噛ミング30学習による小学生の咀嚼の習慣と口腔内状態に関する介入研究

The aim of this study was to investigate the relationship between chewing behavior and oral conditions in elementary school children based on an intervention study. The subjects were allocated into an intervention group (5th grade students, n=81) and a control group (5th grade students, n=39) in 2 elementary schools in Tokushima Prefecture, Japan. Eating habits were self-reported using a questionnaire in both groups. The PMA index (Schour-Massler index) of each subject in the intervention group was assessed. The school lunch program “Chewing 30” was performed 5 times per year using a chewing counter. After the completion of the program, a significant difference in behavior change regarding “sufficient chewing” was observed between the intervention and control groups (p<0.01). The participants in the intervention group were sub-divided into 2 groups based on the change of “sufficient chewing”. The PMA index of the non-improved group significantly increased (p<0.05), while that of the improved group showed no significant difference. These results suggest an association between insufficient chewing behavior and gingival inflammation in elementary school children. The program “Chewing 30” might be effective to prevent gingival inflammation in addition to promoting sufficient chewing.　本研究では，小学生の咀嚼習慣と口腔内状態との関連性を介入研究にて調査することを目的とした． 　徳島県内にある2つの小学校のうち，1校の5年生（81名）を介入群とし，他校の5年生（39名）をコントロール群として，食習慣に関する保健調査を実施した．介入群では，児童それぞれのPMA index（Schour-Massler index）を評価した．さらに，1年間を通して計5回学校給食時に咀嚼計を用いた「噛ミング30学習」を実施した． 　介入終了後，“よく嚙む” 項目においてコントロール群と介入群では有意な差が認められた（p<0.01）．“よく嚙む” 項目の変化の有無により，介入群を2つのグループに分類した．“よく嚙む” 項目の非改善群ではPMA index中央値が有意に増加していた（p<0.05）が，改善群ではPMA index中央値の増加は認められなかった． 　これらの結果は，小学生において，不十分な咀嚼習慣と歯肉の炎症に関連性があることを示している．「噛ミング30学習」は，よく嚙むことを促すだけでなく，歯肉炎の予防にも効果がある可能性が示唆された

ToF-SIMS analysis of carbonaceous particles in the sample catcher of the Hayabusa spacecraft

Three carbonaceous category 3 particles (RA-QD02-0180, RB-QD04-0037-01, and RB-QD04-0047-02) returned in the sample catcher from the Hayabusa spacecraft were analyzed by time of flight-secondary ion mass spectrometry (ToF-SIMS) to establish an analytical procedure for determination of their origins. By the different analytical schemes, the three particles gave distinct elemental and molecular ions, in which the organic carbons commonly appear to be associated with nitrogen, silicon, and/or fluorine. The particles could be debris of silicon rubber and fluorinated compounds and are therefore man-made artifacts rather than natural organic matter

TIGIT/CD155 axis mediates resistance to immunotherapy in patients with melanoma with the inflamed tumor microenvironment

Background Patients with cancer benefit from treatment with immune checkpoint inhibitors (ICIs), and those with an inflamed tumor microenvironment (TME) and/or high tumor mutation burden (TMB), particularly, tend to respond to ICIs; however, some patients fail, whereas others acquire resistance after initial response despite the inflamed TME and/or high TMB. We assessed the detailed biological mechanisms of resistance to ICIs such as programmed death 1 and/or cytotoxic T-lymphocyte-associated protein 4 blockade therapies using clinical samples. Methods We established four pairs of autologous tumor cell lines and tumor-infiltrating lymphocytes (TILs) from patients with melanoma treated with ICIs. These tumor cell lines and TILs were subjected to comprehensive analyses and in vitro functional assays. We assessed tumor volume and TILs in vivo mouse models to validate identified mechanism. Furthermore, we analyzed additional clinical samples from another large melanoma cohort. Results Two patients were super-responders, and the others acquired resistance: the first patient had a non-inflamed TME and acquired resistance due to the loss of the beta-2 microglobulin gene, and the other acquired resistance despite having inflamed TME and extremely high TMB which are reportedly predictive biomarkers. Tumor cell line and paired TIL analyses showed high CD155, TIGIT ligand, and TIGIT expression in the tumor cell line and tumor-infiltrating T cells, respectively. TIGIT blockade or CD155-deletion activated T cells in a functional assay using an autologous cell line and paired TILs from this patient. CD155 expression increased in surviving tumor cells after coculturing with TILs from a responder, which suppressed TIGIT+ T-cell activation. Consistently, TIGIT blockade or CD155-deletion could aid in overcoming resistance to ICIs in vivo mouse models. In clinical samples, CD155 was related to resistance to ICIs in patients with melanoma with an inflamed TME, including both primary and acquired resistance. Conclusions The TIGIT/CD155 axis mediates resistance to ICIs in patients with melanoma with an inflamed TME, promoting the development of TIGIT blockade therapies in such patients with cancer

Unexpected Complication of R-CHOP Chemotherapy: Rapidly Progressive Bronchiolitis Obliterans Syndrome

Background: Bronchiolitis obliterans syndrome (BOS) is the term used for the progressive obliteration of small airways before the patient has had a confirmatory lung biopsy. It is also recognized as a transplant-related complication. There have been no reports of BOS during initial standard chemotherapy. Case presentation: A 50-year-old woman with newly diagnosed follicular lymphoma grade 2, stage 3A, presented with hypoxia and progressive dyspnoea after the fifth cycle of R-CHOP. High-resolution computed tomography showed air trapping enhanced at the end-expiratory phase. Pulmonary function testing revealed severe obstructive and restrictive failure without bronchodilator response. We diagnosed BOS based on current criteria and treated the patient with glucocorticoids and cyclosporin. She was discharged home on oxygen therapy. However, soon after discharge, her respiratory symptoms deteriorated and she was hospitalized in a palliative care unit. She died of respiratory failure within a year of symptom onset. Conclusions: This is the first case report to describe rapidly progressive BOS in a patient undergoing R-CHOP treatment, which strongly suggests the condition was caused by the chemotherapy. Although a pathological diagnosis was not obtained, the clinical diagnosis of BOS was important so that the patient could receive appropriate treatment and palliative care based on the prognosis of this incurable condition

What Factors Are Associated with Good Performance in Children with Cochlear Implants? From the Outcome of Various Language Development Tests, Research on Sensory and Communicative Disorders Project in Japan: Nagasaki Experience

ObjectivesWe conducted multi-directional language development tests as a part of the Research on Sensory and Communicative Disorders (RSVD) in Japan. This report discusses findings as well as factors that led to better results in children with severe-profound hearing loss.MethodsWe evaluated multiple language development tests in 33 Japanese children with cochlear implants (32 patients) and hearing aid (1 patient), including 1) Test for question and answer interaction development, 2) Word fluency test, 3) Japanese version of the Peabody picture vocabulary test-revised, 4) The standardized comprehension test of abstract words, 5) The screening test of reading and writing for Japanese primary school children, 6) The syntactic processing test of aphasia, 7) Criterion-referenced testing (CRT) for Japanese language and mathematics, 8) Pervasive development disorders ASJ rating scales, and 9) Raven's colored progressive matrices. Furthermore, we investigated the factors believed to account for the better performances in these tests. The first group, group A, consisted of 14 children with higher scores in all tests than the national average for children with hearing difficulty. The second group, group B, included 19 children that scored below the national average in any of the tests.ResultsOverall, the results show that 76.2% of the scores obtained by the children in these tests exceeded the national average scores of children with hearing difficulty. The children who finished above average on all tests had undergone a longer period of regular habilitation in our rehabilitation center, had their implants earlier in life, were exposed to more auditory verbal/oral communication in their education at affiliated institutions, and were more likely to have been integrated in a regular kindergarten before moving on to elementary school.ConclusionIn this study, we suggest that taking the above four factors into consideration will have an affect on the language development of children with severe-profound hearing loss

Parkinson’s disease-associated iPLA2-VIA/PLA2G6 regulates neuronal functions and α-synuclein stability through membrane remodeling

Mutations in the iPLA2-VIA/PLA2G6 gene are responsible for PARK14-linked Parkinson’s disease (PD) with α-synucleinopathy. However, it is unclear how iPLA2-VIA mutations lead to α-synuclein (α-Syn) aggregation and dopaminergic (DA) neurodegeneration. Here, we report that iPLA2-VIA–deficient Drosophila exhibits defects in neurotransmission during early developmental stages and progressive cell loss throughout the brain, including degeneration of the DA neurons. Lipid analysis of brain tissues reveals that the acyl-chain length of phospholipids is shortened by iPLA2-VIA loss, which causes endoplasmic reticulum (ER) stress through membrane lipid disequilibrium. The introduction of wild-type human iPLA2-VIA or the mitochondria–ER contact site-resident protein C19orf12 in iPLA2-VIA–deficient flies rescues the phenotypes associated with altered lipid composition, ER stress, and DA neurodegeneration, whereas the introduction of a disease-associated missense mutant, iPLA2-VIA A80T, fails to suppress these phenotypes. The acceleration of α-Syn aggregation by iPLA2-VIA loss is suppressed by the administration of linoleic acid, correcting the brain lipid composition. Our findings suggest that membrane remodeling by iPLA2-VIA is required for the survival of DA neurons and α-Syn stability

ToF-SIMS analysis of carbonaceous particles in the sample catcher of the Hayabusa spacecraft

Three carbonaceous category 3 particles (RA-QD02-0180, RB-QD04-0037-01, and RB-QD04-0047-02) returned in the sample catcher from the Hayabusa spacecraft were analyzed by time of flight-secondary ion mass spectrometry (ToF-SIMS) to establish an analytical procedure for determination of their origins. By the different analytical schemes, the three particles gave distinct elemental and molecular ions, in which the organic carbons commonly appear to be associated with nitrogen, silicon, and/or fluorine. The particles could be debris of silicon rubber and fluorinated compounds and are therefore man-made artifacts rather than natural organic matter

Twin CHCH Proteins, CHCHD2, and CHCHD10: Key Molecules of Parkinson’s Disease, Amyotrophic Lateral Sclerosis, and Frontotemporal Dementia

Mutations of coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) and 10 (CHCHD10) have been found to be linked to Parkinson&#8217;s disease (PD), amyotrophic lateral sclerosis (ALS), and/or frontotemporal lobe dementia (FTD). CHCHD2 and CHCHD10 proteins, which are homologous proteins with 54% identity in amino acid sequence, belong to the mitochondrial coiled-coil-helix-coiled-coil-helix (CHCH) domain protein family. A series of studies reveals that these twin proteins form a multimodal complex, producing a variety of pathophysiology by the disease-causing variants of these proteins. In this review, we summarize the present knowledge about the physiological and pathological roles of twin proteins, CHCHD2 and CHCHD10, in neurodegenerative diseases

PINK1-Mediated Phosphorylation of Parkin Boosts Parkin Activity in <i>Drosophila</i>

<div><p>Two genes linked to early onset Parkinson's disease, <i>PINK1</i> and <i>Parkin</i>, encode a protein kinase and a ubiquitin-ligase, respectively. Both enzymes have been suggested to support mitochondrial quality control. We have reported that Parkin is phosphorylated at Ser65 within the ubiquitin-like domain by PINK1 in mammalian cultured cells. However, it remains unclear whether Parkin phosphorylation is involved in mitochondrial maintenance and activity of dopaminergic neurons <i>in vivo</i>. Here, we examined the effects of Parkin phosphorylation in <i>Drosophila</i>, in which the phosphorylation residue is conserved at Ser94. Morphological changes of mitochondria caused by the ectopic expression of wild-type Parkin in muscle tissue and brain dopaminergic neurons disappeared in the absence of PINK1. In contrast, phosphomimetic Parkin accelerated mitochondrial fragmentation or aggregation and the degradation of mitochondrial proteins regardless of PINK1 activity, suggesting that the phosphorylation of Parkin boosts its ubiquitin-ligase activity. A non-phosphorylated form of Parkin fully rescued the muscular mitochondrial degeneration due to the loss of PINK1 activity, whereas the introduction of the non-phosphorylated Parkin mutant in <i>Parkin</i>-null flies led to the emergence of abnormally fused mitochondria in the muscle tissue. Manipulating the Parkin phosphorylation status affected spontaneous dopamine release in the nerve terminals of dopaminergic neurons, the survivability of dopaminergic neurons and flight activity. Our data reveal that Parkin phosphorylation regulates not only mitochondrial function but also the neuronal activity of dopaminergic neurons <i>in vivo</i>, suggesting that the appropriate regulation of Parkin phosphorylation is important for muscular and dopaminergic functions.</p></div

Constitutive expression of SE Parkin impairs motor behavior.

<p>(<b>A</b>) LacZ and WT, SA or SE Parkin were expressed under the control of <i>MHC-GAL4</i> in the <i>w-</i> background. WT and SA Parkin improved the motor activity in older flies, whereas SE Parkin compromised motor activity throughout the trials. LacZ served as a control. The values are presented as the mean ± SE from 20 trials. Male flies were used for the assay. **<i>P</i><0.01 <i>vs</i>. <i>LacZ</i>; #<i>P</i><0.05. Flies expressing SE Parkin had decreased climbing ability compared with flies expressing WT or SA Parkin throughout the trial (<i>P</i><0.01). (<b>B</b>) Muscle-specific expression of Parkin SE under control of <i>MHC-GAL4</i> failed to rescue the motor defect of the <i>PINK1^-/-</i> flies. The loss of climbing ability in the <i>PINK1^-/-</i> flies was rescued by expression of WT and SA Parkin. The values represent the mean ± SE from 20 trials. Male flies were used for the assay. **<i>P</i><0.01 <i>vs</i>. <i>LacZ</i>. Flies expressing SE Parkin had decreased climbing ability compared with flies expressing WT or SA Parkin throughout the trial (<i>P</i><0.01).</p