Marked intestinal trans-differentiation by autoimmune gastritis along with ectopic pancreatic and pulmonary trans-differentiation.

BACKGROUND: Autoimmune gastritis (AIG) is a prevalent chronic inflammatory disease with oncogenic potential that causes destruction of parietal cells and severe mucosal atrophy. We aimed to explore the distinctive gene expression profiles, activated signaling pathways, and their underlying mechanisms. METHODS: A comprehensive gene expression analysis was conducted using biopsy specimens from AIG, Helicobacter pylori-associated gastritis (HPG), and non-inflammatory normal stomachs. Gastric cancer cell lines were cultured under acidic (pH 6.5) conditions to evaluate changes in gene expression. RESULTS: Gastric mucosa with AIG had a unique gene expression profile compared with that with HPG and normal mucosa, such as extensively low expression of ATP4A and high expression of GAST and PAPPA2, which are involved in neuroendocrine tumorigenesis. Additionally, the mucosa with AIG and HPG showed the downregulation of stomach-specific genes and upregulation of small intestine-specific genes; however, intestinal trans-differentiation was much more prominent in AIG samples, likely in a CDX-dependent manner. Furthermore, AIG induced ectopic expression of pancreatic digestion-related genes, PNLIP, CEL, CTRB1, and CTRC; and a master regulator gene of the lung, NKX2-1/TTF1 with alveolar fluid secretion-related genes, SFTPB and SFTPC. Mechanistically, acidic conditions led to the downregulation of master regulator and stemness control genes of small intestine, suggesting that increased environmental pH may cause abnormal intestinal differentiation in the stomach. CONCLUSIONS: AIG induces diverse trans-differentiation in the gastric mucosa, characterized by the transactivation of genes specific to the small intestine, pancreas, and lung. Increased environmental pH owing to AIG may cause abnormal differentiation of the gastric mucosa.

A searchable image resource of Drosophila GAL4 driver expression patterns with single neuron resolution.

Precise, repeatable genetic access to specific neurons via GAL4/UAS and related methods is a key advantage of Drosophila neuroscience. Neuronal targeting is typically documented using light microscopy of full GAL4 expression patterns, which generally lack the single-cell resolution required for reliable cell type identification. Here, we use stochastic GAL4 labeling with the MultiColor FlpOut approach to generate cellular resolution confocal images at large scale. We are releasing aligned images of 74,000 such adult central nervous systems. An anticipated use of this resource is to bridge the gap between neurons identified by electron or light microscopy. Identifying individual neurons that make up each GAL4 expression pattern improves the prediction of split-GAL4 combinations targeting particular neurons. To this end, we have made the images searchable on the NeuronBridge website. We demonstrate the potential of NeuronBridge to rapidly and effectively identify neuron matches based on morphology across imaging modalities and datasets.

Autoimmune gastritis induces aberrant DNA methylation reflecting its carcinogenic potential.

BACKGROUND: Autoimmune gastritis (AIG) is a chronic inflammatory condition in gastric mucosa and is associated with increased cancer risk, though not as high as that by Helicobacter pylori (H. pylori)-associated gastritis (HPG). Although aberrant DNA methylation is induced by HPG and the level correlates with the risk of gastric cancer, DNA methylation induction by AIG is unknown. METHODS: Gastric mucosa samples from the corpus were collected from 12 people with AIG without H. pylori infection, 10 people with HPG, and eight healthy volunteers. Genome-wide DNA methylation analysis was conducted using Infinium Methylation EPIC array. Gene expression was analyzed by quantitative RT-PCR. RESULTS: The AIG samples had extensive aberrant DNA methylation but presented unique methylation profiles against the HPG samples after correction of leucocyte fractions. Comparison between the AIG and HPG samples showed that AIG induced methylation, but less than HPG, in overall CpG sites and also in promoter CpG islands. Promoter CpG islands of tumor-suppressor genes in the pathway of cell cycle, cell adhesion, p53, and WNT were highly methylated in the AIG samples, but more so in the HPG samples. The expression levels of IL1B and IL8, secreted by macrophage, were significantly lower in the AIG samples than in the HPG samples, suggesting that a difference in inflammatory response affected the degree and patterns of aberrant DNA methylation. CONCLUSIONS: AIG induced aberrant DNA methylation in gastric mucosa. However, the degree of DNA methylation was less than that by HPG, which reflected carcinogenic risk.

An unbiased template of the Drosophila brain and ventral nerve cord.

The fruit fly Drosophila melanogaster is an important model organism for neuroscience with a wide array of genetic tools that enable the mapping of individual neurons and neural subtypes. Brain templates are essential for comparative biological studies because they enable analyzing many individuals in a common reference space. Several central brain templates exist for Drosophila, but every one is either biased, uses sub-optimal tissue preparation, is imaged at low resolution, or does not account for artifacts. No publicly available Drosophila ventral nerve cord template currently exists. In this work, we created high-resolution templates of the Drosophila brain and ventral nerve cord using the best-available technologies for imaging, artifact correction, stitching, and template construction using groupwise registration. We evaluated our central brain template against the four most competitive, publicly available brain templates and demonstrate that ours enables more accurate registration with fewer local deformations in shorter time.

Cell types and neuronal circuitry underlying female aggression in Drosophila.

Aggressive social interactions are used to compete for limited resources and are regulated by complex sensory cues and the organism's internal state. While both sexes exhibit aggression, its neuronal underpinnings are understudied in females. Here, we identify a population of sexually dimorphic aIPg neurons in the adult Drosophila melanogaster central brain whose optogenetic activation increased, and genetic inactivation reduced, female aggression. Analysis of GAL4 lines identified in an unbiased screen for increased female chasing behavior revealed the involvement of another sexually dimorphic neuron, pC1d, and implicated aIPg and pC1d neurons as core nodes regulating female aggression. Connectomic analysis demonstrated that aIPg neurons and pC1d are interconnected and suggest that aIPg neurons may exert part of their effect by gating the flow of visual information to descending neurons. Our work reveals important regulatory components of the neuronal circuitry that underlies female aggressive social interactions and provides tools for their manipulation.

A connectome and analysis of the adult Drosophila central brain.

The neural circuits responsible for animal behavior remain largely unknown. We summarize new methods and present the circuitry of a large fraction of the brain of the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses in, and proofread such large data sets. We define cell types, refine computational compartments, and provide an exhaustive atlas of cell examples and types, many of them novel. We provide detailed circuits consisting of neurons and their chemical synapses for most of the central brain. We make the data public and simplify access, reducing the effort needed to answer circuit questions, and provide procedures linking the neurons defined by our analysis with genetic reagents. Biologically, we examine distributions of connection strengths, neural motifs on different scales, electrical consequences of compartmentalization, and evidence that maximizing packing density is an important criterion in the evolution of the fly's brain.

Animal brains of all sizes, from the smallest to the largest, work in broadly similar ways. Studying the brain of any one animal in depth can thus reveal the general principles behind the workings of all brains. The fruit fly Drosophila is a popular choice for such research. With about 100,000 neurons ­ compared to some 86 billion in humans ­ the fly brain is small enough to study at the level of individual cells. But it nevertheless supports a range of complex behaviors, including navigation, courtship and learning. Thanks to decades of research, scientists now have a good understanding of which parts of the fruit fly brain support particular behaviors. But exactly how they do this is often unclear. This is because previous studies showing the connections between cells only covered small areas of the brain. This is like trying to understand a novel when all you can see is a few isolated paragraphs. To solve this problem, Scheffer, Xu, Januszewski, Lu, Takemura, Hayworth, Huang, Shinomiya et al. prepared the first complete map of the entire central region of the fruit fly brain. The central brain consists of approximately 25,000 neurons and around 20 million connections. To prepare the map ­ or connectome ­ the brain was cut into very thin 8nm slices and photographed with an electron microscope. A three-dimensional map of the neurons and connections in the brain was then reconstructed from these images using machine learning algorithms. Finally, Scheffer et al. used the new connectome to obtain further insights into the circuits that support specific fruit fly behaviors. The central brain connectome is freely available online for anyone to access. When used in combination with existing methods, the map will make it easier to understand how the fly brain works, and how and why it can fail to work correctly. Many of these findings will likely apply to larger brains, including our own. In the long run, studying the fly connectome may therefore lead to a better understanding of the human brain and its disorders. Performing a similar analysis on the brain of a small mammal, by scaling up the methods here, will be a likely next step along this path.

Input Connectivity Reveals Additional Heterogeneity of Dopaminergic Reinforcement in Drosophila.

Different types of Drosophila dopaminergic neurons (DANs) reinforce memories of unique valence and provide state-dependent motivational control [1]. Prior studies suggest that the compartment architecture of the mushroom body (MB) is the relevant resolution for distinct DAN functions [2, 3]. Here we used a recent electron microscope volume of the fly brain [4] to reconstruct the fine anatomy of individual DANs within three MB compartments. We find the 20 DANs of the γ5 compartment, at least some of which provide reward teaching signals, can be clustered into 5 anatomical subtypes that innervate different regions within γ5. Reconstructing 821 upstream neurons reveals input selectivity, supporting the functional relevance of DAN sub-classification. Only one PAM-γ5 DAN subtype γ5(fb) receives direct recurrent feedback from γ5ß'2a mushroom body output neurons (MBONs) and behavioral experiments distinguish a role for these DANs in memory revaluation from those reinforcing sugar memory. Other DAN subtypes receive major, and potentially reinforcing, inputs from putative gustatory interneurons or lateral horn neurons, which can also relay indirect feedback from MBONs. We similarly reconstructed the single aversively reinforcing PPL1-γ1pedc DAN. The γ1pedc DAN inputs mostly differ from those of γ5 DANs and they cluster onto distinct dendritic branches, presumably separating its established roles in aversive reinforcement and appetitive motivation [5, 6]. Tracing also identified neurons that provide broad input to γ5, ß'2a, and γ1pedc DANs, suggesting that distributed DAN populations can be coordinately regulated. These connectomic and behavioral analyses therefore reveal further complexity of dopaminergic reinforcement circuits between and within MB compartments.

Prevalence of reflux esophagitis in obese Japanese undergoing bariatric surgery.

BACKGROUND: Currently, the data on the relationship between obesity and gastroesophageal reflux disease (GERD) in Asian populations are scarce. METHODS: The aim of this study is to investigate the prevalence of reflux esophagitis (RE) among obese Japanese patients in each body mass index (BMI) range group. In addition, we aim to investigate the risk factors for RE in obese Japanese patients. The present retrospective cohort study included 674 obese Japanese patients who underwent bariatric surgery between January 2003 and April 2016. The patients were stratified into five groups based on BMI range. RESULTS: The mean BMI was 42.7 ± 9.24 kg/m2. The prevalence of RE among each of the groups was as follows: Group 1 (BMI 30-34.9) = 20.7%; Group 2 (BMI 35-39.9) = 24.0%; Group 3 (BMI 40-44.9) = 25.2%; Group 4 (BMI 45-49.9) = 26.7%; and Group 5 (BMI ≥50) = 24.8%. Overall, the prevalence of RE was 24.2% in our study. Furthermore, no significant difference in BMI was noted between the RE and non-RE groups (43.4 ± 9.3 kg/m2 and 42.5 ± 10.2 kg/m2, respectively; p = 0.24). According to the multivariate logistic regression model, gender, Helicobacter pylori infection status, GERD-related symptoms, and hiatal hernia were significantly correlated with RE. CONCLUSION: Our study shows that the prevalence of RE in severely obese Japanese patients was significantly higher than the average prevalence of RE in Japan. However, the prevalence of RE did not increase with BMI in our cohort.

Conservation and divergence of related neuronal lineages in the Drosophila central brain.

Wiring a complex brain requires many neurons with intricate cell specificity, generated by a limited number of neural stem cells. Drosophila central brain lineages are a predetermined series of neurons, born in a specific order. To understand how lineage identity translates to neuron morphology, we mapped 18 Drosophila central brain lineages. While we found large aggregate differences between lineages, we also discovered shared patterns of morphological diversification. Lineage identity plus Notch-mediated sister fate govern primary neuron trajectories, whereas temporal fate diversifies terminal elaborations. Further, morphological neuron types may arise repeatedly, interspersed with other types. Despite the complexity, related lineages produce similar neuron types in comparable temporal patterns. Different stem cells even yield two identical series of dopaminergic neuron types, but with unrelated sister neurons. Together, these phenomena suggest that straightforward rules drive incredible neuronal complexity, and that large changes in morphology can result from relatively simple fating mechanisms.

Current status of first- and second-line Helicobacter pylori eradication therapy in the metropolitan area: a multicenter study with a large number of patients.

BACKGROUND: The environment surrounding Helicobacter pylori eradication treatment is dramatically changing. Recently, vonoprazan, a first-in-class potassium-competitive acid blocker (P-CAB), was introduced onto the market in 2015. The aging of Japan's demographic structure is becoming pronounced. In this study, we examined the trend of the eradication rate of H. pylori in the metropolitan area and examined factors concerning successful eradication. METHODS: We collected data from 20 hospitals in the Tokyo metropolitan area on patients who received first-line eradication therapy with a proton-pump inhibitor (PPI)/P-CAB, amoxicillin, and clarithromycin for 1 week and second-line eradication therapy with a PPI/P-CAB, amoxicillin, and metronidazole for 1 week from 2013 to 2018. The annual eradication rate and associated factors for successful eradication were analyzed. RESULTS: We collected data of 4097 and 3572 patients in the first- and second-line eradication therapies, respectively. The eradication rate decreased from 2013 to 2014 and increased again from 2015 to 2018 with the first-line therapy [the eradication rates in 2013, 2014, 2015, 2016, 2017 and 2018 were 71.8%, 63.7%, 78.5%, 84.6%, 89.7 and 90.1%, respectively, in the per protocol (PP)]. The second-line eradication rates were 90.0%, 82.6%, 88.8%, 87.5%, 91.8% and 90.1% in 2013, 2014, 2015, 2016, 2017 and 2018, respectively, in PP. Vonoprazan was an independent factor for successful eradication in not only first-line, but also second-line eradication. Age over 75 years was an independent factor for eradication failure in both first- and second-line eradication therapies. CONCLUSION: The eradication rate improved from 2015 to 2018 with the first-line therapy because of the introduction of vonoprazan in the market. The eradication rates with first- and second-line regimens in elderly patients were lower than those in younger patients.

Early gastric cancer successfully treated by endoscopic submucosal resection 1 year after laparoscopic sleeve gastrectomy with duodenal-jejunal bypass.

This case involved a 64-year-old female patient with a BMI of 35.3 kg/m2 and poorly controlled type 2 diabetes mellitus. Preoperative upper gastrointestinal endoscopy revealed chronic, atrophic gastritis. Helicobacter pylori antibody was negative. The patient underwent laparoscopic sleeve gastrectomy with duodenal-jejunal bypass as a metabolic surgery to treat obesity and type 2 diabetes mellitus. At 1 year postoperatively, routine endoscopy detected a flat elevated lesion at the distal gastric sleeve, near the posterior wall of the antrum; biopsy revealed adenocarcinoma. Endoscopic submucosal resection was performed without complication. This case shows the advantage of laparoscopic sleeve gastrectomy with duodenal-jejunal bypass in screening the excluded stomach as compared to laparoscopic Roux-en-Y gastric bypass. Therefore, laparoscopic sleeve gastrectomy with duodenal-jejunal bypass can be a viable alternative to laparoscopic Roux-en-Y gastric bypass for regions where gastric cancer is endemic.

FluoRender: joint freehand segmentation and visualization for many-channel fluorescence data analysis.

BACKGROUND: Image segmentation and registration techniques have enabled biologists to place large amounts of volume data from fluorescence microscopy, morphed three-dimensionally, onto a common spatial frame. Existing tools built on volume visualization pipelines for single channel or red-green-blue (RGB) channels have become inadequate for the new challenges of fluorescence microscopy. For a three-dimensional atlas of the insect nervous system, hundreds of volume channels are rendered simultaneously, whereas fluorescence intensity values from each channel need to be preserved for versatile adjustment and analysis. Although several existing tools have incorporated support of multichannel data using various strategies, the lack of a flexible design has made true many-channel visualization and analysis unavailable. The most common practice for many-channel volume data presentation is still converting and rendering pseudosurfaces, which are inaccurate for both qualitative and quantitative evaluations. RESULTS: Here, we present an alternative design strategy that accommodates the visualization and analysis of about 100 volume channels, each of which can be interactively adjusted, selected, and segmented using freehand tools. Our multichannel visualization includes a multilevel streaming pipeline plus a triple-buffer compositing technique. Our method also preserves original fluorescence intensity values on graphics hardware, a crucial feature that allows graphics-processing-unit (GPU)-based processing for interactive data analysis, such as freehand segmentation. We have implemented the design strategies as a thorough restructuring of our original tool, FluoRender. CONCLUSION: The redesign of FluoRender not only maintains the existing multichannel capabilities for a greatly extended number of volume channels, but also enables new analysis functions for many-channel data from emerging biomedical-imaging techniques.

Stem Cell-Intrinsic, Seven-up-Triggered Temporal Factor Gradients Diversify Intermediate Neural Progenitors.

Building a sizable, complex brain requires both cellular expansion and diversification. One mechanism to achieve these goals is production of multiple transiently amplifying intermediate neural progenitors (INPs) from a single neural stem cell. Like mammalian neural stem cells, Drosophila type II neuroblasts utilize INPs to produce neurons and glia. Within a given lineage, the consecutively born INPs produce morphologically distinct progeny, presumably due to differential inheritance of temporal factors. To uncover the underlying temporal fating mechanisms, we profiled type II neuroblasts' transcriptome across time. Our results reveal opposing temporal gradients of Imp and Syp RNA-binding proteins (descending and ascending, respectively). Maintaining high Imp throughout serial INP production expands the number of neurons and glia with early temporal fate at the expense of cells with late fate. Conversely, precocious upregulation of Syp reduces the number of cells with early fate. Furthermore, we reveal that the transcription factor Seven-up initiates progression of the Imp/Syp gradients. Interestingly, neuroblasts that maintain initial Imp/Syp levels can still yield progeny with a small range of early fates. We therefore propose that the Seven-up-initiated Imp/Syp gradients create coarse temporal windows within type II neuroblasts to pattern INPs, which subsequently undergo fine-tuned subtemporal patterning.

Mechanochromic Dynamic Covalent Elastomers: Quantitative Stress Evaluation and Autonomous Recovery.

Stress evaluation in polymeric materials is important in order to not only spot danger in them before serious failure, but also precisely interpret the destructive mechanism, which can improve the lifetime and durability of polymeric materials. Here, we are able to visualize stress by color changes, as well as quantitatively estimate the stress in situ, in segmented polyurethane elastomers with diarylbibenzofuranone-based dynamic covalent mechanophores. We prepared films of the segmented polyurethanes, in which the mechanophores were incorporated in the soft segments, and efficiently activated them by mechanical force. Cleavage of the mechanophores during uniaxial elongation and their recovery after the removal of the stress were quantitatively evaluated by in situ electron paramagnetic resonance measurements, accompanied by drastic color changes.

Changes in the first line Helicobacter pylori eradication rates using the triple therapy-a multicenter study in the Tokyo metropolitan area (Tokyo Helicobacter pylori study group).

BACKGROUND AND AIM: Helicobacter pylori (H. pylori) infection is a strong risk factor for the development of gastric cancer. In 2013, the Japanese government approved H. pylori eradication therapy in patients with chronic gastritis as well as peptic ulcer. However, the continuing decline in eradication rates for first-line H. pylori eradication therapies is an urgent problem. In this study, we investigated changes in the first-line eradication rate from 2001 to 2010. METHODS: Eradication rates for 7-day triple therapy [proton pump inhibitor (rabeprazole 20 mg, lansoprazole 60 mg, or omeprazole 40 mg)+amoxicillin 1500 mg + clarithromycin (CAM) 400 or 800 mg, daily] were collated from 14 hospitals in the Tokyo metropolitan area. The urea breath test was used for the evaluation of eradication. The cut-off value was less than 2.5%. RESULTS: The yearly eradication rates (intention to treat/per protocol) were 78.5/79.5% (2001, n=242), 71.2%/72.9% (2002, n=208), 67.8%/70.5% (2003, n=183), 75.6%/84.6% (2004, n=131), 56.4%/70.5% (2005, n=114), 70.5%/75.8% (2006, n=271), 67.4%/82.0% (2007, n=135), 64.0%/76.3% (2008, n=261), 60.5%/74.3% (2009, n=329), and 66.5%/78.8% (2010, n=370), respectively. Examination of eradication rates according to CAM dosage revealed an eradication rate of 65.6% (383/584) for CAM 400 mg daily, and 68.5% (1124/1642) for CAM 800 mg daily, with no significant difference seen between dosages. CONCLUSION: In recent years, eradication rates for first-line triple therapy have obviously decreased, but no noticeable decrease has occurred after 2001.

Whole-brain neural network analysis (connectomics) using cell lineage-based neuron-labeling method.

The brain is a computing machine that receives input signals from sensory neurons, calculates best responses to changing environments, and sends output signals to motor muscles. How such computation is materialized remains largely unknown. Understanding the entire wiring network of neural connections in the brain, which is recently called the connectomics (connection + omics), should provide indispensable insights on this problem.To resolve the circuit diagram from the tangled thickets of neural fibers, only a small subset of neurons should be visualized at one time. Previous studies visualized such selective cells by injecting dyes or by detecting specific molecules or gene expression patterns using antibodies and expression driver strains. These approaches were unfortunately not efficient enough for identifying all the brain cells in a comprehensive and systematic manner.Neurons are generated by neural stem cells. The entire neural population can therefore be divided into a finite number of families - or clones - of the cells that are the progeny of each single stem cell. The central brain of the fruit fly Drosophila melanogaster consists of about 15,000 neurons per side and is made by utmost 100 stem cells. By genetically labeling one of such stem cells and tracing the projection patterns of its progeny in the adult brain, we were able to identify the neural projections of almost all the clonal cell groups.To visualize these neural projections, we made serial optical sections of the fly brain using laser confocal microscopy. Because of its relatively small size (0.6-mm wide and less than 0.3-mm thick), the entire fly brain can be imaged using high-resolution objectives with n.a. 1.2. Neuronal fibers are visualized by ectopically expressed cytoplasmic and membrane-bound fluorescent proteins, and the output synaptic sites are visualized with ectopically expressed tag proteins that are fused with the proteins associated with synaptic vesicles. In addition, density of all the synapses was visualized using an antibody against synaptic proteins. Signal distributions of the latter data were put into the template using 3D non-linear elastic morphing. The data of other channels are morphed with the same formula. By doing so, neural projection data obtained from different brain samples can directly be compared in the 3D space.Neurons generated by each stem cell turned out to form lineage-specific sets of projections that arborize in distinct regions of the brain, arguably serving specific aspects of brain functions. We named such clonally associated projection units the clonal units. Different parts of the brain were formed by distinct sets of overlapping clonal units. By tracing the projections made by each clonal unit, we were able to establish a comprehensive connection diagram between different brain regions. Microscopic analysis of neuronal fibers thus leads to the understanding of the entire brain neural network.

Classification of Physiological 18F-fluorodeoxyglucose Uptake in the Large Intestine: a Preliminary Study.

Varying degrees of physiological uptake of 18F-fluorodeoxyglucose (FDG) are often noted in the large intestine and can be problematic when interpreting positron emission tomography (PET) images. In relation to colorectal tumor detection with FDG PET, we tentatively classified physiological FDG uptake in the large intestine according to its patterns and intensity. Subjects were 144 asymptomatic individuals (109 men, 35 women; mean age 57.5 ± 10.1 years) in our cancer screening program who underwent total colonoscopy within 24 days of FDG PET study and showed no evidence of colonic lesions on colonoscopy. Distinct FDG uptake on FDG PET images was classified into four types: focal, defined as distinctly nodular and visible on at least 4 axial; localized, 2 to 8 cm with SUVmean ≥ 4; diffuse, > 8 cm with SUVmean ≥ 4; and mixed, of more than one type. SUVmeans were examined by placing multiple circular regions of interest of 1 cm in diameter on the axial images. We found 21 distinct FDG uptakes matching our criteria in 20 of 144 subjects (13.9%): focal (n = 4), localized (n = 1), diffuse (n = 14), and mixed (n = 1; focal and diffuse). With regard to colorectal tumor detection, 6 subjects (4.2%) with focal or localized type of uptake were considered at risk of false-positive tumor identification, and 15 subjects (10.4%) with diffuse type of uptake were considered at risk of their tumors being missed at the site of FDG uptake. To confirm the feasibility of our criteria, this classification should be tested with a larger number of subjects.

A systematic nomenclature for the insect brain.

Despite the importance of the insect nervous system for functional and developmental neuroscience, descriptions of insect brains have suffered from a lack of uniform nomenclature. Ambiguous definitions of brain regions and fiber bundles have contributed to the variation of names used to describe the same structure. The lack of clearly determined neuropil boundaries has made it difficult to document precise locations of neuronal projections for connectomics study. To address such issues, a consortium of neurobiologists studying arthropod brains, the Insect Brain Name Working Group, has established the present hierarchical nomenclature system, using the brain of Drosophila melanogaster as the reference framework, while taking the brains of other taxa into careful consideration for maximum consistency and expandability. The following summarizes the consortium's nomenclature system and highlights examples of existing ambiguities and remedies for them. This nomenclature is intended to serve as a standard of reference for the study of the brain of Drosophila and other insects.

[Current status of diagnosis of H. pylori infection].

Helicobacter pylori infection can be diagnosed by several methods using serum, urine, stool, breath or gastric samples taken at endoscopic examination. Some methods such as a stool antigen test (SAT), an urea breath test (UBT) or gastric biopsy-based tests such as a rapid urease test (RUT), histology or culture reveal active infection. UBT or SAT is recommended for determining the success of eradication treatment. While serum and urine antibodies show exposure to H. pylori, positive results do not necessarily indicate that the infection is ongoing. We need to know the characters of each test and choose appropriate one considering clinical conditions.

Trends of second-line eradication therapy for Helicobacter pylori in Japan: a multicenter study in the Tokyo metropolitan area.

BACKGROUND: In Japan, the eradication rate of first-line therapy for Helicobacter pylori (H. pylori) with a proton pump inhibitor (PPI), amoxicillin (AMPC) and clarithromycin (CAM) has been decreasing because of a high prevalence of CAM resistance. A possible decrease of the eradication rate for second-line therapy with a PPI, AMPC and metronidazole (MNZ) is of concern. The aim of this study is to assess the trends in second-line eradication therapy for H. pylori in Japan. MATERIALS AND METHODS: We accumulated data retrospectively on patients administered second-line eradication therapy for Helicobacter pylori with a PPI, AMPC, and MNZ for 1 week after failure of first-line eradication therapy with a PPI, AMPC and CAM at 15 facilities in the Tokyo metropolitan area in Japan from 2007 to 2011. Trends for second-line eradication rates in modified intention-to-treat (ITT) analyses were investigated. Second-line eradication rates were categorized by three PPIs (rabeprazole (RPZ), lansoprazole (LPZ) or omeprazole (OMZ)) and evaluated. RESULTS: We accumulated data on 1373 patients. The overall second-line eradication rate was 92.4%. Second-line eradication rates in 2007, 2008, 2009, 2010 and 2011 were 97.7, 90.6, 94.5, 91.8 and 91.8%, respectively, with no significant trends revealed. Second-line eradication rates categorized by three PPIs for the entire 5-year period were 91.6, 93.4 and 92.4% (RPZ, LPZ and OPZ, respectively) with no significant differences among the three PPIs. CONCLUSIONS: From 2007 to 2011, there were no significant trends in the second-line eradication rates and the rates remained consistently high. From the viewpoint of high prevalence of CAM resistance in Japan, triple therapy with PPI, AMPC and MNZ may be a better strategy for first-line therapy compared to triple therapy with PPI, AMPC and CAM.