Near-surface softening and healing in eastern Honshu associated with the 2011 magnitude-9 Tohoku-Oki Earthquake.

The near-surface part of the crust, also called the skin of the earth, is the arena of human activity of which the stiffness is of great concern to engineers in infrastructure construction. The stiffness reduction of near-surface geomaterials also plays a vital role in geohazards triggering. However, the physical mechanism behind the material softening is still not fully understood. Here, we report a coseismic shear-wave velocity reduction in the near surface by up to a few tens of percent during the strongest shaking from the 11 March 2011 Tohoku-Oki Earthquake and a subsequent two-stage healing process including a rapid recovery within a few minutes and a slow recovery over many years. We also present a theoretical contact model between mineral grains in geomaterials containing multiple metastable contacts at small separations due to the oscillatory hydration interaction, which can explain the emergence of different stages in the healing process.

Targeted next-generation sequencing identified a novel variant of SOX10 in a Chinese family with Waardenburg syndrome type 2.

OBJECTIVE: Waardenburg syndrome type 2 (WS2) is an autosomal dominant syndrome, characterized by bright blue eyes, hearing loss, and depigmented patches of hair and skin. It exhibits high phenotypic and genetic heterogeneity. We explored the molecular etiology in a Chinese family with WS2. METHODS: We recruited a three-generation family with three affected members. Medical history was obtained from all family members who underwent detailed physical examinations and audiology tests. Genomic DNA was extracted from peripheral blood of each individual, and 139 candidate genes associated with hearing loss were sequenced using Illumina HiSeq 2000 (Illumina Inc., San Diego, CA, USA) and verified by Sanger sequencing. RESULTS: Genetic evaluation revealed a novel nonsense heterozygous variant, NM_006941.4: c.342G>A (p.Trp114Ter) in exon 2 of the SOX10 gene in the three affected patients; no unaffected family member carried the variation. We did not detect the variation in 500 Chinese individuals with normal hearing or in 122 unrelated Chinese families with hearing loss, suggesting that it was specific to our patients. CONCLUSIONS: We identified a novel heterozygous nonsense variation in a family with syndromic hearing loss and WS2. Our findings expand the pathogenic spectrum and strengthen the clinical diagnostic role of SOX10 in patients with WS2.

The mutation frequencies of GJB2, GJB3, SLC26A4 and MT-RNR1 of patients with severe to profound sensorineural hearing loss in northwest China.

OBJECTIVE: To expose the spectrum and frequency of GJB2, GJB3, SLC26A4 and MT-RNR1 in northwest China and to investigate the underlying causative genes in patients without common mutations. METHODS: We analyzed the mutation screening results of GJB2, GJB3, SLC26A4 and MT-RNR1 in 398 unrelated severe-to-profound probands with bilateral, symmetrical sensorineural hearing loss. Subsequently, we selected 10 probands with a significant family history of inherited hearing loss (HL) that did not have the above four common gene mutations to perform next-generation sequencing (NGS) of 139 known deafness genes, followed by co-segregation analysis of all available family members. RESULTS: Among the 398 patients, 69 (17.34%) had the biallelic GJB2 gene mutations, and the most common mutations were c.235delC, c.109G>A and c.299_300delAT, with allele frequencies of 12.31%, 3.38% and 3.89%, respectively. A total of 63 (15.83%) cases with biallelic SLC26A4 mutations were detected, and the most common pathogenic alleles were c.919-2A>G, c.2168A>G and c.1174A>T, with allele frequencies of 9.17%, 2.26% and 0.88%, respectively. Mitochondrial gene mutations were detected in 9 (2.26%) patients, with 5 cases of mitochondrial DNA (mtDNA) m.1555A>G mutation and 4 cases of mtDNA m.1095T>C mutation. In 10 probands with a clear family history of HL, NGS showed two novel pathogenic variants in 2 families, including c.4129C>T/c.3268C>T in LOXHD1, c.334G>A/c.2968G>T in CDH23. Sanger sequencing confirmed that these variants segregated with the HL in each family. CONCLUSIONS: Our results showed that GJB2 and SLC26A4 were the two major HL-causing genes in northwest China. The most common mutation alleles in GJB2 were c.235delC, c.109G>A and c.299_300delAT, and those in SLC26A4 were c.919-2A>G, c.2168A>G and c.1174A>T. In addition, both genes and their loci can be used as the first selection of deafness gene screening. Additionally, for patients who did not have mutations of these common genes, NGS provided an efficient diagnosis for increasing known deafness genes.

Targeted next-generation sequencing identifies a novel frameshift EYA1 variant causing branchio-otic syndrome in a Chinese family.

OBJECTIVE: To evaluate the genotype-phenotype correlation of branchio-otic syndrome (BOS) in a Chinese family. METHODS: The proband in this study was an 18-month-old boy with hearing loss, preauricular pit, and branchial fistula without a renal anomaly. We collected blood samples from 6 family members, including 4 who were affected by the syndrome. Targeted next-generation sequencing and Sanger sequencing were performed to identify pathogenic mutations in this family. RESULTS: Pedigree analysis indicated that the mode of inheritance in the family was consistent with the autosomal dominant pattern. Hearing loss was the most common manifestation, occurring in 4 patients. Other findings included preauricular pits (n=2), cervical fistulas (n=3) and abnormal pinnae (n=4). None of the patients had renal anomalies. Evaluation by pure-tone audiometry and temporal bone imaging demonstrated bilateral mixed hearing loss, as well as middle ear and inner ear deformities, in two patients. Mutational analysis of candidate genes in the selected patients led to the identification of a novel frameshift variant NM_000503.4: c.1075_1077delinsAT (p.Gly359Ilefs*7) in the EYA1 gene. CONCLUSIONS: The EYA1 c.1075_1077delinsAT mutation is the causative variant in the Chinese family with BOS, although the penetrance is variable within patients.

The new antihypertensive drug iptakalim activates ATP-sensitive potassium channels in the endothelium of resistance blood vessels.

AIM: To investigate the mechanisms underlying the activation of ATP-sensitive potassium channels (K(ATP)) by iptakalim in cultured rat mesenteric microvascular endothelial cells (MVECs). METHODS: Whole-cell KATP currents were recorded in MVECs using automated patch clamp devices. Nucleotides (ATP, ADP and UDP) were added to the internal perfusion system, whereas other drugs were added to the cell suspension on NPC-1 borosilicate glass chips. RESULTS: Application of iptakalim (10 and 100 µmol/L) significantly increased the whole-cell K(ATP) currents, which were prevented by the specific K(ATP) blocker glibenclamide (1.0 µmol/L). The opening of K(ATP) channels by iptakalim depended upon the intracellular concentrations of ATP or NDPs: iptakalim activated K(ATP) channels when the intracellular ATP or NDPs were at 100 or 1000 µmol/L, and was ineffective when the non-hydrolysable ATP analogue ATPγS (1000 µmol/L) was infused into the cells. In contrast, the K(ATP) opener pinacidil activated K(ATP) channels when the intracellular concentrations of ATP or NDPs ranged from 10 to 5000 µmol/L, and even ATPγS (1000 µmol/L) was infused into the cells. CONCLUSION: Iptakalim activates K(ATP) channels in the endothelial cells of resistance blood vessels with a low metabolic status, and this activation is dependent on both ATP hydrolysis and ATP ligands.

Comparison of complications of the suprameatal approach and mastoidectomy with posterior tympanotomy approach in cochlear implantation: a meta-analysis.

BACKGROUND: Cochlear implantation (CI) is a popular procedure to preserve hearing in patients with severe-to-profound hearing loss. Evidence shows that the suprameatal approach (SMA) may help reducing the risk of the incidence of complications and shortening the surgery time, but there is still dispute. OBJECTIVES: The aim of this study was to compare the incidence of complications of SMA and the mastoidectomy with posterior tympanotomy approach (MPTA), and to find whether SMA yields better outcomes than MPTA. METHODS: We searched PubMed, the Cochrane Library, the Web of Science and Chinese Biomedical Literature databases, Chinese National Knowledge Infrastructure, the Chinese Science and Technology Journal Full-Text database, and Wangfang database. The latest data was accessed in March 2013. Review Manager 5.1 software was used for comprehensive quantification data analysis. RESULTS: Three studies were included in the meta-analysis, composed of 799 participants and reporting major and minor complications. The meta-analysis indicated no statistically significant difference in major and minor complications between the two approaches, except for facial nerve and chorda tympani injuries (OR = 0.13; 95% CI: 0.02, 0.67; p = 0.02; I(2) = 0%). CONCLUSIONS: Current evidence suggests that SMA may be clearly a good alternative to the classical surgery technique for CI in terms of reducing the incidence of facial nerve injury and chorda tympani sacrifice.

[Study on display of acupuncture meridian based on electric signal transfer characteristics].

OBJECTIVE: To analyze the real-time effects of electroacupuncture (EA) stimulation by means of multiport network theory and measurement of the electric signals transfer coefficient, so as to explore a way for determining the running course of acupuncture meridian and for characterizing its physiological activities in the living body. METHODS: The body was modeled as a complex inhomogeneous 3-dimensions multi-port network, and the meridians were assumed to be "the most smoothly channels for signal transmission". Experiments were performed in 12 beheaded toads whose forelimbs and hindlimbs were divided into proportional coordinates. A concentric electrode with a conical tip was inserted into the toad leg for electrical stimulation of the local muscle, and another electrode alike was inserted into different spots of the limbs to detect the spreading signals in a 3-dimensional scanning mode. Following detecting the response electric voltage values of various spots and calculating their transfer coefficients, the spots which acquired a maximum signal value were considered to be the "acupoints". The imaginary connective lines passing the "acupoints" were regarded as the running courses of acupuncture meridians. RESULTS: A total of twelve 3-dimensional curves were detected based on the connected lines of electric signal transfer function extremum spots 2 mm beneath the skin of the ipsilateral fore- and hind-limbs of 12 spinal toads. CONCLUSION: The present study initially validates the feasibility of electric signal transfer coefficient measurement for displaying the running course of acupuncture meridian in the toad fore- and hindlimbs.

Analysis of quality of clinical practice guidelines for otorhinolaryngology in China.

OBJECTIVE: To evaluate the quality of clinical practice guidelines (CPGs) for otorhinolaryngology in China. MATERIALS AND METHODS: A systematic search of relevant literature databases (CBM, WANFANG, VIP, CNKI, China Guideline Clearinghouse) published between 1978 and March 2012 was undertaken to identify and select CPGs related to otorhinolaryngology. Four independent reviewers assessed the eligible guidelines using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. Their degree of agreement was evaluated using the intraclass correlation coefficient (ICC). RESULT: From 170 citations, 21 relevant guidelines were included. The overall agreement among reviewers was moderate (ICC = 0.87; 95% confidence interval [CI], 0.78-0.91). The scores for each of the AGREE domains were the following: "scope and purpose" (mean ± standard error [SE] = 45.4±4.4; ICC = 0.92), "stakeholder involvement" (mean ± SE = 30.4±3.1; ICC = 0.81), "rigor of development" (mean ± SE = 20.9±2.8; ICC = 0.87), "clarity of presentation" (mean ± SE = 48.8±3.7; ICC = 0.80), "applicability" (mean ± SE = 12.6±1.7; ICC = 0.72), and "editorial independence" (mean ± SE = 6.2±0.8; ICC = 0.76). Three guidelines (14%) mentioned updates, and the average update frequency was 7 years. None used the GRADE system. CONCLUSION: The quality of otorhinolaryngology guidelines in China is low. Greater efforts are needed to provide high-quality guidelines that serve as a useful and reliable tool for clinical decision-making in this field.