first report the ligand dependence of the photo-and the electroluminescence of green InP/ZnSeS/ZnS quantum dots in QD-LED devices.

Moving sport tourism refers to travel that combines sport activity and tours to a particular destination. Although moving sport tourism is one of the fastest growing segments of the sport tourism industry, it is still lack of relatedknowledge and academic studies. Hence, this study is conducted to explore the characteristics of moving sport tourism and to provide implications for sport tourism industry and future research. For this, ten participants who regularly participated in bicycle tours for the last 10 years were recruited for this study. The sample consisted of 9 males and 1 female. The average age of the participants was 44.6 years of which all but 2 had a full-time job. The average period of participating in bicycle tour was 7.9 years. For analysing data, content analysis approach was used. Interviews were tape recoded and data were multiple reviewed to identify the similar themes and to categorize them into conceptual constructs. Results suggest two requirements of moving sport tourism(moving and concurrent), three characteristics of moving sport tourism(self-directed, exploring, non-linear, purposive-riding, partial competitive, cultural touring) and two categories of moving sport tourism(full moving sport tourism and partial moving sport tourism). Implications for sport tourism industry and future studies were discussed.

Objective: A number of epidemiological studies have reported that decreased serum bilirubin, an endogenous antioxidant, is associated with cardiovascular disease. However, previous Mendelian randomization analyses conducted using a single sample have shown no evidence of association. Approach and Results: A 2-sample summary Mendelian randomization study was performed by obtaining exposure and outcome data from separate nonoverlapping samples. We utilized data from the KoGES (Korean Genome and Epidemiology Study; n=25 406) and KCPS-II (Korean Cancer Prevention Study-II; n=14 541) biobank for serum bilirubin and stroke, respectively. Using KoGES, a total of 1784 single nucleotide polymorphisms associated with serum bilirubin levels were discovered using a genome-wide significance threshold ( P −8 ), of which 10 single nucleotide polymorphisms were identified as independent ( R 2 P =0.046). This association increased in magnitude when restricting the analysis to ischemic stroke cases (odds ratio, 0.302 [95% CI, 0.105–0.868]; P =0.026). Conclusions: Our findings provide evidence of significant causal relationship between high levels of bilirubin and decreased stroke risk in Korean population in agreement with observational approaches. This highlights the potential for bilirubin to serve as a therapeutic target for oxidative stress-related diseases such as stroke and suggests that previous findings were not a consequence of unmeasured confounding.

Objectives: Mechanical stimuli are essential for the maintenance of periodontal ligament (PDL) homeostasis. Although there are several studies on atrophic changes in PDL due to occlusal hypofunction, the underlying mechanism is still unknown. Here, we aimed to explore the changes of gene expression in occlusal hypofunctional PDL and elucidate the related role in maintaining the PDL homeostasis.Methods: To investigate the transcriptomic difference between control and hypofunctional PDL tissue from patients, RNA sequencing was performed on 34 human teeth. The atrophic changes in PDL were evaluated by histological analysis. The effect of the Bardet-Biedl syndrome 7 (BBS7) knockdown was evaluated by the RT-qPCR, Western blot, wound healing, and tubule formation assay.Results: We detected that the expression of BBS7 was downregulated in occlusal hypofunctional PDL through RNA sequencing. Dynamic changes, including the number of periodontal ligament cells, alignment of collagen fibers, diameter of blood vessels, appearance of primary cilia, and torturous oxytalan fibers, were observed following occlusal hypofunction. Furthermore, Sonic hedgehog signaling (Shh) activity was closely associated with BBS7 expression in PDL cells. In addition, the cell migration and angiogenesis were also suppressed by BBS7 knockdown in vitro.Conclusion: We suggest that BBS7 plays an essential role in maintaining Shh signaling activity for PDL homeostasis.

Aim This prospective clinical study evaluated the clinical performance of managing cracked teeth with reversible pulpitis through a combination of internal and external splinting and investigated factors that can affect pulp survival after splinting. Methodology Thirty-four teeth diagnosed with cracks and reversible pulpitis were enrolled and treated with bidirectional crack splinting: 1) immediate splinting with a stainless-steel band; 2) internal splinting with crack line removal and resin filling; and 3) external splinting with a temporary crown followed by final crown setting. If the symptoms remained/recurred, root canal treatment was performed. Patients were followed up at 3, 6, and 12 months, then annually thereafter. Kaplan-Meier survival analysis to calculate the survival of the treated teeth and Cox univariate proportional hazards regression model to investigate prognostic factors were performed. Results Twenty-nine (97%) teeth were followed up for up to 4 years. The pulp survival rate was 72% after banding and 91% after final crown cementation. No tooth was extracted (100% tooth survival rate). In the univariate Cox proportional hazard test, pain on percussion was the only statistically significant factor (hazard ratio = 11.77). Teeth with pain on percussion at the first visit had a pulp survival rate of 46% during the follow-up period. In comparison, their counterparts without pain had a 94% pulp survival rate. Conclusions Bidirectional splinting successfully managed cracked teeth with reversible pulpitis. Pain on percussion (mechanical allodynia) may be an important factor in deciding whether to attempt root canal treatment on symptomatic cracked teeth. A step-by-step approach with bidirectional crack splinting should be encouraged for a cracked tooth with a vital pulp without mechanical allodynia rather than preemptive root canal treatment.

Introduction Appropriate occlusal forces can prevent ankylosis after tooth replantation or transplantation. However, the “proper occlusal forces” on periodontal ligament (PDL) healing have not yet been defined due to insufficient in vitro studies and uncertain in vitro models. Herein, we presented a mechanical vibration device as an in vitro model to determine such favorable occlusal forces. Methods Human periodontal ligament stem cells (hPDLSCs) were exposed to mechanical vibration force with 4 frequencies (30, 90, 150, and 210 rpm). Cell viability and the expression of osteogenic differentiation-related genes and proteins were tested in vitro. The calvarial transplantation experiment was performed to assess the bone formation ability of 150 rpm mechanical vibration stimulation (MVS). Results MVS at 150 and 210 rpm significantly reduced cell viability in the early stages. The 150-rpm MVS decreased osteogenic marker expression at the early time point (3 days) but had no harmful effects at the late time point (14 days). Furthermore, hPDLSC cell sheets treated with 150-rpm MVS had potential to decrease bone formation in rat calvarial defects serendipitously and facilitated functional PDL-like tissue formation. Conclusions We found that MVS at a frequency of 150 rpm could provide a strategy for a transient reduction in the osteogenic potential of hPDLSCs and promote PDL-like tissue formation. Thus, 150-rpm MVS could be used as a controllable proper occlusal force to prevent ankylosis and promote PDL healing after tooth replantation or transplantation.

BackgroundWe investigated the safety and immunogenicity of two recombinant COVID-19 DNA vaccine candidates in first-in-human trials. GX-19 contains plasmid DNA encoding SARS-CoV-2 spike protein, and GX-19N contains plasmid DNA encoding SARS-CoV-2 receptor binding domain (RBD) foldon and nucleocapsid protein (NP) as well as plasmid DNA encoding SARS-CoV-2 spike protein.MethodsTwo open-label phase 1 trials of GX-19 and GX-19N safety and immunogenicity were performed in healthy adults aged 19–55 years. GX-19 trial participants received two vaccine injections (1·5 mg or 3·0 mg, 1:1 ratio) four weeks apart. GX-19N trial participants received two 3·0 mg vaccine injections four weeks apart.FindingsBetween June 17 and July 30 and December 28 and 31, 2020, 40 and 21 participants were enrolled in the GX-19 and GX-19N trials, respectively. Thirty-two participants (52·5%) reported 80 treatment-emergent adverse events (AE) after vaccination. All solicited AEs were mild except one case of moderate fatigue reported in the 1·5 mg GX-19 group. Binding antibody responses increased after vaccination in all groups. The geometric mean titers (GMTs) of spike-binding antibodies on day 57 were 85·74, 144·20, and 201·59 in the 1·5 mg, 3·0 mg GX-19 groups and the 3·0 mg GX-19N group, respectively. In GX-19N group, neutralizing antibody response (50% neutralizing titer using FRNT) significantly increased after vaccination, but GMT of neutralizing antibody on day 57 (37.26) was lower than those from human convalescent serum (288.78). GX-19N induced stronger T cell responses than GX-19. The magnitude of GX-19N-induced T cell responses was comparable to those observed in the convalescent PBMCs. GX-19N induced both SARS-CoV-2 spike- and NP-specific T cell responses, and the amino acid sequences of 15-mer peptides containing NP-specific T cell epitopes identified in GX-19N-vaccinated participants were identical with those of diverse SARS-CoV-2 variantsInterpretationGX-19N is safe, tolerated and induces humoral and broad SARS-CoV-2-specific T cell response which may enable cross-reactivity to emerging SARS-CoV-2 variants.FundingThis research was supported by Korea Drug Development Fund funded by Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare (HQ20C0016, Republic of Korea).Research in contextEvidence before this studyTo overcome the COVID-19 outbreak, the development of safe and effective vaccines is crucial. Despite the successful clinical efficacy of the approved vaccines, concerns exist regarding emerging new SARS-CoV-2 variants that have mutated receptor binding domains in the spike protein. We searched PubMed for research articles published up to May 1, 2021, using various combinations of the terms “COVID-19” or “SARS-CoV-2”, “vaccine”, and “clinical trial”. No language or data restrictions were applied. We also searched theClinicalTrials.govregistry and World Health Organization (WHO) draft landscape of COVID-19 candidate vaccines for ongoing trials of COVID-19 vaccines up to May 1, 2021. Ten DNA-based vaccines, including the vaccine candidate reported here, are in ongoing clinical trials. Among these, safety and immunogenicity results were reported from only one phase 1 trial of a DNA vaccine against SARS-CoV-2 (INO-4800). INO-4800 demonstrated favorable safety and tolerability and was immunogenic, eliciting humoral and/or cellular immune responses in all vaccinated subjects. There is only one ongoing clinical trial of a vaccine against SARS-CoV-2 variants (mRNA-1273.351).Added value of this studyThis is the first-in-human phase 1 trial in healthy adults of a recombinant DNA vaccine for COVID-19 (GX-19N) containing the coding regions of both the spike and nucleocapsid proteins. This trial showed that GX-19N is safe, tolerated, and able to induce both humoral and cellular responses. A two-dose vaccination of 3·0 mg GX-19N (on days 1 and 29) induced significant humoral and cellular responses. The neutralizing geometric mean titers in individuals vaccinated with GX-19N were lower than those of human convalescent sera. However, the GX-19N group showed increased T cell responses, which was similar to those analyzed using convalescent PBMCs. Furthermore, GX-19N induced not only SARS-CoV-2 spike-specific T cell responses but also broad nucleocapsid-specific T cell responses, which were also specific to SARS-CoV-2 variants.Implications of all the available evidenceIt is important to note that GX-19N contains a plasmid encoding both the spike and nucleocapsid proteins, and that it showed broad SARS-CoV-2-specific T cell responses, which may allow cross-reactivity with emerging SARS-CoV-2 variants. Based on these safety and immunogenicity findings, GX-19N was selected for phase 2 immunogenicity trials.

Introduction The aim of this study was to evaluate the height growth of Class I and III orthodontic patients according to the Fishman skeletal maturation index (SMI) and to compare it with that of a general population. Methods The study sample included 81 Class I and 71 Class III adolescents who had height measurements and hand-wrist radiographs taken annually and categorized according to SMI. Height completion rate, residual height, height increase per sequential SMI stage, and height velocity were analyzed. Sex differences were evaluated and comparisons between Class I and Class III groups were made. In addition, the height of orthodontic patients was indirectly compared with that of the general population. Results In boys and girls, height completion rate was >90% at SMI 6, residual height was fewer than 10 cm at SMI 7, and height increase per sequential SMI stage was greatest from SMI 6 to SMI 7. Height velocity was greatest from SMI 5 to SMI 6 in boys and from SMI 4 to SMI 5 in girls. Conclusions There was no significant difference in body height parameters for all SMI stages between Class I and Class III adolescents. Adolescents who had orthodontic treatment were not shorter in stature at growth completion compared with the general population.

The present study aimed at evaluating serum immunoglobulin G (IgG) avidity to Porphyromonas gingivalis in elderly patients with mild and severe chronic periodontitis. The avidity of antibodies against P. gingivalis present in the sera of 18 patients with mild chronic periodontitis and 18 patients with severe chronic periodontitis was evaluated using an ammonium thiocyanate-dissociated enzyme-linked immunosorbent assay (ELISA). The results showed that the mean absorbance value in serum IgG antibody titers was significantly higher in the severe chronic periodontitis group than in the mild chronic periodontitis group (198 ± 35 ELISA unit [EU] vs. 142 ± 32 EU, p < 0.01). However, there was no significant difference between the two groups in antibody avidity (65 ± 57 EU vs. 54 ± 27 EU). These findings suggest that humoral immune responses to P. gingivalis between mild and severe chronic periodontitis in elderly patients are characterized by the differences in the quantity rather than the quality of the antibodies.

The present study aimed to detail the relationship between the flow and structure characteristics of the upper airways and airway collapsibility in obstructive sleep apnea. Using a computational approach, we performed simulations of the flow and structure of the upper airways in two patients having different facial morphologies: retruding and protruding jaws, respectively. First, transient flow simulation was performed using a prescribed volume flow rate to observe flow characteristics within upper airways with an unsteady effect. In the retruding jaw, the maximum magnitude of velocity and pressure drop with velocity shear and vortical motion was observed at the oropharyngeal level. In contrast, in the protruding jaw, the overall magnitude of velocity and pressure was relatively small. To identify the cause of the pressure drop in the retruding jaw, pressure gradient components induced by flow were examined. Of note, vortical motion was highly associated with pressure drop. Structure simulation was performed to observe the deformation and collapsibility of soft tissue around the upper airways using the surface pressure obtained from the flow simulation. At peak flow rate, the soft tissue of the retruding jaw was highly expanded, and a collapse was observed at the oropharyngeal and epiglottis levels. NEW & NOTEWORTHY Aerodynamic characteristics have been reported to correlate with airway occlusion. However, a detailed mechanism of the phenomenon within the upper airways and its impact on airway collapsibility remain poorly understood. This study provides in silico results for aerodynamic characteristics, such as vortical structure, pressure drop, and exact location of the obstruction using a computational approach. Large deformation of soft tissue was observed in the retruding jaw, suggesting that it is responsible for obstructive sleep apnea.