Clinical Effects of the Combination of Rhytidectomy and Temporomandibular Joint Disc Repositioning Surgery.

OBJECTIVE: This study aims to investigate the clinical effects of the combination of rhytidectomy and temporomandibular joint (TMJ) disc repositioning surgery in internal derangement (ID) stage IV-V and facial aging patients. METHODS: Eighteen facial aging with bilateral ID IV-V patients were enrolled in this study. All of them had undergone temporomandibular disc repositioning surgery and rhytidectomy by the same surgeon (Yao Min Zhu). Pre-/post-surgical clinical manifestations, facial photography, radiographic data were recorded and analyzed, as well as doctor, patient, third-party evaluation of postsurgical facial appearance satisfaction. RESULTS: The average age of 18 female patients was 52.9. The average of presurgical visual analog pain scale score was 5.94, ranged from 4 to 8. After 6 months, the average of postsurgical visual analog pain scale score was 0.28, ranged from 0 to 1 ( P   >  0.05). The average maximal mouth opening of presurgical and postsurgical was 2.19 and 3.29 cm, ranged from 1.2 to 2.8 cm and 3.0 to 3.5 cm, respectively ( P  < 0.05). Postoperative magnetic resonance imaging showed the location of the bilateral TMJ discs directly above the mandibular condyle. The satisfaction rate of doctors, patients and third-party with facial appearance was 95% to 98%, 96% to 99% and 96% to 99%, respectively, with an average of 95.72%, 98.11%, and 97.50%. CONCLUSIONS: For patients with bilateral ID IV-V and facial aging, the combination of disc repositioning surgery and rhytidectomy is a very feasible procedure to treat TMJ disorders and improve patients' facial appearance and satisfaction.

Outcomes of Treatment With Manipulative Reduction Combine With the Disc-condyle Repositioning Splint in Acute Anterior Disc Displacement Without Reduction.

ABSTRACT: In this report, the authors describe a case of the acute anterior disc displacement without reduction treated by manipulative reduction combined with the disc-condyle repositioning splint to improve the limited mouth opening and relieve the pain, including diagnostic images and treatment performed.

Zika Virus Infection in Tupaia belangeri Causes Dermatological Manifestations and Confers Protection against Secondary Infection.

Animal models of Zika virus (ZIKV) infection have recently been established in mice, guinea pigs, and nonhuman primates. Tree shrews (Tupaia belangeri) are an emerging experimental animal in biomedical applications, but their susceptibility to ZIKV infection has not been explored. In the present study, we show that subcutaneous inoculation of ZIKV led to rapid viremia and viral secretion in saliva, as well as to typical dermatological manifestations characterized by massive diffuse skin rash on the trunk. Global transcriptomic sequencing of peripheral blood mononuclear cells isolated from ZIKV-infected animals revealed systematic gene expression changes related to the inflammatory response and dermatological manifestations. Importantly, ZIKV infection readily triggered the production of high-titer neutralizing antibodies, thus preventing secondary homologous infection in tree shrews. However, neonatal tree shrews succumbed to ZIKV challenge upon intracerebral infection. The tree shrew model described here recapitulates the most common dermatological manifestations observed in ZIKV-infected patients and may greatly facilitate the elucidation of ZIKV pathogenesis and the development of novel vaccines and therapeutics.IMPORTANCE The reemergence of Zika virus (ZIKV) has caused a global public health crisis since 2016, and there are currently no vaccines or antiviral drugs to prevent or treat ZIKV infection. However, considerable advances have been made in understanding the biology and pathogenesis of ZIKV infection. In particular, various animal models have been successfully established to mimic ZIKV infection and its associated neurological diseases and to evaluate potential countermeasures. However, the clinical symptoms in these mouse and nonhuman primate models are different from the common clinical manifestations seen in human ZIKV patients; in particular, dermatological manifestations are rarely recapitulated in these animal models. Here, we developed a new animal model of ZIKV infection in tree shrews, a rat-sized, primate-related mammal. In vitro and in vivo characterization of ZIKV infection in tree shrews established a direct link between ZIKV infection and the immune responses and dermatological manifestations. The tree shrew model described here, as well as other available animal models, provides a valuable platform to study ZIKV pathogenesis and to evaluate vaccines and therapeutics.

Virus-like particles produced in Saccharomyces cerevisiae elicit protective immunity against Coxsackievirus A16 in mice.

Hand, foot, and mouth disease (HFMD) has caused significant morbidity and mortality in the Asia-Pacific regions, particularly in infants and young children. Coxsackievirus A16 (CA16) represents one of the major causative agents for HFMD, and the development of a safe and effective vaccine preventing CA16 infections has become a public health priority. In this study, we have developed a yeast system for the production of virus-like particles (VLPs) for CA16 by co-expressing P1 and 3CD of CA16 in Saccharomyces cerevisiae. These VLPs exhibit similarity in both protein composition and morphology as empty particles from CA16-infected cells. Immunization with CA16 VLPs in mice potently induced CA16-specific IgG and neutralization antibodies in a dose-dependent manner. IgG subclass isotyping revealed that IgG1 and lgG2b were dominantly induced by VLPs. Meanwhile, cytokine profiling demonstrated that immunization with VLPs significantly induced the secretion of IFN-γ, indicating potent cellular immune response. Furthermore, in vivo challenge experiments showed that passive immunization with anti-VLPs sera conferred full protection against lethal CA16 challenge in neonate mice. Taken together, our data demonstrated that VLPs produced in yeast might have the potential to be further developed as a vaccine candidate against HFMD.

Lipid nanoparticle-encapsulated mRNA antibody provides long-term protection against SARS-CoV-2 in mice and hamsters.

Monoclonal antibodies represent important weapons in our arsenal to against the COVID-19 pandemic. However, this potential is severely limited by the time-consuming process of developing effective antibodies and the relative high cost of manufacturing. Herein, we present a rapid and cost-effective lipid nanoparticle (LNP) encapsulated-mRNA platform for in vivo delivery of SARS-CoV-2 neutralization antibodies. Two mRNAs encoding the light and heavy chains of a potent SARS-CoV-2 neutralizing antibody HB27, which is currently being evaluated in clinical trials, were encapsulated into clinical grade LNP formulations (named as mRNA-HB27-LNP). In vivo characterization demonstrated that intravenous administration of mRNA-HB27-LNP in mice resulted in a longer circulating half-life compared with the original HB27 antibody in protein format. More importantly, a single prophylactic administration of mRNA-HB27-LNP provided protection against SARS-CoV-2 challenge in mice at 1, 7 and even 63 days post administration. In a close contact transmission model, prophylactic administration of mRNA-HB27-LNP prevented SARS-CoV-2 infection between hamsters in a dose-dependent manner. Overall, our results demonstrate a superior long-term protection against SARS-CoV-2 conferred by a single administration of this unique mRNA antibody, highlighting the potential of this universal platform for antibody-based disease prevention and therapy against COVID-19 as well as a variety of other infectious diseases.

Development and evaluation of a reverse transcription-loop-mediated isothermal amplification assay for rapid detection of enterovirus 71.

Human enterovirus 71 (EV71) is the major etiological agent of hand, foot, and mouth disease (HFMD), which is a common infectious disease in young children and infants. EV71 can cause various clinical manifestations and has been associated with severe neurological complications; it has resulted in fatalities during recent outbreaks in Asian-Pacific regions since 1997. The early and rapid detection is critical for prevention and control of EV71 infection, since no vaccine or antiviral drugs are currently available. In this study, a simple and sensitive reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay was developed for rapid detection of EV71. The detection limit of the RT-LAMP assay was approximately 0.01 PFU per reaction mixture, and no cross-reactive amplification with other enteroviruses was observed. The assay was evaluated further with 40 clinical specimens and exhibited 92.9% sensitivity and 100% specificity. This RT-LAMP assay may become a useful alternative in clinical diagnosis of EV71, especially in resource-limited hospitals or rural clinics of China and other countries in the Asian-Pacific region.

Antibody dependent enhancement infection of enterovirus 71 in vitro and in vivo.

BACKGROUND: Human enterovirus 71 (EV71) has emerged as a significant cause of acute encephalitis and deaths in young children. The clinical manifestations caused by EV71 varied from mild hand, foot and mouth disease to severe neurological complications and deaths, but its pathogenesis remains elusive. Antibody dependent enhancement (ADE) infection has been reported in various viruses and has been shown to contribute to disease severity. RESULTS: In this study, the presence of sub-neutralizing antibody was demonstrated to enhance EV71 infection in THP-1 cells and increase the mortality of EV71 infection in a suckling mouse model. Further, a secondary infection model was established to characterize the correlation between ADE and disease severity, and primary asymptomatic EV71 infection was shown to increase the mortality of the secondary EV71 infection in suckling mice. CONCLUSIONS: Together, these in vitro and in vivo experiments strongly supported the hypothesis of ADE infection of EV71. The present findings indicate ADE might contribute to the pathogenesis of severe EV71 infection, and raise practical issues of vaccine development and antibody-based therapy.

Measurements of buccal gingival and alveolar crest thicknesses of premolars using a noninvasive method.

AIMS: Knowledge of gingival thickness (GT) and alveolar crest thickness (ACT) is essential for performing various surgical and non-surgical procedures in oral healthcare. However, a noninvasive, no-radiation and reproducible method for measuring GT and ACT is not yet determined. This study aimed to measure the buccal GT and ACT of premolars using 15-MHz B-mode ultrasonography (US) and to explore the relationship between GT and ACT. MATERIAL AND METHODS: The GT in four swine mandibles was measured using15-MHz B-mode US and using K-file needles to gauge the accuracy of US. B-mode US at 15 MHz was also used to measure periodontal tissue structures including buccal GT3 (3 mm apical to the gingival margin) and ACT in 400 premolars of 50 human participants with healthy periodontium. RESULTS: There was a strong positive correlation between US and invasive K-file needle measurements of GT in swine mandibles (p<0.05). The correlation between buccal GT3 and ACT of premolars was moderately positive (p<0.05). The gingiva of the maxillary premolars and ACT of the maxillary first premolars were thicker in men than in women (p<0.05). CONCLUSIONS: B-mode US at 15 MHz is a valid and reliable method for measuring GT and ACT and for evaluating their relationship.

A nanostructured anti-biofilm surface widens the efficacy against spindle-shaped and chain-forming rod-like bacteria.

Current control of pathogenic bacteria at all biomaterial interfaces is poorly attuned to a broad range of disease-causing pathogens. Leading antimicrobial surface functionalization strategies with antimicrobial peptides (AMPs), defensins, have not shown their promised efficacy. One of the main problems is the lack of stability and swift clearance from the surface. Surface nanotopography bearing sharp protrusions is a non-chemical solution that is intrinsically stable and long-lasting. Previously, the geometrically ordered arrays of nanotipped spines repelled or rapidly ruptured bacteria that come into contact. The killing properties so far work on cocci and rod-like bacteria, but there is no validation of the efficacy of protrusional surfaces on pathogenic bacteria with different sizes and morphologies, thus broadening the utility of such surfaces to cover increasingly more disease entities. Here, we report a synthetic analogue of nanotipped spines with a pyramidal shape that show great effectiveness on species of bacteria with strongly contrasting shapes and sizes. To highlight this phenomenon in the field of dental applications where selective bacterial control is vital to the clinical success of biomaterial functions, we modified the poly(methyl)-methacrylate (PMMA) texture and tested it against Streptococcus mutans, Enterococcus faecalis, Porphyromonas gingivalis, and Fusobacterium nucleatum. These nanopyramids performed effectively at levels well above those of normal and roughened PMMA biomaterials for dentistry and a model material for general use in medicine and disease transmission in hospital environments.

Susceptibility of Armigeres subalbatus Coquillett (Diptera: Culicidae) to Zika virus through oral and urine infection.

BACKGROUND: Zika virus (ZIKV) disease outbreaks have been occurring in South America since 2015, and has spread to North America. Because birth defects and cases of Guillain Barré have been associated with infection with ZIKV, this has drawn global attention. ZIKV is generally considered an Aedes-transmitted pathogen. The transmission of ZIKV through blood by Aedes mosquito bites has been recognized as the major transmission route. However, it is not clear whether there are other transmission routes that can cause viral infection in mosquitos. The aim of the present study is to describe the susceptibility of Armigeres subalbatus, which often develop in human waste lagoons, to ZIKV, through oral infection in adult mosquitoes and urine infection in larvae. METHODOLOGY/PRINCIPAL FINDINGS: Five-day-old female Ar. subalbatus ingested infectious blood meals containing ZIKV. After 4, 7, and 10 days of ingesting infectious blood meals, ZIKV could be detected in the midguts, salivary glands, ovaries, and collected saliva of mosquitoes. The ZIKV infection rate (IR) on day 10 reached 40% in salivary glands and 13% in saliva, indicating that these mosquitoes were able to transmit ZIKV. In addition, ZIKV infection was also discovered in mosquito ovaries, suggesting the possibility of vertical transmission of virus. Moreover, Ar. subalbatus transmitted ZIKV to infant mice bitten by infectious mosquitoes. In a second experiment, 1st-instar larvae of Ar. subalbatus were reared in water containing ZIKV and human urine. After pupation, pupae were placed in clean water and transferred to a mosquito cage for emergence. Although ZIKV RNA was detected in all of the larvae tested, ZIKV was not detected in the saliva of any adult Ar. subalbatus. Considering that there are more uncontrollable factors in nature than in the laboratory environment, the possibility that the virus is transmitted to adult mosquitoes via larvae is very small period. CONCLUSIONS/SIGNIFICANCE: Adult Ar. subalbatus could be infected with ZIKV and transmit ZIKV through mosquito bites. Therefore, in many rural areas in China and in undeveloped areas of other Asian countries, the management of human waste lagoons in the prevention and control of Zika disease should be considered. Corresponding adjustments and modifications should also be made in prevention and control strategies against ZIKV.

Synovial Chondromatosis of the Temporomandibular Joint: A clinical and arthroscopic study of 16 cases.

OBJECTIVES: Present and overview the clinical finding, management and arthroscopic study of Synovial Chondromatosis (SC) cases in Temporomandibular Joint (TMJ) treated by our team. STUDY DESIGN: During year 2008-2018, 16 TMJ SC cases were treated and reviewed. The clinical manifestations, radiographic data, arthroscopic study and pathologic findings were recorded and analyzed. RESULTS: Average age of first visit was 32.68. The ratio of male/female was 2/14, right/left was 7/9. The most common symptoms were pain, continuous crepitus and limited mouth opening (LMO). All cases were examined by computed tomography (CT) and magnetic resonance imaging (MRI) preoperative and proved by pathology postoperative. The diagnostic rates of CT and MRI were 12.5% and 93.75% respectively. 1 case could not be detected by both, but by arthroscopy. Particles in all cases occurred in the upper joint cavity and were all removed by arthroscopic technique. No recurrence was found after 3 years follow-up. CONCLUSIONS: MRI and arthroscopic technique could be the first choice in the diagnosis and treatment of SC. Most cases were in stage 3 of the disease at the first visit. Low recurrence rate may be attributed to the improvement of intra-articular environment after surgery. Larger sample sizes are needed for further study.

Intranasal infection and contact transmission of Zika virus in guinea pigs.

Zika virus (ZIKV) is primarily transmitted to humans through mosquito bites or sexual contact. The excretion and persistence of contagious ZIKV in various body fluids have been well documented in ZIKV patients; however, the risk of direct contact exposure remains unclear. Here, we show that guinea pigs are susceptible to ZIKV infection via subcutaneous inoculation route; infected guinea pigs exhibit seroconversion and significant viral secretion in sera, saliva, and tears. Notably, ZIKV is efficiently transmitted from infected guinea pigs to naïve co-caged animals. In particular, intranasal inoculation of ZIKV is fully capable of establishing infection in guinea pigs, and viral antigens are detected in multiple tissues including brain and parotid glands. Cynomolgus macaques also efficiently acquire ZIKV infection via intranasal and intragastric inoculation routes. These collective results from animal models highlight the risk of exposure to ZIKV contaminants and raise the possibility of close contact transmission of ZIKV in humans.

Novel recombinant chimeric virus-like particle is immunogenic and protective against both enterovirus 71 and coxsackievirus A16 in mice.

Hand-foot-and-mouth disease (HFMD) has been recognized as an important global public health issue, which is predominantly caused by enterovirus 71 (EV-A71) and coxsackievirus A16 (CVA16). There is no available vaccine against HFMD. An ideal HFMD vaccine should be bivalent against both EV-A71 and CVA16. Here, a novel strategy to produce bivalent HFMD vaccine based on chimeric EV-A71 virus-like particles (ChiEV-A71 VLPs) was proposed and illustrated. The neutralizing epitope SP70 within the capsid protein VP1 of EV-A71 was replaced with that of CVA16 in ChiEV-A71 VLPs. Structural modeling revealed that the replaced CVA16-SP70 epitope is well exposed on the surface of ChiEV-A71 VLPs. These VLPs produced in Saccharomyces cerevisiae exhibited similarity in both protein composition and morphology as naive EV-A71 VLPs. Immunization with ChiEV-A71 VLPs in mice elicited robust Th1/Th2 dependent immune responses against EV-A71 and CVA16. Furthermore, passive immunization with anti-ChiEV-A71 VLPs sera conferred full protection against lethal challenge of both EV-A71 and CVA16 infection in neonatal mice. These results suggested that this chimeric vaccine, ChiEV-A71 might have the potential to be further developed as a bivalent HFMD vaccine in the near future. Such chimeric enterovirus VLPs provide an alternative platform for bivalent HFMD vaccine development.

Global transcriptomic analysis of human neuroblastoma cells in response to enterovirus type 71 infection.

Human enterovirus type 71 (EV71) is the major pathogen of hand-foot-and-mouth disease (HFMD) and has been associated with severe neurological disease and even death in infants and young children. The pathogenesis of EV71 infection in the human central nervous system remains unclear. In this study, human whole genome microarray was employed to perform transcriptome profiling in SH-SY5Y human neuroblastoma cells infected with EV71. The results indicated that EV71 infection lead to altered expression of 161 human mRNAs, including 74 up-regulated genes and 87 down-regulated genes. Bioinformatics analysis indicated the possible roles of the differentially regulated mRNAs in selected pathways, including cell cycle/proliferation, apoptosis, and cytokine/chemokine responses. Finally, the microarray results were validated using real-time RT-PCR with high identity. Overall, our results provided fundamental information regarding the host response to EV71 infection in human neuroblastoma cells, and this finding will help explain the pathogenesis of EV71 infection and virus-host interaction.