Comparison of dental plaque flora between intellectually disabled patients and healthy individuals: a cross-sectional study.

Periodontal diseases, including gingivitis, are highly prevalent in individuals with intellectual disability (ID). In particular, gingivitis can be difficult to cure owing to the lack of patient cooperation. Here, we evaluated differences in the oral bacterial flora between individuals with ID (n = 16) and healthy controls (n = 14) to facilitate the development of strategies for the prevention of periodontal disease in people with ID. Our results showed no significant difference in the number of decayed, missing, and filled teeth between the two groups. However, there were significant differences in the median papillary-marginal-attached index, plaque index, and gingival index between groups (P < 0.0001). Additionally, the mean probing depth in the ID group was significantly higher than that in the control group (P < 0.0001). The diversity of oral flora in people with ID and concurrent gingivitis was significantly lower than that of healthy individuals without periodontal disease. The relative abundances of Tannerella spp. and Treponema spp. were significantly higher in the ID group than in the control group at the genus level (P = 0.0383 and 0.0432, respectively), whereas that of Porphyromonas spp. was significantly lower in the ID group (P < 0.0001). Overall, our findings provided important insights into differences in the oral microbiota between patients with ID and healthy controls.

Difficult intubation and postoperative aspiration pneumonia associated with Moebius syndrome: a case report.

BACKGROUND: Moebius syndrome is a rare congenital disorder characterized by non-progressive palsy of the abducens (VI) and facial (VII) cranial nerves. Its common features include dysfunctions associated with other cranial nerves, orofacial abnormalities, skeletal muscle hypotonia, and other systemic disorders of differing severities. There are several concerns in the perioperative management of patients with Moebius syndrome. CASE PRESENTATION: We present a report on the management of general anesthesia of a 14-year-old male patient with Moebius syndrome who was scheduled for mandibular cystectomy. The patient was diagnosed with Moebius syndrome at the age of 7 years based on his clinical manifestations of nerve palsy since birth and cranial nerve palsy of the trigeminal (V), facial (VII), glossopharyngeal (IX), vagus (X), and sublingual nerves (XII). The patient's oral morphological abnormalities made intubation difficult. He also experienced dysphagia and aspiration pneumonia on a daily basis. Oral secretions were frequently suctioned postoperatively. However, after discharge, the patient developed aspiration pneumonia and was readmitted to the hospital. CONCLUSIONS: The main problem arising when administering general anesthesia to patients with this syndrome is difficult airway management. The oral abnormalities in these patients, such as small jaw and extreme dental stenosis, make mask ventilation and intubation difficult. Furthermore, this syndrome often involves respiratory impairment and dysphagia due to cerebral nerve palsy, so there is a high risk of postoperative respiratory complications. Since multiple organs are affected in patients with Moebius syndrome, appropriate perioperative management strategies must be prepared for these patients.

Vacuum-driven fluid manipulation by a piezoelectric diaphragm micropump for microfluidic droplet generation with a rapid system response time.

Recently, we developed a convenient microfluidic droplet generation device based on vacuum-driven fluid manipulation with a piezoelectric diaphragm micropump. In the present study built on our previous work, we investigate the influence of settings applied to the piezoelectric pump, such as peak-to-peak drive voltage (Vp-p ) and wave frequency, on droplet generation characteristics. Stepwise adjustments to the drive voltage in ±10-Vp-p increments over the range of 200-250 Vp-p during droplet creation revealed that the droplet generation rate could be reproducibly controlled at a specific drive voltage. The droplet generation rate switched within <0.5 s after the input of a new voltage. Although the droplet generation rate depended on the drive voltage, this setting had almost no influence on droplet size. The frequency over the selected range (50-60 Hz) did not markedly influence the droplet generation rate or droplet size. We show that the current fluid manipulation system can be conveniently used for both droplet generation and for rapid droplet reading, which is required in many microfluidic-based applications.

Longitudinal study of dental caries incidence associated with Streptococcus mutans and Streptococcus sobrinus in patients with intellectual disabilities.

BACKGROUND: Mutans streptococci (Streptococcus mutans and S. sobrinus) are considered to be major etiologic agents of dental caries. Using a polymerase chain reaction method, we detected those bacteria from 145 outpatients (6-30 years old) with intellectual disabilities (ID) and their presence was compared with the incidence of dental caries. METHODS: Plaque samples were collected from all erupted tooth sites in subjects with a sterile toothbrush. A dental examination was performed to determine the number of decayed and filled teeth (DFT score) in permanent dentition using the WHO caries diagnostic criteria. A Mann-Whitney U-test was employed to compare the caries scores between combinations of the bacteria, and with a Wilcoxon rank test used to compare caries scores between the baseline and after 1 year. RESULTS: Among all subjects, S. mutans and S. sobrinus were possessed by 78.7 and 83.5%, respectively, while 13.1% were positive for S. mutans alone, 17.9% for S. sobrinus alone, and 65.6% for both organisms, with 3.4% were negative for both. The mean DFT score of subjects positive for both S. mutans and S. sobrinus at after 1 year was significantly higher than that of those positive for S. mutans alone (P < 0.01). The increase in caries increment was also significantly greater in subjects with both bacteria detected (P < 0.001). CONCLUSION: Our results indicate that patients with ID harboring both S. mutans and S. sobrinus have a significantly higher incidence of dental caries than those with S. mutans alone.

Characterization of disease-specific alterations in metabolites and effects of mesenchymal stromal cells on dystrophic muscles.

Introduction: Duchenne muscular dystrophy (DMD) is a genetic disorder caused by mutations in the dystrophin-encoding gene that leads to muscle necrosis and degeneration with chronic inflammation during growth, resulting in progressive generalized weakness of the skeletal and cardiac muscles. We previously demonstrated the therapeutic effects of systemic administration of dental pulp mesenchymal stromal cells (DPSCs) in a DMD animal model. We showed preservation of long-term muscle function and slowing of disease progression. However, little is known regarding the effects of cell therapy on the metabolic abnormalities in DMD. Therefore, here, we aimed to investigate the mechanisms underlying the immunosuppressive effects of DPSCs and their influence on DMD metabolism. Methods: A comprehensive metabolomics-based approach was employed, and an ingenuity pathway analysis was performed to identify dystrophy-specific metabolomic impairments in the mdx mice to assess the therapeutic response to our established systemic DPSC-mediated cell therapy approach. Results and Discussion: We identified DMD-specific impairments in metabolites and their responses to systemic DPSC treatment. Our results demonstrate the feasibility of the metabolomics-based approach and provide insights into the therapeutic effects of DPSCs in DMD. Our findings could help to identify molecular marker targets for therapeutic intervention and predict long-term therapeutic efficacy.

Effect of Lacticaseibacillus rhamnosus L8020 on the abundance of periodontal pathogens in individuals with intellectual disability: a randomized clinical trial.

OBJECTIVES: Gingivitis refers to inflammation of the gingiva and its connective tissues. Research has revealed a higher prevalence of gingivitis in individuals with intellectual disability than in healthy individuals. Milk fermented with Lacticaseibacillus rhamnosus L8020 (L8020 yogurt) inhibits the accumulation of periodontal disease-related pathogens in vitro and alleviates the symptoms of periodontal disease. The aim of this study was to investigate the influence of L8020 yogurt on oral microbiota and the abundance of four periodontal pathogens (Tannerella forsythia, Porphyromonas gingivalis, Prevotella intermedia, and Treponema denticola) and on the microbiota in individuals with intellectual disability and gingivitis. METHOD AND MATERIALS: Forty-one outpatients with intellectual disability participated in this study. To examine the effects of daily consumption of L8020 yogurt, the patients were randomly divided into L8020 (test group, n = 21) and placebo (n = 20) yogurt groups. All patients consumed 80 g of yogurt for 12 weeks. Oral examination was performed before the first intake of yogurt and dental plaque was collected before and after the intake of yogurt. DNA was extracted from dental plaque and subjected to next-generation sequencing. RESULTS: The relative abundance of T forsythia was significantly lower in the test group than in the placebo group. Additionally, the relative abundance of the four pathogens reduced after 84 days of consuming L8020 yogurt compared with that after consuming placebo yogurt. CONCLUSION: Mixing L rhamnosus L8020 with probiotic products that are consumed daily would be effective in suppressing the increase in periodontal disease-causing bacteria and beneficial for individuals with intellectual disability.

Caries prevalence associated with Streptococcus mutans and Streptococcus sobrinus in Japanese schoolchildren.

BACKGROUND: Streptococcus mutans and Streptococcus sobrinus are known to be associated with dental caries in humans. AIM: We used a polymerase chain reaction method to detect S. mutans and S. sobrinus in 128 Japanese schoolchildren and then compared their presence with the dental caries experience. DESIGN: Plaque samples were collected from all erupted tooth sites with a sterile toothbrush, and dental examinations were performed to determine the numbers of decayed and filled teeth in primary (dft) and permanent (DFT) dentition using the WHO caries diagnostic criteria. Fisher's PLSD test was employed to compare caries scores between combinations of the detected bacteria. RESULTS: Streptococcus mutans and S. sobrinus were present in 38.3% and 68.0%, respectively, whereas 14.8% were positive for S. mutans alone, 44.5% for S. sobrinus alone, and 23.5% for both S. mutans and S. sobrinus, with 17.2% negative for both. The DFT, dft, and total (DFT + dft) scores for subjects positive for both S. mutans and S. sobrinus were significantly higher than those positive for S. mutans alone (P < 0.05, in triplicate). CONCLUSION: These results suggest that schoolchildren harbouring both S. mutans and S. sobrinus have a significant higher dental caries experience in both permanent and primary teeth as compared to those with S. mutans alone.

Enhanced cell survival and therapeutic benefits of IL-10-expressing multipotent mesenchymal stromal cells for muscular dystrophy.

BACKGROUND: Multipotent mesenchymal stromal cells (MSCs) are potentially therapeutic for muscle disease because they can accumulate at the sites of injury and act as immunosuppressants. MSCs are attractive candidates for cell-based strategies that target diseases with chronic inflammation, such as Duchenne muscular disease (DMD). We focused on the anti-inflammatory properties of IL-10 and hypothesized that IL-10 could increase the typically low survival of MSCs by exerting a paracrine effect after transplantation. METHODS: We developed a continuous IL-10 expression system of MSCs using an adeno-associated virus (AAV) vector. To investigate the potential benefits of IL-10 expressing AAV vector-transduced MSCs (IL-10-MSCs), we examined the cell survival rates in the skeletal muscles after intramuscular injection into mice and dogs. Systemic treatment with IL-10-MSCs derived from dental pulp (DPSCs) was comprehensively analyzed using the canine X-linked muscular dystrophy model in Japan (CXMDJ), which has a severe phenotype similar to that of DMD patients. RESULTS: In vivo bioluminescence imaging analysis revealed higher retention of IL-10-MSCs injected into the hindlimb muscle of mice. In the muscles of dogs, myofiber-like tissue was formed after the stable engraftment of IL-10-MSCs. Repeated systemic administration of IL-10-DPSCs into the CXMDJ model resulted in long-term engraftment of cells and slightly increased the serum levels of IL-10. IL-10-hDPSCs showed significantly reduced expression of pro-inflammatory MCP-1 and upregulation of stromal-derived factor-1 (SDF-1). MRI and histopathology of the hDPSC-treated CXMDJ indicated the regulation of inflammation in the muscles, but not myogenic differentiation from treated cells. hDPSC-treated CXMDJ showed improved running capability and recovery in tetanic force with concomitant increase in physical activity. Serum creatine kinase levels, which increased immediately after exercise, were suppressed in IL-10-hDPSC-treated CXMDJ. CONCLUSIONS: In case of local injection, IL-10-MSCs could maintain the long-term engraftment status and facilitate associated tissue repair. In case of repeated systemic administration, IL-10-MSCs facilitated the long-term retention of the cells in the skeletal muscle and also protected muscles from physical damage-induced injury, which improved muscle dysfunction in DMD. We can conclude that the local and systemic administration of IL-10-producing MSCs offers potential benefits for DMD therapy through the beneficial paracrine effects of IL-10 involving SDF-1.

Treatment of dental caries in a patient with Joubert syndrome without the use of sedatives: A case study.

BACKGROUND: Joubert syndrome (JS) is a rare autosomal recessive inherited ciliopathy caused by gene mutation. Manifestations can include intermittent dyspnea, apnea, ataxia, and other nervous system abnormalities. CASE PRESENTATION: The patient was a 21-year-old female with JS, severe intellectual disability, cerebral palsy, and epilepsy. Dental caries in both mandibular lower first molars was diagnosed by a local dentist, and the patient was referred to us for further treatment. Although her oral hygiene was good, the dental caries had reached the vicinity of the dental pulp. The caries had developed symmetrically on both first molars and was completely covered with the gingiva. As she was hesitant to receive treatment without anxiolysis, we considered using general anesthesia or intravenous sedation. However, we were recommended against it by the patient's family doctor because of the risk of apneic episodes in JS. Accordingly, dental treatment was performed over multiple days through physical behavior adjustment, while providing oxygenation (3 L/min) in preparation for an apneic episode. The dental treatment was successfully completed with a good postoperative outcome. CONCLUSIONS: Dental treatment can be safely performed in patients with JS through physical behavior adjustment, thereby minimizing the risk of an apnea attack.

Five-year longitudinal study of dental caries risk associated with Streptococcus mutans and Streptococcus sobrinus in individuals with intellectual disabilities.

Streptococcus mutans (S. mutans) and Streptococcus sobrinus (S. sobrinus) are important etiologic agents in human dental caries. Using quantitative real-time polymerase chain reaction assays for the presence of those strains, we examined 145 outpatients with intellectual disability (ID), calculated the proportion of each of these strains to total bacteria, and compared dental caries incidence over 5 years. Plaque samples were collected from all erupted tooth sites, and dental examinations were performed annually to determine numbers of decayed, missing, and filled teeth (DMFT score; World Health Organization caries diagnostic criteria). Elevated DMFT scores were calculated as ∆DMFT, and sites of newly affected caries (∆SNAC) were identified. Sixty-six patients had both strains. The proportion of S. mutans to total bacteria was moderately correlated with DMFT in year 2, ∆DMFT in years 2 and 5, and ∆SNAC in years 2 and 5 (correlation coefficient = 0.470, P < 0.001), while the proportion of S. sobrinus to total bacteria was moderately correlated with DMFT in years 2 and 5, ∆DMFT in years 1, 2, and 5, and ∆SNAC in years 2 and 5 (correlation coefficient = 0.695, P < 0.001). Individuals with ID who harbored both bacterial strains had a higher risk of dental caries and a significantly higher proportion of S. sobrinus to total bacteria.

Prevalence of Porphyromonas gingivalis fimA genotypes in Japanese children.

Porphyromonas gingivalis FimA fimbriae have been classified into 6 genotypes (types I-V and Ib) based on the diversity of the fimA genes encoding the fimbrial subunits. We investigated the prevalence of fimA genotype in Japanese children. Dental plaque specimens were obtained from 400 subjects (age; 2 to 15 years), including 134 with healthy gingiva, 239 with gingivitis and 27 with periodontitis, and then analyzed by polymerase chain reaction. P. gingivalis was detected in 1.5%, 10.0% and 29.6% of these subjects, respectively. Significant differences were observed with regard to P. gingivalis infection among the groups [chi-squared analysis: gingivitis vs. healthy, P < 0.01, odds ratio (OR) = 7.4; periodontitis vs. healthy, P < 0.001, OR = 27.8]. In P. gingivalis-positive subjects with periodontitis, the most prevalent fimA types were type Ib/type II combination (37.5%) and type IV (37.5%), followed by type II (25.0%), while type IV (33.3%) and type II (29.2%) were most often detected in those with gingivitis. Our results suggest that the presence of P. gingivalis is associated with periodontal diseases, and that the type II, IV and Ib/II combination are the most common among fimA genotypes.