Clinical application of endoscopic soft palate augmentation in the treatment of velopharyngeal insufficiency.

Velopharyngeal structure augmentation with the injection of autologous fat tissue into the nasal mucosa of the soft palate has been reported previously. However, as the injection points in the velopharyngeal space cannot be observed directly, these injections may be difficult to perform accurately. This report describes a new endoscope-assisted approach in which the materials for velopharyngeal structure augmentation are administered while observing the injection points directly, also enabling adjustment of the amount of material injected. A case series of five patients aged 8-16 years who underwent endoscopic soft palate augmentation under general anaesthesia is reported. Autologous fat tissue was injected into the nasal mucosa of the soft palate using a needle-type device of an endoscope, and the effects of the treatment were evaluated. The injections were performed successfully, and the velopharyngeal function was improved. This new technique of endoscopy-assisted augmentation was useful for the treatment of velopharyngeal insufficiency.

Implications of nasopharynx-associated lymphoid tissue (NALT) in the development of allergic responses in an allergic rhinitis mouse model.

BACKGROUND: Nasopharynx-associated lymphoid tissue (NALT) serves as an important inductive site for mucosal immunity in the upper respiratory tract. Despite its importance in the mucosal immune system, little is known regarding the role of NALT in airway allergic immune responses. We aimed to elucidate the role of NALT in the induction of upper airway allergic responses in a mouse model. METHODS: Inhibitor of DNA binding/differentiation 2 (Id2)(-/-) and Id2(+/-) mice was exposed to the ovalbumin (OVA)-induced allergic rhinitis model, because the former resulted in the NALT deficiency. The allergic parameters, such as allergic symptoms, serum OVA-specific immunoglobulin E (IgE) levels, eosinophil infiltration, and cytokine profiles in the nasal mucosa, were compared between Id2(-/-) and Id2(+/-) groups. RESULTS: NALT-null, Id2(-/-) mice displayed significantly lower allergic responses compared with Id2(+/-) mice, as demonstrated by lower levels of allergic symptoms, serum OVA-specific IgE, eosinophilic infiltration, and local Th2 cytokine transcriptions. To determine which of two factors, that is, the absence of NALT or the alteration of immunocompetent cell populations caused by the Id2 deficiency, has a larger effect on the attenuated allergic immune responses in Id2(-/-) mice, lethally irradiated Id2(-/-) mice were engrafted with C57BL/6 wild-type bone marrow cells and showed still significantly lower allergic immune responses compared with equally treated Id2(+/-) mice. In addition, IgE class switch recombination-associated molecules, such as ε immunoglobulin heavy-chain germline gene transcript, ε mRNA, and activation-induced cytidine deaminase mRNA, were detected in NALT from OVA-sensitized wild-type mice. CONCLUSION: These results show the critical role of NALT for the induction of allergic responses in the upper airway at least in part by means of class switching to IgE in situ.

Expression of Id2 in the second heart field and cardiac defects in Id2 knock-out mice.

The inhibitor of differentiation Id2 is expressed in mesoderm of the second heart field, which contributes myocardial and mesenchymal cells to the primary heart tube. The role of Id2 in cardiac development is insufficiently known. Heart development was studied in sequential developmental stages in Id2 wildtype and knockout mouse embryos. Expression patterns of Id2, MLC-2a, Nkx2.5, HCN4, and WT-1 were analyzed. Id2 is expressed in myocardial progenitor cells at the inflow and outflow tract, in the endocardial and epicardial lineage, and in neural crest cells. Id2 knockout embryos show severe cardiac defects including abnormal orientation of systemic and pulmonary drainage, abnormal myocardialization of systemic and pulmonary veins, hypoplasia of the sinoatrial node, large interatrial communications, ventricular septal defects, double outlet right ventricle, and myocardial hypoplasia. Our results indicate a role for Id2 in the second heart field contribution at both the arterial and the venous poles of the heart.

Pebbles and sand on asteroid (162173) Ryugu: In situ observation and particles returned to Earth.

The Hayabusa2 spacecraft investigated the C-type (carbonaceous) asteroid (162173) Ryugu. The mission performed two landing operations to collect samples of surface and subsurface material, the latter exposed by an artificial impact. We present images of the second touchdown site, finding that ejecta from the impact crater was present at the sample location. Surface pebbles at both landing sites show morphological variations ranging from rugged to smooth, similar to Ryugu's boulders, and shapes from quasi-spherical to flattened. The samples were returned to Earth on 6 December 2020. We describe the morphology of >5 grams of returned pebbles and sand. Their diverse color, shape, and structure are consistent with the observed materials of Ryugu; we conclude that they are a representative sample of the asteroid.

Sample collection from asteroid (162173) Ryugu by Hayabusa2: Implications for surface evolution.

The near-Earth asteroid (162173) Ryugu is thought to be a primitive carbonaceous object that contains hydrated minerals and organic molecules. We report sample collection from Ryugu's surface by the Hayabusa2 spacecraft on 21 February 2019. Touchdown images and global observations of surface colors are used to investigate the stratigraphy of the surface around the sample location and across Ryugu. Latitudinal color variations suggest the reddening of exposed surface material by solar heating and/or space weathering. Immediately after touchdown, Hayabusa2's thrusters disturbed dark, fine grains that originate from the redder materials. The stratigraphic relationship between identified craters and the redder material indicates that surface reddening occurred over a short period of time. We suggest that Ryugu previously experienced an orbital excursion near the Sun.

An artificial impact on the asteroid (162173) Ryugu formed a crater in the gravity-dominated regime.

The Hayabusa2 spacecraft investigated the small asteroid Ryugu, which has a rubble-pile structure. We describe an impact experiment on Ryugu using Hayabusa2's Small Carry-on Impactor. The impact produced an artificial crater with a diameter >10 meters, which has a semicircular shape, an elevated rim, and a central pit. Images of the impact and resulting ejecta were recorded by the Deployable CAMera 3 for >8 minutes, showing the growth of an ejecta curtain (the outer edge of the ejecta) and deposition of ejecta onto the surface. The ejecta curtain was asymmetric and heterogeneous and it never fully detached from the surface. The crater formed in the gravity-dominated regime; in other words, crater growth was limited by gravity not surface strength. We discuss implications for Ryugu's surface age.

Alterations of myc, myb, and rasHa proto-oncogenes in cancers are frequent and show clinical correlation.

Alterations of c-myc, c-rasHa, or c-myb oncogenes were found in more than one-third of human solid tumors. Amplification of c-myc occurred in advanced, widespread tumors or in aggressive primary tumors. Apparent allelic deletions of c-rasHa and c-myb can be correlated with progression and metastasis of carcinomas and sarcomas.

The surface composition of asteroid 162173 Ryugu from Hayabusa2 near-infrared spectroscopy.

The near-Earth asteroid 162173 Ryugu, the target of the Hayabusa2 sample-return mission, is thought to be a primitive carbonaceous object. We report reflectance spectra of Ryugu's surface acquired with the Near-Infrared Spectrometer (NIRS3) on Hayabusa2, to provide direct measurements of the surface composition and geological context for the returned samples. A weak, narrow absorption feature centered at 2.72 micrometers was detected across the entire observed surface, indicating that hydroxyl (OH)-bearing minerals are ubiquitous there. The intensity of the OH feature and low albedo are similar to thermally and/or shock-metamorphosed carbonaceous chondrite meteorites. There are few variations in the OH-band position, which is consistent with Ryugu being a compositionally homogeneous rubble-pile object generated from impact fragments of an undifferentiated aqueously altered parent body.

Hayabusa2 arrives at the carbonaceous asteroid 162173 Ryugu-A spinning top-shaped rubble pile.

The Hayabusa2 spacecraft arrived at the near-Earth carbonaceous asteroid 162173 Ryugu in 2018. We present Hayabusa2 observations of Ryugu's shape, mass, and geomorphology. Ryugu has an oblate "spinning top" shape, with a prominent circular equatorial ridge. Its bulk density, 1.19 ± 0.02 grams per cubic centimeter, indicates a high-porosity (>50%) interior. Large surface boulders suggest a rubble-pile structure. Surface slope analysis shows Ryugu's shape may have been produced from having once spun at twice the current rate. Coupled with the observed global material homogeneity, this suggests that Ryugu was reshaped by centrifugally induced deformation during a period of rapid rotation. From these remote-sensing investigations, we identified a suitable sample collection site on the equatorial ridge.

The geomorphology, color, and thermal properties of Ryugu: Implications for parent-body processes.

The near-Earth carbonaceous asteroid 162173 Ryugu is thought to have been produced from a parent body that contained water ice and organic molecules. The Hayabusa2 spacecraft has obtained global multicolor images of Ryugu. Geomorphological features present include a circum-equatorial ridge, east-west dichotomy, high boulder abundances across the entire surface, and impact craters. Age estimates from the craters indicate a resurfacing age of [Formula: see text] years for the top 1-meter layer. Ryugu is among the darkest known bodies in the Solar System. The high abundance and spectral properties of boulders are consistent with moderately dehydrated materials, analogous to thermally metamorphosed meteorites found on Earth. The general uniformity in color across Ryugu's surface supports partial dehydration due to internal heating of the asteroid's parent body.

Images from the surface of asteroid Ryugu show rocks similar to carbonaceous chondrite meteorites.

The near-Earth asteroid (162173) Ryugu is a 900-m-diameter dark object expected to contain primordial material from the solar nebula. The Mobile Asteroid Surface Scout (MASCOT) landed on Ryugu's surface on 3 October 2018. We present images from the MASCOT camera (MASCam) taken during the descent and while on the surface. The surface is covered by decimeter- to meter-sized rocks, with no deposits of fine-grained material. Rocks appear either bright, with smooth faces and sharp edges, or dark, with a cauliflower-like, crumbly surface. Close-up images of a rock of the latter type reveal a dark matrix with small, bright, spectrally different inclusions, implying that it did not experience extensive aqueous alteration. The inclusions appear similar to those in carbonaceous chondrite meteorites.

A role for the helix-loop-helix protein Id2 in the control of oligodendrocyte development.

Compared to neurons, the intracellular mechanisms that control glial differentiation are still poorly understood. We show here that oligodendrocyte lineage cells express the helix-loop-helix proteins Mash1 and Id2. Although Mash1 has been found to regulate neuronal development, we found that in the absence of Mash1 oligodendrocyte differentiation occurs normally. In contrast, we found that overexpression of Id2 powerfully inhibits oligodendrocyte differentiation, that Id2 normally translocates out of the nucleus at the onset of differentiation, and that absence of Id2 induces premature oligodendrocyte differentiation in vitro. These findings demonstrate that Id2 is a component of the intracellular mechanism that times oligodendrocyte differentiation and point to the existence of an as yet unidentified MyoD-like bHLH protein necessary for oligodendrocyte differentiation.

Elevation of matrix metalloproteinases and interleukin-6 in the culprit coronary artery of myocardial infarction.

BACKGROUND: Interleukin-6 (IL-6) and metalloproteinases (MMPs) are involved in the instability of vulnerable plaque associated with the induction of acute myocardial infarction (AMI). We examined the regional changes of cytokines, MMPs and adhesion molecules in patients with AMI to elucidate how these factors are involved in the onset of AMI. MATERIALS AND METHODS: One hundred and twenty-two patients with AMI were included. Blood was aspirated from the culprit coronary artery with a thrombectomy catheter, and was also sampled from peripheral veins during the coronary intervention. Control samples were obtained from the peripheral blood of age-matched patients. RESULTS: The serum levels of IL-6 (P < 0.05), tumour necrosis factor-alpha (P < 0.005), MMP-1 (P < 0.001), MMP-13 (P < 0.001), soluble intercellular adhesion molecule-1 (P < 0.005), and soluble vascular cellular adhesion molecule-1 (P < 0.05) in peripheral blood were significantly higher in the AMI group than in the controls. Aspirated serum contained significantly higher levels of IL-6 (P < 0.001), MMP-1 (P < 0.001), and MMP-13 (P < 0.05) compared to the peripheral blood of AMI. Serum IL-6 levels were significantly higher in the aspirated than in the peripheral blood in the patients hospitalized within 6 h and 6-12 h, but were similar in the aspirated and peripheral blood of the patients hospitalized 12-24 h after the onset of AMI. There were no differences between the aspirated serum and peripheral blood in the levels of interleukin-1beta and MMP-2. CONCLUSIONS: The levels of MMP-1, MMP-13 and IL-6 were higher in the culprit coronary artery than in the peripheral blood. These factors appear to be involved in the early stage of AMI.

An uncommon cleft subtype of unilateral cleft lip and palate.

The finding that the vomer plays a crucial role in maxillary growth suggests that the bilateral cleft configuration of unilateral cleft lip and palate (UCLP), in which the vomer is detached from the non-cleft-side secondary hard palate, negatively influences palatal development, and this hypothesis was tested. Sixty persons with complete UCLP, including those with the vomer detached from (n = 30, b-UCLP) and attached to (n = 30, u-UCLP) the secondary hard palate, were analyzed morphologically, with the use of cast models taken at 10 days, 3 mos, and 12 mos of age. The anterio-posterior palatal length at 12 mos of age in those with b-UCLP was significantly shorter than that in those with u-UCLP, by 8.7% (p < 0.05). In addition, palatal width development in the first year in those with b-UCLP was also significantly retarded. These results suggest that the uncommon bilateral cleft subtype in UCLP should be included in the cleft classification.

Responses of marine organisms to physical and chemical impacts.

Studies on the effects of a variety of exogenous and anthropogenic environmental factors, including endocrine disruptors, heavy metals, UV light, high temperature, and others, on marine organisms have been presented at the 2nd Bilateral Seminar Italy-Japan held in November 2006. Reports were discussed in order to reveal the current situation of marine ecosystems, aiming at evaluation and prediction of environmental risks.

Measurement of edge density profiles of Large Helical Device plasmas using an ultrashort-pulse reflectometer.

We report here on the application of an ultrashort-pulse reflectometer (USPR) to Large Helical Device in National Institute for Fusion Science. An impulse with picosecond pulse width is used as a source in an USPR. Since the bandwidth of a source is inversely related to the pulse width, we can utilize the frequency range of microwave to millimeter-wave by using wide band transmission lines. The density profiles can be reconstructed by collecting time-of-flight signal of each frequency component of an impulse reflected from each cutoff layer. Remote control system using super science information network has been introduced to the present USPR system.

Species generalization and differences in Hedgehog pathway regulation of fungiform and circumvallate papilla taste function and somatosensation demonstrated with sonidegib.

Species generalization in the profound, modality-specific effects of Hedgehog pathway inhibition (HPI) in taste organ homeostasis and sensation is shown. With the HPI, cancer drug sonidegib, we demonstrate that the rat taste system, in addition to mouse, is regulated by Hedgehog signaling. After sonidegib treatment for 16-36 days in rat, there is loss of taste buds (TB) in soft palate, in fungiform (FP) and circumvallate papillae (CV), and elimination of taste responses from chorda tympani and glossopharyngeal nerves. The retained innervation in FP and CV during HPI cannot sustain TB. Responses to tactile stimuli are not altered, and temperature responses are reduced only after 28 days treatment, demonstrating modality-specific effects. Rat FP and neural effects are similar to those in mouse whereas TB and neural response effects from the rat CV are much more severe. When recovery is introduced in mouse after prolonged, 48 days HPI, the TB in CV are restored whereas those in FP are not. Overall, Hedgehog signaling regulation is shown to generalize to the rat taste system, and the modality-specific controls in taste organ sensation are affirmed. The reported, debilitating taste disturbances in patients who use HPI drugs can be better understood based on these data.

Disruption of the splicing enhancer sequence within exon 27 of the dystrophin gene by a nonsense mutation induces partial skipping of the exon and is responsible for Becker muscular dystrophy.

The mechanism of exon skipping induced by nonsense mutations has not been well elucidated. We now report results of in vitro splicing studies which disclosed that a particular example of exon skipping is due to disruption of a splicing enhancer sequence located within the exon. A nonsense mutation (E1211X) due to a G to T transversion at the 28th nucleotide of exon 27 (G3839T) was identified in the dystrophin gene of a Japanese Becker muscular dystrophy case. Partial skipping of the exon resulted in the production of truncated dystrophin mRNA, although the consensus sequences for splicing at both ends of exon 27 were unaltered. To determine how E1211X induced exon 27 skipping, the splicing enhancer activity of purine-rich region within exon 27 was examined in an in vitro splicing system using chimeric doublesex gene pre-mRNA. The mutant sequence containing G3839T abolished splicing enhancer activity of the wild-type purine-rich sequence for the upstream intron in this chimeric pre-mRNA. An artificial polypurine oligonucleotide mimicking the purine-rich sequence of exon 27 also showed enhancer activity that was suppressed by the introduction of a T nucleotide. Furthermore, the splicing enhancer activity was more markedly inhibited when a nonsense codon was created by the inserted T residue. This is the first evidence that partial skipping of an exon harboring a nonsense mutation is due to disruption of a splicing enhancer sequence.

Relationship between metabolic syndrome components and vascular properties in Japanese type 2 diabetic patients without cardiovascular disease or nephropathy.

To investigate the effect of metabolic syndrome (MS) components on early atherosclerosis markers, i.e., urinary albumin excretion rate (UAE), pulse wave velocity (PWV), and carotid intima-media thickness (IMT), we studied 536 Japanese patients with type 2 diabetes without cardiovascular disease or nephropathy. The MS definition by ATP III was employed. UAE, PWV, and IMT increased significantly with increasing the number of components even before fulfilling the diagnosis of MS. UAE was significantly influenced by high blood pressure, high triglycerides, and low HDL cholesterol. PWV was significantly increased by high blood pressure. IMT was significantly increased by high blood pressure and abdominal obesity. Multiple regression analysis, including MS components and putative risk factors, indicated that the number of MS components, age and glycosylated HbA1C were independent determinants of UAE, PWV, and IMT. LDL cholesterol and male gender were independent determinants of IMT. In conclusion, UAE, PWV, and IMT increased according to increasing the number of MS in type 2 diabetic patients without cardiovascular disease or diabetic nephropathy. The current observation considering the modifiable factors may help to identify patients who are at high risk of experiencing cardiovascular disease.