High spatial-density, cladding-pumped 6-mode 7-core fiber amplifier for C-band operation.

We present a C-band 6-mode 7-core fiber amplifier in an all-fiberized cladding-pumped configuration for space division multiplexed transmission supporting a record 42 spatial channels. With optimized fiber components (e.g. passively cooled pump laser diode, pump coupler, pump stripper), high power multimode pump light is coupled to the active fiber without any noticeable thermal degradation and an average gain of 18 dB and noise figure of 5.4 dB are obtained with an average differential modal gain of 3.4 dB.

Stent as a bridge to surgery or immediate colectomy for malignant right colonic obstruction: propensity-scored, national database study.

BACKGROUND: The aim of this study was to compare perioperative outcomes of urgent colectomy and placement of a self-expanding metallic stent followed by colectomy for patients with malignant right colonic obstruction. Right-sided malignant obstruction is less common than left-sided. Stenting for malignant left colonic obstruction has been reported to reduce postoperative complications. However, the impact of stenting for malignant right colonic obstruction remains undefined. METHODS: The study included patients with right-sided malignant obstruction or stenosis undergoing colectomy between April 2012 and March 2017 identified from a nationwide database. Propensity score matching analysis was used to compare mortality and morbidity rates, proportion receiving a stoma and postoperative stay between urgent colectomy and stent groups. RESULTS: From 9572 patients, 1500 pairs were generated by propensity score matching. There was no significant difference in in-hospital mortality between the urgent colostomy and stent groups (1·6 versus 0·9 per cent respectively; P = 0·069). Complications were more common after urgent colectomy than stenting (22·1 versus 19·1 per cent; P = 0·042). Surgical-site infection was more likely with urgent colectomy (7·1 versus 4·4 per cent; P = 0·001). There was no significant difference between the two groups in anastomotic leakage (3·8 versus 2·6 per cent; P = 0·062). The proportion of patients needing a stoma was higher with urgent colectomy than primary treatment with stents (5·1 versus 1·7 per cent; P < 0·001). Postoperative stay was longer after urgent colectomy (15 versus 13 days; P < 0·001). CONCLUSION: Stenting followed by colectomy in patients with malignant right colonic obstruction may provide more favourable perioperative outcomes than urgent colectomy.

ANTECEDENTES: El objetivo de este estudio fue comparar los resultados perioperatorios entre la colectomía urgente y la colocación de una endoprótesis (stent) metálica autoexpandible seguida de colectomía en pacientes con obstrucción maligna del colon derecho. La obstrucción maligna del colon derecho es menos frecuente que la del colon izquierdo. Se ha demostrado que la colocación de una endoprótesis en la obstrucción maligna del colon izquierdo reduce las complicaciones postoperatorias. Sin embargo, el impacto de la colocación de una endoprótesis en la obstrucción maligna del colon derecho no está definido. MÉTODOS: Los pacientes con obstrucción o estenosis maligna del colon derecho sometidos a colectomía desde abril de 2012 hasta marzo de 2017 se analizaron a partir de una base de datos nacional. Se realizó un análisis mediante emparejamiento por puntaje de propensión para comparar la mortalidad, la morbilidad, el porcentaje de pacientes en los que se realizó un estoma y la estancia postoperatoria entre los grupos de colectomía urgente y endoprótesis. RESULTADOS: A partir de 9.572 pacientes, se generaron 1.500 parejas mediante emparejamiento por puntaje de propensión. No hubo diferencias significativas en la mortalidad hospitalaria entre los dos grupos (1,6% versus 0,9%, P = 0,07). Las complicaciones fueron más frecuentes después de la colectomía urgente en comparación con las endoprótesis (22,1% versus 19,1%, P = 0,04). La infección del sitio quirúrgico ocurrió con mayor frecuencia en el grupo de la colectomía urgente en comparación con el grupo de endoprótesis (7,1% versus 4,4%, P = 0,001). No se observaron diferencias significativas en la fuga anastomótica entre los dos grupos (3,8% versus 2,6%, P = 0,06). La proporción de pacientes que precisaron estomas fue mayor con la colectomía urgente en comparación con aquellos tratados inicialmente con endoprótesis (5,1% versus 1,7%, P < 0,001). La estancia postoperatoria fue más larga después de la colectomía urgente que tras la colocación de una endoprótesis (15 días versus 13 días, P < 0,001) CONCLUSIÓN: En pacientes con obstrucción maligna del colon derecho, la colocación de una endoprótesis seguida de colectomía puede proporcionar resultados perioperatorios más favorables en comparación con la colectomía urgente.

Establishment process of a magic trait allele subject to both divergent selection and assortative mating.

Sexual selection and divergent selection are among the major driving forces of reproductive isolation, which could eventually result in speciation. A magic trait is defined such that a single trait is subject to both divergent selection and mate choice through phenotype-based assortative mating. We are here interested in the evolutionary behavior of alleles at a genetic locus responsible for a magic trait in a finite population. We assume that, in a pair of homogeneous subpopulations, a mutant allele arises at the magic trait locus, and theoretically obtain the probability that the new allele establishes in the population, or the establishment probability. We also show an analytical expression for the trajectory of allele frequency along the establishment, from which the time required for the establishment is obtained, or the establishment time. Under this model, divergent selection simply favors the new allele to fix where it is beneficial, whereas assortative mating works against rare alleles. It is theoretically demonstrated that the fate of the new allele is determined by the relative contributions of the two selective forces, divergent selection and assortative mating, when the allele is rare so that the two selective forces counteract. Our theoretical results for the establishment probability and time allow us to understand the relative role of random genetic drift in the establishment process of a magic trait allele in a finite population.

Clarifying differences in injury patterns between ground-level falls and falls from heights among the elderly in Japan.

OBJECTIVES: With the progress of aging, fall injuries have become a global public health issue. This research was conducted to describe in detail situations of injury occurrence among the elderly by distinguishing between falls from heights and ground-level falls. We assume that different fall mechanisms occur in different situations and result in a wide range of consequences. STUDY DESIGN: This is a registry-based descriptive study. METHODS: The analysis included 55,126 patients with fall injuries, aged 65 years and more, having an Injury Severity Score (ISS) ≧9, and registered in a trauma registry in Japan between 2004 and 2015. We described patients' distribution in terms of age, severity, outcome, season, time, and injured body parts by gender and fall mechanisms. RESULTS: Falls from heights (n = 15,748) were more common among men and those younger than 75 years. Ground-level falls (n = 39,378) were more common among women and those older than 75 years. The ISS was high in men and for those who fell from heights. Falls from heights were common in autumn, whereas ground-level falls were common in winter. Both mechanisms occurred frequently during the daytime. The head and lower extremities were the most commonly injured parts for those who fell from heights and ground-level falls, respectively. Injuries to the head, chest, spine, upper extremities, and pelvis were common among those who fell from heights. Injuries to the lower extremities were common in ground-level fallers. Among those who fell from heights, women had more frequent lower extremity injuries than did men. Among ground-level fallers, men had more frequent head injuries than did women. The highest case-fatality rate was recorded for abdominal injuries among those who fell from heights and head injuries among ground-level fallers. In both mechanisms of injury, the case-fatality rate of limbs was the lowest. CONCLUSIONS: Our study showed different patterns between falls from heights and ground-level falls, whereas previous studies rarely distinguished between these two fall mechanisms.

Si-based Mach-Zehnder wavelength/mode multi/demultiplexer for a WDM/MDM transmission system.

We propose and experimentally demonstrate a low-loss and low-crosstalk Mach-Zehnder mode/wavelength multi/demultiplexer for WDM/MDM transmission based on a Si-photonics platform. A broadband 3-dB mode divider, which is also newly devised here, makes it possible to compose a Mach-Zehnder filter for "mode" and "wavelength" simultaneously. Transmission characteristics of fabricated 3-dB mode dividers are in excellent agreement with theoretical results. Mach-Zehnder filters using the 3-dB mode divider with a free spectral range (FSR) of 20 and 1 nm are also fabricated and the modal crosstalk is less than -24 dB in the 40-nm wavelength range for the MZ filter with an FSR of 20 nm. The tuning of the peak wavelength position by the TiN heater is also demonstrated.

A sexually dimorphic peptidergic system in the lower spinal cord controlling penile function in non-human primates.

STUDY DESIGN: Experimental animal study. OBJECTIVES: Although a population of gastrin-releasing peptide (GRP) neurons in the lumbar spinal cord has an important role in erection and ejaculation in rats, little information exists on this GRP system in primates. To identify the male-specific GRP system in the primate spinal cord, we studied the lumbosacral cord in macaque monkeys as a non-human primate model. SETTING: University laboratory in Japan. METHODS: To determine the gene sequence of GRP precursors, the rhesus macaque monkey genomic sequence data were searched, followed by phylogenetic analysis. Subsequently, immunocytochemical analysis for GRP was performed in the monkey spinal cord. RESULTS: We have used bioinformatics to identify the ortholog gene for GRP precursor in macaque monkeys. Phylogenetic analysis suggested that primate prepro-GRP is separated from that of other mammalian species and clustered to an independent branch as primates. Immunocytochemistry for GRP further demonstrated that male-dominant sexual dimorphism was found in the spinal GRP system in monkeys as in rodents. CONCLUSION: We have demonstrated in macaque monkeys that the GRP system in the lower spinal cord shows male-specific dimorphism and may have an important role in penile functions not only in rodents but also in primates. SPONSORSHIP: Tissues of Nihonzaru (Japanese macaque monkeys) were provided in part by National Institutes of Natural Sciences (NINS) through the National Bio-Resource Project (NBRP) of the MEXT, Japan. This work was supported in part by KAKENHI from the Japan Society for the Promotion of Science (JSPS) (to KT; 15KK0343, 15J40220 and HS; 15K15202, 15KK0257, 15H05724).

Relativistic jet activity from the tidal disruption of a star by a massive black hole.

Supermassive black holes have powerful gravitational fields with strong gradients that can destroy stars that get too close, producing a bright flare in ultraviolet and X-ray spectral regions from stellar debris that forms an accretion disk around the black hole. The aftermath of this process may have been seen several times over the past two decades in the form of sparsely sampled, slowly fading emission from distant galaxies, but the onset of the stellar disruption event has not hitherto been observed. Here we report observations of a bright X-ray flare from the extragalactic transient Swift J164449.3+573451. This source increased in brightness in the X-ray band by a factor of at least 10,000 since 1990 and by a factor of at least 100 since early 2010. We conclude that we have captured the onset of relativistic jet activity from a supermassive black hole. A companion paper comes to similar conclusions on the basis of radio observations. This event is probably due to the tidal disruption of a star falling into a supermassive black hole, but the detailed behaviour differs from current theoretical models of such events.

Susceptibility of isogeneic ginbuna Carassius auratus langsdorfii Temminck et Schlegel to cyprinid herpesvirus-2 (CyHV-2) as a model species.

Herpesviral haematopoietic necrosis (HVHN), caused by cyprinid herpesvirus-2 (CyHV-2), has affected the commercial production of the goldfish Carassius auratus and gibelio carp Carassius auratus gibelio. High water temperature treatments are reported to reduce the mortality rate of infected goldfish and elicit immunity in the survivors. To define the mechanism by which this intervention induces resistance, clonal ginbuna Carassius auratus langsdorfii, which is closely related to both species and has been used in fish immunology, may represent a promising model species. In this study, we investigated the susceptibility of clonal ginbuna strains to CyHV-2 and the effect of high water temperature treatment on infected ginbuna and goldfish. Experimental intraperitoneal infection with CyHV-2 at 25 °C caused 100% mortality in ginbuna strains, which was accompanied by histopathological changes typical of HVHN. Both infected ginbuna S3n strain and goldfish, exposed to high temperature for 6 days [shifting from 25 °C (permissive) to 34 °C (non-permissive)], showed reduced mortalities after the 1st inoculation, and subsequent 2nd virus challenge to 0%, indicating induction of immunity. It was concluded that ginbuna showed a similar susceptibility and disease development in CyHV-2 infection compared to goldfish, suggesting that ginbuna can be a useful fish model for the study of CyHV-2 infection and immunity.

Post-operative swallowing in multiple system atrophy.

BACKGROUND: Some patients with multiple system atrophy (MSA) require surgical interventions such as tracheostomy and aspiration prevention. Few studies have investigated the postoperative clinical course of MSA patients. The aim of this study was to determine a management strategy for dysphagia and respiratory disorder in MSA. METHODS: From 2001 to 2014, 18 MSA patients (13 males and 5 females, 52-76 years) underwent tracheostomy (TR, n = 11) or laryngeal closure (LC, n = 12). Five patients underwent LC following TR. Vocal fold impairment, the degree of dysphagia and pre/post-operative oral ingestion, and postoperative survival time were evaluated retrospectively. Swallowing function was assessed using the penetration aspiration scale (PAS). RESULTS: TR was performed due to respiratory disorder in seven patients and due to dysphagia in four patients. PAS scores ranged 1-8 in TR patients and 7-8 in LC patients. Seven of 11 patients who underwent TR displayed worsened PAS scores, and no patients displayed improved PAS scores following TR. All patients who underwent LC regained complete or partial oral intake after surgery. There were no significant differences in postoperative survival time between the two groups. CONCLUSIONS: Considering the impacts of TR and LC on survival time, postoperative feeding and swallowing, LC is a good option for treating MSA patients with dysphagia.

Time trend analyses of child pedestrian morbidity in Japan.

OBJECTIVES: Road traffic injuries, particularly pedestrian injuries, are a major health issue among children worldwide. The present study quantitatively analyzed the time trends of child pedestrian injuries in Japan from 1975 to 2013 by age. STUDY DESIGN: Time trend analysis of nationally aggregated data. METHODS: We analyzed police data on pedestrian injuries requiring medical treatment among children aged 0-15 years occurring between 1975 and 2013. To quantify the time trends of pedestrian injury morbidity rates and to identify change-points in the trends, joinpoint regression analysis was applied by age group. Children were categorized into the age groups of 0-3, 4-6, 7-9, 10-12, and 13-15 years old. RESULTS: Preschool children aged 0-6 years old showed continuous declining trends throughout the study period; these declining trends accelerated in the 2000s. School-age children aged 7-15 years old showed minimal changes from the early 1970s to the 1990s; of this age group, children aged 7-12 years old showed slight but significant declining trends in the first half and increasing trends in the latter half of this period. Children aged 7-15 years old showed declining trends in the 2000s. Despite the consistent declining trends among all age groups in the 2000s, the younger age groups showed steeper declines during this period. CONCLUSIONS: The declining trends in all age groups in the 2000s may reflect the improved traffic environments in Japan although the environmental approaches are not yet sufficiently adopted yielding modest effects. The continuing contrast between preschool and school-age children may reflect different behaviour changes by age such as more restricted outdoor activities among young children.

Comparison of Volumetric and Diametric Analysis in Endovascular Repair of Descending Thoracic Aortic Aneurysm.

OBJECTIVES: The aim was to evaluate computed tomography angiography (CTA) volumetric and diametric analysis after endovascular repair of descending thoracic aortic aneurysms (DTAAs) and its correlation with and applicability for clinical follow up. METHODS: Fifty-four consecutive endovascular repairs for DTAA were retrospectively evaluated from 2008 to 2014. All patients underwent pre-operative CTA and at least one post-operative CTA at 6 months. Fifty-four pre-operative and 137 post-operative CTAs were evaluated (using the Ziosoft 2 software) to analyze the aneurysm and thrombus volume, the maximum aneurysm diameter, and their changes at the last follow up CTA (mean 30.5 months; range 6.5-66.4 months). A statistical analysis was performed to assess the correlation between diameter and volume changes, as well as association with endoleaks. The cut off point to predict endoleaks was determined using a receiver operating characteristic (ROC) curve. The predictive accuracy of volume change versus diameter change for Type I endoleak was analyzed. RESULTS: The mean pre-operative aneurysm diameter, aneurysm volume, and thrombus volume were 56.7 ± 11.7 mm, 145.8 ± 120.0 mL, and 48.8 ± 54.8 mL, respectively. Within the observational period, a mean decrease of -27.9 ± 30.5% in the aortic volume and -15.9 ± 15.4% in diameter was observed. Correlation between aneurysm diameter and volume changes was good (r = 0.854). Volume and diameter changes were significantly different between groups with and without endoleaks (volume change 16.9 ± 38.8% vs. -35.6 ± 23.1%, p < .001; diameter change 8.0 ± 12.1% vs. -18.8 ± 14.3%, p < .001). A pre-operative thrombus volume percentage of <11.3% and increase in aneurysm volume +11.6% were predictive factors for Type II and Type I endoleak, respectively. The accuracy of a >10% volume increase in predicting a Type I endoleak was higher (accuracy 96.3%, sensitivity 75%, and specificity 98%) than a >5 mm diameter increase (accuracy 92.6%, sensitivity 25%, and specificity 98%). CONCLUSIONS: CT volumetric analysis is a more reliable modality for predicting endoleaks after endovascular repair for DTAA than diameter analysis.

Isolation and characterization of novel polymorphic microsatellite loci in large yellow croaker (Larimichthys crocea).

The large yellow croaker (Larimichthys crocea) is one of the largest marine net-cage cultured species in the oceans around China. In the present study, we isolated and characterized 13 polymorphic microsatellite markers from genomic libraries of L. crocea. Loci were screened for 10 wild specimens from 2 sites in southeast of China. All loci were polymorphic. The number of alleles per locus ranged from 2 to 21. The expected heterozygosity ranged from 0.233 to 0.838 and observed heterozygosity ranged from 0.527 to 0.935. Eleven loci were highly informative (polymorphic information content >0.5). Significant deviation from Hardy-Weinberg equilibrium was observed at 3 loci after Bonferroni's correction. The microsatellite loci may be valuable tools for studying the genetic diversity and genetic structure for conservation planning of the fish.

Strategic development of a multivariate calibration model for the uniformity testing of tablets by transmission NIR analysis.

The use of transmission near infrared spectroscopy (TNIRS) is of particular interest in the pharmaceutical industry. This is because TNIRS does not require sample preparation and can analyze several tens of tablet samples in an hour. It has the capability to measure all relevant information from a tablet, while still on the production line. However, TNIRS has a narrow spectrum range and overtone vibrations often overlap. To perform content uniformity testing in tablets by TNIRS, various properties in the tableting process need to be analyzed by a multivariate prediction model, such as a Partial Least Square Regression modeling. One issue is that typical approaches require several hundred reference samples to act as the basis of the method rather than a strategically designed method. This means that many batches are needed to prepare the reference samples; this requires time and is not cost effective. Our group investigated the concentration dependence of the calibration model with a strategic design. Consequently, we developed a more effective approach to the TNIRS calibration model than the existing methodology.

Genomewide association study identifies HAS2 as a novel susceptibility gene for adult asthma in a Japanese population.

BACKGROUND: It is increasingly clear that asthma is not a single disease, but a disorder with vast heterogeneity in pathogenesis, severity, and treatment response. To date, 30 genomewide association studies (GWASs) of asthma have been performed, including by our group. However, most gene variants identified so far confer relatively small increments in risk and explain only a small proportion of familial clustering. OBJECTIVE: To identify additional genetic determinants of susceptibility to asthma using a selected Japanese population with reduced tobacco smoking exposure. METHODS: We performed a GWAS by genotyping a total of 480 098 single-nucleotide polymorphisms (SNPs) for a Japanese cohort consisting of 734 healthy controls and 240 patients with asthma who had smoked for no more than 10 pack-years. The SNP with the strongest association was genotyped in two other independent Japanese cohorts consisting of a total of 531 healthy controls and 418 patients with asthma who had smoked for no more than 10 pack-years. For the hyaluronan synthase 2 (HAS2) gene, we investigated SNP-gene associations using an expression quantitative trait loci (eQTL) database and also analysed its gene expression profiles in 13 different normal tissues. RESULTS: In the discovery GWAS, a SNP located upstream of HAS2, rs7846389, showed the strongest statistical significance (P = 1.43 × 10(-7) ). In the two independent replication cohorts, rs7846389 was consistently associated with asthma (nominal P = 0.0152 and 0.0478 in the first and second replication cohorts, respectively). In the meta-analysis, association of rs7846389 with susceptibility to asthma reached the level of genomewide significance (P = 7.92 × 10(-9) ). This variant was strongly correlated with HAS2 mRNA expression. The strongest expression of the gene was detected in the lung. CONCLUSIONS: Our study identified HAS2 as a novel candidate gene for susceptibility to adult asthma.

Highly expressed cytoplasmic FcεRIß in human mast cells functions as a negative regulator of the FcRγ-mediated cell activation signal.

BACKGROUND: We recently reported that the interaction between Lyn and FcεRIß is indispensable for FcεRI-mediated human mast cell (MC) activation and that FcεRIß functions as an amplifier of FcεRI-mediated activation signal. Some of FcεRIß in cytoplasm appeared not to be co-localized with FcεRIα. The function of FcεRIß in the cytoplasm remains unknown. METHODS: The localization of FcεRIß and FcεRIα in giant papillae specimens from patients with allergic keratoconjunctivitis and of FcεRIß, FcεRIα, and Lyn in cultured human MCs was examined using confocal microscopy. FcεRIß was overexpressed using an adenovirus vector system. Mediators were measured by enzyme immunoassays or enzyme-linked immunosorbent assays. RESULTS: In the subepithelial region, FcεRIß was mainly localized in the cell membrane of MCs. In the perivascular region, FcεRIß expression was scattered throughout the cytoplasm and in the cell membrane of MCs. Overexpression of FcεRIß in MCs mainly increased its cytoplasmic expression and slightly up-regulated cell surface FcεRI expression. However, overexpression of FcεRIß in MCs resulted in down-regulation of the tyrosine phosphorylation levels of FcεRIß and Syk and down-regulation of the Ca(2+) influx soon after FcεRI aggregation and then resulted in down-regulation of degranulation, PGD2 synthesis, and production of a set of cytokines. This negative regulatory effect may be due to inhibition of the redistribution of Lyn to small patches within the plasma membrane. CONCLUSION: Cytoplasmic FcεRIß, which is not co-localized with FcεRIα, may function as a negative regulator, as it can capture important signalling molecules such as Lyn.

The pharmacokinetics and safety profiles of belimumab after single subcutaneous and intravenous doses in healthy Japanese volunteers.

WHAT IS KNOWN AND OBJECTIVES: Belimumab is a recombinant human monoclonal antibody that binds and antagonizes the biological activity of soluble B-lymphocyte stimulator (BLyS) protein. BLyS appears to play a role in the pathogenesis of systemic lupus erythematosus, and the biological profile of belimumab suggests that it may have a therapeutic benefit in the treatment for the disease. In this healthy Japanese subjects study, we investigated the pharmacokinetics and safety of a single subcutaneous and intravenous injection of belimumab administered as a 200 mg/mL liquid formulation. METHODS: This was an open-label, randomized, parallel-group, single-dose study in healthy Japanese subjects. Each subject received a single intravenous infusion or a subcutaneous injection of 200 mg belimumab. The pharmacokinetic parameters and safety parameters including local tolerance (injection site), biomarkers, immunogenicity and adverse events were evaluated up to 70 days post-dosing. RESULTS: After a single intravenous or a subcutaneous administration of 200 mg belimumab, all 16 subjects completed the study. There were no serious adverse events or adverse events related to injection site reactions. All seven adverse events were considered mild or moderate in intensity and deemed unrelated to belimumab except for cellulitis following intravenous administration. The bioavailability of the single subcutaneous dose of 200 mg belimumab in the subjects was estimated to be 77·5%. Time to the maximum serum concentration after subcutaneous injection was 6·5 days (median). The geometric mean terminal half-life was comparable between the two administration routes (17·7 days intravenous and 15·9 days subcutaneous). Serum immunoglobulin G level decreased slightly after each treatment. No subjects were found to produce antibelimumab antibodies. WHAT IS NEW AND CONCLUSIONS: A favourable absolute bioavailability in healthy Japanese subjects was seen following a subcutaneous injection of 200 mg belimumab. Considering the intersubject variability, exposures were consistent with those previously observed in healthy non-Japanese subjects. Safety and biomarker data were also consistent with previous non-Japanese clinical studies.

Mechanism of the dependence of hepatitis B virus genotype G on co-infection with other genotypes for viral replication.

Hepatitis B virus (HBV) is classified into several genotypes. Genotype G (HBV/G) is characterised by worldwide dispersion, low intragenotypic diversity and a peculiar sequence of the precore and core region (stop codon and 36-nucleotide insertion). As a rule, HBV/G is detected in co-infection with another genotype, most frequently HBV/A2. In a previous in vivo study, viral replication of HBV/G was significantly enhanced by co-infection with HBV/A2. However, the mechanism by which co-infection with HBV/A2 enhances HBV/G replication is not fully understood. In this study, we employed 1.24-fold HBV/A2 clones that selectively expressed each viral protein and revealed that the core protein expressing construct significantly enhanced the replication of HBV/G in Huh7 cells. The introduction of the HBV/A2 core promoter or core protein or both genomic regions into the HBV/G genome showed that both the core promoter and core protein are required for efficient HBV/G replication. The effect of genotype on the interaction between foreign core protein and HBV/G showed that HBV/A2 was the strongest enhancer of HBV/G replication. Furthermore, Western blot analysis of Dane particles isolated from cultures of Huh7 cells co-transfected by HBV/G and a cytomegalovirus (CMV) promoter-driven HBV/A2 core protein expression construct indicated that HBV/G employed HBV/A2 core protein during particle assembly. In conclusion, HBV/G could take advantage of core proteins from other genotypes during co-infection to replicate efficiently and to effectively package HBV DNA into virions.

Clinicopathological features of colorectal polyps: evaluation of the 'predict, resect and discard' strategies.

AIM: 'Predict, resect and discard' strategies for diminutive and small colonic polyps are considered to be cost effective for treating colorectal cancers. The aim of this study was to determine, retrospectively, the histological features of colonic polyps resected by endoscopic procedures or surgery using an updated database. METHOD: We retrospectively analysed the clinicopathological features of colorectal polyps, less than 20 mm in size, which were removed by endoscopy from January 2009 to November 2011 at the National Cancer Center Hospital (NCCH) in Tokyo, Japan. RESULTS: Less than 1% of diminutive polyps (≤ 5 mm) were classified as mucosal high-grade neoplasia (Category 4), and no submucosal invasion by carcinoma (Category 5) lesions were noted. However, 3% of small polyps (6-9 mm) were classified as Category 5; of these, 6% were submucosal deep invasive cancers. Morphologically, depressed components were observed more frequently in carcinomas than in adenomas in both small and large polyps (10-20 mm). CONCLUSION: In light of the 'predict, resect and discard' strategies for small polyps, we should pay attention to the possible clinical malignancy of small and large polyps. We recommend that these strategies should be applied selectively and that they should be informed by accurate endoscopic evaluations.

Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM), the most common cause of sudden death in the young, is an autosomal dominant disease characterized by ventricular hypertrophy accompanied by myofibrillar disarrays. Linkage studies and candidate-gene approaches have demonstrated that about half of the patients have mutations in one of six disease genes: cardiac beta-myosin heavy chain (c beta MHC), cardiac troponin T (cTnT), alpha-tropomyosin (alpha TM), cardiac myosin binding protein C (cMBPC), ventricular myosin essential light chain (vMLC1) and ventricular myosin regulatory light chain (vMLC2) genes. Other disease genes remain unknown. Because all the known disease genes encode major contractile elements in cardiac muscle, we have systematically characterized the cardiac sarcomere genes, including cardiac troponin I (cTnI), cardiac actin (cACT) and cardiac troponin C (cTnC) in 184 unrelated patients with HCM and found mutations in the cTnI gene in several patients. Family studies showed that an Arg145Gly mutation was linked to HCM and a Lys206Gln mutation had occurred de novo, thus strongly suggesting that cTnI is the seventh HCM gene.

Prediction of nodal metastasis based on intraoral sonographic findings of the primary lesion in early-stage tongue cancer.

The aim of this study was to clarify the correlation between imaging findings obtained using intraoral ultrasonography (US) and pathological findings of tongue cancers, and to examine the predictive value of intraoral US findings with respect to occult nodal metastasis. This was a retrospective study based on the medical records of 123 patients with T1-2N0 tongue cancer. The depth of invasion (DOI) on intraoral US was positively correlated with the pathological invasion depth (PID) (ρ = 0.7080, P < 0.0001). Receiver operating characteristic analyses revealed an optimal DOI cut-off value of 4.1 mm and optimal PID cut-off value of 3.9 mm to detect nodal metastasis. Regarding the margin shape of the primary tumour on intraoral US, the incidence of nodal metastasis was significantly higher for the permeated type than for the pressure type (P < 0.001) and wedge-shaped type (P = 0.002). Furthermore, tumours with peritumoural vascularity assessed by power Doppler US had a significantly higher incidence of nodal metastasis than tumours without (P = 0.003). The sensitivity, specificity, and accuracy of the permeated type to predict nodal metastasis was 53.6%, 95.8%, and 86.2%, respectively. These results suggest that intraoral US findings closely reflect pathological findings and could be useful to predict occult nodal metastasis in patients with early-stage tongue cancer.