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Carbapenemase‐producing gram‐negative bacteria (CP‐GNB) infections threaten public health with high mortality, morbidity and treatment costs. Although frequencies remain low in Australia (total number of CP‐GNB infections reported was 907 in 2022), blaIMP‐4 has established low levels of endemicity in many states. Imipenemase metallo‐β‐lactamase types alone accounted for more than half of all carbapenemases in carbapenemase‐producing Enterobacterales isolates in Australia, particularly in Enterobacter cloacae complex. New Delhi metallo‐β‐lactamase constitutes almost 25% of all carbapenemases in Australia and was identified predominantly in Escherichia coli. The OXA‐48‐like carbapenemases include almost 10% of all carbapenemases and are mainly seen in Klebsiella pneumoniae and E. coli. Although K. pneumoniae carbapenemase‐type carbapenemases are rare in Australia, some local outbreaks have occurred. Most carbapenem‐resistant (CR) Pseudomonas aeruginosa strains in Australia do not produce carbapenemases. Finally, OXA‐23‐like carbapenemases are overwhelmingly positive in CR‐Acinetobacter baumannii strains in Australia. Treatment of CR‐GNB infections challenges physicians. Of 10 new antibiotics active against at least some CR‐GNB infections that are approved by the US Food and Drug Administration, just three are approved for use in Australia. In this context, there is still an unmet need for novel antibacterials that can be used for the treatment of CR‐GNB infections in Australia, as well as a pressing requirement for new mechanisms to 'de‐link' antibiotic sales from their availability. In this narrative review, we aim to overview the epidemiology and clinical significance of carbapenem resistance in Australia as it pertains to Enterobacterales, P. aeruginosa and A. baumannii. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus DNA polymerase processivity factor UL44 is transported into the nucleus by importin (IMP) α/β through a classical nuclear localization signal (NLS), and this region is susceptible to cdc2‐mediated phosphorylation at position T427. Whilst phosphorylation within and close to the UL44 NLS regulates nuclear transport, the details remain elusive, due to the paucity of structural information regarding the role of negatively charged cargo phosphate groups. We addressed this issue by studying the effect of UL44 T427 phosphorylation on interaction with several IMPα isoforms by biochemical and structural approaches. Phosphorylation decreased UL44/IMPα affinity 10‐fold, and a comparative structural analysis of UL44 NLS phosphorylated and non‐phosphorylated peptides complexed with mouse IMPα2 revealed the structural rearrangements responsible for phosphorylation‐dependent inhibition of UL44 nuclear import. [ABSTRACT FROM AUTHOR]

ABSTRACTCarbapenem-resistant Enterobacterales (CRE) are some of the most important pathogens causing infections, which can be challenging to treat. We identified four blaIMP-carrying CRE isolates and collected clinical data. The transferability and stability of the plasmid were verified by conjugation, successive passaging, and plasmid elimination assays. The IncC blaIMP-4-carrying pIMP4-ECL42 plasmid was successfully transferred into the recipient strain, and the high expression of traD may have facilitated the conjugation transfer of the plasmid. Interestingly, the plasmid showed strong stability in clinical isolates. Whole-genome sequencing was performed on all isolates. We assessed the sequence similarity of blaIMP -harboring plasmid from our institution and compared it to plasmids for which sequence data are publicly available. We found that four blaIMP-carrying CRE belonged to four different sequence types. The checkerboard technique and time-kill assays were used to investigate the best antimicrobial therapies for blaIMP-carrying CRE. The time-kill assay showed that the imipenem of 1× minimum inhibitory concentration (MIC) alone had the bactericidal or bacteriostatic effect against IMP-producing strains at 4–12 h in vitro. Moreover, the combination of tigecycline (0.5/1/2 × MIC) and imipenem (0.5/1 × MIC) showed a bactericidal effect against the blaIMP-26-carrying CRECL60 strain.IMPORTANCECarbapenem-resistant Enterobacterales (CRE) are an urgent public health threat, and infections caused by these microorganisms are often associated with high mortality and limited treatment options. This study aimed to determine the clinical features, molecular characteristics, and plasmid transmissible mechanisms of blaIMP carriage as well as to provide a potential treatment option. Here, we demonstrated that conjugated transfer of the IncC blaIMP-4-carrying plasmid promotes plasmid stability, so inhibition of conjugated transfer and enhanced plasmid loss may be potential ways to suppress the persistence of this plasmid. The imipenem alone or tigecycline-imipenem combination showed a good bactericidal effect against IMP-producing strains. In particular, our study revealed that imipenem alone or tigecycline-imipenem combination may be a potential therapeutic option for patients who are infected with IMP-producing strains. Our study supports further trials of appropriate antibiotics to determine optimal treatment and emphasizes the importance of continued monitoring of IMP-producing strains in the future.

Glutamate (Glu) plays important physiological roles in protein synthesis and muscle flesh quality. Despite existing studies on the effects of Glu on fish muscle quality, the underlying mechanism thereof remains unclear. To illustrate the effects of Glu on the flesh quality of triploid crucian carp, fish were fed a diet with added 3.2% Glu (no additional Glu was used as a control). Results showed that dietary Glu promoted the expression levels of genes related to the growth of muscle fibers, thereby promoting the development of the sarcolemma and regulating the hardness and springiness of muscle. Moreover, dietary Glu improved muscle protein deposition via AMPK/mTOR signaling pathway activation. Besides, aspartate, Glu, and inosine monophosphate (IMP) levels in muscle were markedly enhanced by dietary Glu supplementation. In summary, Glu improves flesh quality and growth of triploid crucian carp by regulating protein synthesis, protein retention and flavor compound deposition.

ABSTRACT: Inosine monophosphate (IMP) plays a significant role in meat taste, yet the molecular mechanisms controlling IMP deposition in muscle tissues still require elucidation. The present study systematically and comprehensively explores the molecular network governing IMP deposition in different regions of Jingyuan chicken muscle. Two muscle groups, the breast and leg, were examined as test materials. Using nontargeted metabolomic sequencing, we screened and identified 20 metabolites that regulate IMP-specific deposition. We maintained regular author and institution formatting, used clear, objective, and value-neutral language, and avoided biased or emotional language. We followed a consistent footnote style and formatting features and used precise word choice with technical terms where appropriate. Out of these, 5 were identified as significant contributors to the regulation of IMP deposition. We explained technical term abbreviations when first used and ensured a logical flow of information with causal connections between statements. The results indicate that PGM1, a key enzyme involved in synthesis, is higher in the breast muscle compared to the leg muscle, which may provide an explanation for the increased deposition of IMP in the breast muscle. We aimed for a clear structure with logical progression, avoided filler words, and ensured grammatical correctness. The activity of key enzymes (PKM2, AK1, AMPD1) involved in this process was higher in the breast muscle than in the leg muscle. In the case of IMP degradation metabolism, the activity of its participating enzyme (PurH) was lower in the breast muscle than in the leg muscle. These findings suggest that the increased deposition of IMP in Jingyuan chickens' breast muscle may result from elevated metabolism and reduced catabolism of key metabolites. In summary, a metaomic strategy was utilized to assess the molecular network regulation mechanism of IMP-specific deposition in various segments of Jingyuan chicken. These findings provide insight into genetic improvement and molecular breeding of meat quality traits for top-notch broilers.

(1) Background: Pseudomonas aeruginosa is a Gram-negative bacterium with several intrinsic and acquired antimicrobial resistance mechanisms. The spread of carbapenemase-encoding genes, an acquired mechanism, enables carbapenem resistance in clinical settings. Detection of the carbapenemase-producer strains is urgent. Therefore, we aimed to characterize carbapenemase production in the clinical strains of P. aeruginosa at a tertiary-care center. (2) Methods: We included clinical strains of P. aeruginosa (from August 2011 to December 2018) with resistance towards at least one carbapenem. Strains were isolated in a tertiary-care center in Mexico City. Antimicrobial susceptibility profiles were determined by broth microdilution. Screening for carbapenemase-encoding genes was performed in all strains. Phenotypic assays (CarbaNP and mCIM) were conducted. Additional modifications to mCIM were also tested. (3) Results: One-hundred seventy-one P. aeruginosa strains out of 192 included in this study were resistant towards at least one of the carbapenems tested. Forty-seven of these strains harbored a carbapenemase-encoding gene. VIM (59.6%) and GES (23.4%) were the most frequently found carbapenemases in our study, followed by IMP (14.9%). (4) Among the most frequent carbapenemase genes identified, metallo-ß-lactamases were the most prevalent, which impair new treatment options. Searching for carbapenemase genes should be performed in resistant isolates to stop transmission and guide antimicrobial treatment. [ABSTRACT FROM AUTHOR]

Abstract Background Since the first report of carbapenem-resistant Klebsiella pneumoniae isolates in China in 2007, the prevalence of CRKP and CRE has increased significantly. However, the molecular characteristics of IMP-producing Klebsiella pneumoniae (IMPKp) are rarely reported. Methods A total of 29 IMPKp isolates were collected from a Chinese tertiary hospital from 2011 to 2017. Clinical IMPKp were identified by VITEK®MS, and further analyzed by whole-genome DNA sequencing with HiSeq and PacBio RSII sequencer. Sequencing data were analyzed using CSI Phylogeny 1.4, Resfinder, PlasmidFinder and the MLST tool provided by the Centre for Genomic Epidemiology. The analysis results were visualized using iTOL editor v1_1. The open reading frames and pseudogenes were predicted using RAST 2.0 combined with BLASTP/BLASTN searches against the RefSeq database. The databases CARD, ResFinder, ISfinder, and INTEGRALL were performed for annotation of the resistance genes, mobile elements, and other features. The types of bla IMP in clinical isolates were determined by BIGSdb-Pasteur. Integrons were drawn by Snapgene, and the gene organization diagrams were drawn by Inkscape 0.48.1. Results Four novel ST type, including ST5422, ST5423, ST5426 and ST5427 were identified. The IMP-4 and IMP-1 were the dominant IMP type. The majority of bla IMP-carrying plasmids belonged to IncN and IncHI5. Two novel bla IMP-carrying integrons (In2146 and In2147) were uncovered. A novel variant bla IMP-90 presented in novel integron In2147 has been identified. Conclusions IMPKp showed low prevalence in China. Novel molecular characteristics of IMPKp have been identified. Continuous monitoring of IMPKp shall also be carried out in the future.

Background: Acinetobacter baumannii is regarded as a significant cause of death in hospitals. The WHO recently added carbapenem-resistant Acinetobacter baumannii (CRAB) to its global pathogen priority list. There is a dearth of information on CRAB from our region. Methods: Fifty CRAB isolates were collected from four main hospitals in Bahrain for this study. Bacterial identification and antibiotic susceptibility tests were carried out using the BD PhoenixTM and VITEK-2 compact, respectively. Using conventional PCR, these isolates were further screened for carbapenem resistance markers (blaOXA-51, blaOXA-23, blaOXA-24, blaOXA-40, blaIMP, blaNDM, blaVIM, and blaKPC). Results: All of the isolates were resistant to imipenem (100%), meropenem (98%), and cephalosporins (96–98%), followed by other commonly used antibiotics. All these isolates were least resistant to gentamicin (64%). The detection of resistance determinants showed that the majority harbored blaOXA-51 (100%) and blaIMP (94%), followed by blaOXA-23 (82%), blaOXA-24 (46%), blaOXA-40 (14%), blaNDM (6%), blaVIM (2%), and blaKPC (2%). Conclusion: The study isolates showed a high level of antibiotic resistance. Class D carbapenemases were more prevalent in our CRAB isolate collection. The resistance genes were found in various combinations. This study emphasizes the importance of strengthening surveillance and stringent infection control measures in clinical settings to prevent the emergence and further spread of such isolates. [ABSTRACT FROM AUTHOR]

To investigate the flavor profile of triploid rainbow trout from Qinghai Province, high performance liquid chromatography (HPLC) and headspace solid phase microextraction (HS-SPME) combined with gas chromatography-mass spectrometry (GC-MS) were used to analyze the flavor compounds of fish cultured in net cages from Longyangxia, Gongboxia and Laxiwa. Results showed that the inosinic acid (IMP) content of farmed rainbow trout in Qinghai Province was 176~242 mg/100 g. The IMP content of rainbow trout in Gongboxia and Laxiwa was significantly higher than that in Longyangxia group (P

Background: Since the first report of carbapenem-resistant Klebsiella pneumoniae isolates in China in 2007, the prevalence of CRKP and CRE has increased significantly. However, the molecular characteristics of IMP-producing Klebsiella pneumoniae (IMPKp) are rarely reported. Methods: A total of 29 IMPKp isolates were collected from a Chinese tertiary hospital from 2011 to 2017. Clinical IMPKp were identified by VITEK®MS, and further analyzed by whole-genome DNA sequencing with HiSeq and PacBio RSII sequencer. Sequencing data were analyzed using CSI Phylogeny 1.4, Resfinder, PlasmidFinder and the MLST tool provided by the Centre for Genomic Epidemiology. The analysis results were visualized using iTOL editor v1_1. The open reading frames and pseudogenes were predicted using RAST 2.0 combined with BLASTP/BLASTN searches against the RefSeq database. The databases CARD, ResFinder, ISfinder, and INTEGRALL were performed for annotation of the resistance genes, mobile elements, and other features. The types of blaIMP in clinical isolates were determined by BIGSdb-Pasteur. Integrons were drawn by Snapgene, and the gene organization diagrams were drawn by Inkscape 0.48.1. Results: Four novel ST type, including ST5422, ST5423, ST5426 and ST5427 were identified. The IMP-4 and IMP-1 were the dominant IMP type. The majority of blaIMP-carrying plasmids belonged to IncN and IncHI5. Two novel blaIMP-carrying integrons (In2146 and In2147) were uncovered. A novel variant blaIMP-90 presented in novel integron In2147 has been identified. Conclusions: IMPKp showed low prevalence in China. Novel molecular characteristics of IMPKp have been identified. Continuous monitoring of IMPKp shall also be carried out in the future. [ABSTRACT FROM AUTHOR]

The current state of research in computer science education outlines gender differences in motivation, interest, and elective subject decisions in favor of male students. This study takes an exploratory approach to examine the gender differences in the interdisciplinary STEM profile subject Informatik, Mathematik, Physik (in short: subject IMP), which combines the three subjects of computer science, mathematics, and physics. A survey was conducted involving n = 336 (m = 236, f = 88, o = 12) subject IMP students in the 10th grade attending a Gymnasium in Baden-Württemberg, Germany. The deciding factors for choosing the subject, subject interest, motivation, and more were measured using a questionnaire. Overall, the subject IMP is most chosen by male students. For those students choosing the subject IMP, no statistically significant gender differences in subject interest in IMP, mathematics, and the STEM area or in motivation and vocational orientation in natural science and engineering were found in contrast to the state of research. The interdisciplinary character of the subject IMP could be more appealing to girls than computer science by itself. We conclude that, with a higher participation rate of female students, the subject IMP could be a first step in getting more women into STEM fields. [ABSTRACT FROM AUTHOR]

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The prompt detection of carbapenemases among Gram-negative bacteria isolated from patients' clinical infection samples and surveillance cultures is important for the implementation of infection control measures. In this context, we evaluated the effectiveness of replacing phenotypic tests for the detection of carbapenemase producers with the immunochromatographic Carbapenem-Resistant K.N.I.V.O. Detection K-Set lateral flow assay (LFA). In total, 178 carbapenem-resistant Enterobacterales and 32 carbapenem-resistant Pseudomonas aeruginosa isolated in our hospital were tested with both our established phenotypic and molecular testing procedures and the LFA. The Kappa coefficient of agreement for Enterobacterales was 0.85 (p < 0.001) and 0.6 (p < 0.001) for P. aeruginosa. No major disagreements were observed and notably, in many cases, the LFA detected more carbapenemases than the double meropenem disc test, especially regarding OXA-48 in Enterobacterales and VIM in P. aeruginosa. Overall, the Carbapenem-Resistant K.N.I.V.O. Detection K-Set was very effective and at least equivalent to the standard procedures used in our lab. However, it was much faster as it provided results in 15 min compared to a minimum of 18–24 h for the phenotypic tests. [ABSTRACT FROM AUTHOR]

Abstract Insulin-like growth factor 2 (IGF2) mRNA binding proteins (IMPs) family belongs to a highly conserved family of RNA-binding proteins (RBPs) and is responsible for regulating RNA processing including localization, translation and stability. Mammalian IMPs (IMP1-3) take part in development, metabolism and tumorigenesis, where they are believed to play a major role in cell growth, metabolism, migration and invasion. IMPs have been identified that are expressed in ovary, placenta and embryo. The up-to-date evidence suggest that IMPs are involved in folliculogenesis, oocyte maturation, embryogenesis, implantation, and placentation. The dysregulation of IMPs not only contributes to carcinogenesis but also disturbs the female reproduction, and may participate in the pathogenesis of reproductive diseases and obstetric syndromes, such as polycystic ovary syndrome (PCOS), pre-eclampsia (PE), gestational diabetes mellitus (GDM) and gynecological tumors. In this review, we summarize the role of IMPs in female reproductive pathophysiology, and hope to provide new insights into the identification of potential therapeutic targets.

Bowen Wu,1 Li Tan,2 Weihua Wang,3 Xingzhong Feng,4 Dan Yan1,5,6 1Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Center of Pharmaceutical Technology, Tsinghua University, Beijing, People’s Republic of China; 4Tsinghua University Yuquan Hospital, Beijing, People’s Republic of China; 5Beijing Institute of Clinical Pharmacy, Beijing, People’s Republic of China; 6Beijing Key Laboratory for Evaluation of Rational Drug Use, Beijing, People’s Republic of ChinaCorrespondence: Xingzhong Feng, Tsinghua University Yuquan Hospital, No. 5 Shijingshan Road, Shijingshan District, Beijing, People’s Republic of China, Email fengxz9797@sina.com Dan Yan, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong’an Road, Xicheng District, Beijing, People’s Republic of China, Email pharmsci@126.comBackground: Imidazole Propionate (ImP) is a new marker of Type 2 diabetes mellitus (T2DM), which can induce impaired glucose metabolism and weaken the efficacy of metformin. An extensive exploration into literature suggests that ImP may be associated with stool consistency.Purpose: Through an in-depth study of the relationship between stool consistency, bile acids, fecal microbiota and ImP, we intend to explore the mechanism driving the ImP content difference in T2DM.Patients Under Study and Methods: This is a single-center, prospective, cross-sectional study. Plasma ImP and stool consistency were analyzed among 96 diabetic subjects and 45 healthy subjects. All subjects were divided into the stool consistency normal (N) group and the stool consistency abnormal group, of which the abnormal group was sub-divided into the hard stool (H) group and the soft stool (S) group. After identifying the correlation between ImP and stool consistency, we analyzed the influence of bile acids and fecal microbiota on ImP in diabetic subjects.Results: For T2DM patients, the ImP level of the abnormal stool consistency group was significantly higher than that of the normal stool consistency group (P < 0.001). Results were verified in 45 healthy subjects (P = 0.002). ImP was significantly associated with taurocholic acid (TCA) (P = 0.003) in feces, taurodeoxycholate (TDCA) (P = 0.003), glycochenodeoxycholate (GCDCA) (P = 0.021), and glycocholic acid (GCA) (P = 0.031) in plasma. The Shannon index of Group N was significantly higher than that of Group H (P = 0.041) and Group S (P = 0.003).Conclusion: ImP was higher in diabetic patients with abnormal stool consistency than in those with normal stool consistency, which was related to the proportion of bile acids and fecal microbial structure. These findings may improve our understanding of ImP and contribute to the treatment of T2DM by improving stool consistency.Keywords: ImP, T2DM, stool consistency, bile acids

Several carbapenemases have been identified globally in Enterobacteriaceae. In Japan, IMP-type carbapenemase is the most prevalent, although cases of carbapenemase-producing Enterobacteriaceae (CPE) bacteremia are still scarce. The present case series and literature review aimed to elucidate the clinical characteristics and treatment strategies for IMP-type CPE bacteremia. Clinical data on pediatric cases of IMP-type CPE bacteremia at the Tokyo Metropolitan Children's Medical Center between 2010 and 2020 were collected, and a review of past studies of IMP-type CPE bacteremia has been provided. Five pediatric episodes of IMP-type CPE bacteremia were identified. Our review of previous literature on IMP-type CPE bacteremia revealed 24 adult patients, but no pediatric patients. All 29 cases had underlying diseases, and 23 (79%) received combination therapy. The median duration of antibiotic therapy was 14 days (interquartile range: 9–14 days). The overall mortality rate was 38% (11/29). The mortality rates associated with monotherapy and combination therapy were 67% (4/6) and 30% (7/23), respectively. We report the first case series of IMP-type CPE bacteremia in children. Our review of past studies suggests that combination therapy might lead to better survival outcomes in patients with IMP-type CPE bacteremia. Further research is needed to establish an optimal treatment strategy for IMP-type CPE bacteremia. [ABSTRACT FROM AUTHOR]

(1) Background: Pseudomonas aeruginosa is a Gram-negative bacterium with several intrinsic and acquired antimicrobial resistance mechanisms. The spread of carbapenemase-encoding genes, an acquired mechanism, enables carbapenem resistance in clinical settings. Detection of the carbapenemase-producer strains is urgent. Therefore, we aimed to characterize carbapenemase production in the clinical strains of P. aeruginosa at a tertiary-care center. (2) Methods: We included clinical strains of P. aeruginosa (from August 2011 to December 2018) with resistance towards at least one carbapenem. Strains were isolated in a tertiary-care center in Mexico City. Antimicrobial susceptibility profiles were determined by broth microdilution. Screening for carbapenemase-encoding genes was performed in all strains. Phenotypic assays (CarbaNP and mCIM) were conducted. Additional modifications to mCIM were also tested. (3) Results: One-hundred seventy-one P. aeruginosa strains out of 192 included in this study were resistant towards at least one of the carbapenems tested. Forty-seven of these strains harbored a carbapenemase-encoding gene. VIM (59.6%) and GES (23.4%) were the most frequently found carbapenemases in our study, followed by IMP (14.9%). (4) Among the most frequent carbapenemase genes identified, metallo-ß-lactamases were the most prevalent, which impair new treatment options. Searching for carbapenemase genes should be performed in resistant isolates to stop transmission and guide antimicrobial treatment.

The assembly of complex neural circuits requires that stem cells generate diverse types of neurons in the correct temporal order. Pioneering work in the Drosophila embryonic ventral nerve cord has shown that neural stem cells are temporally patterned by the sequential expression of rapidly changing transcription factors to generate diversity in their progeny. In recent years, a second temporal patterning mechanism, driven by the opposing gradients of the Imp and Syp RNA-binding proteins, has emerged as a powerful way to generate neural diversity. This long-range temporal patterning mechanism is utilized in the extended neural stem cell lineages of the postembryonic fly brain. Here, we review the role played by Imp and Syp gradients in several neural stem cell lineages, focusing on how they specify sequential neural fates through the post-transcriptional regulation of target genes, including the Chinmo and Mamo transcription factors. We further discuss how upstream inputs, including hormonal signals, modify the output of these gradients to couple neurogenesis with the development of the organism. Finally, we review the roles that the Imp and Syp gradients play beyond the generation of diversity, including the regulation of stem cell proliferation, the timing of neural stem cell lineage termination, and the coupling of neuronal birth order to circuit assembly. [ABSTRACT FROM AUTHOR]

Biomolecular condensates have recently retained much attention since they provide a fundamental mechanism of cellular organization. Among those, cytoplasmic RNP granules selectively and reversibly concentrate RNA molecules and regulatory proteins, thus contributing to the spatio-temporal regulation of associated RNAs. Extensive in vitro work has unraveled the molecular and chemical bases of RNP granule assembly. The signaling pathways controlling this process in a cellular context are however still largely unknown. Here, we aimed at identifying regulators of cytoplasmic RNP granules characterized by the presence of the evolutionarily conserved IGF2BP/Imp/ZBP1 RNA binding protein. We performed a high-content image-based RNAi screen targeting all Drosophila genes encoding RNA binding proteins, phosphatases and kinases. This led to the identification of dozens of genes regulating the number of Imp+ RNP granules in S2R+ cells, among which components of the MAPK pathway. Combining functional approaches, phospho-mapping and generation of phospho-variants, we further showed that the EGF.R signaling inhibits Imp+ RNP granule assembly through activation of MAPK/Rolled and Imp S15 phosphosite. This work illustrates how signaling pathways can regulate cellular condensate assembly by post-translational modifications of specific components., (© 2024. Published by The Company of Biologists Ltd.)

Objective: We investigated a rapid detection method for carbapenemase-producing gram-negative bacilli (CP-GNR) using meropenem (MEPM) to assess the efficiency of the antimicrobial susceptibility testing., Methods: We used the function that can monitor the growth curve with the resistant bacteria monitoring function (RAISUS S4). Rapid detection of CP-GNR was performed using RAISUS S4 in two types of antimicrobial susceptibility testing, the RAISUS 18-hour method (18-h method) and RAISUS rapid method (rapid method) for Enterobacterales (F-GNR) and non-fermenting Gram-negative bacilli (NF-GNR)., Results: When F-GNR were based on MEPM MIC ≥ 0.25 μg/mL, CP-GNR were detected with a sensitivity of 100% (58/58) for the 18-h method and 98.3% (57/58) for the rapid method; the shortest detection times were 5.3 and 4.0 h, respectively. When NF-GNR were based on MEPM MIC > 8 μg/mL, it was possible to detect CP-GNR with 100% sensitivity (58/58) in both methods. Furthermore, in the analysis using the 18-h method for monitoring resistant bacteria, when ≥ 2 µg/mL was used as the screening concentration for F-GNR, approximately 50% of the resistant genotypes, NDM, GES, and KPC, were detected in approximately 7 h. However, detecting the IMP and VIM took 11-12 h., Conclusions: The 18-h and rapid methods with RAISUS S4 were highly correlated with the results of the microdilution method of CLSI, and CP-GNR detection was rapid using a function that can monitor the growth curve with RAISUS S4., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Acinetobacter baumannii is regarded as a significant cause of death in hospitals. The WHO recently added carbapenem-resistant Acinetobacter baumannii (CRAB) to its global pathogen priority list. There is a dearth of information on CRAB from our region. Methods: Fifty CRAB isolates were collected from four main hospitals in Bahrain for this study. Bacterial identification and antibiotic susceptibility tests were carried out using the BD PhoenixTM and VITEK-2 compact, respectively. Using conventional PCR, these isolates were further screened for carbapenem resistance markers (blaOXA-51, blaOXA-23, blaOXA-24, blaOXA-40, blaIMP, blaNDM, blaVIM, and blaKPC). Results: All of the isolates were resistant to imipenem (100%), meropenem (98%), and cephalosporins (96–98%), followed by other commonly used antibiotics. All these isolates were least resistant to gentamicin (64%). The detection of resistance determinants showed that the majority harbored blaOXA-51 (100%) and blaIMP (94%), followed by blaOXA-23 (82%), blaOXA-24 (46%), blaOXA-40 (14%), blaNDM (6%), blaVIM (2%), and blaKPC (2%). Conclusion: The study isolates showed a high level of antibiotic resistance. Class D carbapenemases were more prevalent in our CRAB isolate collection. The resistance genes were found in various combinations. This study emphasizes the importance of strengthening surveillance and stringent infection control measures in clinical settings to prevent the emergence and further spread of such isolates.

Motivated by algorithmic information theory, the problem of program discovery can help find candidates of underlying generative mechanisms of natural and artificial phenomena. The uncomputability of such inverse problem, however, significantly restricts a wider application of exhaustive methods. Here we present a proof of concept of an approach based on IMP, a high-level imperative programming language. Its main advantage is that conceptually complex computational routines are more succinctly expressed, unlike lower-level models such as Turing machines or cellular automata. We investigate if a more expressive higher-level programming language can be more efficient at generating approximations to algorithmic complexity of recursive functions. • We explore an inverse problem for model discovery based on principles of algorithmic information. • The method can help find candidates of underlying generative mechanisms and first principles. • A proof of concept based on IMP, a high-level imperative programming language, is provided. • IMP expressions are succinct, unlike lower-level models such as formal automata. • We investigate if a more expressive higher-level programming language can be more efficient. [ABSTRACT FROM AUTHOR]

This study is an empirical research which examined the effect of AL practiced by branch managers on the implementation of planned organisational changes by assistant branch managers in the case of the banking industry in Ethiopia. To ensure representativeness, the research sampled Commercial Bank of Ethiopia (CBE) among the government banks and Oromia International Bank (OIB) among the private banks. The respondents of the study are randomly selected managers and assistant managers of the branches operating under Addis Ababa districts. The research hypothesised that authentic leadership positively predicts the planned organisational change implementation. The research employed a quantitative and two-phase cross-sectional research design. The study developed and followed a model incorporating AL as an independent variable and POCI as an outcome variable. The regression analysis was employed to examine the data. The study found that AL has positively predicted POCI, and therefore, the hypothesis was supported. [ABSTRACT FROM AUTHOR]

Bacterial pneumonia is considered one of the most virulent diseases with high morbidity and mortality rates, especially in hospitalized patients. Moreover, bacterial resistance increased over the last decades which limited the therapy options to carbapenem antibiotics. Hence, the metallo-β-lactamase-producing bacteria were deliberated as the most deadly and ferocious infectious agents. Sulphadiazine-ZnO hybrids biological activity was explored in vitro and in vivo against metallo-β-lactamases (MBLs) producing Klebsiella pneumoniae. Docking studies against NDM-1 and IMP-1 MBLs revealed the superior activity of the 3a compound in inhibiting both MBLs enzymes in a valid reliable docking approach. The MBLs inhibition enzyme assay revealed the remarkable sulphadiazine-ZnO hybrids inhibitory effect against NDM-1 and IMP-1 MBLs. The tested compounds inhibited the enzymes both competitively and noncompetitively. Compound 3b-ZnO showed the highest antibacterial activity against the tested metallo-β-lactamase producers with an inhibition zone (IZ) diameter reaching 43 mm and a minimum inhibitory concentration (MIC) reaching 2 µg/mL. Sulphadiazine-ZnO hybrids were tested for their in vitro cytotoxicity in a normal lung cell line (BEAS-2Bs cell line). Higher cell viability was observed with 3b-ZnO. Biodistribution of the sulphadiazine-ZnO hybrids in the lungs of uninfected rats revealed that both [124I]3a-ZnO and [124I]3b-ZnO hybrids remained detectable within the rats' lungs after 24 h of endotracheal aerosolization. Moreover, the residence duration in the lungs of [124I]3b-ZnO (t1/2 4.91 h) was 85.3%. The histopathological investigations confirmed that compound 3b-ZnO has significant activity in controlling bacterial pneumonia infection in rats. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor 2 (IGF2) mRNA binding proteins (IMPs) family belongs to a highly conserved family of RNA-binding proteins (RBPs) and is responsible for regulating RNA processing including localization, translation and stability. Mammalian IMPs (IMP1-3) take part in development, metabolism and tumorigenesis, where they are believed to play a major role in cell growth, metabolism, migration and invasion. IMPs have been identified that are expressed in ovary, placenta and embryo. The up-to-date evidence suggest that IMPs are involved in folliculogenesis, oocyte maturation, embryogenesis, implantation, and placentation. The dysregulation of IMPs not only contributes to carcinogenesis but also disturbs the female reproduction, and may participate in the pathogenesis of reproductive diseases and obstetric syndromes, such as polycystic ovary syndrome (PCOS), pre-eclampsia (PE), gestational diabetes mellitus (GDM) and gynecological tumors. In this review, we summarize the role of IMPs in female reproductive pathophysiology, and hope to provide new insights into the identification of potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Introduction: The emergence and global spread of carbapenemases produced by Klebsiella pneumoniae is a serious problem to health services worldwide. K. pneumoniae, belonging to the Enterobacteriaceae family, is commonly found in the human gastrointestinal tract and environment, especially in the hospital environment. Carbapenem is administered as the first treatment for severe infections created by multi-drug resistant K. pneumoniae. Despite the fact that the carbapenemase-producing K. pneumoniae has become more prevalent in Iran, few investigations have probed into the prevalence of different carbapenemase genes in Iran. Method: The aim of this study was to examine the prevalence of carbapenemase genes in K. pneumoniae from 2010 to 2018 in Iran. PubMed and Scopus databases were searched for the articles published between 2010 and 2018 in Iran. Results: A total of 25 papers published between 2012 and 2018 were selected. The highest frequency of blaNDM, blaIMP, blaVIM, blaKPC and, blaOXA48 genes were related to cities of Shiraz in 2017 [23 (26.14%)], Hamedan in 2017 [2 (50%)], Babol in 2015 [15 (41.66%)], Isfahan in 2013 [65 (44.83%)] and, and Isfahan in 2018 [90 (76.27%)], respectively. The results showed that the frequency of blaNDM, blaOXA48, and blaIMP genes increased in 2017 and 2018, and there was an increase in the frequency of the blaVIM gene in 2014 and 2015, and the blaKPC gene in 2013. The highest percentage of carbapenemases genes isolated in Iran were related to blaKPC [145 (37.08%)], blaOXA48 [118 (30.18%)], and blaNDM [88 (22.51%)], and the lowest percentages were reported in blaIMP [4 (1.02%)], and blaVIM [36 (9.21%)], respectively. Conclusion: The results of our review showed that blaNDM and blaOXA48 carbapenemase genes have been increasing in Iran, and it seems that traveling is one of the most important factors in the transmission of carbapenemase genes.

The current state of research in computer science education outlines gender differences in motivation, interest, and elective subject decisions in favor of male students. This study takes an exploratory approach to examine the gender differences in the interdisciplinary STEM profile subject Informatik, Mathematik, Physik (in short: subject IMP), which combines the three subjects of computer science, mathematics, and physics. A survey was conducted involving n = 336 (m = 236, f = 88, o = 12) subject IMP students in the 10th grade attending a Gymnasium in Baden-Württemberg, Germany. The deciding factors for choosing the subject, subject interest, motivation, and more were measured using a questionnaire. Overall, the subject IMP is most chosen by male students. For those students choosing the subject IMP, no statistically significant gender differences in subject interest in IMP, mathematics, and the STEM area or in motivation and vocational orientation in natural science and engineering were found in contrast to the state of research. The interdisciplinary character of the subject IMP could be more appealing to girls than computer science by itself. We conclude that, with a higher participation rate of female students, the subject IMP could be a first step in getting more women into STEM fields.

Detection and differentiation of explosives is an issue of immediacy for security and environmental monitoring. At present, the most operated explosive system combines primary and secondary explosives. Although various advances are presently equipped for identifying primary explosives, the insensitive nature of secondary explosives makes their detection and differentiation challenging. Here, we report three coordination nanosheets (CNs) AM-8-Eu, AM-8-Tb, and AM-8-Zn containing three-way terpyridine ligands (AM-8) and Eu(III), Tb(III), and Zn(II) ions. These CNs act as a highly selective platform for detecting unexplored high-energy explosive 1,1-Diamino-2,2-dinitro ethylene (FOX-7) in solid and solution phases. For AM-8-Zn, calculated molecular electrostatic surface potential revealed two modes of interactions for triaminotrinitrobenzene (TATB) and FOX-7, producing two distinct spectral responses. Digital analysis of these responses revealed a complimentary implication (IMP)/not implication (NIMP) logic function. Finally, the unique feature of IMP gate is used to define all possible sixteen distinct binary Boolean operations on two logic values for "functional completeness". The detection and differentiation of such insensitive high-energy explosives TATB and FOX-7, where Boolean logic can process information through distinct binary responses in solid and solution phases, have not been witnessed hitherto in a single chemical platform. [Display omitted] • Three novel luminescent coordination nanosheets (CNs) were prepared. • Detection and differentiation of unexplored high-energy explosive FOX-7 and TATB performed in solid and solution phases. • DFT study revealed different ESPs of the CNs favor two different modes of interaction with TATB and FOX-7. • Digital analysis revealed a complimentary implication (IMP)/not implication (NIMP) logic function. • Unique feature of IMP gate is used to define "functional completeness ". [ABSTRACT FROM AUTHOR]

The prompt detection of carbapenemases among Gram-negative bacteria isolated from patients’ clinical infection samples and surveillance cultures is important for the implementation of infection control measures. In this context, we evaluated the effectiveness of replacing phenotypic tests for the detection of carbapenemase producers with the immunochromatographic Carbapenem-Resistant K.N.I.V.O. Detection K-Set lateral flow assay (LFA). In total, 178 carbapenem-resistant Enterobacterales and 32 carbapenem-resistant Pseudomonas aeruginosa isolated in our hospital were tested with both our established phenotypic and molecular testing procedures and the LFA. The Kappa coefficient of agreement for Enterobacterales was 0.85 (p < 0.001) and 0.6 (p < 0.001) for P. aeruginosa. No major disagreements were observed and notably, in many cases, the LFA detected more carbapenemases than the double meropenem disc test, especially regarding OXA-48 in Enterobacterales and VIM in P. aeruginosa. Overall, the Carbapenem-Resistant K.N.I.V.O. Detection K-Set was very effective and at least equivalent to the standard procedures used in our lab. However, it was much faster as it provided results in 15 min compared to a minimum of 18–24 h for the phenotypic tests.

Objectives: We identified a novel hybrid plasmid simultaneously carrying bla NDM-1 and bla IMP-4 in an ST20-K28 carbapenem-resistant Klebsiella pneumoniae (CRKP) strain AZS099 and reported its detailed genetic and phenotypic characterization. Methods: Antimicrobial susceptibility was characterized using broth microdilution method. Complete genome characteristics and plasmid detailed analysis were carried out by PacBio Sequel and Illumina sequencing and further bioinformatics analysis. Conjugation assay, S1-PFGE, Southern blot, plasmid stability, and fitness cost were conducted to the phenotypic characterization of this novel hybrid plasmid. Results: AZS099 was isolated from a blood specimen obtained from a 3-month baby who presented with biliary tract infection. Susceptibility testing showed that AZS099 was resistant to almost all β-lactams examined, including cephalosporins, combinations of β-lactams and β-lactamase inhibitors, carbapenems, and aztreonam. PacBio and Illumina sequencing together with S1-PFGE and Southern blot showed that bla NDM-1 and bla IMP-4 were simultaneously located on a 296 kb IncFIB(K)/IncHI1B/IncX3 plasmid (pAZS099-NDM-IMP), which consists of four main parts that came from four different types of plasmids. The region harboring bla IMP-4 is located in a class 1 integron designated as In0 , which is located in an IS6100 - IS26 transposon-like structure with a total length of ~5 kb. The region harboring bla NDM-1 is located in the Tn125 transposon remnant. Conjugation and transformation assay confirmed that the plasmid pAZS099-NDM-IMP has the potential for horizontal transfer and displayed high stability (retention rate > 95%). Furthermore, growth curve assessment confirmed that the presence of pAZS099-NDM-IMP exhibits no growth pressure on bacteria. Conclusion: Our research reported a hybrid plasmid coharboring bla NDM-1 and bla IMP-4 in an ST20-K28 CRKP strain. The emergence of novel hybrid plasmid could threaten the control of antimicrobial resistance and should be closely supervised. [ABSTRACT FROM AUTHOR]

Background: Acinetobacter baumannii is a common cause of multi-drug (MDR)-resistant infections worldwide. The epidemiological and molecular characteristics of MDR-A. baumannii in Jordan is not known. Methods: A. baumannii isolates were collected from 2010 to 2020 from three tertiary hospitals in Jordan. Demographic and clinical data, isolates information, antibiotic susceptibility patterns, phenotypic, and molecular characterization of carbapenem resistance genes were performed. Results: A total of 622 A. baumannii isolates were collected during the study period. Most isolates were from males, aged 18–60 years, Jordanian, from infected wounds, and were patients in surgery or critical care units. Among patients from whom A. baumannii was isolated, associated risk factors for MDR were adults over 60, males, critically ill patients and infected wounds (OR 4.14, 2.45, 10, 7, respectively, p < 0.0001). Incidence rates from 2010 to 2015 showed a slight increase in MDR (3.75/1000 to 4.46/1000). Resistance patterns indicated high resistance for most cephalosporins, carbapenems, and fluoroquinolones, moderate resistance for trimethoprim/sulfamethoxazole and ampicillin/sulbactam, low resistance for aminoglycosides and tetracyclines, while colistin and tigecycline, have the lowest resistance rates. 76.8% of A. baumannii isolates were MDR and 99.2% were carbapenem-resistant. All isolates were positive for the OXA-51 gene (100%), 98.5% were positive for the OXA-23 gene, 26.6% for the VIM gene, while KPC and IMP genes were almost not detected (0% and 0.8% respectively). Conclusions: This is the first large, multicentric, prolonged study that provides insights into A. baumannii infections in Jordan. Attention to patients at higher risk is important for early identification. Colistin and tigecycline were the most effective antimicrobials. [ABSTRACT FROM AUTHOR]

Severe traumatic brain injury (TBI) is associated with high rates of mortality and long‐term disability linked to neurochemical abnormalities. Although purine derivatives play important roles in TBI pathogenesis in preclinical models, little is known about potential changes in purine levels and their implications in human TBI. We assessed cerebrospinal fluid (CSF) levels of purines in severe TBI patients as potential biomarkers that predict mortality and long‐term dysfunction. This was a cross‐sectional study performed in 17 severe TBI patients (Glasgow Coma Scale <8) and 51 controls. Two to 4 h after admission to ICU, patients were submitted to ventricular drainage and CSF collection for quantification of adenine and guanine purine derivatives by HPLC. TBI patients' survival was followed up to 3 days from admission. A neurofunctional assessment was performed through the modified Rankin Scale (mRS) 2 years after ICU admission. Purine levels were compared between control and TBI patients, and between surviving and non‐surviving patients. Relative to controls, TBI patients presented increased CSF levels of GDP, guanosine, adenosine, inosine, hypoxanthine, and xanthine. Further, GTP, GDP, IMP, and xanthine levels were different between surviving and non‐surviving patients. Among the purines, guanosine was associated with improved mRS (p = 0.042; r = −0.506). Remarkably, GTP displayed predictive value (AUC = 0.841, p = 0.024) for discriminating survival versus non‐survival patients up to 3 days from admission. These results support TBI‐specific purine signatures, suggesting GTP as a promising biomarker of mortality and guanosine as an indicator of long‐term functional disability. [ABSTRACT FROM AUTHOR]

Pear decline, induced by the phytoplasma 'Candidatus Phytoplasma pyri', transmitted by pear psyllids, is one of the most devastating diseases on Pyrus communis in Europe and North America. Investigations of pear psyllids in 4 pear orchards in lower Austria showed the presence of Cacopsylla pyri, C. pyricola and C. pyrisuga at all locations. PCR analyses revealed overall phytoplasma infection rates for C. pyri of 5.4%, for C. pyricola, of 4.6%, for C. pyrisuga remigrants of 9.6% and for C. pyrisuga emigrants of 0%. The rates of PCR-positive C. pyri and C. pyricola individuals varied greatly in the course of the year, and the highest infection rates were observed in late summer, autumn and in late winter. In transmission experiments with healthy pear seedlings, winterform individuals of C. pyri and C. pyricola transmitted the pathogen to 19.2% (5 out of 26) and 4.8% (2 out of 41) of the test plants, respectively. The vectoring ability of C. pyrisuga was experimentally proven for the first time, and in transmission experiments with remigrants, 9.5% (2 out of 21) of the pear seedlings were infected. Our data indicate a significant risk of pathogen transmission in pear orchards during the greater part of the year, especially in late winter, early spring and autumn. Multilocus sequence analysis by aid of the genes aceF and imp allowed the discrimination between 15 phytoplasma types. Three so far undescribed aceF genotypes and four undescribed imp genotypes were identified. [ABSTRACT FROM AUTHOR]

With the continuous improvements in human diet, there is an ever-increasing demand for high-quality chicken, so it is particularly important for poultry breeders to carry out the breeding of high-quality broilers in a timely fashion. Inosine monophosphate (IMP) is a flavor-enhancing substance, which plays a critical role in the umami taste of the muscle, making the content of IMP an important umami taste indicator. Currently, research on the deposition mechanism of IMP in chicken is not only necessary for chicken breeders to promote the production of high-quality meat and poultry but also to meet the human demand for chicken meat. In this paper, the research history of IMP, its structure and taste mechanisms, the pathway and influencing factors of de novo IMP synthesis, and the key genes regulating IMP synthesis and metabolism are briefly summarized. Our aim was to lay a theoretical foundation and provide scientific background and research directions for further research on high-quality broiler breeding. [ABSTRACT FROM AUTHOR]

ObjectivesWe identified a novel hybrid plasmid simultaneously carrying blaNDM-1 and blaIMP-4 in an ST20-K28 carbapenem-resistant Klebsiella pneumoniae (CRKP) strain AZS099 and reported its detailed genetic and phenotypic characterization.MethodsAntimicrobial susceptibility was characterized using broth microdilution method. Complete genome characteristics and plasmid detailed analysis were carried out by PacBio Sequel and Illumina sequencing and further bioinformatics analysis. Conjugation assay, S1-PFGE, Southern blot, plasmid stability, and fitness cost were conducted to the phenotypic characterization of this novel hybrid plasmid.ResultsAZS099 was isolated from a blood specimen obtained from a 3-month baby who presented with biliary tract infection. Susceptibility testing showed that AZS099 was resistant to almost all β-lactams examined, including cephalosporins, combinations of β-lactams and β-lactamase inhibitors, carbapenems, and aztreonam. PacBio and Illumina sequencing together with S1-PFGE and Southern blot showed that blaNDM-1 and blaIMP-4 were simultaneously located on a 296 kb IncFIB(K)/IncHI1B/IncX3 plasmid (pAZS099-NDM-IMP), which consists of four main parts that came from four different types of plasmids. The region harboring blaIMP-4 is located in a class 1 integron designated as In0, which is located in an IS6100-IS26 transposon-like structure with a total length of ~5 kb. The region harboring blaNDM-1 is located in the Tn125 transposon remnant. Conjugation and transformation assay confirmed that the plasmid pAZS099-NDM-IMP has the potential for horizontal transfer and displayed high stability (retention rate > 95%). Furthermore, growth curve assessment confirmed that the presence of pAZS099-NDM-IMP exhibits no growth pressure on bacteria.ConclusionOur research reported a hybrid plasmid coharboring blaNDM-1 and blaIMP-4 in an ST20-K28 CRKP strain. The emergence of novel hybrid plasmid could threaten the control of antimicrobial resistance and should be closely supervised.

Inosine monophosphate (IMP) is an indicator of meat taste, and the molecular mechanism underlying IMP deposition in muscle tissues is important to developing superior poultry breeds. The aim of this study was to identify the key proteins regulating IMP deposition in different muscle groups of 180-day-old Jingyuan chickens (Hen) using a proteomics-based approach. We identified 1,300 proteins in the muscle tissues of Jingyuan chickens, of which 322 were differentially expressed between the breast and leg muscles (129 proteins were highly expressed in breast muscles and 193 proteins were highly expressed in leg muscles). PGM1, PKM2, AK1, AMPD1, and PurH/ATIC were among the differentially expressed proteins (DEPs) involved in the purine metabolism pathway, of which purH was highly expressed in leg muscles, while the others were highly expressed in breast muscles. The proteomics screening results were verified by PRM, qPCR, and western blotting, showing consistency with the proteomics results. Our findings are not only significant in terms of protecting the Jingyuan chicken germplasm resources, but also provide the molecular basis for generating high-quality broiler chicken breeds.