C-terminal peptide of preproorexin enhances brain-derived neurotrophic factor expression in rat cerebrocortical cells and recognition memory in mice.

During the production of orexin A and B from preproorexin, a common precursor protein, in hypothalamic orexin neurons, C-terminal peptide (herein called preproorexin C-peptide) is concomitantly produced via post-translational processing. The predicted three-dimensional structure of preproorexin C-peptide is similar among mammalian species, suggestive of a conserved function in the mammalian brain. However, C-peptide has long been regarded as a non-functional peptide. We herein examined the effects of rat and/or mouse preproorexin C-peptide on gene expression and cell viability in cultured rat cerebrocortical cells and on memory behavior in C57BL/6J mice. Rat and mouse C-peptides both increased brain-derived neurotrophic factor (Bdnf) mRNA levels. Moreover, C-peptide enhanced high K+-, glutamate-, and BDNF-induced increases in Bdnf mRNA levels without affecting forskolin-induced Bdnf expression. H-89, a protein kinase A inhibitor, blocked C-peptide-induced Bdnf expression, whereas rolipram, a phosphodiesterase inhibitor, enhanced this effect. Intracellular cyclic AMP concentrations were elevated by C-peptide. These results demonstrate that preproorexin C-peptide promoted Bdnf mRNA expression by a cyclic AMP-dependent mechanism. Eleven amino acids at the N terminus of rat preproorexin C-peptide exerted similar effects on Bdnf expression as full-length preproorexin C-peptide. Preproorexin C-peptide also exerted protective effects against CoCl2-induced neuronal cell death. An intracerebroventricular injection of mouse preproorexin C-peptide induced c-fos and Bdnf expression in the cerebral cortex and hippocampus and enhanced novel object recognition memory in mice. Collectively, the present results show that preproorexin C-peptide is a functional substance, at least in some pharmacological and neuronal settings.

Food odor perception promotes systemic lipid utilization.

Food cues during fasting elicit Pavlovian conditioning to adapt for anticipated food intake. However, whether the olfactory system is involved in metabolic adaptations remains elusive. Here we show that food-odor perception promotes lipid metabolism in male mice. During fasting, food-odor stimulation is sufficient to increase serum free fatty acids via adipose tissue lipolysis in an olfactory-memory-dependent manner, which is mediated by the central melanocortin and sympathetic nervous systems. Additionally, stimulation with a food odor prior to refeeding leads to enhanced whole-body lipid utilization, which is associated with increased sensitivity of the central agouti-related peptide system, reduced sympathetic activity and peripheral tissue-specific metabolic alterations, such as an increase in gastrointestinal lipid absorption and hepatic cholesterol turnover. Finally, we show that intermittent fasting coupled with food-odor stimulation improves glycemic control and prevents insulin resistance in diet-induced obese mice. Thus, olfactory regulation is required for maintaining metabolic homeostasis in environments with either an energy deficit or energy surplus, which could be considered as part of dietary interventions against metabolic disorders.

Tongue pressure waveform analysis for ascertaining the influence of tongue muscle composition on articulation.

BACKGROUND: Rate force development is associated with performance and muscle composition in whole-body muscle. Although rate force development on tongue muscle can be examined using tongue pressure waveform, there have been only few investigations on this topic. OBJECTIVES: This study's main purpose was to investigate the reliability of tongue pressure waveform analysis and its relationship with articulation and tongue muscle composition. In addition, we also investigated the association between tongue muscle composition and articulation. METHODS: Forty-five community-dwelling individuals aged >20 years participated. We analysed tongue pressure waveform, including maximum tongue pressure (MTP), time to peak, mean rate of tongue force development and peak rate of tongue force development (PRTFD). We also assessed oral diadochokinesis. Magnetic resonance imaging of the tongue provided data on tongue muscle composition, including tongue volume, fat mass, lean muscle mass and fat percentage. We evaluated the reliability of tongue pressure waveform analysis. Moreover, we examined the coefficients between tongue pressure waveform analysis, oral diadochokinesis and tongue composition. RESULTS: We detected a high reliability of MTP and PRTFD. MTP and PRTFD were significantly correlated with tongue muscle composition. MTP was not significantly correlated with oral diadochokinesis. PRTFD was significantly positively correlated with oral diadochokinesis. Tongue fat mass and fat percentage were negatively correlated with oral diadochokinesis of /ta/ and /ka/. CONCLUSIONS: Peak rate of tongue force development is a highly reliable method for tongue pressure analysis and is useful for elucidating the functional importance of tongue muscle function on articulation. We speculated that fatty infiltration of the tongue adversely affects articulation.

Association between polymorphism at IGF-1 rs35767 gene locus and long-term decline in renal function: a Japanese retrospective longitudinal cohort study.

BACKGROUND: Insulin-like growth factor-1 (IGF-1) acts on glucose and protein metabolism and human growth and also influences blood pressure and renal function. This study investigated whether the single-nucleotide polymorphism of IGF-1, rs35767, plays a role in metabolic syndrome indicators, including blood pressure, glucose metabolism, uric acid levels, and renal function. METHODS: In this retrospective longitudinal cohort study, blood samples from 1506 Japanese individuals were collected and used for genotyping for variant rs35767: T > C in the IGF-1 upstream promoter. Data were analyzed to identify associations between IGF-1 genotypes and patient biochemical parameters, including the components of metabolic syndrome and the long-term change in renal function. RESULTS: The cohort rs35767 genotypes included 650 CC carriers (43.2%), 687 TC carriers (45.6%), and 169 TT carriers (11.2%). Multiple regression analysis revealed no association between IGF-1 genotype and blood pressure, glycated hemoglobin level, and serum uric acid level. However, in females, blood pressure was negatively correlated with the TT genotype. Longitudinal observation revealed that the decline in eGFR over 10 years was greater in TT (- 18.51 ± 1.04 mL/min/1.73m2) than in CC carriers (- 16.38 ± 0.52 mL/min/1.73m2; P < 0.05). CONCLUSION: The present study suggests that renal function declines faster in individuals with the TT genotype at the IGF-1 rs35767 locus than in those with the CC genotype, suggesting that the TT genotype is associated with the long-term chronological decline in renal function.

Near-sudden unexpected death in a patient with epilepsy undergoing hemodialysis: a case report.

Sudden unexpected death in epilepsy (SUDEP) has been defined as a sudden/unexpected, witnessed/unwitnessed, nontraumatic, and nondrowning death in epileptic patients with/without seizure evidence and documented status epilepticus. Identified as the leading cause of epilepsy-related deaths, SUDEP cases are highly unrecognized and underreported due to diagnostic difficulty. We report a case of a successfully revived hemodialysis patient who developed cardiopulmonary arrest after a witnessed convulsive seizure. Electroencephalogram revealed epileptic abnormalities. Therefore, this case could be seizure-induced cardiopulmonary arrest and near-SUDEP. Hence, the possibility of SUDEP should be considered even in hemodialysis patients having conventional coronary risk factors for sudden cardiac death.

Age-related composition changes in swallowing-related muscles: a Dixon MRI study.

BACKGROUND: Dysphagia is considered a social problem in the super-aging society. However, age-related changes in swallowing-related muscles have not been fully deciphered. AIMS: We aimed to identify intramuscular fatty infiltration and muscle atrophy in multiple swallowing-related muscles on magnetic resonance imaging (MRI). Moreover, an appropriate muscle strength parameter for the evaluation of swallowing-related muscle mass was examined. METHODS: We analyzed the Dixon MRI results of 20 elderly and 20 young adults without head and neck cancer, stroke, neuromuscular disease, or whole-body sarcopenia to evaluate intramuscular fatty infiltration (IMF) and lean muscle mass (LMM) in the tongue, geniohyoid, and pharyngeal muscles. The pharyngeal lumen size was also assessed. Tongue pressure, jaw-opening strength, occlusal force, and head-lifting strength were evaluated within a week before and after MRI. RESULTS: Aging significantly affected the IMF of the swallowing-related muscles, and the tongue muscle was most affected, followed by the pharyngeal muscle and then the geniohyoid muscle. Only the LMM of the geniohyoid muscle significantly decreased with aging. The pharyngeal lumen size did not significantly differ between the elderly and young participants, and only tongue pressure was significantly correlated with tongue, geniohyoid, and pharyngeal muscle mass. CONCLUSIONS: IMF is primarily associated with age-related composition changes in swallowing-related muscles, and it is commonly observed in the tongue and pharyngeal muscles. The geniohyoid muscle is more at risk of muscle atrophy rather than fatty infiltration. In addition, tongue pressure can be a parameter for the evaluation of swallowing-related muscle mass.

Association Among Age-Related Tongue Muscle Abnormality, Tongue Pressure, and Presbyphagia: A 3D MRI Study.

Muscle aging such as sarcopenia adversely affects motor activities. However, few studies have elucidated the aging physiological mechanism of tongue concerted with the changes muscle composition. The present study aimed to examine the tongue composition changes to detect the effect of tongue fat mass on tongue pressure and swallowing function with aging. Twenty community-dwelling elderly without head and neck cancer, stroke, or neuromuscular disease and 20 healthy young were included. Tongue volume, tongue fat mass, tongue lean muscle mass, and tongue fat percentage were evaluated with 3D magnetic resonance imaging (MRI) and Dixon MRI. Tongue pressure was also measured. Swallowing function among elderly individuals was assessed via videofluorography, which was evaluated using the penetration-aspiration scale (PAS) and normalized residue ratio scale (NRRS). Tongue fat mass and tongue fat percentage significantly increased with aging. The tongue fat percentage of elderly participants was 20%, which was two times greater than that of young participants. No significant difference was observed in tongue volume and tongue lean muscle mass. A significantly negative correlation was observed between tongue fat mass and tongue fat percentage as well as tongue pressure. Conversely, tongue volume was not significantly correlated with tongue pressure. Tongue muscle composition exhibited no effect in the PAS and NRRS. Increase of fat mass is a major change in tongue composition with aging, which is associated with low tongue pressure. Thus, attention must be paid not only to tongue quantity but also to the quality of tongue muscles.

Neutropenia related to an azathioprine metabolic disorder induced by an inosine triphosphate pyrophosphohydrolase (ITPA) gene mutation in a patient with PR3-ANCA-positive microscopic polyangiitis
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A 68-year-old Japanese man was monitored for chronic kidney disease (CKD), with unknown primary disease starting in 2014. His serum creatinine (sCr) was stable at ~ 2.5 mg/dL for ~ 2 years. Two weeks before admission, he had bloody sputum, and sCr increased to 4.63 mg/dL. Soon after admission, the patient developed a high fever with pigment spots on the legs. A kidney biopsy was performed. The kidney specimens showed necrotizing and crescentic glomerulonephritis without granuloma formation. An additional blood-sampling test revealed high titers of PR3-ANCA, and we diagnosed PR3-ANCA-positive microscopic polyangiitis (MPA). Treatment with intravenous steroid pulse therapy and intermittent pulse intravenous cyclophosphamide therapy was started for remission induction. With these treatments, sCr improved to ~ 3.0 mg/dL. Azathioprine (AZA) was added for remission-maintenance therapy. Three days later, the dose of AZA was increased from 50 to 100 mg/day, and the number of neutrophils decreased to 30/µL. After withdrawal of AZA, neutrophil levels gradually recovered. We suspected that an abnormal metabolism of AZA was responsible for the neutropenia. Therefore, we analyzed three AZA metabolism-associated genes for mutations: thiopurine S-methyltransferase (TPMT), inosine triphosphate pyrophosphohydrolase (ITPA), and nucleoside diphosphate linked moiety X-type motif 15 (NUDT15), and we identified ITPA 94C>A mutation. This was a rare case of PR3-positive MPA with AZA-induced severe neutropenia that was possibly due to an ITPA gene mutation. This case suggests that ITPA gene mutation is related to the adverse reactions of AZA in Japanese patients. We have to pay attention to severe neutropenia when we use AZA, especially in Asian patients with CKD.
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Clinical study of splint therapeutic efficacy for the relief of temporomandibular joint discomfort.

PURPOSE: This study aimed to evaluate the relationship between displacement of the mandibular condyle/disc due to occlusal splint insertion with splint therapy and changes in discomfort of the temporomandibular joint (TMJ), and to clarify the relationships between the outcomes over time of temporomandibular discomfort and TMJ magnetic resonance imaging (MRI) findings at the initiation of splint therapy. MATERIALS AND METHODS: A total of 75 patients admitted to hospital with discomfort around the TMJ were evaluated. A visual analogue scale for TMJ discomfort was administered during visits for approximately 3 months following the initiation of splint therapy. At the start of splint therapy, magnetic resonance imaging (MRI) was performed with and without splint insertion, and condyle and disc movements were evaluated. Disc balance, disc position and function, disc configuration, joint effusion, osteoarthritis, and bone marrow were evaluated. Linear regression and multiple regression analyses were used to clarify relationships between changes in discomfort and the factors evaluated. RESULTS: There was no significant correlation between TMJ discomfort and condyle/disc movement with splint insertion. TMJ discomfort was significantly relieved by splint therapy regardless of temporomandibular MRI findings. Unilateral anterior disc displacement and marked or extensive joint effusion fluid were significantly improved with splint therapy. CONCLUSION: Discomfort tended to remit with splint therapy regardless of temporomandibular MRI findings. Improvement of TMJ discomfort appears more likely to occur in patients with unilateral anterior disc displacement and with an apparent organic disorder, such as a joint effusion.

Evaluation of the role of splint therapy in the treatment of temporomandibular joint pain on the basis of MRI evidence of altered disc position.

OBJECTIVE: To clarify whether altering temporomandibular joint (TMJ) condyle and disc positions by occlusal splint (splint) therapy relieves TMJ pain and to determine whether splint therapy facilitates improvement of the ranges of condyle and articular disc motions. STUDY DESIGN: A total of 150 joints of 75 patients admitted with TMJ pain/discomfort were evaluated. A visual analog scale for TMJ pain was administered during visits following the start of splint treatment. At the start of splint treatment, MRI was performed with/without splint insertion, after which condyle/disc movements were evaluated. Disc position and function, disc configuration, joint effusion, osteoarthritis, and the bone marrow were evaluated. Pearson's correlation coefficients, linear regression, and multiple regression analyses were used for statistical analysis. RESULTS: Splint-related anterior movement of the condyle was related to TMJ pain. With a biconvex disc and/or bone marrow abnormality, splint treatment was ineffective for reducing TMJ pain. CONCLUSION: Splint therapy was not likely to be successful for any kind of TMJ abnormalities, such as bone marrow abnormalities and/or a biconvex disc appearance on MRI.

Prevalence of temporomandibular disorders among junior high school students who play wind instruments.

OBJECTIVES: This study investigated whether playing wind instruments has adverse effects on musculoskeletal functions among junior high school students who play in music clubs. MATERIAL AND METHODS: The study included 210 junior high school students (35 boys, 175 girls) belonging to 1 of 4 different school clubs that practiced playing wind instruments more than 6 days/week. The mean age of the participants was 14 years. The study was performed using a questionnaire survey and an electromyographic examination of jaw and cervical muscle activities during playing wind instruments. RESULTS: The prevalence of temporomandibular disorders (TMD) among the children playing woodwind (WW) or brass wind (BW) instruments was higher than in those playing non-wind (NW) instruments. Long duration of playing WW with a reed mouthpiece or BW with a small mouthpiece was suggested to affect the incidence of TMD, which was more marked in girls than in boys, irrespective of height or weight. Muscle activity in the masseter muscle during playing an instrument was significantly higher in the BW with a small mouthpiece group than in the NW group (p < 0.05). In cervical muscles, muscle activity of both the sternocleidomastoid and trapezius muscles was higher during playing BW than in the case of other instruments, and activity in the sternocleidomastoid muscle was significantly higher in the BW with a small mouthpiece group than in the case of other instrument groups (p < 0.05). CONCLUSIONS: Playing wind instruments may have adverse effects on musculoskeletal functions among junior high school students playing in music clubs as compared with playing NW instruments. The prevalence of TMD among the students playing wind instruments was higher than in those playing other instruments. Long duration of playing those instruments affects musculoskeletal function, and this effect is more marked in girls than in boys, irrespective of height or weight.

An autopsy case that manifested no convincing histological changes of severe renal failure after hematopoietic stem cell transplantation.

A 48-year-old Japanese woman, who had been diagnosed with smoldering adult T-cell leukemia, was admitted to our hospital for hematopoietic stem cell transplantation (HSCT) because of an acute exacerbation of her disease. After myeloablative conditioning procedures, comprising cytarabine with cyclophosphamide and total body irradiation, the HLA-matched unrelated bone marrow stem cells were infused (day 0). Her serum creatinine concentration, having been 0.6 mg/dL at baseline, began to increase from day 1 and was 2.3 mg/L on day 7. Hemodialysis was required to treat fluid overload and worsening uremia on days 8 and 9. On day 10, she presented with refractory hypotension and died due to multi-organ failure on day 12. Renal pathology at autopsy showed no specific histological changes to which her clinically severe acute kidney injury (AKI) was attributable. This case suggests that post-HSCT AKI is not necessarily accompanied by apparent renal histologic damage, even if it is clinically serious.

Comparison of joint pain in patients diagnosed with and without articular disc displacement without reduction based on the Research Diagnostic Criteria for Temporomandibular Disorders.

OBJECTIVE: We compared joint pain (JP) in patients diagnosed with and without articular disc displacement without reduction (ADD) based on the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) and identified the characteristics of each JP. STUDY DESIGN: Fifty-eight patients with restricted mouth opening and pain in temporomandibular joint (TMJ) and with a magnetic resonance imaging diagnosis of ADD were selected. Diagnosis of ADD + JP and nonADD + JP was made with the use of the RDC/TMD. RESULTS: A multiple regression analysis of the data disclosed a positive correlation between range of motion on maximum assisted mouth opening and visual analog scale (VAS) (severity of JP) in the ADD + JP group, and between chronic pain grade (CPG) and VAS in the nonADD + JP group. A significant difference was observed between ADD + JP and nonADD + JP groups in CPG; CPG was higher in the nonADD + JP than in the ADD + JP group. CONCLUSIONS: It is suggested that JP related and unrelated to ADD can indicate different types of disease.

Movement of the mandibular condyle and articular disc on placement of an occlusal splint.

OBJECTIVE: The aim of this study was to evaluate, with the use of magnetic resonance images, mandibular condyle and articular disc movement on occlusal splint application. STUDY DESIGN: Thirty-five subjects were classified into "Pain" and "No-pain" groups based on visual analog scale scoring of temporomandibular joint (TMJ) pain and were categorized as bilateral normal disc (ND), unilateral anterior disc displacement (ADD), or bilateral ADD position. t test and analysis of variance with multiple comparisons were used for statistical analyses. RESULTS: Pain and No-pain groups showed significant anteroinferior and rotated movement of the condyle on splint application, but the disc did not significantly move in the Pain group. Of all groups, anteroposterior movement of the condyle and disc with the splint was significantly less in the unilateral ADD group. CONCLUSIONS: TMJ pain was associated with decreased movement of the articular disc. Disc and condyle movement was different in the unilateral ADD group in the presence of a splint compared with the ND and bilateral ADD groups.

Causes of persistent joint pain after arthrocentesis of temporomandibular joint.

PURPOSE: The present study was undertaken to elucidate the factors responsible for the failure of arthrocentesis to cure persistent joint pain in patients with nonreducing articular disc displacement in the temporomandibular joint (TMJ). PATIENTS AND METHODS: Thirty-six patients with internal derangement of the TMJ were selected. Magnetic resonance imaging was used to examine the configuration and position of the articular discs, cortical changes, and bone marrow abnormalities in the condyle and the presence of joint effusion. Arthrocentesis was then performed, and the patients were followed for 6 weeks. The results were then classified as poor or improved. RESULTS: The effects of arthrocentesis did not depend on the configuration of the disc, disc position and motion, or bone marrow abnormalities. Joints with no or minimal amounts of joint effusion achieved a good response to arthrocentesis. Joints with erosive cortical changes of the condyle were less responsive to arthrocentesis. CONCLUSION: Persistent joint pain after arthrocentesis is generally associated with extensive amounts of joint effusion or erosive cortical changes of the condyle.

Correlation between MRI evidence of degenerative condylar surface changes, induction of articular disc displacement and pathological joint sounds in the temporomandibular joint.

OBJECTIVES: The relationship of bony changes in the condylar surfaces in articular disc displacement without reduction in temporomandibular joint (TMJ) was investigated using diagnostic imaging. The study also evaluated whether the bony changes in the condylar surfaces limit disc and condyle motion, and produce pathological joint sounds. MATERIALS AND METHODS: Thirty-seven joints in 28 patients diagnosed with degenerative bony changes in the condylar surfaces radiographically and anterior disc displacement without reduction using magnetic resonance imaging (MRI) were studied. The bony changes were assessed by radiographic examination and classified into two types: pathological bone changes (PBCs) including erosion, osteophyte formation and deformity, and adaptive bone changes (ABCs) including flattening and concavity. MRI was performed on the TMJ to examine the configuration and position of the discs. Joint sounds in the TMJ were determined using electrovibratograghy with a joint vibration analysis. RESULTS: The articular disc motion to the condyle in the PBC group was smaller than in the ABC group irrespective of the configuration of the disc, even though there were no significant differences between the two types of bony changes in the disc position during jaw closing. The joint vibration analysis of the TMJ showed that joint sounds with a higher frequency were observed in the PBC group than in the ABC group. High energy levels needed to produce the higher frequencies (over 300 Hz) were observed only in the PBC group.

Efficacy of a new jet nozzle for removal of carious dentin with an air abrasion system.

A new version of an air abrasion device, which expelled abrasive sodium bicarbonate powder, was fabricated to remove carious tissue. This device had a motor-driven mechanism to control the amount of powder expelled. The purpose of this study was to estimate the abrading efficacy of this device, in particular the new jet nozzle, for removal of carious dentin. Powder was supplied to the handpiece by a rotary gear attached to the powder control motor. Two types of jet nozzles, a cylinder-type and a bugle-type, were fabricated and evaluated. The duct of bugle-type nozzle had an isthmus to increase the air pressure on the powder and to spread it out in a cone-shaped flow. Results obtained showed that the bugle-type jet nozzle exhibited a more prominent abrasive capability. Compared to the cylinder-type nozzle, it was thus more effective in removing the carious dentin which remained in the undercut region of the cavities.

Allergy to metal caused by materials used for intermaxillary fixation: case report.

A 21-year-old man with no history of contact allergy developed eczema over his entire body 2 days after he had had intermaxillary fixation (IMF) of a mandibular fracture. Patch testing showed a strong reaction to nickel so the arch bars and wires that had been used for fixation were removed and replaced with resin brackets, elastic bands, and a chin cap. The eczema disappeared 2 days later.

Application of a specially designed palatal lift prosthesis to a patient with velopharyngeal incompetence due to severe brain injury.

This article reports the evaluation of the therapeutic effect of a palatal lift prosthesis with a specially designed connection between the anterior denture base and the palatal lifting plate in a patient with velopharyngeal incompetence due to severe brain injury.

Collaboration of a dentist and speech-language pathologist in the rehabilitation of a stroke patient with dysarthria: a case study.

OBJECTIVE: To elucidate the effectiveness of the collaboration of a dentist and speech-language pathologist (SLP) in the rehabilitation of a stroke patient with dysarthria. DESIGN: A clinical case report treated in the rehabilitation hospital and dental surgery. SUBJECT: A 71-year-old Japanese man who was admitted to the rehabilitation hospital for speech rehabilitation 2 years and 5 months after a stroke. METHODS: Provision of prosthesis (palatal lift prosthesis + palatal augmentation prosthesis) for improving velopharyngeal incompetence (VPI) and articulation by dentist, and speech behavioural management by SLP including self-monitoring and bio-feedback training using the See-Scape. RESULTS: Speech behavioural management proved useful for promoting improvement in speech intelligibility to a functionally sufficient level after improving VPI by prosthesis. CONCLUSION: The collaborative efforts of the dentist and SLP in the rehabilitation of post-stroke patients with velopharyngeal incompetence should be encouraged.