The importance of taste on swallowing function.

The world's population is aging. Pneumonia is the leading cause of death among the older adults, with aspiration pneumonia being particularly common. Aspiration pneumonia is caused by a decline in swallowing function. Causes can include age-related sarcopenia of swallowing muscles, cognitive decline, cerebrovascular and other diseases or even changes in individual taste preference. Currently, the main treatment approach for dysphagia is resistance training of swallowing-related muscles. This approach has not been effective and establishment of novel methods are required. In this review, we introduce and discuss the relationship between taste, taste preference, carbonation and swallowing function. Taste and preference improve swallowing function. Recently, it has been shown that a carbonated beverage that combines the functionality of a thickening agent, the appeal of taste, and the stimulation of carbonation improves swallowing function. This may be very useful in the recovery of swallowing function. It is important to note that deliciousness is based not only on taste and preference, but also on visual information such as food form. Umami taste receptors are expressed not only in taste buds but also in skeletal muscle and small intestine. These receptors may be involved in homeostasis of the amino acid metabolic network, i.e., the process of amino acid ingestion, intestine absorption, and storage in skeletal muscle. Proper stimulation of umami receptors in organs other than taste buds may help maintain nutritional status and muscle mass. Umami receptors are therefore a potential therapeutic target for dysphagia.

Vitamin D3 Promotes Not Motor Coordination but Motor Skill Learning without Influence on Muscle Function.

Although motor coordination or motor skill learning are improved by taking vitamin D in the animal experiment, muscle function have not been estimated. Here we examined the effect of vitamin D3 administration on motor coordination and motor skill learning, muscle strength, and muscle volume in mice fed a vitamin D deficient diet. In mice fed a vitamin D deficient diet, serum calcium and 25(OH)D3 concentrations were measured. We then conducted Rotarod test, beam walking assay, micro-CT analysis, and forelimb grip strength test. Administration of vitamin D3 elongated the retention time in the Rotarod test in a time dependent manner. In contrast, the time to reach a beam goal box in beam walking assay was not changed in mice administered with vitamin D3, compared to the control. Oral administration of vitamin D3 did not affect muscle strength nor muscle volume. Oral administration of vitamin D3 promotes not motor coordination but motor skill learning and does not affect muscle function.

Weaning from Tube Feeding Post Stroke by Eating, Swallowing, and Nutritional Support In-Home: A Case Report.

In many cases, enteral tube feeding is begun after stroke without adequate assessment of feeding ability, swallowing function, and nutritional status. A 72-year-old man was recovering at home after a stroke and consulted us because he wanted to resume taking food by mouth. He had tube feeding for 13 months after the stroke. We offered him feeding and swallowing training and proper nutrition guidance by visiting dental staff and managerial dietitians at home and concluded the patient was sufficiently able to take oral food. After 4 months, the patient was completely weaned from tube feeding.

Nutritional Management in a 101-Year-Old Woman with Physical Inactivity and General Weakness: A Case Report.

Japan has the world's highest life longevity, and centenarian patients are no longer rare. However, sufficient information related to centenarians is not available. Herein, we report the case of a 101-year-old centenarian woman who recovered from extreme inactivity and general weakness, mainly through nutritional management at home, to understand instances of nutritional management in centenarians. The patient developed lethargy, with a rapid decline in activity levels and food intake. She was diagnosed with senility by a primary doctor. We concluded that she had no problems with feeding and swallowing and predicted that her motivation to eat had decreased. We planned an intervention that lasted three months. To reduce the risk of aspiration, we paid attention to her posture while eating. To stimulate her appetite, we increased the variety and color of food items. To consider both the texture of food and safety, we changed the form of foods from paste (IDDSI Level 4)-like to solid food of regular size as much as possible. We recommended that the patient consume her favorite sweet between meals to enjoy eating. Two and half months after the initial intervention, the patient's inactivity and general weakness improved dramatically, which was recognized by her willingness to eat, laugh loudly, and hum, although she could not speak clearly. The patient finally was able to have dinner with her family.

Effects of Carbonated Thickened Drinks on Pharyngeal Swallowing with a Flexible Endoscopic Evaluation of Swallowing in Older Patients with Oropharyngeal Dysphagia.

This study aimed to determine the efficacy of carbonated and sweetened drinks added to thickened liquids, which are routinely used for patients with dysphagia to improve dysphagia. Patients swallowed thin liquid (Thin), thickened liquid (Thick), carbonated thin drink (C-Thin), and carbonated thickened drink (C-Thick) in random order. Penetration and/or aspiration were scored using the Penetration−Aspiration Scale (PAS). The residue was scored using the Yale Pharyngeal Residue Severity Rating Scale (YPR-SRS). Swallowing reflex initiation was scored using the Hyodo score. The subjective difficulty of swallowing was scored on a face scale. We analyzed 13 patients with a mean age of 79.6 ± 9.6 years. PAS was significantly lower in the C-Thick group than the Thin group (p < 0.05). Swallowing reflex initiation was significantly different between the Thin and Thick (p < 0.01) groups; moreover, post hoc analysis revealed that it was significantly lower in the C-Thick group than the Thin group (p < 0.01). The subjective difficulty of swallowing in the C-Thick was significantly lower than the Thick group (p < 0.05). C-Thick was easier to swallow than Thick and may improve penetration and/or aspiration in older patients with dysphagia with complex diseases.

Contact Co-culture of Osteoblasts and Sympathetic Neuronal Cells Promotes Differentiation of Both Cell Types.

BACKGROUND/AIM: Bone and nerve reconstruction is crucial for treating various diseases of the oral and maxillofacial region. However, the relationship between bone and nervous system has not yet been fully elucidated. Therefore, we aimed to examine the interaction between osteoblasts and neuronal cells in contact co-culture. MATERIAL AND METHODS: Osteoblasts and sympathetic neuronal cells were grown in contact co-culture. Microscopic observation, a mineralization assay, immunofluorescence staining, and DNA microarray analysis were performed. RESULTS: Microscopic observation revealed morphological changes in the osteoblasts that were cocultured with sympathetic neuronal cells. Contact co-culture enhanced osteoblast calcification and upregulated a neuronal marker. Not only osteoblast differentiation signals, but also neuronal signals were increased in murine osteoblasts that were co-cultured with rat sympathetic neuronal cells. We also found that not only rat neuron differentiation signals, but also osteoblast differentiation signals were increased in rat sympathetic neuronal cells that were co-cultured with murine osteoblasts. CONCLUSION: In the contact co-culture with osteoblasts and sympathetic neuronal cells, the sympathetic neuronal cells promoted osteoblast differentiation, and the osteoblasts promoted neuron differentiation.

A Case of Necrotizing Periodontitis in a Care-Requiring Elderly Person Treated and Managed by Interprofessional Collaboration.

BACKGROUND: Necrotizing periodontitis (NP) is a reactive and destructive inflammatory process that occurs in response to bacterial infection. Predisposing factors such as compromised host immune responses contribute significantly to NP pathogenesis. NP occasionally progresses to a more advanced and life-threatening state. CASE PRESENTATION: A 73-year-old man in need of nursing care visited our dental clinic with severe gingival pain and intraoral bleeding. He had a disability and was immunocompromised because his medical history included cerebral infarction and type 2 diabetes mellitus. He was diagnosed with NP based on his typical symptoms, such as prominent bleeding and suppurative discharge from the gingiva, in addition to crater-shaped ulcerations of the interdental papillae. To improve daily oral hygiene, periodontists, dentists, and dental hygienists educated care workers and other staff at the nursing home on appropriate oral cleansing, including brushing three times a day using the Bass technique. Basic periodontal therapy, including whole-mouth scaling and debridement of the root surfaces using hand and ultrasonic instruments, was also performed. After this basic treatment of NP, we extracted the hopeless teeth. Currently, dentists visit the patient fortnightly to manage his oral hygiene. To date, good oral health has been maintained.

A Case of Drastic Reduction of Membranous Substances in the Pharynx by Interprofessional Cooperative Oral Care.

Membranous substances in the pharynx are occasionally observed in tube feeding patients during the fiberoptic endoscopic evaluation of swallowing. Although the mechanism of the formation of these deposits sometimes causes problems, such as dysphagia, asphyxia, or aspiration pneumonia, a 91-year-old male complained about difficulty of swallowing. He had a history of cerebral infarction and aspiration pneumonitis. There was a large amount of oral desquamated epithelium, dental plaque, and calculus in his mouth. Nurses and care workers administered oral care such as rubbing the tongue and buccal mucosa daily. Dentists and oral hygienists visited and provided special oral care three times per week. At least for 77 days, the patient had no recurrence of pneumonitis. The oral desquamated epithelium and membranous substances in the pharynx decreased drastically. 2 months after the first examination, the patient was able to start rehabilitation with food. Some studies have indicated that pharyngeal deposits are derived from the oral mucosa, and through our case, we realized the importance of daily oral care by interprofessional work to reduce membranous substances in the pharynx.

A Case of Myxoma Arising in the Buccal Mucosa.

Myxomas arising in the oral and maxillofacial areas are extremely rare. This study reports a case of myxoma arising in the soft tissue beneath the buccal mucosa of an 86-year-old man.

Semaphorin 3A Promotes Dendrite Elongation of Osteocytes in Association with Down-regulation of CDK6.

BACKGROUND: Osteocytes, which comprise over 90% of all bone cells, communicate with osteoblasts and osteoclasts to regulate each other's physiological function via dendrites, suggesting that dendrite elongation plays a vital role for bone regeneration. We examined the effect of semaphorin 3A (SEMA3A) on dendritic processes of an osteocyte cell line, since in previous work we found it to be essential for promoting osteoblast differentiation. MATERIALS AND METHODS: Dendrite length was analyzed by Cellomics Array Scan VTI quantitatively in osteocyte-like cell line, MLO-Y4 cells. We performed cell proliferation assay. Gene and protein expression was examined by real-time reverse-transcriptase polymerase chain reaction and western blotting, respectively. RESULTS: Both total and average dendrite length were significantly increased in MLO-Y4 cells stimulated with SEMA3A compared to control. E11 protein was up-regulated upon SEMA3A stimulation. Moreover, cyclin-dependent kinase 6 (CDK6) was down-regulated in a time-dependent manner. Taken together, these results suggest that SEMA3A regulates dendrites of osteocytes in association with down-regulation of CDK6. SEMA3A may be a promising drug to apply for bone tissue engineering.

Muscle regulatory factors regulate T1R3 taste receptor expression.

T1R3 is a T1R class of G protein-coupled receptors, composing subunit of the umami taste receptor when complexed with T1R1. T1R3 was originally discovered in gustatory tissue but is now known to be expressed in a wide variety of tissues and cell types such the intestine, pancreatic ß-cells, skeletal muscle, and heart. In addition to taste recognition, the T1R1/T1R3 complex functions as an amino acid sensor and has been proposed to be a control mechanism for the secretion of hormones, such as cholecystokinin, insulin, and duodenal HCO3(-) and activates the mammalian rapamycin complex 1 (MTORC1) to inhibit autophagy. T1R3 knockout mice have increased rate of autophagy in the heart, skeletal muscle and liver. Thus, T1R3 has multiple physiological functions and is widely expressed in vivo. However, the exact mechanisms regulating T1R3 expression are largely unknown. Here, we used comparative genomics and functional analyses to characterize the genomic region upstream of the annotated transcriptional start of human T1R3. This revealed that the T1R3 promoter in human and mouse resides in an evolutionary conserved region (ECR). We also identified a repressive element located upstream of the human T1R3 promoter that has relatively high degree of conservation with rhesus macaque. Additionally, the muscle regulatory factors MyoD and Myogenin regulate T1R3 expression and T1R3 expression increases with skeletal muscle differentiation of murine myoblast C2C12 cells. Taken together, our study raises the possibility that MyoD and Myogenin might control skeletal muscle metabolism and homeostasis through the regulation of T1R3 promoter activity.

Usability of surgical treatment in cases of bisphosphonate-related osteonecrosis of the jaw stage 2 with sequestrum.

OBJECTIVE: This retrospective study was conducted to reveal usability of surgical treatment in the cases of bisphosphonate-related osteonecrosis of the jaw (BRONJ) stage 2 with sequestrum. PATIENTS AND METHODS: Study subjects included 18 patients having BRONJ stage 2 with sequestrum and 12 non-BRONJ patients with nearly equal clinical states of BRONJ stage 2. Patient characteristics, frequency of inciting factors of osteonecrosis, and treatment results were compared between BRONJ group and non-BRONJ groups. In addition, correlation between treatment methods (conservative therapy, sequestrum curettage, and sequestrectomy) and treatment results and correlation between the administration route of bisphosphonates (BPs) (oral or intravenous) and treatment results were examined statistically. The Student's t-test and Fisher's exact test were performed for statistical analysis. RESULTS: Patient characteristics, frequency of inciting factors of osteonecrosis, and treatment results showed no significant differences between the two groups. In the BRONJ group, treatment result of sequestrectomy was significantly better than conservative therapy/sequestrum curettage (P < 0.001), however, no significant difference was observed in the non-BRONJ group. No significant difference was found in correlation between the administration route of BPs and treatment results in the BRONJ group. CONCLUSION: Treatment outcome of sequestrectomy was better than conservative therapy/sequestrum curettage in BRONJ stage 2 cases with sequestrum.

Limited mouth opening with a square mandible configuration: a case of masticatory muscle tendon-aponeurosis hyperplasia.

Most clinicians throughout the world are probably unaware of the existence of masticatory muscle tendon-aponeurosis hyperplasia (MMTAH), potentially leading to misdiagnoses such as temporomandibular joint disorder (TMD). Here, we introduce this disease from the viewpoint of education. In February 2013, a 39-year-old woman presented with limited mouth opening. Her facial configuration was characterized by a square mandible. There was no evidence of TMD. Magnetic resonance imaging (MRI) showed bilateral enlargement of the masseter muscles. Additionally, a 'thick' aponeurosis of the anterior aspect of the masseter muscle was noted bilaterally. On maximal mouth opening, intraoral palpation along the anterior border of the masseter muscle confirmed a hard cord-like structure, consistent with the findings on MRI. MMTAH was diagnosed. When clinicians notice limited mouth opening on oral examination, they should be knowledgeable about diseases associated with limited mouth opening and a square mandibular configuration, such as MMTAH.

Donepezil prevents RANK-induced bone loss via inhibition of osteoclast differentiation by downregulating acetylcholinesterase.

OBJECTIVE: Donepezil, an inhibitor of acetylcholinesterase (AChE) targeting the brain, is a common medication for Alzheimer's disease. Interestingly, a recent clinical study found that administration of this agent is associated with lower risk of hip fracture independently of falling, suggesting its direct effect on bone tissues as well. AChE has been reported to be involved in osteoblast function, but the role of AChE on osteoclastogenesis still remains unclear. We analyzed the effect of AChE and donepezil on osteoclastogenesis in vivo and in vitro. METHODS: Cell-based assays were conducted using osteoclasts generated in cultures of murine bone marrow macrophages (BMMs) with receptor activator of nuclear factor-kappa B ligand (RANKL). The effect of donepezil was also determined in vivo using a mouse model of RANKL-induced bone loss. RESULTS: Recombinant AChE in BMMs cultured with RANKL further promoted RANKL-induced tartrate-resistant acid phosphatase (TRAP)-positive osteoclast differentiation. RANKL also upregulated AChE expression in BMMs. RNA interference-mediated knockdown of AChE significantly inhibited RANKL-induced osteoclast differentiation and suppressed gene expression specific for osteoclasts. AChE upregulated expression of RANK, the receptor of RANKL, in BMMs. Donepezil decreased cathepsin K expression in BMMs and the resorptive function of osteoclasts on dentine slices. Donepezil decreased RANK expression in BMMs, resulting in the inhibition of osteoclast differentiation with downregulation of c-Fos and upregulation of Id2. Moreover, administration of donepezil prevented RANKL-induced bone loss in vivo, which was associated with the inhibition of bone resorption by osteoclasts. CONCLUSIONS: AChE promotes osteoclast differentiation in vitro. Donepezil inhibits osteoclast function in vitro and prevents bone loss by suppressing bone resorption in vivo, suggesting the possibility that donepezil reduces fracture risk in patients with Alzheimer's disease.

Netrin-4 derived from murine vascular endothelial cells inhibits osteoclast differentiation in vitro and prevents bone loss in vivo.

Bone is a highly vascularized organ, thus angiogenesis is a vital process during bone remodeling. However, the role of vascular systems in bone remodeling is not well recognized. Here we show that netrin-4 inhibits osteoclast differentiation in vitro and in vivo. Co-cultures of bone marrow macrophages with vascular endothelial cells markedly inhibited osteoclast differentiation. Adding a neutralizing antibody, or RNA interference against netrin-4, restored in vitro osteoclast differentiation. Administration of netrin-4 prevented bone loss in an osteoporosis mouse model by decreasing the osteoclast number. We propose that vascular endothelial cells interact with bone in suppressing bone through netrin-4.

Expression of TLE3 by bone marrow stromal cells is regulated by canonical Wnt signaling.

Transducing-like enhancer of split 3 (TLE3), one of the Groucho/TLE family members, targets Runx2 transcription and suppresses osteoblast differentiation in bone marrow stromal cells (BMSCs). Here, we identify Wnt responsive elements of the TLE3 promoter region through comparative genomic and functional analyses and show that expression of TLE3 is increased by Wnt signaling, which is important for osteoblast differentiation. We also demonstrated that TLE3 is able to suppress canonical Wnt signaling in BMSCs. Taken together, our data suggest that induction of TLE3 by Wnt signaling is part of a negative feedback loop active during osteoblast differentiation.

Reduced expression of p63 has prognostic implications for patients with esophageal squamous cell carcinoma.

The p63 gene is a member of the p53 family that plays a role in cell differentiation, development and carcinogenesis. The relationship between p63 expression and the prognosis of esophageal squamous cell carcinoma (ESCC) remains unknown. The present study examines the clinical impact of p63 in patients with ESCC. Resected specimens from 180 patients with ESCC were immunostained for p63 and p53. After establishing a cut-off value for p63 expression, we statistically examined its clinical impact and relationship to p53 expression. At a 50% cut-off value for p63 expression, the 5-year overall survival was significantly longer in p63-positive (46.4%) than -negative patients (11.1%, p=0.05). Among the 180 ESCC patients, 171 (95.0%) were p63 immunoreactive and only 9 (5.0%) were negative. The correlation between p63 status and clinicopathological parameters was not significant, although p63-negativity tended to correlate with distant metastasis (p=0.06) and clinical stage (p=0.08). Univariate analysis demonstrated significant correlations between patient survival and tumor diameter, depth of invasion, lymphatic invasion, vascular invasion, lymph node metastasis and distant metastasis. The survival of patients who did not express p63 and p53 was obviously unfavorable (p=0.03). Multivariate analysis revealed that only lymph node metastasis was a critical independent prognostic marker for overall survival (p=0.0015). Expression of p63 was not an independent prognostic factor for overall survival in this study (p=0.69). These data suggest that, although a reduced expression of p63 is infrequent, it has a prognostic impact upon patients with ESCC.