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To find the adverse effects induced by cypermethrin, the ecotoxicological model copepods Tigriopus japonicus and Paracyclopina nana were exposed under cypermethrin, which is a widely used type-II pyrethroid insecticide in agriculture. Despite its large-scale application as insecticide in agriculture, little information is available on its adverse effects on aquatic invertebrates. In this study, the toxicity of cypermethrin on two copepods was assessed based on life parameters (growth rate and reproduction), oxidative stress and consequent antioxidant enzymatic activities, and gene expression profiles of antioxidants. The acute toxicity alone demonstrated that P. nana is less tolerant and sensitive against cypermethrin, compared to T. japonicus. However, under chronic exposure, life parameters of both P. nana and T. japonicus were severely affected by cypermethrin. Among antioxidant enzymatic activities, superoxide dismutase (SOD) and glutathione S-transferase (GST), in particular, demonstrated significant increase in response to cypermethrin. Furthermore, temporal-mRNA expression profile showed modulations in antioxidant related genes in response to cypermethrin. Our results provide the underlying toxic mechanism of cypermethrin and the oxidative stress defense mechanism and species-specific tolerance against cypermethrin in two model copepods species.

While pollution due to nano- and micro-sized plastics (NMPs) and hypoxic conditions both occur in coastal areas, the deleterious potential of co-exposure to hypoxia and NMPs (hypoxia and micro-sized plastics, HMPs; hypoxia and nano-sized plastics, HNPs) is largely unclear. Here, we provide evidence for multigenerational effects of HMP and HNP in the marine rotifer Brachionus plicatilis by investigating changes in its life traits, antioxidant system, and hypoxia-inducible factor (HIF) pathway using an orthogonal experimental design, with nanoscale and microscale particles measuring 0.05 μm and 6.0 μm in diameter, respectively, and hypoxic conditions of 0.5 mg/L for six generations. Combined exposure to NMPs and hypoxia caused a significant decrease in fecundity and overproduction of reactive oxygen species (ROS). The HIF pathway and circadian clock genes were also significantly upregulated in response to HMP and HNP exposure. In particular, synergistic deleterious effects of HNP were evident, suggesting that size-dependent toxicity can be a major driver of the effects of hypoxia and NMP co-exposure. After several generations of exposure, ROS levels returned to basal levels and transcriptomic resilience was observed, although rotifer reproduction remained suppressed. These findings help eluciating the underlying molecular mechanisms involved in responses to plastic pollution in hypoxic conditions.

This is the first study to analyze the whole-genome sequence of B. manjavacas Australian (Aus.) strain through combination of Oxford Nanopore long-read seq, resulting in a total length of 108.1 Mb and 75 contigs. Genome-wide detoxification related gene families in B. manjavacas Aus. strain were comparatively analyzed with those previously identified in other Brachionus spp., including B. manjavacas German (Ger.) strain. Most of the subfamilies in detoxification related families (CYPs, GSTs, and ABCs) were highly conserved and confirmed orthologous relationship with Brachionus spp., and with accumulation of genome data, clear differences between genomic repertoires were demonstrated the marine and the freshwater species. Furthermore, strain-specific genetic variations were present between the Aus. and Ger. strains of B. manjavacas. This whole-genome analysis provides in-depth review on the genomic structural differences for detoxification-related gene families and further provides useful information for comparative ecotoxicological studies and evolution of detoxification mechanisms in Brachionus spp.

To analyze various adverse events (AEs) related to the peroral endoscopic myotomy (POEM) procedure and to analyze whether these AEs are related to an extended hospital stay.Patients admitted for POEM for esophageal motility disorders from August 2012 to February 2020 at 5 centers were retrospectively collected. Length of hospital stay, AEs during or after the POEM procedure were analyzed.Of the 328 patients, 63.1% did not have any AEs, but 2.4% had major AEs, and 33.4% had minor AEs. Major AEs included mucosal injury, bleeding, and hemothorax, accounting for 1.5%, 0.6%, and 0.3%, respectively. Among the minor AEs, pneumoperitoneum was the most common gas-related AEs. Among non-gas-related minor AEs, pneumonia was the most common at 4.6%, followed by pain, fever, and pleural effusion. All major AEs had meaningful delayed discharge and significantly extended hospital stay compared to the no AEs group (median differences range 4.5-9.0 days). Among gas-related minor AEs, except for 4 cases of emphysema, the extended hospital stay was meaningless. All non-gas-related minor AEs was associated with a significant prolongation of hospital stay compared to that in the no AEs group (median differences range 2.0-4.0 days).In conclusion, most gas-related minor AEs do not significantly affect the patient's clinical course. However, subcutaneous emphysema and minor non-gas related AEs such as pneumonia, pain, fever, and pleural effusion can prolong the hospital stay, therefore careful observation is required. Efforts will be made to reduce major AEs that significantly prolong hospitalization.

Brachionus spp. rotifers have been proposed as model organisms for ecotoxicological studies. We analyzed the whole-genome sequence of B. paranguensis through NextDenovo, resulting in a total length of 106.2 Mb and 71 contigs. The N50 and the GC content were 4.13 Mb and 28%, respectively. A total of 18,501 genes were predicted within the genome of B. paranguensis. Prominent detoxification-related gene families of phase I and II detoxifications have been investigated. In parallel with other Brachionus rotifers, high gene expansion was observed in CYP clan 3 and GST sigma class in B. paranguensis. Moreover, species-specific expansion of sulfotransferase (SULTs) and gain of UDP-glucuronosyltransferases (UGTs) through horizontal gene transfer has been specifically found within B. plicatilis complex. This whole-genome analysis of B. paranguensis provides a basis for molecular ecotoxicological studies and provides useful information for comparative studies of the evolution of detoxification mechanisms in Brachionus spp.

Although heavy metals are long familiar for their toxicity and carcinogenicity, they are being introduced into the aquatic systems from various industrial operations. The remedial measures of heavy metals are of great importance owing to their recalcitrant character and persistence in the environment. Higher accumulation and prolonged exposure of heavy metals cause deleterious health effects on humans as well as various aquatic life forms. To treat heavy metal discharges from industrial wastewater, technologies for the reduction of toxic substances are often required to meet technology-based treatment standards. This chapter discusses various types of newly developed and freshly applicable treatment processes and technologies for the removal of heavy metals from various industrial wastewaters. Physicochemical removal processes include chemical precipitation, coagulation and flocculation, flotation, ion exchange, reverse osmosis, ultrafiltration, ion exchange, membrane filtration, electrochemical treatment, photocatalysis, and nanotechnology. Besides, chemical methods are considered to be the most suitable treatment methods for toxic inorganic compounds produced by various industries that cannot be removed using any biological and physical techniques.

The G protein-coupled receptor (GPCR) superfamily plays a fundamental role in both sensory functions and the regulation of homeostasis, and is highly conserved across the eukaryote taxa. Its functional diversity is related to a conserved seven-transmembrane core and invariant set of intracellular signaling mechanisms. The interplay between these properties is key to the evolutionary success of GPCR. As this superfamily originated from a common ancestor, GPCR genes have evolved via lineage-specific duplications through the process of adaptation. Here we summarized information on GPCR gene families in rotifers and cladocerans based on their evolutionary position in aquatic invertebrates and their potential application in ecotoxicology, ecophysiology, comparative endocrinology, and pharmacology. Phylogenetic analyses were conducted to examine the evolutionary significance of GPCR gene families and to provide structural insight on their role in aquatic invertebrates. In particular, most GPCR gene families have undergone sporadic evolutionary processes, but some GPCRs are highly conserved across species despite the dynamics of GPCR evolution. Overall, this review provides a better understanding of GPCR evolution in aquatic invertebrates and expand our knowledge of the potential application of these receptors in various fields.

BACKGROUND AND AIM Bleeding after endoscopic submucosal dissection (ESD) is a main adverse event. To date, although there have been several studies about risk factors for post-ESD bleeding, there has been few predictive model for post-ESD bleeding with large volume cases. We aimed to design a prediction model for post-ESD bleeding using a classification tree model. METHODS We analyzed a prospectively established cohort of patients with gastric neoplasms treated with ESD from 2007 to 2016. Baseline characteristics were collected for a total of 5080 patients, and the bleeding risk was estimated using variable statistical methods such as logistic regression, AdaBoost, and random forest. To investigate how bleeding was affected by independent predictors, the classification and regression tree (CART) method was used. The prediction tree developed for the cohort was internally validated. RESULTS Post-ESD bleeding occurred in 262 of 5080 patients (5.1%). In multivariate logistic regression, ongoing antithrombotic use during the procedure, cancer pathology, and piecemeal resection were significant risk factors for post-ESD bleeding. In the CART model, the decisive variables were ongoing antithrombotic agent use, resected specimen size ≥49 mm, and patient age

Heat shock proteins (Hsp) are class of conserved and ubiquitous stress proteins present in all living organisms from primitive to higher level. Various studies have demonstrated multiple cellular functions of Hsp in living organisms as an important biomarker in response to abiotic and biotic stressors including temperature, salinity, pH, hypoxia, environmental pollutants, and pathogens. However, full understanding on the mechanism and pathway involved in the induction of Hsp still remains challenging, especially in aquatic invertebrates. In this study, the entire Hsp family and subfamily members in the marine rotifers Brachionus spp., one of the cosmopolitan ecotoxicological model organisms, have been genome-widely identified. In Brachionus spp. Hsp family was comprised of Hsp10, small hsp (sHsp), Hsp40, Hsp60, Hsp70/105, and Hsp90, with highest number of genes found within Hsp40 DnaJ homolog subfamily C members. Also, the differences in the orientation of the conserved motifs within Hsp family may have induced differences in transcriptional gene modulation in response to thermal stress in Brachionus koreanus. Overall, Hsp family-specific domains were highly conserved in all three Brachionus spp., relative to Homo sapiens and across other animal taxa and these findings will be helpful for future ecotoxicological studies focusing on Hsps.

Copepods in the genus Tigriopus are widely distributed in the intertidal zone worldwide. To assess differences in fatty acid (FA) metabolism among congeneric species in this genus inhabiting polar and temperate environments, we analyzed and compared FA profiles of the Antarctic copepod Tigriopus kingsejongensis and the temperate copepod T. japonicus. Higher amounts of total FAs were found in the Antarctic copepod T. kingsejongensis than the temperate copepod T. japonicus under administration of the identical amount of Tetraselmis suecica. To determine the genomic basis for this, we identified fatty acid metabolism-related genes in an improved genome of T. kingsejongensis. The total length of the assembled genome was approximately 338 Mb with N50 = 1.473 Mb, 938 scaffolds, and a complete Benchmarking Universal Single-Copy Orthologs value of 95.8%. A total of 25,470 genes were annotated using newly established pipeline. We identified eight elongation of very long-chain fatty acid protein (Elovl) genes and nine fatty acid desaturase (Fad) genes in the genome of T. kingsejongensis. In addition, fatty acid profiling suggested that the duplicated Δ5/6 desaturase gene in T. kingsejongensis is likely to play an essential role in synthesis of different FAs in T. kingsejongensis to those in T. japonicus. However, further experimental research is required to validate our in silico findings. This study provides a better understanding of fatty acid metabolism in the Antarctic copepod T. kingsejongensis.

The rapid growth of industrialization and urbanization results in deterioration of freshwater systems around the world, rescinding the ecological balance. Among many factors that lead to adverse effects in aquatic ecology, metals are frequently discharged into aquatic ecosystems from natural and anthropogenic sources. Metals are highly persistent and toxic substances in trace amounts and can potentially induce severe oxidative stress in aquatic organisms. In this study, adverse effects of the two metal elements zinc (maximum concentration of 167.25 mg/L) and mercury (104.2 mg/L) were examined using Chlorella vulgaris under acute and chronic exposure period (48 h and 7 days, respectively). The metal-induced adverse effects have been analyzed through photosynthetic pigment content, total protein content, reactive oxygen species (ROS) generation, antioxidant enzymatic activities, namely catalase and superoxide dismutase (SOD) along with morphological changes in C. vulgaris. Photosynthetic pigments were gradually reduced (~32-100% reduction) in a dose-dependent manner. Protein content was initially increased during acute (~8-12%) and chronic (~57-80%) exposure and decreased (~44-56%) at higher concentration of the two metals (80%). Under the two metal exposures, 5- to 7-fold increase in ROS generation indicated the induction of oxidative stress and subsequent modulations in antioxidant activities. SOD activity was varied with an initial increase (58-129%) followed by a gradual reduction (~3.7-79%), while ~1- to 12-fold difference in CAT activity was observed in all experimental condition (~83 to 1605%). A significant difference was observed in combined toxic exposure (Zn+Hg), while comparing the toxic endpoint data of individual metal exposure (Zn and Hg alone). Through this work, lethal effects caused by single and combined toxicity of zinc and mercury were assessed, representing the significance of appropriate monitoring system to trim down the release of metal contaminants into the aquatic ecosystems.

The Java medaka (Oryzias javanicus) is distributed in tropical brackish water and is considered as an ecotoxicological experimental organism for assessing diverse pollutions and global climate change effects in the ocean. In this study, we sequenced and assembled the genome of O. javanicus using the Oxford Nanopore technique and anchored the scaffolds to the 24 genetic linkage map of a sister species Oryzias melastigma. The assembled genome consisted of 773 scaffolds including 24 LG-based scaffolds, and the estimated genome length was 846.3 Mb (N50 = 19.3 Mb), containing 24,498 genes. As detoxification processes are crucial in aquatic organisms, antioxidant-related genes including glutathione S-transferases, superoxide dismutase, catalase, and glutathione peroxidase were identified in this study. In the genome of O. javanicus, a total of 21 GSTs, 4 SODs, 1 CAT, and 7 GPxs were identified and showed high similarities between sister species O. melastigma and Oryzias latipes. In addition, despite having 8 classes of cytosolic GSTs family, medaka showed no presence of GST pi and sigma classes, which are predominantly found in carp and salmon, but not in neoteleostei. This study adds another set to genome-library of Oryzias spp. and is a useful resource for better understanding of the molecular ecotoxicology.

Global warming is a big concern for all organisms and many efforts have been made to reveal the potential effects of temperature elevation on aquatic organisms. However, limited studies on molecular mechanistic approaches on physiological effects due to temperature changes are available. Here, we investigated the effects of temperature changes on life parameters (e.g., population growth [total number of rotifers], and lifespan), oxidative stress levels and antioxidant activities (e.g., glutathione S-transferase [GST], catalase [CAT], superoxide dismutase [SOD]) with expression levels in the monogonont marine rotifer Brachionus plicatilis. The changes in temperatures led to significant reduction (P 0.05) in lifespan, possibly due to significant decrease (P 0.05) in antioxidant activities, reducing the potential to cope with significant elevation in the temperature-induced oxidative stress in B. plicatilis. To further assess the actual induction and clearance of reactive oxygen species (ROS), N-acetyl-L-cysteine was used to examine whether the temperature-induced oxidative stress could be successfully scavenged. Furthermore, expression patterns of the antioxidant-related genes (GSTs, SODs, and CATs) were down- or upregulated (P 0.05) in response to different temperatures in B. plicatilis. Overall, these findings indicate that ROS-mediated oxidative stress led to cellular damage and antioxidant defense system, resulting in deleterious effects on life parameters in rotifer.

To examine the effect of salinity and temperature in the marine tropical rotifer Brachionus rotundiformis, we analyzed various in vivo life cycle parameters, fatty acid (FA) composition, and transcriptional levels of elongation of very long-chain fatty acid (Elovl) and fatty acid desaturase (Fad) genes. In the case of life cycle parameters, the reproduction of B. rotundiformis showed the highest fecundity under 5 practical saline unit (PSU) and 30 °C conditions, while the concentrations of total FAs were the highest in 15 PSU and 25 °C-exposed groups, respectively. Besides, changes in culture condition (salinity and temperature) resulted in a decrease in n-3 FAs. Therefore, the correlation between nutrient components and the total yield should be considered to determine the optimal culture conditions for B. rotundiformis. The changes in the transcriptional level of Elovl and Fad genes appear to be involved in the compositional modulations of FA, and in particular, Elovl9b could be suggested as useful biomarker due to its temperature-dependent modulation.

Global warming, increase of the atmospheric temperature leading to changes in climate, is a growing environmental concern for all organisms including marine organisms, and many efforts have been made to reveal the potential adverse effects on the systematics of aquatic organisms in response to the temperature changes. To examine the effects of temperature shifts on copepods in temperate and polar regions, we compared the life parameters and gene expression profiles of the de novo lipogenesis (DNL) pathway and heat shock protein (hsp) genes in the temperate copepod Tigriopus japonicus (T. japonicus) and the Antarctic copepod Tigriopus kingsejongensis (T. kingsejongensis). The median lethal temperature (LT50) and no observed effect level (NOEL) in the temperate copepod T. japonicus were determined to be 35.3 and 32 °C, respectively, in response to a temperature increase of 2 °C a day. In the Antarctic copepod T. kingsejongensis, the LT50 and NOEL were determined to be 24.8 and 12 °C, respectively. In addition, delayed developmental time and impaired fecundity were observed (P

Objective Notch receptors are heterodimeric transmembrane proteins that regulate cell fate, such as differentiation, proliferation, and apoptosis. Dysregulated Notch pathway signaling has been observed in glioblastomas, as well as in other human malignancies. Nerve growth factor (NGF) is essential for cell growth and differentiation in the nervous system. Recent reports suggest that NGF stimulates glioblastoma proliferation. However, the relationship between NGF and Notch1 in glioblastomas remains unknown. Therefore, we investigated expression of Notch1 in a glioblastoma cell line (U87-MG), and examined the relationship between NGF and Notch1 signaling. Methods We evaluated expression of Notch1 in human glioblastomas and normal brain tissues by immunohistochemical staining. The effect of NGF on glioblastoma cell line (U87-MG) was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. To evaluate the relationship between NGF and Notch1 signaling, Notch1 and Hes1 expression were evaluated by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. To confirm the effects of NGF on Notch1 signaling, Notch1 and Hes1 small interfering RNAs (siRNAs) were used. Results In immunohistochemistry, Notch1 expression was higher in glioblastoma than in normal brain tissue. MTT assay showed that NGF stimulates U87-MG cells in a dose-dependent manner. RT-PCR and Western blot analysis demonstrated that Notch1 and Hes1 expression were increased by NGF in a dose-dependent manner. After transfection with Notch1 and Hes1 siRNAs, there was no significant difference between controls and 100 nM NGF-β, which means that U87-MG cell proliferation was suppressed by Notch1 and Hes1 siRNAs. Conclusion These results indicate that NGF stimulates glioblastoma cell proliferation via Notch1 signaling through Hes 1.

To understand the adverse outcome in response to bisphenol A and its analogs bisphenol F and S (BPA, BPF, and BPS), we examined acute toxicity, life parameter, and defensome in the marine rotifer Brachionus koreanus. Among the bisphenol analogs, BPA showed the highest acute toxicity and then BPF and BPS, accordingly in the view of descending magnitude of toxicity. In life parameters including life span and reproduction, BPA, BPF, and BPS were found to cause adverse effect. Both intracellular ROS level and GST activity were significantly increased (P 0.05) in response to each dosage of bisphenol analogs exposures. In response to bisphenol analogs, defensomes of phase I, II, and III detoxification mechanism demonstrated inverse relationship between the lipophilicity of bisphenol analogs and the expression patterns of defensomes. BPA and BPF were found to have significant modulation (P 0.05) in the expression of cytochrome P450 (CYP) and GST genes. In phase III, BPS with comparatively lower lipophilicity demonstrated highly diversified expressional pattern, suggesting that BPS is likely caused less toxicity compared to BPA and BPF. In this study, via phase I, II, and III detoxification mechanism, bisphenol A and its analogs F and S demonstrated specific detoxification mechanism in rotifer.

The concept and pathological diagnostic criteria of gastric adenoma (dysplasia) differ between Western countries and Japan, and discrepancies between histopathological examinations before and after endoscopic resection may occur. Therefore, the natural history of adenoma should be interpreted and the treatment strategy of adenoma established. It is recommended that endoscopic resection be performed for high-grade dysplasia due to the potential higher risk of progression to carcinoma. For low-grade dysplasia, the risk of malignant transformation is relatively low. However, resection is considered the first approach for the purpose of diagnosis and treatment. If resection is not feasible, the alternative may be to use argon plasma coagulation for selected lesions that are less likely to be malignant. When Helicobacter pylori infection is detected, eradication therapy is recommended to reduce the risk of metachronous lesions. Post-resection follow-up should be performed within 1 year to detect synchronous lesions and then follow-up endoscopy at 1 or 2-year intervals may be considered for metachronous lesions.

Background and aim Recently, the application of hemostatic powder to the bleeding site has been used to treat active upper gastrointestinal bleeding (UGIB). We aimed to assess the effectiveness of the polysaccharide hemostatic powder (PHP) in patients with non-variceal UGIB. Methods We reviewed prospectively collected 40 patients with UGIB treated with PHP therapy between April 2016 and January 2017 (PHP group) and 303 patients with UGIB treated with conventional therapy between April 2012 and October 2014 (conventional therapy group). We compared the rate of successful hemostasis and the rebleeding between the two groups after as well as before propensity score matching using the Glasgow-Blatchford score and Forrest classification. Results Thirty patients treated with the PHP and 60 patients treated with conventional therapy were included in the matched groups. Baseline patient characteristics including comorbidities, vital signs, and bleeding scores were similar in the matched groups. The rate of immediate hemostasis and 7-day and 30-day rebleeding were also similar in the two groups before and after matching. In the subgroup analysis, no significant differences in immediate hemostasis or rebleeding rate were noted between PHP in monotherapy and PHP combined with a conventional hemostatic method. At 30 days after the therapy, there were no significant PHP-related complications or mortality. Conclusions Given its safety, the PHP proved feasible for endoscopic treatment of UGIB, having similar effectiveness as that of conventional therapy. The PHP may become a promising hemostatic method for non-variceal UGIB.

The aim of this study was to analyze long-term clinical and oncologic outcomes in patients with early-stage adenocarcinoma of the esophagogastric junction (AEG) managed with either endoscopic resection (ER) or surgery. The inclusion criteria were AEG, meeting classic or expanded indications for ER of early gastric cancer, and complete resection. A total of 66 patients with Siewert type II AEG were included (ER group, n = 38; vs. surgery group, n = 28). The mean age of the ER group was greater than that of the surgery group (mean ± SD, 66.9 ± 9.7 vs. 58.5 ± 10.4 years, respectively; p = 0.001). Compared to the ER group, macroscopically flat or depressed-type lesions were more common (47.4 vs. 89.3%; p = 0.001), and mean lesion size was larger in the surgery group (13.3 ± 8.4 vs. 18.6 ± 11.0 mm; p = 0.039). One intensive care unit admission and subsequent surgery-related death occurred in the surgery group (1/28 vs. 0/38 in the ER group; p = 0.424). During follow-up, recurrence was detected in both groups (4/38 vs. 1/28; p = 0.385). Overall survival and 5-year disease-free survival did not differ between the groups (93.3 vs. 92.9%; p = 0.282 and 88.0 vs. 100.0%; p = 0.066). Once complete resection is achieved in patients with AEG who met the expanded criteria for endoscopic submucosal dissection of gastric cancer, there was no significant difference in clinical outcomes between ER and surgery.

Background Although propofol has been widely used for sedation during esophagogastroduodenoscopy (EGD), adverse events including hypoxia and hypotension may be a concern in the propofol-based sedation. We aimed to analyze whether administration of midazolam would improve safety and efficacy of propofol-based sedation in EGD. Methods One hundred twenty patients who were scheduled to undergo diagnostic EGD were randomly assigned to either midazolam plus propofol (MP) or propofol alone groups. In the MP group, 2mg of midazolam and 10mg of propofol were given initially. In the propofol alone group, 40-60mg of propofol was given initially. In both groups, 20mg of propofol was given repeatedly to maintain moderate sedation as needed. Vital signs including oxygen saturation were monitored every 2 minutes. After the patients fully recovered, satisfaction score was investigated from endoscopists, nurses and patients, respectively. Results The baseline characteristics did not differ between the MP and propofol alone groups. The mean required doses of propofol was (mean±standard deviation) 0.3±0.3 mg/kg and 0.8±0.2 mg/kg in the MP and propofol alone groups, respectively (P 0.999; endoscopist, 73.3% vs. 80.0%, P=0.064; nurse, 73.3% vs. 76.7%, P=0.551). Conclusion Adding midazolam to propofol did not reduced the safety and efficacy, sedation using propofol alone could be suitable for sedation during diagnostic EGD.

G protein-coupled receptors (GPCRs) are considered to have originated from early evolution of eukaryotic species, therefore, the genome-wide identification of GPCR genes can provide insight into the adaptive strategy and evolutionary tendency in an animal taxon. Here, we identified a total 216 full-length GPCR genes in the marine water flea Diaphanosoma celebensis genome, which were classified into five distinct classes (A, B, C, F, and other). Phylogenetic comparison of GPCRs in D. celebensis to those in humans (Homo sapiens), fruitfly (Drosophila melanogaster), and freshwater water flea (Daphnia magna) reveals a high level of orthological relationship of amine, neuropeptide, and opsin receptor repertoire, while purinergic and chemokine receptors were highly differentiated in humans. Our findings suggest sporadic evolutionary processes within the GPCR gene families identified in D. celebensis. In this study, these results may provide a better understanding on the evolution of GPCRs, and expand our knowledge of the cladoceran GPCR gene repertories which in part, mediate cell physiological mechanisms in response to various environmental stimuli.

Microplastics are ubiquitous environmental pollutants and a great threat to the aquatic environment. Due to their small size (ranging from 1 µm to 5 mm), microplastics be easily ingested by a wide range of organisms and can serve as a vector for various contaminants. In this study, additive or possible synergistic effects of microplastics and zinc were demonstrated through sex-specific alterations in behavior, redox status, and modulation of detoxification-related genes in Daphnia magna, with males being more sensitive than females with stronger modulations of antioxidant responses, particularly on glutathione S-transferases expressions. Furthermore, we demonstrated microplastics may act as vectors for metals (Zn2+) in the aquatic environment in D. magna, with reduced bio-concentration of the total Zn concentration, inducing greater toxicity. Our findings demonstrated synergistic toxicity of the heavy metal Zn and microplastics and could contribute to greater understanding of sex-specific effects of microplastics in aquatic organisms.

iTRAQ proteomic profiling was conducted to examine the proteomic responses of the Antarctic copepod Tigriopus kingsejongensis under ultraviolet B (UVB) exposure. Of the 5507 proteins identified, 3479 proteins were annotated and classified into 25 groups using clusters of orthologous genes analysis. After exposing the T. kingsejongensis to 12 kJ/m2 UVB radiation, 77 biological processes were modulated over different time periods (0, 6, 12, 24, and 48 h) compared with the control. A Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that UVB exposure in T. kingsejongensis downregulated ribosome and glyoxylate and dicarboxylate metabolism at all time points. Furthermore, antioxidant and chaperone proteins were highly downregulated in response to UVB exposure, causing protein damage and activating apoptotic processes in the 48 h UVB exposure group. These proteomic changes show the mechanisms that underlie the detrimental effects of UVB on the cellular defense systems of the Antarctic copepod T. kingsejongensis.

Constant evolution of omics-technologies has provided access to identification of various important gene families. Recently, genome assemblies on widely used ecotoxicological model species, including rotifers and copepods have been completed and representative detoxification-related gene families have been discovered for biomarker genes. However, despite ubiquitous presence of stress-response proteins, limited information on full genome-wide report on heat shock proteins (Hsps) is available. Various studies have demonstrated multiple cellular functions of Hsps in living organisms as an important biomarker in response to abiotic and biotic stressors, however, full genome-wide identification of Hsps, particularly in aquatic invertebrates, has not been reported. This is the first study to report the entire Hsps and basal gene expression levels in three regional-specific copepods: Tigriopus japonicus and kingsejongensis, Paracyclopina nana, and Eurytemora affnis, and how each Hsp family gene is regulated at a basal level.

Purpose Bleeding is one of the most serious complications of advanced gastric cancer (AGC) and is associated with a poor prognosis. This study aimed to evaluate the clinical outcomes of endoscopic hemostasis for bleeding in patients with unresectable AGC. Materials and Methods This study included 106 patients with bleeding associated with gastric cancer who had undergone endoscopic hemostasis between January 2010 and December 2013. Clinical characteristics, treatment outcomes, including rates of successful endoscopic hemostasis and rebleeding, risk factors for rebleeding, and overall survival (OS) were investigated. Results Successful initial hemostasis was achieved in 83% of patients. Rebleeding occurred in 28.3% of patients within 30 days. The median OS after initial hemostasis was lower in patients with rebleeding than in those without rebleeding (2.7 and 3.9 months, respectively, P=0.02). There were no significant differences in disease status and rebleeding rates among patients with partial response or stable disease (n=4), progressive disease (n=64), and first diagnosis of disease (n=38). Univariate and multivariate analyses (P=0.038 and 0.034, respectively) revealed that transfusion of ≥5 units of RBCs was a significant risk factor for rebleeding. Conclusions Despite favorable success rates of endoscopic hemostasis for bleeding associated with gastric cancer, the 30-day rebleeding rate was 28.3% and the median OS was significantly lower in patients with rebleeding than in those without rebleeding. Massive transfusion (≥5 units of RBCs) was the only significant risk factor for rebleeding. Patients with bleeding associated with AGC who have undergone massive transfusion should be observed closely following endoscopic hemostasis. Further research on approaches to reduce rebleeding rate and prevent death is needed.

[Purpose] The purpose of this study was three kinds of stretching methods and measured the change in the thickness of the piriform muscle in real time using ultrasound images and compared the medial rotation angle of the coxal articulation. [Subjects and Methods] Fourty-five subjects who attend B University in Cheonan, divided into three groups. The subjects in these three groups then underwent stretching with flexion of coxal articulation over 90°, stretching with flexion of coxal articulation under 90°, and muscle energy technique (MET) application. The main outcome measures were piriform muscle thickness and medial rotation angle of the coxal articulation. [Results] All groups showed decreased piriform muscle thickness and increased medial rotation angle of the coxal articulation. [Conclusion] Based on the above results, three kinds of piriform muscle stretching methods are effective of reduce muscle thickness and increase medial rotation angle of the coxal articulation.

Background/Aims: Few studies have evaluated the effect of Helicobacter pylori infection on the prognosis of patients diagnosed with gastric cancer (GC) after curative surgery. We investigated the association between the H. pylori infection status and clinical outcome after surgery. Methods: We as-sessed the H. pylori status of 314 patients who underwent curative resection for GC. The H. pylori status was examined using a rapid urease test 2 months after resection. Patients were followed for 10 years after surgery. Results: An H. pylori infection was observed in 128 of 314 patients. The median follow-up period was 93.5 months. A Kaplan-Meier analysis indicated that patients with H. pylori had a higher cumula-tive survival rate than those who were negative for H. pylori. Patients with stage II cancer who tested negative for H. py-lori were associated with a poor outcome. In a multivariate analysis, H. pylori-negative status was a significant indepen-dent prognostic factor for poor overall survival. Conclusions: Having a negative H. pylori infection status seems to indicate poor prognosis for patients with GC who have undergone curative resection. Further prospective controlled studies are needed to evaluate the mechanism by which H. pylori af-fects GC patients after curative surgery in Korea. (Gut Liver 2017;11:635-641)

Contrast-induced encephalopathy after cerebral angiography is a rare complication and until now, only few cases have been reported. This paper reports on contras-induced encephalopathy mimicking meningoencephalitis after cerebral angiography by using iodixanol, an iso-osmolar non-ionic contrast agent. A 58-year-old woman underwent cerebral angiography for the evaluation of multiple intracranial aneurysms. A few hours later, she had persistent headache, vomiting, fever, and seizures. Brain computed tomography (CT) showed sulcal obliteration of right cerebral hemisphere and cerebrospinal fluid profile was unremarkable. The next day, she developed left side hemiparesis, sensory loss, and left-sided neglect with drowsy mentality. Brain magnetic resonance imaging (MRI) showed cerebral swelling with leptomeningeal enhancement in the right parieto-occipital lobe without sign of ischemia or hemorrhage. The patient was managed with intravenous dexamethasone, mannitol and anticonvulsant. There was a progressive neurological improvement with complete resolution of the symptoms at day 6. This observation highlights that contrast-induced encephalopathy can be caused by an iso-osmolar non-ionic contrast agent. This rare entity should be suspected if neurologic deterioration after cerebral angiography is not explained by other frequent causes such as acute infarction or hemorrhage.

Triclosan (TCS) is an antimicrobial agent that has been widely dispersed and detected in the marine environment. However, the effects of TCS in marine invertebrates are poorly understood. In this study, the effects of TCS on life cycle history (e.g. mortality and fecundity) along with cellular reactive oxygen species (ROS) levels, GSH content, antioxidant enzymatic activities, and mRNA expression levels of oxidative stress-mediated genes were measured in the copepod Tigriopus japonicus. The no observed effect concentration (NOEC) and median lethal concentration (LC50) of TCS in the adult stage were determined to be 300μg/L and 437.476μg/L, respectively, while in the nauplius stages the corresponding values were 20μg/L, and 51.76μg/L, respectively. Fecundity was significantly reduced (P

We have used the cyclopoid copepod Paracyclopina nana to understand responses to the temperature shift. To determine the changes of molecular mechanisms, which would lead to physiological changes in P. nana, we investigated mRNA expression involved in lipogenesis, the area of lipid droplets, the ratio of fatty acids, and life parameters (growth and fecundity) in response to temperature changes (15, 20, and 30 °C) with comparative control at 25 °C. Setting the temperature 25 °C as a standard point, there were increases in mRNA expression, the area of the lipid droplets, and fatty acid composition at temperatures below the standard (15 °C), while all the markers mentioned above significantly decreased at higher temperatures than the standard (25 °C). Through fecundity and growth rate experiments, daily nauplii production was reduced and growth retardation was observed at both 15 and 20 °C, but no noticeable differences in the two parameters were observed at 30 °C compared to the control (25 °C). This study provides a better understanding of the effects of temperature on lipogenesis in copepods.

Oxyntic gland polyp/adenoma is a recently reported rare neoplasm previously called gastric adenocarcinoma of fundic gland type (chief cell predominant type). We report a case of oxyntic gland adenoma curatively treated with endoscopic mucosal resection. On endoscopy, a small, round polypoid lesion was observed in the fundus of the stomach of a 33-year-old man. He underwent endoscopic mucosal resection with a cap for diagnostic and therapeutic purposes, and was diagnosed as having oxyntic gland adenoma with high-grade dysplasia. On immunohistochemical analysis, the tumor was positive for MUC6 and negative for MUC5AC and MUC2. Our case suggests that endoscopic mucosal resection with immunohistochemical analysis might be useful for correctly diagnosing an uncertain lesion suspected as an oxyntic gland adenoma.

2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) is widely dispersed endocrine disrupting chemicals (EDCs) in the aquatic ecosystem. Due to its devastating effect on marine organisms and insufficient database on toxicology, we investigated the adverse effects of BDE-47 on life parameters and antioxidant defense system following the reactive oxygen species (ROS) production in the monogonont rotifer Brachionus koreanus. In B. koreanus, the reduction in life cycle, fecundity, and population growth were observed in response to BDE-47. 50μg/L BDE-47 significantly reduced (P

Background and Aims Endoscopic submucosal dissection (ESD) is a useful method for complete resection of early gastric cancer (EGC). However, there are still some patients who undergo additional gastrectomy after ESD because of non-curative resection. There is no model that can accurately predict non-curative resection of ESD. We aimed to create a model for predicting non-curative resection of ESD in patients with EGC. Patients and methods We reviewed the medical records, including all gross findings of EGC, of patients who underwent ESD for EGCs. We divided the patients into a non-curative resection group and a curative resection group. The clinicopathologic characteristics were compared between the groups to identify the risk factors for non-curative resection of ESD. We created a scoring system based on logistic regression modeling and bootstrap validation. Results Of 1639 patients who had undergone ESD for EGCs, 272 were identified as being treated non-curatively with ESD. A large tumor size (≥20 mm), tumor location in the upper body of the stomach, the presence of ulcer, fusion of gastric folds, the absence of mucosal nodularity, spontaneous bleeding, and undifferentiated tumor histology were associated with non-curative resection of ESD. Points of risk scores were assigned for these variables based on the β coefficient as follows: tumor size (≥20 mm), 2 points; tumor location in the upper body of the stomach, 1 point; ulcer, 2 points; fusion of gastric folds, 2 points; absence of mucosal nodularity, 1 point; spontaneous bleeding, 1 point; and undifferentiated histology, 2 points. Our risk scoring model showed good discriminatory performance on internal validation (bootstrap-corrected area under the receiver operating characteristic curve, 0.7004; 95% confidence interval, 0.6655-0.7353). Conclusions We developed a validated prediction model that can be used to identify patients who will undergo non-curative resection of ESD. Our prediction model can provide useful information for making decisions about the treatment of EGC before performing ESD.

BACKGROUND AND AIM We evaluated probe-based confocal laser endomicroscopy (pCLE) in the margin delineation of early gastric cancer (EGC) for endoscopic submucosal dissection in comparison with white-light imaging with chromoendoscopy (CE). METHODS We conducted a prospective, randomized controlled study from November 2013 to October 2014 in a tertiary referral hospital. A total of 101 patients scheduled for endoscopic submucosal dissection due to differentiated EGC were randomized into pCLE and CE groups (pCLE 51, CE 50). Markings were made by electrocautery at the proximal and distal tumor margins, as determined by either pCLE or CE. The distance from the marking to the tumor margin was measured in the resected specimen histopathologically and was compared between the two groups by a linear mixed model. RESULTS Among 104 lesions, 80 lesions with 149 markings (pCLE 68, CE 81) were analyzed after excluding undifferentiated EGCs (n = 8) and unidentifiable markings (n = 13). Although the complete resection rate showed no difference between the groups (94.6% vs 93.2%, P = 1.000), the median distance from the marking to the margin was shorter in the pCLE group (1.3 vs 1.8 mm, P = 0.525) and the proportion of the distance

To evaluate the effects of ultraviolet B (UV-B) radiation at the developmental, reproductive, and molecular levels in aquatic invertebrates, we measured UV-B-induced acute toxicity, impairments in developmental and reproductive traits, and UV-B interaction with the entire family of cytochrome P450 (CYP) genes in the intertidal benthic copepod Tigriopus japonicus. We found a significant, dose-dependent reduction (P

Gastrointestinal (GI) leakage, fistulae, and perforations can be serious and life threatening. There has been a paradigm shift in the management approach of these conditions, from surgical to conservative, including endoscopic management. Here, we report two cases of endoscopic closure of a GI fistula and perforation using polyglycolic acid (PGA) sheets with fibrin glue. The first case is of an anastomotic leak detected after subtotal gastrectomy with gastroduodenostomy. After failed application of endoclips, a PGA sheet was applied, and the fistula was successfully closed. The second case was of a 15-mm large perforated gastric ulcer, which was also successfully closed with a PGA sheet. This is the first case report that PGA sheet was used for the treatment of overt perforation. The outcome of these cases suggest that endoscopic closure using PGA sheets can be considered as a useful alternative for the management of GI leakage, fistulae, and perforations.

In marine ecosystems, salinity fluctuations are critical in modulating energy balance, inducing stress proteins, providing reproductive success and affecting the distribution of copepods. Salinity induces osmotic stress in organisms when they are not in their optimal condition and the stressful status increase the energy demand required for osmoregulation, which in turn reflects in all biological processes. Effects of salinity stress on life history traits and tolerance are species-specific. In this study, we used the estuarine cyclopoid copepod Paracyclopina nana to understand the responses towards the hypo (5 ppt) and hypersalinity (25 and 30 ppt) conditions, and compared that with the control (15 ppt). We investigated the life cycle parameters (e.g. growth and fecundity), fatty acid (FA) synthesis, lipid accumulation (as lipid droplets [LDs]) and modulation of heat shock proteins (hsps) in response to salinity stress. As a result, life cycle parameters and FA synthesis, LDs, and modulation of hsps were found highly dependent on salinity changes in P. nana. Particularly, hypersalinity resulted in developmental retardation, reduced fecundity, decreased FA synthesis, a drop in lipid accumulation, and modulation of stress response proteins, suggesting that P. nana devoted increased energy to cope with the osmotic imbalance due to salinity stress in hypersalinity conditions. This finding provides a better understanding of how salinity affects in vivo endpoints and the relevant molecular responses in estuarine copepods. Statement of relevance We envisage that this manuscript will be helpful to understand salinity-dependent lipid composition changes in copepods and optimize the optimal salinity for the mass culture for this species. Considering the small size (~ 600 μm) of P. nana and its potential as live feeds for finfish larviculture, the present findings have considerable importance for the aquaculture industry.

The copepod Tigriopus japonicus has been widely used as an experimental species in the field of ecotoxicology. We have sequenced and assembled the whole genome of T. japonicus with comparative analysis of gene families that represent detoxification phases in two additional public genomes of Tigriopus spp., namely, T. californicus and T. kingsejongensis. The total length of the T. japonicus assembled genome was 196.6 Mb with an N50 value of 10.65 Mb and consisted of 339 scaffolds and 25,143 annotated genes. The detoxification gene families encoding cytochrome P450s (CYP450s), glutathione S-transferases (GSTs), and ATP-binding cassette (ABC) proteins in Tigriopus spp. have shown species-dependent diversity in several gene sets, suggesting that these genes have undergone a species-specific expansion to increase their fitness to different marine habitats and environmental pressures. Our study will provide a better understanding of the detoxification system in Tigriopus spp. and will contribute to various areas of research, including ecotoxicology.

Various xenobiotics are constantly being released and accumulated into the aquatic environments and consequently, the aquatic organisms are continuously being exposed to exogenous stressors. Among various xenobiotic detoxifying enzymes, Glutathione S-transferase (GST) is one of the major xenobiotic detoxifying enzyme which is widely distributed among living organisms and thus, understanding of the nature of GSTs is crucial. Previous studies have shown GST activity in response to various xenobiotics yet, full identification of GSTs in marine invertebrates is still limited. This review covers information on the importance of GSTs as a biomarker for emerging chemicals and their response to wide ranges of environmental pollutants as well as in-depth phylogenetic analysis of marine invertebrates, including recently identified GSTs belonging to rotifers (Brachionus spp.) and copepods (Tigriopus japonicus and Paracyclopina nana), with unique class-specific features of GSTs, as well as a new suggestion of GST evolutionary pathway.

To understand effects of two widely used antidepressant on the antioxidant defense mechanism in the marine rotifer Brachionus koreanus, we assessed acute toxicity and measured population growth, reactive oxygen species (ROS) levels, glutathione (GSH) levels, and antioxidant enzymatic activities (GST, GR, and SOD) in response to fluoxetine hydrochloride (FLX) and sertraline hydrochloride (SER). The no observed effect concentration-24 h of fluoxetine and sertraline were 1000 μg/L and 450 μg/L, respectively, whereas the median lethal concentration (LC50)-24 h of fluoxetine and sertraline were 1560 μg/L and 507 μg/L, respectively. Both fluoxetine and sertraline caused significant reduction (P0.05) in the population growth rate indicating that both antidepressants have a potential adverse effect on life cycle parameters of B. koreanus. The intracellular ROS level and GSH level were significantly modulated (P0.05) in response to fluoxetine and sertraline. In addition, antioxidant enzymatic activities have shown significant modulation (P0.05) in response to FLX and SER in B. koreanus. Furthermore, transcriptional profiles of antioxidant genes (GSTs, SODs, and GR) have shown modulation in response to FLX compared to SER-exposed B. koreanus. Our results indicate that fluoxetine and sertraline induce oxidative stress, leading to reduction in the population density and modulation of antioxidant defense mechanism in the marine rotifer B. koreanus.

Background/Aims Achalasia is a chronic, progressive motility disorder of the esophagus. The sigmoid-type achalasia is an advanced stage of achalasia characterized by severe dilatation and tortuous angulation of the esophageal body. Peroral endoscopic myotomy (POEM) has been reported to provide excellent clinical outcomes for achalasia, including the sigmoid type, but the restoration of esophageal morphology and function remain poorly described. The aim of our study is to investigate esophageal restoration after POEM for sigmoid-type achalasia. Methods From 98 patients with achalasia who underwent POEM in the Yonsei University Health System from 2013 to 2018, we recruited 13 patients with sigmoid-type achalasia (7 male; mean age 53.3 years) and assessed morphological and manometric changes in the esophagus. Results Clinical success (Eckardt score < 3) was achieved in all cases. After POEM, the average angle of esophageal tortuosity became more obtuse (91.5° vs 114.6°, P = 0.046), esophageal body diameter decreased (67.6 vs 49.8 mm, P = 0.002), and esophagogastric junction opening widened (6.4 vs 9.5 mm, P = 0.048). Patients whose esophageal tortuosity did not improve had longer durations of symptoms than patients with improvement (80.2 vs 636 months, P < 0.001). An absence of peristalsis was observed in all patients pre- and post-POEM. Conclusions POEM resulted in excellent clinical outcomes and morphologic improvement in sigmoid-type achalasia. These results suggest that the improvement of esophageal tortuosity through POEM reflects a reduced esophageal burden.

To examine how tributyltin (TBT), a model obesogen, affects the lipid metabolism in the marine rotifer Brachionus koreanus, we carried out life-cycle studies and determined the in vitro and in silico interactions of retinoid X receptor (RXR) with TBT, the transcriptional levels of RXR and lipid metabolic genes, and the fatty acid content. The lethal concentration 10% (LC10) was determined to be 5.12 μg/L TBT, and negative effects on ecologically relevant end points (e.g., decreased lifespan and fecundity) were detected at 5 μg/L TBT. On the basis of these findings, subsequent experiments were conducted below 1 μg/L TBT, which did not show any negative effects on ecologically relevant end points in B. koreanus. Nile red staining analysis showed that after exposure to 1 μg/L TBT, B. koreanus stored neutral lipids and had significantly increased transcriptional levels of RXR and lipid metabolism-related genes compared to the control. However, the content of total fatty acids did not significantly change at any exposure level. In the single fatty acids profile, a significant increase in saturated fatty acids (SFAs) 14:0 and 20:0 was observed, but the contents of omega-3 and omega-6 fatty acids were significantly decreased. Also, a transactivation assay of TBT with RXR showed that TBT is an agonist of Bk-RXR with a similar fold-induction to the positive control. Taken together, these results demonstrate that TBT-modulated RXR signaling leads to increase in transcriptional levels of lipid metabolism-related genes and the synthesis of SFAs but decreases the content of polyunsaturated fatty acids (PUFAs). Our findings support a wider taxonomic scope of lipid perturbation due to xenobiotic exposure that occurs via NRs in aquatic animals.

Metal pollution is one of the major threats to the aquatic environment due to its high bio-concentrations and toxicity. Although numerous studies have been conducted to understand detoxification and toxicity mechanisms in aquatic invertebrates, most of them were limited in laboratory study. Here, we investigated adverse effects of the contaminated-natural seawater on the marine rotifer Brachionus koreanus. Field seawater was collected from five different sites of Youngil Bay, South Korea where pollution by metals is predicted due to industrial discharges from nearby steel industry complexes. The marine rotifer B. koreanus was exposed to different seawater samples, and we found decreased population growth rates with highly induced transcriptional level of detoxification-related genes. Our finding shows a link between the induction of metal-mediated regulation of detoxification genes in B. koreanus and concentration of heavy metals present in various seawater samples, implying those biomarker genes can be useful to assess the toxicity of metal polluted natural seawaters. Our results are helpful to validate and establish biomarker genes for early risk assessment of metal contamination in the natural sea water.

The eradication rates for Helicobacter pylori have decreased in Korea although the prevalence of this bacterium has also decreased. Antibiotic resistance is likely to be a crucial factor in H. pylori eradication success, and we therefore mapped these resistance patterns nationwide in Korea.Five hundred and ninety adult subjects were prospectively enrolled from 2017 to 2018 from 15 centers across six geographic areas of Korea. A total of 580 biopsy tissues had been sampled from these patients during an upper endoscopy and were frozen at -80°C and delivered to a central laboratory. The agar dilution method was used to determine the minimum inhibitory concentration of amoxicillin, clarithromycin, metronidazole, tetracycline, ciprofloxacin, and levofloxacin for each H. pylori isolate.The culture success rate was 60.2% (349/580). Resistance rates against clarithromycin, metronidazole, amoxicillin, tetracycline, levofloxacin, and ciprofloxacin were 17.8%, 29.5%, 9.5%, 0%, 37.0%, and 37.0%, respectively. The geographic distribution of metronidazole and quinolone resistance was highly variable. Some subjects had multiple H. pylori strains in the antrum and body of the stomach and showed a heterogeneous resistance profile between these anatomic areas. The H. pylori multidrug resistance (MDR) rate was 25.2% (88/349) among amoxicillin, clarithromycin, metronidazole, tetracycline, and quinolone and 11.2% (39/349) among four of these major antibiotics except for quinolone. The Seoul and Chungcheong areas showed a relatively lower MDR rate.The antibiotic resistance of H. pylori differs by drug and geographic area in Korea. Detailed nationwide antibiotic resistance mapping is needed to develop an effective H. pylori eradication strategy.