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Background: Cholera can result in the expulsion of important microbiota from the gut and result in death if left untreated. The disease transmits mainly via drinking water carrying Vibrio cholerae; and household contacts (HHC) of cholera patients are at elevated risk during the first week of infection. The gut microbiota profiles of HHC-children of cholera patients at Dhaka city slums were investigated before (day 0) and after (day 8) delivery of chlorinated water as part of the major study 'CHoBI7 trial (cholera-hospital-based intervention for 7 days)'., Result: Results of sequencing and analysis of bacterial community DNA revealed the predominance of two bacterial phyla: Bacteroidetes and Firmicutes at day 0 with a relative abundance of 62 ± 6 (mean ± SEM%) and 32 ± 7, respectively. The pattern reversed at day 8 with a decreased relative abundance of Bacteroidetes (39 ± 12; p = 0.034) and an increased abundance of Firmicutes (49 ± 12; p = 0.057). Of 65 bacterial families confirmed at day 0, six belonging to Proteobacteria including Vibrionaceae disappeared at day 8. Interestingly, the relative abundance of four Firmicutes families-Lachnospiraceae, Bifidobacteriaceae, Clostridiaceae, and Ruminococcaceae was increased in all five study children at day 8., Conclusion: The observed exclusion of pathogenic Proteobacteria and enhancement of beneficial Firmicutes in the gut of children delivered with chlorinated water as part of WASH intervention reflect a great promise of the CHoBI7 program in preventing cholera and improving child health., (© 2023. The Author(s).)

A prostate-targeted biopsy (TB) core is usually collected from a site where magnetic resonance imaging (MRI) indicates possible cancer. However, the extent of the lesion is difficult to accurately predict using MRI or TB alone. Therefore, we performed several biopsies around the TB site (perilesional [p] TB) and analyzed the association between the positive cores obtained using TB and pTB and the Prostate Imaging Reporting and Data System (PI-RADS) scores. This retrospective study included patients who underwent prostate biopsies. The extent of pTB was defined as the area within 10 mm of a TB site. A total of 162 eligible patients were enrolled. Prostate cancer (PCa) was diagnosed in 75.2% of patients undergoing TB, with a positivity rate of 50.7% for a PI-RADS score of 3, 95.8% for a PI-RADS score of 4, and 100% for a PI-RADS score of 5. Patients diagnosed with PCa according to both TB and pTB had significantly higher positivity rates for PI-RADS scores of 4 and 5 than for a PI-RADS score of 3 ( p < 0.0001 and p = 0.0009, respectively). Additional pTB may be performed in patients with PI-RADS ≥ 4 regions of interest for assessing PCa malignancy.

In 2022, one of its worst cholera outbreaks began in Bangladesh and the icddr,b Dhaka hospital treated more than 1300 patients and ca. 42,000 diarrheal cases from March-1 to April-10, 2022 1 . Here, we present genomic attributes of V. cholerae O1 responsible for the 2022 Dhaka outbreak and 960 7th pandemic El Tor (7PET) strains from 88 countries. Results show strains isolated during the Dhaka outbreak cluster with 7PET wave-3 global clade strains, but comprise subclade BD-1.2, for which the most recent common ancestor appears to be that responsible for recent endemic cholera in India. BD-1.2 strains are present in Bangladesh since 2016, but not establishing dominance over BD-2 lineage strains 2 until 2018 and predominantly associated with endemic cholera. In conclusion, the recent shift in lineage and genetic attributes, including serotype switching of BD-1.2 from Ogawa to Inaba, may explain the increasing number of cholera cases in Bangladesh., (© 2023. The Author(s).)

Vibrio cholerae O1 El Tor, causative agent of the ongoing seventh cholera pandemic, is native to the aquatic environment of the Ganges Delta, Bay of Bengal (GDBB). Recent studies traced pandemic strains to the GDBB and proposed global spread of cholera had occurred via intercontinental transmission. In the research presented here, NotI-digested genomic DNA extracted from V. cholerae O1 clinical and environmental strains isolated in Bangladesh during 20042014 was analyzed by pulsed-field gel electrophoresis (PFGE). Results of cluster analysis showed 94.67% of the V. cholerae strains belonged to clade A and included the majority of clinical strains of spatio-temporal origin and representing different cholera endemic foci. The rest of the strains were estuarine, all environmental strains from Mathbaria, Bangladesh, and occurred as singletons, clustered in clades B and C, or in the small clades D and E. Cluster analysis of the Bangladeshi strains and including 157 El Tor strains from thirteen countries in Asia, Africa, and the Americas revealed 85% of the total set of strains belonged to clade A, indicating all were related, yet did not form an homogeneous cluster. Overall, 15% of the global strains comprised multiple small clades or segregated as singletons. Three sub-clades could be discerned within the major clade A, reflecting distinct lineages of V. cholerae O1 El Tor associated with cholera in Asia, Africa, and the Americas. The presence in Asia and the Americas of non-pandemic V. cholerae O1 El Tor populations differing by PFGE and from strains associated with cholera globally suggests different ecotypes are resident in distant geographies., Competing Interests: Declaration of Competing Interest The research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

Comparative genomic analysis of Vibrio cholerae El Tor associated with endemic cholera in Asia revealed two distinct lineages, one dominant in Bangladesh and the other in India. An in-depth whole-genome study of V. cholerae El Tor strains isolated during endemic cholera in Bangladesh (1991 to 2017) included reference genome sequence data obtained online. Core genome phylogeny established using single nucleotide polymorphisms (SNPs) showed V. cholerae El Tor strains comprised two lineages, BD-1 and BD-2, which, according to Bayesian phylodynamic analysis, originated from paraphyletic group BD-0 around 1981. BD-1 and BD-2 lineages overlapped temporally but were negatively associated as causative agents of cholera during 2004 to 2017. Genome-wide association study (GWAS) revealed 140 SNPs and 31 indels, resulting in gene alleles unique to BD-1 and BD-2. Regression analysis of root to tip distance and year of isolation indicated early BD-0 strains at the base, whereas BD-1 and BD-2 subsequently emerged and progressed by accumulating SNPs. Pangenome analysis provided evidence of gene acquisition by both BD-1 and BD-2, of which six crucial proteins of known function were predominant in BD-2. BD-1 and BD-2 diverged and have distinctively different genomic traits, namely, heterogeneity in VSP-2, VPI-1, mobile elements, toxin encoding elements, and total gene abundance. In addition, the observed phage-inducible chromosomal island-like element (PLE1), and SXT ICE elements (ICE TET ) in BD-2 presumably provided a fitness advantage for the lineage to outcompete BD-1 as the etiological agent of endemic cholera in Bangladesh, with implications for global cholera epidemiology. IMPORTANCE Cholera is a global disease with specific reference to the Bay of Bengal Ganges Delta where Vibrio cholerae O1 El Tor, the causative agent of the disease showed two circulating lineages, one dominant in Bangladesh and the other in India. Results of an in-depth genomic study of V. cholerae associated with endemic cholera during the past 27 years (1991 to 2017) indicate emergence and succession of the two lineages, BD-1 and BD-2, arising from a common ancestral paraphyletic group, BD-0, comprising the early strains and short-term evolution of the bacterium in Bangladesh. Among the two V. cholerae lineages, BD-2 supersedes BD-1 and is predominant in the most recent endemic cholera in Bangladesh. The BD-2 lineage contained significantly more SNPs and indels, and showed richness in gene abundance, including antimicrobial resistance genes, gene cassettes, and PLE to fight against bacteriophage infection, acquired over time. These findings have important epidemic implications on a global scale.

Interorganellar cross talk is often mediated by membrane contact sites (MCSs), which are zones where participating membranes come within 30 nm of one another. MCSs have been found in organelles, including the endoplasmic reticulum, Golgi bodies, endosomes, and mitochondria. Despite its seeming ubiquity, reports of MCS involving mitochondrion-related organelles (MROs) present in a few anaerobic parasitic protozoa remain lacking. Entamoeba histolytica, the etiological agent of amoebiasis, possesses an MRO called the mitosome. We previously discovered several Entamoeba -specific transmembrane mitosomal proteins (ETMPs) from in silico and cell-biological analyses. One of them, ETMP1 (EHI&#95;175060), was predicted to have one transmembrane domain and two coiled-coil regions and was demonstrated to be mitosome membrane integrated based on carbonate fractionation and immunoelectron microscopy (IEM) data. Immunoprecipitation analysis detected a candidate interacting partner, EH domain-containing protein (EHD1; EHI&#95;105270). We expressed hemagglutinin (HA)-tagged EHD1 in E. histolytica, and subsequent immunofluorescence and IEM data indicated an unprecedented MCS between the mitosome and the endosome. Live imaging of a green fluorescent protein (GFP)-EHD1-expressing strain demonstrated that EHD1 is involved in early endosome formation and is observed in MCS between endosomes of various sizes. In vitro assays using recombinant His-EHD1 demonstrated ATPase activity. MCSs are involved in lipid transfer, ion homeostasis, and organelle dynamics. The serendipitous discovery of the ETMP1-interacting partner EHD1 led to the observation of the mitosome-endosome contact site in E. histolytica. It opened a new view of how the relic mitochondria of Entamoeba may likewise be involved in organelle cross talk, a conserved feature of mitochondria and other organelles in general. IMPORTANCE Membrane contact sites (MCSs) are key regulators of interorganellar communication and have been widely demonstrated between various organelles. However, studies on MCSs involving mitochondrion-related organelles (MROs), present in some anaerobic parasitic protozoans, remain scarce. Entamoeba histolytica, the etiological agent of amoebiasis, possesses an MRO called the mitosome. This organelle is crucial for cellular differentiation and disease transmission, thereby significantly contributing to the amoeba's parasitic lifestyle. Our recent discovery of the interaction between the Entamoeba -specific transmembrane mitosomal protein (ETMP1) and EH domain-containing protein (EHD1) showcases a newly found mitosome-endosome contact site in E. histolytica. This finding reflects the idea that despite their substantially divergent and reduced nature, MROs like mitosomes conserve mechanisms for interorganellar cross talk. We posit lipid and ion transport, mitosome fission, and quality control as potential processes that are mediated by the ETMP1-EHD1-tethered mitosome-endosome contact site in E. histolytica.

Purpose: To compare the real-world effectiveness of antipsychotic treatments focusing on long-acting injectable antipsychotic medications (LAIs) and antipsychotic polytherapies except polytherapy involving clozapine (APEC) for patients with schizophrenia., Methods: This prospective study was conducted over a 19-month period in 12 psychiatric emergency hospitals in Japan. Patients who were newly admitted to psychiatric emergency wards between September 2019 and March 2020 because of acute onset or exacerbation of Schizophrenia and Other Psychotic Disorders as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, were included. All patients were followed for one-year after discharge or until March 31, 2021. The primary outcome was the risk of treatment failure defined as psychiatric rehospitalization, discontinuation of medication, death, or continuation of hospitalization for one year. Cox proportional hazards multivariate regression was used for analyses., Results: A total of 1011 patients were enrolled (women, 53.7%; mean [SD] age, 47.5 [14.8] years). During follow-up, 588 patients (58.2%) experienced treatment failure including rehospitalization (513 patients), discontinuation of medication (17 patients), death (11 patients), and continuation of hospitalization for one-year (47 patients). Switching to LAIs (hazard ratio [HR] 0.810, 95%CI 0.659-0.996) and APEC (HR 0.829, 95%CI 0.695-0.990) were significantly associated with a low rate of treatment failure., Conclusions: Switching to LAIs and APEC in early non-responders seems to be beneficial for the prevention of treatment failure in acutely admitted patients with schizophrenia. The risk of treatment failure was about 19% and 17% lower in patients treated with LAIs and APEC, respectively, than in patients treated without them., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Five novel strains of Serratia fonticola that produce FONA, a minor extended-spectrum beta-lactamase (ESBL), were isolated during routine surveillance of ESBL-producing Enterobacteriaceae in imported chicken meat in Japan in 2017 and 2018. These strains exhibited a clear ESBL phenotype in susceptibility tests carried out in the presence of clavulanic acid; however, all strains tested negative in a multiplex polymerase chain reaction assay used to detect TEM, SHV, and CTX-M β-lactamase genes. After identification of the bacterial species as S. fonticola, full length bla FONA genes were amplified and the DNA sequences were determined. The bla FONA genes from all 5 strains were different from those previously reported (bla FONA-1 to bla FONA-6 ); they clustered close to one another but were distinct from previously reported bla FONA genes in a phylogenic analysis based on amino acid sequences.

Streptococcus pyogenes (group A streptococcus; GAS) is an important gram-positive human pathogen capable of causing diseases ranging from mild superficial skin and pharyngeal infections to more severe invasive diseases, including streptococcal toxic shock syndrome (STSS). GAS produces a T protein, and T serotyping has considerable discriminatory power for epidemiological characterization of GAS. To clarify the relationship between STSS and pharyngitis in Japan, we examined the T serotypes of GAS strains isolated from clinical specimens of streptococcal infections (STSS, 951 isolates; pharyngitis, 16268 isolates) from 2005 to 2017. The most prevalent T serotype from pharyngitis isolates was T12, followed by T1, T4, and TB3264. The most prevalent T serotype from STSS isolates was T1, followed by TB3264. Trend of increase and decrease in the frequency of T1 or TB3264 isolation from pharyngitis was correlated with that of STSS patients. The increase of T1 or TB3264 strain-infection in pharyngitis patients may increase the probability of causing STSS, indicating that careful monitoring of GAS serotypes is essential for the prediction of rapid increase of STSS in time to develop effective management strategies., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Extended-spectrum β-lactamases (ESBLs) form the most important resistance determinants prevalent worldwide. Data on ESBL-producing Escherichia coli from poultry and livestock are scarce in India. We present data on the functional and genomic characterization of ESBL-producing E. coli obtained from poultry in India. The whole genome sequences of 28 ESBL-producing E. coli were analyzed comprising of 12 broiler chicken E. coli isolates, 11 free-range chicken E. coli isolates, and 5 human extraintestinal pathogenic E. coli . All of the 28 ESBL-producing E. coli isolates were tested for antibiotic susceptibilities, in vitro conjugation, and virulence-associated phenotypic characteristics. A total of 13 sequence types were identified from the poultry E. coli , which included globally successful sequence types such as ST117 (9%), ST131 (4.3%), and ST10 (4.3%). The most common ESBL gene detected in poultry E. coli genomes was bla CTX-M-15 (17%). Also, FIB (73%) and FII (73%) were the most common plasmid replicons identified. Conjugation experiments demonstrated 54 (7/13), 30 (3/10), and 40% (2/5) of broiler, free-range, and human ExPEC E. coli to be able to transfer their ESBL genes, respectively. The in vitro virulence-associated phenotypic tests revealed the broiler, free-range, and human ExPEC isolates to be comparable in biofilm formation, resistance to serum bactericidal activity, adherence, and invasion capabilities. Our overall results showed prevalence of virulence phenotypes among the diverse ESBL-producing E. coli from poultry; while certain E. coli clones from broiler-poultry may indeed have the potential to cause infection in humans., (Copyright © 2019 Hussain, Shaik, Ranjan, Suresh, Sarker, Semmler, Wieler, Alam, Watanabe, Chakravortty and Ahmed.)

Severe invasive group A Streptococcus (GAS) infection evades anti-bacterial immunity by attenuating the cellular components of innate immune responses. However, this loss of protection is compensated for by interferon (IFN)-γ-producing immature myeloid cells (γIMCs), which are selectively recruited upon severe invasive GAS infection in mice. Here, we demonstrate that γIMCs provide this IFN-γ-mediated protection by sequentially sensing GAS through two distinct pattern recognition receptors. In a mouse model, GAS is initially recognized by Toll-like receptor 2 (TLR2), which promptly induces interleukin (IL)-6 production in γIMCs. γIMC-derived IL-6 promotes the upregulation of a recently identified GAS-sensing receptor, macrophage-inducible C-type lectin (Mincle), in an autocrine or paracrine manner. Notably, blockade of γIMC-derived IL-6 abrogates Mincle expression, downstream IFN-γ production, and γIMC-mediated protection against severe invasive GAS infection. Thus, γIMCs regulate host protective immunity against severe invasive GAS infection via a TLR2-IL-6-Mincle axis., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: The effectiveness of antipsychotic treatments in the acute phase of schizophrenia in actual clinical practice remains somewhat unclear. Therefore, the purpose of the present naturalistic, multi-center study conducted from 1 year starting in September 2017 was to examine the response rate to an initial or second antipsychotic in newly admitted patients with acute-phase schizophrenia, as well as the response rate and quality of augmentation with two antipsychotics in patients who failed to respond to both the initial and second antipsychotics., Results: In total, there were 660 (42.8%) and 243 (15.7%) responders to an initial and a second antipsychotic, respectively; thus, 58.5% of all patients were responders to an initial or second antipsychotic. Among 581 nonresponders (37.7%), the initial antipsychotic or a third antipsychotic was added to the second antipsychotic. Among these patients, 89.8% showed a Clinical Global Impression-Improvement score ≤3 (from 'minimally improved' to 'very much improved'). The rates of adverse events such as hyperglycemia, hyper-low-density lipoprotein cholesterolemia, hypertriglyceridemia, hyperprolactinemia, QTc prolongation, and extrapyramidal symptoms were not high in patients receiving augmentation with two antipsychotics compared with all patients, and no serious adverse events were reported., Conclusion: Antipsychotic augmentation may be an option in acute-phase treatment for patients who do not respond to either an initial or a second antipsychotic., (Copyright © 2019 Elsevier B.V. All rights reserved.)

While Neisseria meningitidis typically exists in an asymptomatic nasopharyngeal carriage state, it may cause potentially lethal diseases in humans, such as septicemia or meningitis, by invading deeper sites in the body. Since the nutrient compositions of human cells are not always conducive to meningococci, N. meningitidis needs to exploit nutrients from host environments. In the present study, the utilization of cysteine by the meningococcal cysteine transport system (CTS) was analyzed for the pathogenesis of meningococcal infections. A N. meningitidis strain deficient in one of the three cts genes annotated as encoding cysteine-binding protein ( cbp ) exhibited approximately 100-fold less internalization into human brain microvascular endothelial cells (HBMEC) than the wild-type strain. This deficiency was restored by complementation with the three cts genes together, and the infectious phenotype of HBMEC internalization correlated with cysteine uptake activity. However, efficient accumulation of ezrin was observed beneath the cbp mutant. The intracellular survival of the cbp mutant in HBMEC was markedly reduced, whereas equivalent reductions of glutathione concentrations and of resistance to reactive oxygens species in the cbp mutant were not found. The cbp mutant grew well in complete medium but not in synthetic medium supplemented with less than 300 μM cysteine. Taking cysteine concentrations in human cells and other body fluids, including blood and cerebrospinal fluid, into consideration, the present results collectively suggest that the meningococcal CTS is crucial for the acquisition of cysteine from human cells and participates in meningococcal nutrient virulence. IMPORTANCE Neisseria meningitidis colonizes at a nasopharynx of human as a unique host and has many strains that are auxotrophs for amino acids for their growth. To cause invasive meningococcal diseases (IMD) such as sepsis and meningitis, N. meningitidis passes through epithelial and endothelial barriers and infiltrates into blood and cerebrospinal fluid as well as epithelial and endothelial cells. However, meningococcal nutrients, including cysteine, become less abundant when it more deeply infiltrates the human body even during inflammation, such that N. meningitidis has to acquire nutrients in order to survive/persist, disseminate, and proliferate in humans. This was the first study to examine the relationship between meningococcal cysteine acquisition and the pathogenesis of meningococcal infections. The results of the present study provide insights into the mechanisms by which pathogens with auxotrophs acquire nutrients in hosts and may also contribute to the development of treatments and prevention strategies for IMD., (Copyright © 2018 Takahashi et al.)

Escherichia coli sequence type 131 (ST131), a pandemic clone responsible for the high incidence of extraintestinal pathogenic E. coli (ExPEC) infections, has been known widely for its contribution to the worldwide dissemination of multidrug resistance. Although other ExPEC-associated and extended-spectrum-β-lactamase (ESBL)-producing E. coli clones, such as ST38, ST405, and ST648 have been studied widely, no comparative genomic data with respect to other genotypes exist for ST131. In this study, comparative genomic analysis was performed for 99 ST131 E. coli strains with 40 genomes from three other STs, including ST38 ( n = 12), ST405 ( n = 10), and ST648 ( n = 18), and functional studies were performed on five in-house strains corresponding to the four STs. Phylogenomic analysis results from this study corroborated with the sequence type-specific clonality. Results from the genome-wide resistance profiling confirmed that all strains were inherently multidrug resistant. ST131 genomes showed unique virulence profiles, and analysis of mobile genetic elements and their associated methyltransferases (MTases) has revealed that several of them were missing from the majority of the non-ST131 strains. Despite the fact that non-ST131 strains lacked few essential genes belonging to the serum resistome, the in-house strains representing all four STs demonstrated similar resistance levels to serum antibactericidal activity. Core genome analysis data revealed that non-ST131 strains usually lacked several ST131-defined genomic coordinates, and a significant number of genes were missing from the core of the ST131 genomes. Data from this study reinforce adaptive diversification of E. coli strains belonging to the ST131 lineage and provide new insights into the molecular mechanisms underlying clonal diversification of the ST131 lineage. IMPORTANCE E. coli , particularly the ST131 extraintestinal pathogenic E. coli (ExPEC) lineage, is an important cause of community- and hospital-acquired infections, such as urinary tract infections, surgical site infections, bloodstream infections, and sepsis. The treatment of infections caused by ExPEC has become very challenging due to the emergence of resistance to the first-line as well as the last-resort antibiotics. This study analyzes E. coli ST131 against three other important and globally distributed ExPEC lineages (ST38, ST405, and ST648) that also produced extended-spectrum β-lactamase (ESBL). This is perhaps the first study that employs the high-throughput whole-genome sequence-based approach to compare and study the genomic features of these four ExPEC lineages in relation to their functional properties. Findings from this study highlight the differences in the genomic coordinates of ST131 with respect to the other STs considered here. Results from this comparative genomics study can help in advancing the understanding of ST131 evolution and also offer a framework towards future developments in pathogen identification and targeted therapeutics to prevent diseases caused by this pandemic E. coli ST131 clone., (Copyright © 2017 Shaik et al.)

Of 19 environmental Escherichia coli (n = 12) and Klebsiella pneumoniae (n = 7) tested for quinolone resistance-related genes qnrA , qnrB , qnrC , qnrS and qepA , four each of E. coli and K. pneumoniae possessed qnrS , and another E. coli isolate possessed a new variant of qepA . This is the first detection of qepA in environmentally dwelling bacteria in Bangladesh.

Background: The gut of human harbors diverse commensal microbiota performing an array of beneficial role for the hosts. In the present study, the major commensal gut bacteria isolated by culturing methods from 15 children of moderate income families, aged between 10 and 24 months, were studied for their response to different antibiotics, and the molecular basis of drug resistance., Results: Of 122 bacterial colonies primarily selected from Luria-Bertani agar, bacterial genera confirmed by analytical profile index (API) 20E ® system included Escherichia as the predominant (52%) organism, followed by Enterobacter (16%), Pseudomonas (12%), Klebsiella (6%), Pantoea (6%), Vibrio (3%), and Citrobacter (3%); while Aeromonas and Raoultella were identified as the infrequently occurring genera. An estimated 11 and 22% of the E. coli isolates carried virulence marker genes stx -2 and eae , respectively. Antimicrobial susceptibility assay revealed 78% of the gut bacteria to be multidrug resistant (MDR) with highest resistance to erythromycin (96%), followed by ampicillin (63%), tetracycline (59%), azithromycin (53%), sulfamethoxazole-trimethoprim (43%), cefixime (39%), and ceftriaxone (33%). PCR assay results revealed 56% of the gut bacteria to possess gene cassette Class 1 integron; while 8, 17.5 and 6% of the strains carried tetracycline resistance-related genes tet A, tet B, and tet D, respectively. The macrolide (erythromycin and azithromycin) resistance marker genes mph A, ere B, and erm B were found in 28, 3 and 5% of bacterial isolates, respectively; while 26, 12, 17, 32, 7, 4 and 3% of the MDR bacterial isolates carried the extended spectrum β-lactamase (ESBL)-related genes e.g., bla TEM , bla SHV , bla CMY-9 , bla CTX-M1 , bla CTX-M2 , bla CMY-2 and bla OXA respectively. Majority of the MDR gut bacteria harbored large plasmids [e.g., 140 MDa (43%), 105 MDa (30%), 90 MDa (14%)] carrying invasion and related antibiotic resistance marker genes., Conclusions: Our results suggest gut of young Bangladeshi children to be an important reservoir for multi-drug resistant pathogenic bacteria carrying ESBL related genes.

Shiga toxin-producing Escherichia coli (STEC) and enterotoxigenic E. coli (ETEC) are important causes of diarrhea in humans and animals worldwide. Although ruminant animals are the main source of STEC, diarrhea due to this pathotype is very low in Bangladesh where ETEC remains the predominant group associated with childhood diarrhea. In the present study, E. coli strains ( n  = 35) isolated from Bangladesh livestock (goats, sheep, and cattle) and poultry (chicken and ducks) were analyzed for the presence of major virulence factors, such as Shiga toxins (STX-1 and STX-2), heat-labile toxin, and heat-stable toxins (STa and STb). Multiplex polymerase chain reaction results revealed 23 (66%) E. coli strains to be virulent possessing either sta ( n  = 5), stx ( stx 1, n  = 8; stx 2, n  = 2), or both ( n  = 8) genes in varying combinations. Thirty-four percent (8/23) of strains from livestock were hybrid type that carried both stx (either stx 1 or stx 2) and ETEC-specific enterotoxin gene sta . Serotyping results revealed that the ETEC strains belonged to five serotypes, namely O36:H5, O174:H-, O152:H8, O109:H51, and O8:H21, while the STEC-producing strains belonged to serotypes O76:H19 ( n  = 3), O43:H2 ( n  = 2), O87:H16 ( n  = 2), OR:H2 ( n  = 1), O110:H16 ( n  = 1), and O152:H8 ( n  = 1). The STEC-ETEC hybrid strains belonged to serotypes O76:H19 ( n  = 3), O43:H2 ( n  = 2), O87:H16, OR:H2, and O152:H8. Forty percent (2/5) of the ETEC and 20% (2/10) of the STEC strains were multidrug resistant with the highest drug resistance (50%) being found in the hybrid strains. Molecular fingerprinting determined by pulsed-field gel electrophoresis and cluster analyses by dendrogram revealed that, genetically, STEC-ETEC hybrid strains were highly heterogeneous. Multidrug-resistant E. coli STEC-ETEC hybrid strains in domesticated animals pose a public health threat for humans in Bangladesh.

Antimicrobial use in food animals selects for antimicrobial resistance in bacteria, which can spread to people. Reducing use of antimicrobials-particularly those deemed to be critically important for human medicine-in food production animals continues to be an important step for preserving the benefits of these antimicrobials for people. The World Health Organization ranking of antimicrobials according to their relative importance in human medicine was recently updated. Antimicrobials considered the highest priority among the critically important antimicrobials were quinolones, third- and fourth-generation cephalosporins, macrolides and ketolides, and glycopeptides. The updated ranking allows stakeholders in the agriculture sector and regulatory agencies to focus risk management efforts on drugs used in food animals that are the most important to human medicine. In particular, the current large-scale use of fluoroquinolones, macrolides, and third-generation cephalosporins and any potential use of glycopeptides and carbapenems need to be addressed urgently., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Vibrio parahaemolyticus is responsible for seafood-related gastroenteritis worldwide. In Bangladesh, diarrhea is endemic and diarrheagenic V. parahaemolyticus serotypes occur naturally in the coastal and estuarine aquatic environment. V. parahaemolyticus strains, isolated from estuarine surface water of the Bay of Bengal villages of Bangladesh during 2006-2008, were tested for the presence of virulence and pandemic-marker genes, serodiversity, and phylogenetic relatedness. PCR analysis of V. parahaemolyticus (n=175) showed 53 (30.3%) strains to possess tdh, the major virulence gene encoding thermostable direct hemolysin. Serotyping results revealed the tdh(+)V. parahaemolyticus strains to belong to 10 different serotypes, of which the O8:K21 (30.2%) and O3:K6 (24.5%) were predominantly non-pandemic and pandemic serotypes, respectively; while O5:K30 and O9:KUT were new. The pandemic markers, orf8 and toxRS(variant), were present only in the pandemic serotype O3:K6 (n=13) and its serovariant O4:K68 (n=2). Temporal distribution of the tdh(+) serotypes revealed the O8:K21 to be predominant in 2006 and 2007, while O3:K6 was the predominant tdh(+) serotype in 2008. Pulsed-field gel electrophoresis (PFGE) of SfiI-digested genomic DNA revealed high genetic diversity among the V. parahaemolyticus strains, while dendrogram constructed with the PFGE patterns formed two major clusters separating the tdh(+) O3:K6 and its pandemic serovariants from the tdh(+) non-pandemic (O8:K21) strains, suggesting different lineages for them. The potential health risk related to the prevalent tdh(+) strains, including the observed temporal change of the predominant tdh(+) serotype, from O8:K21 to the pandemic serotype O3:K6 in estuarine surface waters serving as the major source of drinking water suggests the need for routine environmental monitoring to prevent V. parahaemolyticus infection in Bangladesh., (Copyright © 2016. Published by Elsevier B.V.)

Background: Magnetic resonance imaging (MRI) findings of pilomatricomas have yet to be determined., Purpose: To assess the correlation between MRI and pathological findings of pilomatricomas., Material and Methods: MR images were obtained on patients with histologically proven pilomatricomas using a 1.5-T MR scanner. The images were retrospectively reviewed for size, signal intensity compared with skeletal muscles, and enhancement patterns. Furthermore, we assessed the presence of a reticular appearance, a ring-like appearance, and peritumoral fat stranding., Results: We included 11 consecutive patients with 12 histologically proven pilomatricomas (3 boys/men, 8 girls/women; age range, 4-76 years; mean age, 20 years; median age, 14 years). The tumors were located in the head and neck (n = 6), upper extremities (n = 5), and lower extremities (n = 1). The maximum tumor diameter was in the range of 7-32 mm (mean, 16.5 mm). On T2-weighted (T2W) images, five tumors showed homogeneous hypointensity, whereas six showed reticular hyperintensity and one showed cystic hyperintensity. On fat-suppressed T2W images, nine tumors showed reticular hyperintensity, eight showed ring-like hyperintensity, and five showed peritumoral fat stranding. On fat-suppressed gadolinium-enhanced T1-weighted (T1W) images, one tumor showed no enhancement, whereas three showed reticular enhancement and five showed ring-like enhancement. Histologically, edematous and fibrous stroma was observed in 10 tumors, tumor capsules in 11, and inflammatory cell infiltration of the peritumoral fat tissue in nine., Conclusion: MRI features of pilomatricomas included reticular and ring-like hyperintensities on fat-suppressed T2W images and reticular and ring-like enhancement on fat-suppressed gadolinium-enhanced T1W images., (© The Foundation Acta Radiologica 2015.)

Purpose: To determine the iodine load per body weight (ILPBW) that is minimally required for the detection of pancreatic adenocarcinoma for 80kVp CT imaging., Material and Methods: Institutional review board approval and written informed consent were obtained. Fifty-seven consecutive patients with histopathologically-proven pancreatic adenocarcinoma were assigned to three groups at random according to iodine load (0.5, 0.4, and 0.3gI/kg) and underwent CT at 80kVp. Enhancement of the pancreas and visualization of the tumor were assessed during the pancreatic parenchymal-phase and compared among the three groups. The relationship between the iodine load and tumor conspicuity was also analyzed., Results: The mean CT number of the pancreas (HUpancreas) was higher in the 0.5gI/kg group (158.8HU) than in the 0.4 (121.7HU) and 0.3 (106.6HU) gI/kg groups (P<0.05). Tumor-to-pancreas contrast (HUtumor-to-pancreas) was also higher in 0.5gI/kg group (88.9HU) than in 0.4 (62.2HU) and 0.3 (54.5HU) gI/kg groups (P<0.05). Linear regression between HUpancreas or HUtumor-to-pancreas and ILPBW were expressed as HUpancreas=23.3+263.9×ILPBW (r=0.74, P<0.0001) and HUtumor-to-pancreas=-1.24+174.3×ILPBW (r=0.56, P<0.0001), respectively. The iodine load estimated to achieve an acceptable HUpancreas (>100HU) and HUtumor-to-pancreas (>50HU) were 0.29 and 0.30gI/kg, respectively., Conclusion: An iodine load of 0.3gI/kg was the least amount required for the detection of pancreatic adenocarcinoma at 80kVp CT., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To evaluate the diagnostic performance of noncontrast-enhanced magnetic resonance imaging (MRI) to grade pancreatic fibrosis and to assess hemoglobin (Hb) A1c values., Materials and Methods: Twenty-nine consecutive patients with pancreatic or biliary malignancy who underwent pancreatectomy were evaluated. Patients were classified into three groups: HbA1c < 5.7 (group 1), 5.7 ≤ HbA1c < 6.5 (group 2), and HbA1c ≥ 6.5 (group 3). MRI of the pancreas was performed using a 1.5T MR system. The pancreas-to-muscle signal intensity ratio (SIR) on in- and opposed-phase T1 -, T2 -, and diffusion-weighted images, as well as the apparent diffusion coefficient were calculated. MRI measurements, degrees of pancreatic fibrosis, and HbA1c values were compared using multiple regression analysis and Kruskal-Wallis test., Results: The pancreatic fibrosis grade was negatively correlated with the SIR on in-phase T1 -weighted images (r = -0.67, P = 0.0002). The pancreatic fibrosis grade and HbA1c value were negatively correlated with the SIR on opposed-phase T1 -weighted images (r = -0.47, P = 0.019 and r = -0.51, P = 0.0089, respectively). SIRs on in- and opposed-phase T1 -weighted images were significantly lower in group 3 than in groups 1 and 2 (P < 0.05)., Conclusion: The pancreas-to-muscle SIRs on in- and opposed-phase T1 -weighted images could be a potential biomarker for pancreatic fibrosis and elevated HbA1c values., (© 2015 Wiley Periodicals, Inc.)

Severe fever with thrombocytopenia syndrome virus (SFTSV) is the causative agent of SFTS, an emerging hemorrhagic fever. This disease has a high case fatality rate and is endemic to China, South Korea, and Japan. Because there are currently no effective therapeutics for SFTS, potent and safe antivirals are needed for the treatment of SFTS. The inhibitory effect of T-705 (favipiravir) on the replication of SFTSV in Vero cells was evaluated. Mice lacking the type I interferon receptor (IFNAR(-/-)) were used as an in vivo lethal model for SFTSV infection. T-705, which has been licensed as an anti-influenza drug in Japan, inhibits SFTSV replication both in vitro and in vivo. T-705 inhibited replication of SFTSV in Vero cells by 5 log units, with a 50% inhibitory concentration (IC50) and IC90 of 6.0 µM and 22 µM, respectively. Intraperitoneal or oral administration of T-705 for 5 days to IFNAR(-/-) mice infected with lethal SFTSV significantly improved survival rates (100% survival) without causing body weight loss and reduced the viral load in the serum. Ribavirin also inhibited SFTSV replication. However, it was less effective than T-705 both in vitro and in vivo. A time-of-drug-addition study revealed that therapeutic T-705 treatment of SFTSV infection in IFNAR(-/-) mice was effective. These results suggest that T-705 is a promising candidate for the treatment of SFTS. IMPORTANCE Severe fever with thrombocytopenia syndrome (SFTS), caused by SFTS virus (SFTSV), is a recently identified emerging viral infectious disease. Despite the medical importance of this disease, there are currently neither vaccines nor effective therapeutics for SFTS. T-705, which is a pyrazine derivative, has shown broad antiviral activity against various RNA viruses. The present study demonstrated, for the first time to our knowledge, the efficacy of T-705 in treating SFTSV infection in a mouse lethal model. T-705 showed a high efficacy in the treatment of SFTSV infection in the mouse model, even when treatments were initiated after onset of the disease.

Purpose: To evaluate the contributory value of Fluorine-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography/computed tomography (PET/CT) in the prediction of lymphovascular tumor invasion in patients with lung adenocarcinoma., Materials and Methods: We evaluated F-18 FDG-PET/CT images in 84 patients with histopathologically proven lung adenocarcinoma (37 men and 47 women, age range 39-83 years, mean age 67.0 ± 8.9 years). The maximum standardized uptake values (SUVmax) of the carcinomas were measured from the PET images. The Mann-Whitney U test was conducted to compare the median SUVmax between the tumor groups with and without lymphovascular invasion. In the subgroup patients with no lymph-node metastasis, we also compared the median SUVmax between the tumor groups with and without lymphatic invasion., Results: The tumors with lymphovascular invasion had a significantly (P < 0.0001) greater median SUVmax than those without invasion. In the subgroup patients with no lymph-node metastasis, the median SUVmax was higher in tumors with lymphatic invasion than those without (P = 0.0004). The sensitivity, specificity, and area under the receiver operating characteristic curve for the detection of tumors with lymphovascular invasion were 89, 75 %, and 0.82, respectively, with a cutoff SUVmax value of 2.32., Conclusion: The SUVmax of lung adenocarcinoma is a potential imaging biomarker for predicting tumor lymphovascular invasion.

Purpose: To evaluate the feasibility of diffusion kurtosis (DK) imaging of the pancreas for the assessment of hemoglobin (Hb) A1c values., Materials and Methods: Our Institutional Review Board approved this prospective study and written informed consent was obtained. In all, 102 consecutive patients with suspected pancreatic disease underwent magnetic resonance imaging (MRI), including DK imaging. Patients were classified into three groups according to American Diabetes Association criteria: HbA1c < 5.7% (group 1), 5.7% ≤ HbA1c < 6.5% (group 2), and HbA1c ≥ 6.5% (group 3). Mean kurtosis (MK) and apparent diffusion coefficient (ADC) of pancreatic parenchyma were computed. MRI measurements and HbA1c values were then compared., Results: HbA1c values positively correlated with MK (r = 0.66, P < 0.0001). Group 3 was significantly (P < 0.05) higher (P < 0.05) in MK than groups 1 and 2. The sensitivity, specificity, and area under the ROC curve of the MK for the detection of group 3 were 90%, 88%, and 0.92, respectively., Conclusion: The MK measurement on DK imaging of the pancreas could be a potential biomarker for assessing HbA1c level., (© 2015 Wiley Periodicals, Inc.)

Objective: To assess prospectively the efficacy of arterial spin labelling (ASL) against conventional and diffusion-weighted (DW) MR imaging for differentiating parotid gland tumours., Methods: We included 10 pleomorphic adenomas, 12 Warthin's tumours, and nine malignant tumours of the parotid glands. Only tumours larger than 10 mm were included in this study. All parotid gland tumours underwent T1-weighted, T2-weighted, DW, and ASL imaging. Tumour-to-parotid gland signal intensity ratios (SIRs) and apparent diffusion coefficients (ADCs) of solid components were correlated with these pathologies., Results: SIRs on T2-weighted images and ADCs were higher in pleomorphic adenomas than in Warthin's tumours (p < .01) and malignant tumours (p < .01). SIRs on ASL were higher in Warthin's tumours than in pleomorphic adenomas (p < .01) and malignant tumours (p < .05). Az value of SIRs on ASL for differentiating Warthin's tumours from the other pathologies was 0.982. The sensitivity, specificity, and accuracy of SIRs on ASL for the diagnosis of Warthin's tumours at an optimal SIR threshold of over 8.70 were 91.7%, 94.7%, and 93.5%, respectively., Conclusions: ASL with SIR measurements could non-invasively evaluate tumour blood flow of parotid gland tumours and differentiate Warthin's tumours from pleomorphic adenomas and malignant tumours., Key Points: • ASL non-invasively evaluates tumour blood flow of parotid gland tumours • ASL differentiates Warthin's tumours from pleomorphic adenomas and malignant tumours • ASL cannot differentiate between pleomorphic adenomas and malignant tumours.

Objectives: To evaluate the usefulness of Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18-F FDG-PET/CT) in the prediction of Fuhrman pathological grades of renal clear cell carcinoma (cRCC)., Methods: This retrospective study was approved by our institutional review board, and written informed consent was waived. Thirty-one patients with pathologically proven cRCC underwent 18-F FDG-PET/CT for tumour staging. Maximum standardized uptake value of cRCC (tumour SUVmax) and mean SUV of the liver and spleen (liver and spleen SUVmean) were measured by two independent observers. Tumour SUVmax, tumour-to-liver SUV ratio, and tumour-to-spleen SUV ratio were correlated with the pathological grades., Results: Logistic analysis demonstrated that only the tumour-to-liver SUV ratio was a significant parameter for differentiating high-grade (Fuhrman grades 3 and 4) tumours from low-grade (Fuhrman grades 1 and 2) tumours (P = 0.007 and 0.010 for observers 1 and 2, respectively). Sensitivity, specificity, and positive and negative predictive values for detecting tumours of Fuhrman grades 3 and 4 were 64, 100, 100, and 77%, respectively, for observer 1, and 79, 88, 85, and 83%, respectively, for observer 2., Conclusions: The tumour-to-liver SUV ratio with 18-F FDG-PET/CT appeared to be a valuable imaging biomarker in the prediction of high-grade cRCC., Key Points: • Tumour SUV max was correlated with the Fuhrman grades. • High-grade tumours have significantly higher SUV max than low-grade tumours. • Tumour-to-liver SUV ratio is useful in the prediction of high-grade cRCC.

Purpose: To prospectively determine the feasibility of low-iodine-load and low-tube-voltage computed tomographic (CT) angiographic imaging of the kidney and to evaluate the opacification and image quality compared with moderate-iodine-load and high-iodine-load techniques., Materials and Methods: Institutional review board approval and written informed consent was obtained. One hundred thirteen consecutive patients randomly underwent three protocols for dual-phase renal CT angiographic imaging: high-iodine-load (600 mg iodine per kilogram of body weight at 120 kVp); moderate-iodine-load (400 mg iodine per kilogram of body weight at 80 kVp); and low-iodine-load (contrast agent injection initially prepared at 400 mg iodine per kilogram of body weight but stopped immediately after bolus-tracking trigger at 80 kVp) scanning. CT numbers of vessels and kidneys were measured. CT numbers and signal-to-noise ratio (SNR) were compared with one-way analysis of variance and posthoc Tukey-Kramer test and depiction of vessels and image noise, with Kruskal-Wallis test and pair-wise Mann-Whitney test with Bonferroni correction., Results: Mean iodine weight administered was significantly reduced in order of low- (16.4 g), moderate- (23.5 g), and high-iodine-load (33.7 g) protocols (P < .001). Mean CT numbers of abdominal aorta, renal artery, and renal cortex in first phase were significantly lower with high-iodine-load protocol (308, 274, and 132 HU, respectively) than with moderate- (347, 334, and 156 HU, respectively; P = .001-.006) or low-iodine-load (362, 316, and 161 HU, respectively; P = .001-.003) protocol. Mean CT number of renal vein in second phase was significantly lower with low-iodine-load protocol (223 HU) than with moderate- (299 HU; P < .001) or high-iodine-load (258 HU; P = .020). Mean SNR of renal medulla in second phase was significantly lower (P = .019) with moderate-iodine-load protocol (mean SNR, 7.2) than with high-iodine-load protocol (mean SNR, 10.0). No significant difference in image quality grades was found between high-iodine-load (mean grade, 2.6-2.9), moderate-iodine-load (mean grade, 2.6-3.0), and low-iodine-load (mean grade, 2.6-2.9) protocols (P = .018-.31)., Conclusion: Combined application of low-iodine-load, bolus tracking with saline flushing, and low-tube-voltage scanning is feasible and resulted in substantial reduction of iodine dose for renal CT angiographic imaging without compromising image quality., (RSNA, 2014)

Purpose: The aim of the study was to evaluate the characteristic imaging features and performance of prenatal magnetic resonance (MR) imaging in the diagnosis of placental invasion., Methods: This retrospective study was approved by our institutional review board and written informed consent was waived. Twenty-eight patients (age range 26-39 years; mean age, 33.8 ± 3.1 years) with suspected placental invasion underwent prenatal MR imaging, including 7 patients with placental invasion and 21 without. Two radiologists assessed the presence of seven previously described MR imaging findings associated with placental invasion. Sensitivity, specificity, positive and negative predictive values, and accuracy were calculated. The diagnostic performance was also determined by a receiver-operating-characteristic curve analysis., Results: Three MR imaging findings (uterine bulging, heterogeneous signal intensity in the placenta on T2-weighted images, and hypointense intraplacental bands on T2-weighted images) were significantly more common in patients with placental invasion than in those without (P = 0.020-0.023). The presence of at least two of these three imaging findings yielded a sensitivity, specificity, positive and negative predictive values, and accuracy of 100, 86, 67, 95, and 89%, respectively., Conclusions: The presence of at least two of the three characteristic prenatal MR imaging findings strongly supports a diagnosis of placental invasion.

This study aimed to assess the efficacy of a multimodality imaging approach for differentiating between primary extranodal non-Hodgkin's lymphoma (NHL) and squamous cell carcinoma (SCC) of the maxillary sinus. Twelve NHLs and 29 SCCs of the maxillary sinus were included. CT findings, MR signal intensities, apparent diffusion coefficients (ADCs), and maximum standardized uptake values (SUVmax) were correlated with two pathologies. On CT, permeative growth frequency was greater among NHLs than among SCCs (50 % vs. 10 %; p < 0.01), whereas destructive growth frequency was greater among SCCs than among NHLs (83 % vs. 33 %; p < 0.01). On CT, remaining sinus wall within the tumor was more frequent with NHLs than with SCCs (92 % vs. 34 %; p < 0.01), whereas intratumoral necrosis was more frequent with SCCs than with NHLs (86 % vs. 17 %; p < 0.01). ADCs were lower for NHLs than for SCCs (0.61 vs. 0.95 × 10(-3) mm(2)/s; p < 0.01). No significant differences in MR signal intensities and SUVmax were observed. Tumor growth pattern, remaining sinus wall within the tumor, and intratumoral necrosis were useful CT findings for differentiating between NHLs and SCCs. ADC measurements could assist the differentiation of NHL from SCC.

Purpose: To evaluate whether a hepatic fibrosis index (HFI), quantified on the basis of hepatic contour abnormality, is a risk factor for the development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C., Materials and Methods: Our institutional review board approved this retrospective study and written informed consent was waved. During a 14-month period, consecutive 98 patients with chronic hepatitis C who had no medical history of HCC treatment (56 men and 42 women; mean age, 70.7 years; range, 48-91 years) were included in this study. Gadoxetic acid-enhanced hepatocyte specific phase was used to detect and analyze hepatic contour abnormality. Hepatic contour abnormality was quantified and converted to HFI using in-house proto-type software. We compared HFI between patients with (n=54) and without HCC (n=44). Serum levels of albumin, total bilirubin, aspartate transferase, alanine transferase, percent prothrombin time, platelet count, alpha-fetoprotein, protein induced by vitamin K absence-II, and HFI were tested as possible risk factors for the development of HCC by determining the odds ratio with logistic regression analysis., Results: HFIs were significantly higher in patients with HCC (0.58±0.86) than those without (0.36±0.11) (P<0.001). Logistic analysis revealed that only HFI was a significant risk factor for HCC development with an odds ratio (95% confidence interval) of 26.4 (9.0-77.8) using a cutoff value of 0.395., Conclusion: The hepatic fibrosis index, generated using a computer-aided assessment of hepatic contour abnormality, may be a useful imaging biomarker for the prediction of HCC development in patients with chronic hepatitis C., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: The objective of our study was to compare diffusion kurtosis imaging (DKI) with conventional diffusion-weighted imaging (DWI) for assessing the response to treatment in hypervascular hepatocellular carcinoma (HCC)., Subjects and Methods: Sixty-two consecutive patients with treated or untreated hypervascular HCC underwent MRI of the liver including DKI (b values of 0, 100, 500, 1000, 1500, and 2000 s/mm(2)). The mean kurtosis (MK) and apparent diffusion coefficient (ADC) values of the hepatic parenchyma and of the HCCs were computed. The detectability of viable HCC based on MK and ADC values was compared. We also assessed the correlation between Child-Pugh grades and MK or ADC values., Results: For a total of 112 HCC nodules (viable, n = 63; nonviable, n = 49), the MK value was significantly higher for the viable group (mean ± SD, 0.81 ± 0.11) than for the non-viable group (0.57 ± 0.11) (p < 0.001). The mean ADC value was significantly lower for the viable group (1.44 ± 0.42 × 10(-3) mm(2)/s) than for the nonviable group (1.94 ± 0.52 × 10(-3) mm(2)/s) (p < 0.001). The sensitivity, specificity, and AUC of the ROC curve for the assessment of HCC viability were greater (p < 0.001) using MK (85.7%, 98.0%, and 0.95, respectively; cutoff value = 0.710) than using ADC (79.6%, 68.3%, and 0.77, respectively; cutoff value = 1.535 × 10(-3) mm(2)/s). Although the ADC of hepatic parenchyma was lower in patients with Child-Pugh grade B or C disease than in those with grade A disease (p = 0.02), no significant difference in MK (p = 0.45) was found among the Child-Pugh grades., Conclusion: DKI can be a new option for the assessment of posttherapeutic response in HCC.

Background/aim: Pancreatic stellate cells (PSC) play a critical role in pancreatic fibrosis and the apparent diffusion coefficient (ADC) value based on the diffusion-weighted image (DWI) from magnetic resonance imaging (MRI) may be a predictor of tissue fibrosis. This study aimed to evaluate the pancreas texture from both histopathological and radiological viewpoints and to investigate the effect of pancreas texture on occurrence of postoperative pancreatic fistula (PF)., Patients and Methods: We divided 40 patients into soft-pancreas group and hard-pancreas group, according to the histopathological evaluation of pancreatic fibrosis. We compared ADC values and occurrences of PF between the two groups., Results: Histopathological measurement lengths of interlobular and intralobular fibrosis increased significantly with the progression of fibrosis grade and PSC stage, while PSC stage correlated significantly with fibrosis grade (r=0.868, p<0.001). PF was detected in 14 out of 40 patients, including grade A in 7 patients and grade B/C in 7 patients, but there were no operative deaths. Pancreas texture (soft/hard), determined based on the combination of fibrosis grade and PSC stage, was 16/10 (no PF) and 14/0 (grade A/B/C PF) and the difference in the incidence was significant (p=0.022). Though ADC value was significantly lower in the hard-compared to the soft-pancreas group (1.48±0.42 vs. 1.73±0.27×10(-3) mm(2)/sec; p=0.033), there was no significant difference in ADC value between no PF versus grade A/B/C PF group., Conclusion: Histopathological evaluation of pancreas texture correlated negatively with ADC values and is critical to predict the occurrence of PF., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

OBJECTIVE. The purpose of this study was to evaluate the diagnostic performance of MRI in differentiating thyroid papillary carcinomas from benign thyroid nodules. MATERIALS AND METHODS. The study included 36 patients who had solid thyroid nodules detected by thyroid sonography and underwent MRI. A total of 42 solid thyroid nodules, including 28 benign nodules (maximal diameter range, 6-95 mm; mean diameter [± SD], 23.3 ± 18.1 mm) and 14 papillary carcinomas (maximal diameter range, 11-35 mm; mean, 21.7 ± 8.1 mm) were histopathologically diagnosed. The T1 and T2 signal intensity ratio (SIR) of each thyroid nodule was calculated by measuring the mean signal intensity divided by that of paraspinal muscle. Apparent diffusion coefficient (ADC) values of nodules were also computed. The SIRs and ADCs were then compared between benign nodules and papillary carcinomas. RESULTS. The mean T2 SIR (p < 0.0001) and ADC (p < 0.0001) were significantly lower for papillary carcinomas than for benign nodules, but no significant difference was found in T1 SIR (p = 0.54). The sensitivity, specificity, and AUC for the differentiation of papillary carcinomas were 86%, 100%, and 0.929, respectively, on T2 SIR; 93%, 93%, and 0.929, respectively, on ADC; and 93%, 93%, and 0.929, respectively, on combined T2 SIR and ADC. CONCLUSION. Papillary thyroid carcinomas could be accurately differentiated from benign nodules on the basis of MRI T2 SIR or ADC values.

Infection with Streptococcus agalactiae has long been recognized in infants. In recent years, S. agalactiae is an important cause of morbidity and mortality among adults and among those with underlying medical condition. Several cases of GBS infection and more fulminant disease similar to streptococcal toxic shock syndrome have recently been reported. We report here that 19 S. agalactiae strains were isolated from streptococcal toxic shock-like syndrome cases involving adult patients in Japan between 2009 and 2013. The average age of the patients was 66.3 years. At least one underlying disease was present in 47.4% (9/19) of the patients. The most prevalent serotype among these strains was Ib. All serotype Ib strains belonged to clonal complex 10 and were ciprofloxacin resistant. In contrast, all strains were susceptible to penicillin G, ampicillin, cefazolin, cefotaxime, imipenem, panipenem, and linezolid. The characteristic type distributions of streptococcal toxic shock-like syndrome isolates differed between isolates obtained from vaginal swabs of women and infants with invasive infections., (Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate the multiphase contrast-enhanced magnetic resonance (MR) imaging features of Bacillus Calmette-Guérin (BCG)-induced granulomatous prostatitis (GP)., Materials and Methods: Magnetic resonance images obtained from five patients with histopathologically proven BCG-induced GP were retrospectively analyzed for tumor location, size, signal intensity on T2-weighted images (T2WI) and diffusion-weighted images (DWI), apparent diffusion coefficient (ADC) value, and appearance on gadolinium-enhanced multiphase images. MR imaging findings were compared with histopathological findings., Results: Bacillus Calmette-Guérin-induced GP (size range, 9-40 mm; mean, 21.2 mm) were identified in the peripheral zone in all patients. The T2WI showed lower signal intensity compared with the normal peripheral zone. The DWIs demonstrated high signal intensity and low ADC values (range, 0.44-0.68 × 10(-3) mm(2)/sec; mean, 0.56 × 10(-3) mm(2)/sec), which corresponded to GP. Gadolinium-enhanced multiphase MR imaging performed in five patients showed early and prolonged ring enhancement in all cases of GP. Granulomatous tissues with central caseation necrosis were identified histologically, which corresponded to ring enhancement and a central low intensity area on gadolinium-enhanced MR imaging. The findings on T2WI, DWI, and gadolinium-enhanced images became gradually obscured with time., Conclusion: Bacillus Calmette-Guérin-induced GP demonstrates early and prolonged ring enhancement on gadolinium-enhanced MR imaging which might be a key finding to differentiate it from prostate cancer.

Objective: To quantitatively assess magnetic resonance (MR) imaging findings that help predict early post-therapeutic response in fibroids following uterine artery embolization (UAE)., Methods: Fifteen patients with a total of 52 fibroids underwent UAE. The signal intensity ratio (SIR) on T1-, T2-, diffusion weighted and gadolinium-enhanced images was calculated by dividing the mean signal intensity of fibroids by that of the abdominal rectus muscle. Fibroids were divided into the two groups: affected (post-UAE volume reduction rate>median of all fibroids) and unaffected (

Purpose: To prospectively assess the effect of reduced iodine load to contrast enhancement, image quality, and detectability of hepatocellular carcinomas (HCCs) in hepatic CT with a combination of 80 kVp tube voltage setting and adaptive statistical iterative reconstruction (ASIR) technique in patients with chronic liver disease., Materials and Methods: This HIPAA-compliant study was approved by our institutional review board and written informed consent was obtained in all patients. During a recent 9-month period, 170 consecutive patients (114 men and 56 women; age range, 40-85 years; mean, 67.7 years) with suspected chronic liver diseases were randomized into three CT groups according to the following iodine-load and tube-voltage protocols: 600 milligram per kilogram body weight (mg/kg) iodine load and 120 peak kilovolt (kVp) tube voltage setting (600-120 group), 500 mg/kg and 80 kVp (500-80 group), and 400mg/kg and 80 kVp (400-80 group). Analysis of variance was conducted to evaluate differences in CT number, background noise, signal-to-noise ratio (SNR), effective dose, HCC-to-liver contrast-to-noise ratio (CNR), and figure of merit (FOM). Sensitivity, specificity, and area under the receiver-operating-characteristic curve (AUC) were compared to assess the detectability of HCCs., Results: Vascular and hepatic enhancement in the 400-80 and 500-80 groups was comparable to or greater than that in the 600-120 group (P<.05). Subjective image quality was comparable among the three groups. Sensitivity, specificity, and AUC for detecting HCCs were comparable among the groups. The effective dose was kept low (3.3-4.1 mSv) in all three groups., Conclusion: Iodine load can be reduced by 33% in CT of the liver with a combination of 80 kVp tube voltage setting and ASIR technique, without compromising the contrast enhancement, image quality, and detection of HCCs., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Diffusion-weighted (DW) imaging is commonly used to distinguish between benign and malignant liver lesions., Purpose: To prospectively evaluate the true molecular-diffusion coefficient (D), perfusion-related diffusion coefficient (D*), perfusion fraction (f), and ADC of focal hepatic lesions using a free-breathing intravoxel incoherent motion (IVIM) DW sequence, and to determine if these parameters are useful for characterizing focal hepatic lesions., Material and Methods: One hundred and twenty hepatic lesions (34 metastases, 32 hepatocellular carcinoma [HCC], 33 hemangiomas, and 21 liver cysts) in 74 patients were examined. Mean D, D*, f, and ADC values of hepatic lesions were compared among pathologies. ROC curve analyses were performed to assess the performances of D, D*, f, and ADC values for the characterization of liver lesions as benign or malignant., Results: The mean D and ADC values of benign lesions were greater than those of malignant lesions (P < 0.001). Although the mean D and ADC values of liver cysts were greater than those of hemangiomas (P < 0.001), and these values were not significantly different between metastases and HCCs (P = 0.99). Area under the ROC curve for ADC values (0.98) was significantly greater (P = 0.048) than that for D values (0.96) for the differentiation of benign and malignant lesions. Sensitivity and specificity for the detection of malignant lesion were 89% and 98%, respectively, when an ADC cut-off value of 1.40 was applied., Conclusion: D and ADC values have more potential for characterizing focal hepatic lesions than D* or f values, and for the differentiation of malignancy and benignity., (© The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Unlabelled: L-cysteine is essential for virtually all living organisms, from bacteria to higher eukaryotes. Besides having a role in the synthesis of virtually all proteins and of taurine, cysteamine, glutathione, and other redox-regulating proteins, L-cysteine has important functions under anaerobic/microaerophilic conditions. In anaerobic or microaerophilic protozoan parasites, such as Entamoeba histolytica, L-cysteine has been implicated in growth, attachment, survival, and protection from oxidative stress. However, a specific role of this amino acid or related metabolic intermediates is not well understood. In this study, using stable-isotope-labeled L-cysteine and capillary electrophoresis-time of flight mass spectrometry, we investigated the metabolism of L-cysteine in E. histolytica. [U-(13)C3, (15)N]L-cysteine was rapidly metabolized into three unknown metabolites, besides L-cystine and L-alanine. These metabolites were identified as thiazolidine-4-carboxylic acid (T4C), 2-methyl thiazolidine-4-carboxylic acid (MT4C), and 2-ethyl-thiazolidine-4-carboxylic acid (ET4C), the condensation products of L-cysteine with aldehydes. We demonstrated that these 2-(R)-thiazolidine-4-carboxylic acids serve for storage of L-cysteine. Liberation of L-cysteine occurred when T4C was incubated with amebic lysates, suggesting enzymatic degradation of these L-cysteine derivatives. Furthermore, T4C and MT4C significantly enhanced trophozoite growth and reduced intracellular reactive oxygen species (ROS) levels when it was added to cultures, suggesting that 2-(R)-thiazolidine-4-carboxylic acids are involved in the defense against oxidative stress., Importance: Amebiasis is a human parasitic disease caused by the protozoan parasite Entamoeba histolytica. In this parasite, L-cysteine is the principal low-molecular-weight thiol and is assumed to play a significant role in supplying the amino acid during trophozoite invasion, particularly when the parasites move from the anaerobic intestinal lumen to highly oxygenated tissues in the intestine and the liver. It is well known that E. histolytica needs a comparatively high concentration of L-cysteine for its axenic cultivation. However, the reason for and the metabolic fate of L-cysteine in this parasite are not well understood. Here, using a metabolomic and stable-isotope-labeled approach, we investigated the metabolic fate of this amino acid in these parasites. We found that L-cysteine inside the cell rapidly reacts with aldehydes to form 2-(R)-thiazolidine-4-carboxylic acid. We showed that these 2-(R)-thiazolidine-4-carboxylic derivatives serve as an L-cysteine source, promote growth, and protect cells against oxidative stress by scavenging aldehydes and reducing the ROS level. Our findings represent the first demonstration of 2-(R)-thiazolidine-4-carboxylic acids and their roles in protozoan parasites., (Copyright © 2014 Jeelani et al.)

We characterized Salmonella enterica serovar Typhi isolates from Bangladesh, Indonesia, Taiwan, and Vietnam to investigate their genetic relatedness and antimicrobial resistance. The isolates from Bangladesh and Vietnam were genetically closely related but were distant from those from Indonesia and Taiwan. All but a few isolates from Indonesia and Taiwan were susceptible to all antimicrobials tested. The majority of isolates from Bangladesh and Vietnam were multidrug resistant (MDR) and belonged to the widespread haplotype H58 clone. IncHI1 plasmids were detected in all MDR S. Typhi isolates from Vietnam but in only 15% of MDR isolates from Bangladesh. Resistance genes in the majority of MDR S. Typhi isolates from Bangladesh should reside in the chromosome. Among the isolates from Bangladesh, 82% and 40% were resistant to various concentrations of nalidixic acid and ciprofloxacin, respectively. Several resistance mechanisms, including alterations in gyrase A, the presence of QnrS, and enhanced efflux pumps, were involved in the reduced susceptibility and resistance to fluoroquinolones. Intensive surveillance is necessary to monitor the spread of chromosome-mediated MDR and fluoroquinolone-resistant S. Typhi emerging in Bangladesh., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

A series of outbreaks of infection with Shiga toxin (verocytotoxin)-producing Escherichia coli or enterohemorrhagic E. coli (EHEC) O157:H7 occurred in Japan in 1996, the largest outbreak occurring in primary schools in Sakai City, Osaka Prefecture, where more than 7,500 cases were reported. Although the reason for the sudden increase in the number of reports of EHEC isolates in 1996 is not known, the number of reports has grown to more than 3,000 cases per year since 1996, from an average of 105 reports each year during the previous 5-year period (1991-1995). Despite control measures instituted since 1996, including designating Shiga toxin-producing E. coli infection as a notifiable disease, and nationwide surveillance effectively monitoring the disease, the number of reports remains high, around 3,800 cases per year. Serogroup O157 predominates over other EHEC serogroups, but isolation frequency of non-O157 EHEC has gone up slightly over the past few years. Non-O157 EHEC has recently caused outbreaks where consumption of a raw beef dish was the source of the infection, and some fatal cases occurred. Laboratory surveillance comprised prefectural and municipal public health institutes, and the National Institute of Infectious Diseases has contributed to finding not only multiprefectural outbreaks but recognizing sporadic cases that could have been missed as an outbreak without the aid of molecular subtyping of EHEC isolates. This short overview presents recent information on the surveillance of EHEC infections in Japan.

We here describe the radiologic findings of peritoneal chronic abscess formation due to gallstones lost within the peritoneum during laparoscopic cholecystectomy (LC). A radiologic workup 7 months after LC revealed a soft-tissue mass with contrast enhancement, harboring internal necrosis and punctate calcium located in the Morrison's pouch. The mass exhibited restricted water molecule diffusion, absence of fat deposition, and increased F-18 fluorodeoxy-D-glucose uptake, thus mimicking a malignant tumor. The biopsy revealed an inflammatory granuloma. Another patient with similar findings was treated with percutaneous abscess drainage. Thus, radiologists should be aware of this disease condition and its imaging findings., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: The purpose of this study was to assess computed tomography (CT) and magnetic resonance (MR) imaging findings of salivary gland tumors of the parotid gland with emphasis on intratumoral cystic components., Methods: Seventy-two histopathologically confirmed salivary gland tumors of the parotid gland (44 benign and 28 malignant), which underwent both CT and MR imaging including contrast-enhanced study, were included in this study. We retrospectively reviewed images for the presence, number, occupying rate, margin characteristics, distribution, and predominant MR signal intensity of intratumoral cystic components., Results: The prevalence of cystic components was greater in malignant than benign tumors (79 vs. 50%, p < 0.05). The number and occupying rate were similar between benign and malignant tumors. The irregular margins were more frequent in malignant than benign tumors (73 vs. 27%, p < 0.01). The frequency of eccentric location was greater in benign than malignant tumors (91 vs. 55%, p < 0.01), whereas the frequency of centric location was greater in malignant than benign tumors (32 vs. 0%, p < 0.01). On T1-weighted images, the frequency of hyperintensity was greater in benign than malignant tumors (50 vs. 9%, p < 0.01), whereas that of isointensity was greater in malignant than benign tumors (50 vs. 0%, p < 0.01). Multiple logistic regression analysis showed that the absence of irregular margins of cystic components only was significantly correlated with the presence of benign salivary gland tumors (p < 0.01)., Conclusion: Imaging features of intratumoral cystic components may help to differentiate benign from malignant tumors of the parotid salivary gland.

Purpose: To prospectively assess the contrast enhancement, image quality, radiation dose, and detectability of malignant pancreatic tumors with pancreatic computed tomography (CT) obtained at an 80-kilovolt (peak) (kV[p]) tube voltage setting and reduced iodine dose., Methods: Institutional review board approval and written informed consent were obtained. During a recent 10-month period, 136 patients (66 men and 70 women; age range, 21-86 years; mean ± SD age, 65.9 ± 11.0 years) with suspected pancreatic disease were randomized into 3 groups according to the following iodine-load and tube-voltage protocols: 600 mg of iodine per kilogram body weight (mg/kg) and 120 kV(p) (600-120 group), 500 mg/kg and 80 kV(p) (500-80 group), and 400 mg/kg and 80 kV(p) (400-80 group). Analysis of variance was conducted to evaluate differences in CT number, background noise, signal-to-noise ratio, effective dose, lesion-to-pancreas contrast-to-noise ratio, and figure of merit. Sensitivity, specificity, and area under the receiver-operating-characteristic curve were compared to assess the detectability of malignant pancreatic tumors., Results: The signal-to-noise ratios in vessels were greater (P < 0.05) in the 400-80 and 500-80 groups than in the 600-120 group, and those in pancreas were comparable between the 400-80 and 600-120 groups. No significant difference was found in effective dose, image quality, lesion-to-pancreas contrast-to-noise ratio, or figure of merit between the groups. Sensitivity, specificity, and area under the receiver-operating-characteristic curve for detecting malignant pancreatic tumors were comparable between the groups., Conclusions: Pancreatic CT with an 80-kV(p) setting and 400-mg iodine per kilogram contrast material load facilitates the reduction of iodine dose while maintaining image quality and the detectability of malignant pancreatic tumors.