Effect of Oral Functional Training on Changes in Resting Saliva Secretion in Older Hemodialysis Patients

高齢血液透析患者の口腔乾燥には，日常的な水分摂取の制限と唾液腺自体の加齢性変化が関係していると考えられる．高齢血液透析患者の口腔乾燥改善には，まず十分な安静時唾液の分泌が必要と考え，それを促す手法の一つとして口腔機能訓練に着目した．本研究は，高齢血液透析患者に対して継続的な口腔機能訓練を行い，安静時唾液量の変化から訓練の効果を検証することを目的とした． 研究参加の同意が得られた軽度以上の口腔乾燥を有する高齢血液透析患者を，無作為に2群に分けた．歯科衛生士による口腔機能訓練（唾液腺マッサージ，舌運動訓練）を透析中（週3回）に12週間行った群を介入群，行わなかった群を対照群とした．研究開始前，2週後，4週後，8週後および12週後に，口腔内湿潤度と安静時唾液量を測定した．研究を完了した54名（介入群28名，対照群26名）について，群内および群間の比較には二元配置分散分析を，計測回ごとの多重比較にはBonfferoni法を用いて，統計解析を行った． 口腔機能訓練の実施による変化を検証した結果，口腔内湿潤度は，介入群の主効果および対照群との交互作用も有意であった（F（1,52）＝22.3，p＝0.03，F（4）＝3.5，p＝0.008）．群内の多重比較の結果，介入群は研究開始時と比較して，4週後以降で有意差が認められた（p＜0.05，p＜0.001，p＜0.05）が，対照群は有意差が認められなかった．安静時唾液は，介入群の主効果および対照群との交互作用も有意（F（1,52）＝18.6，p＜0.001，F（3）＝5.3，p＝0.002）であった．群内の多重比較の結果，介入群において，研究開始前と比較して4週後以降（p＜0.05，p＜0.001，p＜0.001）に有意な増加が認められた．一方，対照群において，2週後と12週後，4週後と12週後に有意な増加が認められた（p＜0.05，p＜0.05）．以上より，高齢血液透析患者に対する長期間（4週間以上）の唾液腺マッサージや舌運動訓練による口腔機能訓練は，安静時唾液分泌量を増加させる可能性が示唆された．Introduction:　Daily fluid restriction and aging-related atrophy of saliva glands might cause dry mouth in older hemodialysis patients. We hypothesized that greater saliva secretion is needed to relieve dry mouth and that this could be achieved by providing oral functional training to patients. The aim of this study was to investigate changes in resting saliva secretion after performing oral functional training for older hemodialysis patients with mild dry mouth. Materials and Methods:　Hemodialysis patients with mild dry mouth at Kawashima Hospital gave informed consent to participate in the study. They were then randomly divided into an intervention group (n＝31) and a control group (n＝30). The intervention group was provided oral functional training by a dental hygienist, including saliva gland massage for 30 s and tongue lateral movement for 12 weeks during dialysis treatment. The control group did not receive the training. Overall, 54 participants completed the experiment. Oral wetness was measured using a KISO-WeT Tester, and the amount of resting saliva secreted in 30 s was collected in a cotton roll and weighed. Measurements were implemented at baseline and at 2, 4, 8, and 12 weeks after starting the regimen. Results and Discussion:　In the intervention group, oral wetness at 4, 8, and 12 weeks was significantly higher than that at baseline (p＜0.05, p＜0.001, p＜0.05, respectively). No statistically significant differences were found in the control group. In the intervention group, the amounts of saliva secreted at 4, 8, and 12 weeks were significantly greater than that at baseline (p＜0.05, p＜0.001, p＜0.001, respectively). In the control group, the amount of saliva secreted at 12 weeks was significantly more than that at 2 and 4 weeks (p＜0.05, p＜0.05, respectively). Conclusion:　We concluded that performing oral functional training, which included salivary gland massage and tongue movement training for 4 or more weeks, could increase the amount of resting saliva secretion in older hemodialysis patients with mild dry mouth

Relationships between Skeletal Muscle Mass and Strength, and Jaw-Opening Force in Japanese Community-Dwelling Elderly

【目的】要介護高齢者の一要因である骨格筋量の低下や筋力低下は，嚥下関連筋にも影響を及ぼし，摂食嚥下機能を低下させることが疑われる．本研究では，地域在宅高齢者の骨格筋量・骨格筋力と，口腔機能・摂食嚥下機能との関連性を明らかにすることを目的として，調査を実施した． 【対象と方法】対象は，65歳以上の地域在宅高齢者24名（男性3名，女性21名，平均年齢77.0±5.0 歳）とした．骨格筋量は骨格筋指数（以下，SMI）を，骨格筋力は握力を評価項目として用いた．口腔機能・摂食嚥下機能は開口力・オーラルディアドコキネシス（以下，OD）/ タ/ と/ カ/・RSST・MWST を測定し，骨格筋量と骨格筋力との関連性を検討した．各項目の相関関係をスピアマンの順位相関係数にて解析した．その後，有意な関連のあった項目に年齢，性別を加え，重回帰分析（ステップワイズ法）を行った．さらに，握力の値から，筋力健常群と筋力低下群（男性＜ 26 kg，女性＜ 18 kg）の2群に分類し，口腔機能・摂食嚥下機能の各項目について比較した．2群間比較には，マン・ホイットニーのU 検定を用いて統計解析した． 【結果と考察】SMI と開口力，握力と開口力・OD / タ/ に有意な相関関係が認められた（r＝0.578，p＝0.003；r＝0.640，p＝0.001；r＝0.447，p＝0.029）．重回帰分析の結果，開口力に影響を与える因子としてSMI が挙げられた．また，筋力低下群の開口力は，筋力健常群よりも有意に低い値を示した（p＝0.011）．全身の骨格筋量，骨格筋力の低下は，開口力やOD / タ/ の低下に関連する可能性が考えられた． 【結論】地域在宅高齢者の骨格筋量と骨格筋力は，開口力や舌運動機能に関連する可能性が示唆された．Skeletal muscle mass decreasing and muscle weakness can cause long-term care needs for elderly people. The relationship between skeletal muscle status and muscles relevant to oral function has been little reported. Therefore, the aim of the present study was to survey skeletal muscle status, oral function, and the relationship between the two in community-dwelling elderly people. Twenty-four community-dwelling elderly from two elderly associations in N city, T prefecture enrolled in the present survey (3 males, 21 females; mean age, 77.0±5.0 years). Skeletal muscle index (SMI) was used to assess skeletal muscle mass, grasping power to assess skeletal muscle strength. Oral function was evaluated in terms of jaw-opening force, diadochokinesis, the repetitive saliva swallowing test (RSST), and the modified water swallowing test (MWST). Correlations between parameters were analyzed using Spearman’s correlation coefficient. Consequently stepwise regression analysis was performed with jaw-opening force as objective variable and SMI, grasping force, age and sex as explanatory variables. The subjects were divided into two groups according to standards for grasping force: healthy and muscle weakness (male: ＜26 kgw; female: ＜18 kgw). Parameters were statistically compared between the two groups using the Mann-Whitney U test. There were statistical relationships between SMI and jaw-opening force (r＝0.578, p＝0.003), grasping force and jaw-opening force (r＝0.640, p＝0.001), grasping force and the number of diadochokinetic movement of /ta/ (r＝0.447, p＝0.029). As a result of stepwise regression analysis, SMI was a factor that affects jaw-opening force. In the muscle weakness group, jaw-opening force was less than the value in the healthy group ( p＝ 0.011). It is reasonable that an overall decrease in muscle mass would evoke decreases in muscle strength in both the extremities and the jaw-opening muscles. We confirmed significant relationships between skeletal muscle mass, skeletal muscle strength, and oral function (i.e., jaw-opening force and tongue skilled movement) in Japanese community-dwelling elderly

Simple generation of hairless mice for in vivo imaging

The in vivo imaging of mice makes it possible to analyze disease progress non-invasively through reporter gene expression. As the removal of hair improves the accuracy of in vivo imaging, gene-modified mice with a reporter gene are often crossed with Hos:HR-1 mutant mice homozygous for the spontaneous Hrhr mutation that exhibit a hair loss phenotype. However, it is time consuming to produce mice carrying both the reporter gene and mutant Hrhr gene by mating. In addition, there is a risk that genetic background of the gene-modified mice would be altered by mating. To resolve these issues, we established a simple method to generate hairless mice maintaining the original genetic background by CRISPR technology. First, we constructed the pX330 vector, which targets exon 3 of Hr. This DNA vector (5 ng/µl) was microinjected into the pronuclei of C57BL/6J mice. Induced Hr gene mutations were found in many founders (76.1%) and these mutations were heritable. Next, we performed in vivo imaging using these gene-modified hairless mice. As expected, luminescent objects in their body were detected by in vivo imaging. This study clearly showed that hairless mice could be simply generated by the CRISPR/Cas9 system, and this method may be useful for in vivo imaging studies with various gene-modified mice

A review of clinical characteristics and genetic backgrounds in Alport syndrome

Alport syndrome (AS) is a progressive hereditary renal disease that is characterized by sensorineural hearing loss and ocular abnormalities. It is divided into three modes of inheritance, namely, X-linked Alport syndrome (XLAS), autosomal recessive AS (ARAS), and autosomal dominant AS (ADAS). XLAS is caused by pathogenic variants in COL4A5, while ADAS and ARAS are caused by those in COL4A3/COL4A4. Diagnosis is conventionally made pathologically, but recent advances in comprehensive genetic analysis have enabled genetic testing to be performed for the diagnosis of AS as first-line diagnosis. Because of these advances, substantial information about the genetics of AS has been obtained and the genetic background of this disease has been revealed, including genotype–phenotype correlations and mechanisms of onset in some male XLAS cases that lead to milder phenotypes of late-onset end-stage renal disease (ESRD). There is currently no radical therapy for AS and treatment is only performed to delay progression to ESRD using nephron-protective drugs. Angiotensin-converting enzyme inhibitors can remarkably delay the development of ESRD. Recently, some new drugs for this disease have entered clinical trials or been developed in laboratories. In this article, we review the diagnostic strategy, genotype–phenotype correlation, mechanisms of onset of milder phenotypes, and treatment of AS, among others

看護学部における地域住民参画型教育の取り組みと今後の課題 : 模擬患者の養成と看護OSCEへの参画支援を通して

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Larval pufferfish protected by maternal tetrodotoxin

Marine pufferfish contain tetrodotoxin (TTX), an extremely potent neurotoxin. All species of the genus Takifugu accumulate TTX in the liver and ovaries, although the tissue(s) in which it is localized can differ among species. TTX is the major defense strategy the pufferfish appears to use against predators. TTX is also used as a male-attracting pheromone during spawning. Here we demonstrate an additional (and unexpected) use of maternal TTX in the early larval stages of the Takifugu pufferfish. Predation experiments demonstrated that juveniles of all the species of fish used as predators ingested pufferfish larvae, but spat them out promptly. Liquid Chromatography-Tandem Mass Spectrometry (LC-MSMS) analysis revealed that the pufferfish larvae contain a small quantity of TTX, which is not enough to be lethal to the predators. Immunohistochemical analysis with anti-TTX monoclonal antibody revealed that the TTX is primarily localized in the body surface of the larvae as a layer of protection. Our study showed the female parent of the Takifugu pufferfish vertically transfers TTX to the larvae through its accumulation in the ovaries, and subsequent localization on the body surface of the larvae

Intestinal clock system regulates skeletal homeostasis.

The circadian clock network is an evolutionarily conserved system involved in the regulation of metabolic homeostasis; however, its impacts on skeletal metabolism remain largely unknown. We herein demonstrated that the circadian clock network in the intestines plays pivotal roles in skeletal metabolism such that the lack of the Bmal1 gene in the intestines (Bmal1Int-/- mice) caused bone loss, with bone resorption being activated and bone formation suppressed. Mechanistically, Clock protein interaction with the vitamin D receptor (VDR) accelerated its binding to the VDR response element by enhancing histone acetylation in a circadian-dependent manner, and this was lost in Bmal1Int-/- mice because nuclear translocation of Clock required the presence of Bmal1. Accordingly, the rhythmic expression of VDR target genes involved in transcellular calcium (Ca) absorption was created, and this was not observed in Bmal1Int-/- mice. As a result, transcellular Ca absorption was impaired and bone resorption was activated in Bmal1Int-/- mice. Additionally, sympathetic tone, the activation of which suppresses bone formation, was elevated through afferent vagal nerves in Bmal1Int-/- mice, the blockade of which partially recovered bone loss by increasing bone formation and suppressing bone resorption in Bmal1Int-/- mice. These results demonstrate that the intestinal circadian system regulates skeletal bone homeostasis