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The article describes the case of an 80-year-old man admitted to the hospital due to dizziness and fatigue and was diagnosed with primary myelofibrosis (PMF). Topics discussed include findings on physical examination, clinical characteristics of PMF, and speculation that the coexistence of JAK2V617F and MPLW515R driver mutations may have functional complementation in PMF.

Research on resistance against polymyxins induced by the mcr-1 gene is gaining interest. In this study, using agar dilution method, polymerase chain reaction, and comparative genomic analysis, we investigated the colistin resistance mechanism of clinical E. coli isolates. The minimum inhibitory concentration (MIC) analysis results revealed that of the 515 isolates tested, bacteria with significantly increased MIC levels against colistin were isolated in 2019. Approximately one-fifth (17.14% to 19.65%) of the isolates showed MIC values ≥1 mg/L against colistin in 2015, 2016, and 2017. However, in 2019, up to three-quarters (74.11%, 146/197) of the isolates showed MIC values ≥1 mg/L against colistin indicating an increase in colistin resistance. Six isolates (EC7518, EC4968, EC3769, EC16, EC117, EC195, 1.13%, 6/515) were found to carry the mcr-1 gene and a novel mcr-1 variant with Met2Ile mutation was identified in EC3769. All six strains showed higher MIC levels (MIC=4 mg/L) than any mcr-1- negative strains (MIC ≤ 2 mg/L). Whole-genome sequencing of the six mcr-1 -positive isolates revealed that EC195 carried the highest number of resistance genes (n = 28), nearly a half more than those of the following EC117 (n = 19). Thus, EC195 showed a wider resistance spectrum and higher MIC levels against the antimicrobials tested than the other five isolates. Multi-locus sequence typing demonstrated that these mcr-1 -positive strains belonged to six different sequence types. The six mcr-1 genes were located in three different incompatibility group plasmids (IncI2, IncHI2 and IncX4). The genetic context of mcr-1 was related to a sequence derived from Tn 6330 (IS Apl1 - mcr-1 - pap2 -IS Apl1). Investigations into the colistin resistance mechanism and characterization of the molecular background of the mcr genes may help trace the development and spread of colistin resistance in clinical settings. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa can cause infections in the blood, lungs (pneumonia), or other parts of the body after surgery. To investigate the molecular characteristics of β-lactam antibiotic resistance of P. aeruginosa isolated from a hospital population between 2015 and 2017, in this study, the antimicrobial susceptibility and the resistance gene profile of the bacteria were determined. The Pulsed-field gel electrophoresis (PFGE) was used to characterize the clonal relatedness and sequencing and comparative genomic analysis were performed to analyze the structure of the resistance gene-related sequences. As a result, of the 260 P. aeruginosa strains analyzed, the resistance rates for 6 β-lactam antibiotics ranged from 4.6 to 9.6%. A total of 7 genotypes of 44 β-lactamase genes were identified in 23 isolates (8.9%, 23/260). Four transconjugants from different donors carrying bla CARB-3 exhibited a phenotype of reduced susceptibility to piperacillin–tazobactam, ceftazidime, and cefepime, and 2 transconjugants harboring bla IMP-45 exhibited a phenotype of reduced susceptibility to carbapenems. bla CARB positive isolates (n = 12) presented six PFGE patterns, designated groups A to F. Two bla genes (bla IMP-45 and bla OXA-1) in PA1609 related to a class 1 integron (intI1 - bla IMP-45- bla OXA-1- aac(6′)-Ib7 - catB3 - qacE∆1 - sul1) were encoded on a plasmid (pPA1609-475), while the bla CARB-3 gene of PA1616 also related to a class 1 integron was located on the chromosome. The results suggest that β-lactam antibiotic resistance and clonal dissemination exist in this hospital population. It indicates the necessity for molecular surveillance in tracking β-lactamase-producing strains and emphasizes the need for epidemiological monitoring. [ABSTRACT FROM AUTHOR]

In this work, we characterized a novel chromosome-encoded AmpC β-lactamase gene, bla PRC–1, in an isolate of a newly classified Pseudomonas species designated Pseudomonas wenzhouensis A20, which was isolated from sewage discharged from an animal farm in Wenzhou, China. Susceptibility testing, molecular cloning, and enzyme kinetic parameter analysis were performed to determine the function and enzymatic properties of the β-lactamase. Sequencing and comparative genomic analysis were conducted to clarify the phylogenetic relationship and genetic context of the bla PRC–1 gene. PRC-1 is a 379-amino acid AmpC β-lactamase with a molecular weight of 41.48 kDa and a predicted pI of 6.44, sharing the highest amino acid identity (57.7%) with the functionally characterized AmpC β-lactamase PDC-211 (ARX71249). bla PRC–1 confers resistance to many β-lactam antibiotics, including penicillins (penicillin G, amoxicillin, and amoxicillin-clavulanic acid) and cephalosporins (cefazolin, ceftriaxone, and cefotaxime). The kinetic properties of PRC-1 were compatible with those of a typical class C β-lactamase showing hydrolytic activities against β-lactam antibiotics, and the hydrolytic activity was strongly inhibited by avibactam. The genetic context of bla PRC–1 was relatively conserved, and no mobile genetic element was predicted in its surrounding region. Identification of a novel β-lactamase gene in an unusual environmental bacterium reveals that there might be numerous unknown resistance mechanisms in bacterial populations, which may pose potential risks to human health due to universal horizontal gene transfer between microorganisms. It is therefore of great value to carry out extensive research on the mechanism of antibiotic resistance. [ABSTRACT FROM AUTHOR]

Summary: The clinical and environmental infections caused by AmpC β‐lactamases have been increasingly reported recently. In this study, we characterize the novel chromosome‐encoded AmpC β‐lactamase SFDC‐1 identified in Serratia fonticola strain R28, which was isolated from a rabbit raised on a farm in southern China. SFDC‐1 shared the highest amino acid identity of 79.6% with the functionally characterized AmpC β‐lactamase gene blaYRC‐1, although it had highly homologous functionally uncharacterized relatives in the same species from different sources, including some of the clinical significance. The cloned blaSFDC‐1 exhibited resistance to a broad spectrum of β‐lactam antibiotics, including most cephalosporins with the highest resistance to ampicillin, cefazolin and ceftazidime, with increased MIC levels ≥128‐fold compared with the control strains. The purified SFDC‐1 showed catalytic activities against β‐lactams with the highest catalytic activity to cefazolin. The genetic context of blaSFDC‐1 and its relatives was conserved in the chromosome, and no mobile genetic elements were found surrounding them. [ABSTRACT FROM AUTHOR]

Multidrug-resistant bacteria from different sources have been steadily emerging, and an increasing number of resistance mechanisms are being uncovered. In this work, we characterized a novel resistance gene named aac(2′)-If from an isolate of a novel Providencia species, Providencia wenzhouensis R33 (CCTCC AB 2021339). Susceptibility testing and enzyme kinetic parameter analysis were conducted to determine the function of the aminoglycoside 2′- N -acetyltransferase. Whole-genome sequencing and comparative genomic analysis were performed to elucidate the molecular characteristics of the genome and the genetic context of the resistance gene-related sequences. Among the functionally characterized resistance genes, AAC(2′)-If shares the highest amino acid sequence identity of 70.79% with AAC(2′)-Ia. AAC(2′)-If confers resistance to several aminoglycoside antibiotics, showing the highest resistance activity against ribostamycin and neomycin. The recombinant strain harboring aac(2′)-If (pUCP20- aac(2′)-If /DH5α) showed 256- and 128-fold increases in the minimum inhibitory concentration (MIC) levels to ribostamycin and neomycin, respectively, compared with those of the control strains (DH5α and pUCP20/DH5α). The results of the kinetic analysis of AAC(2′)-If were consistent with the MIC results of the cloned aac(2′)-If with the highest catalytic efficiency for ribostamycin (k cat /K m ratio = [3.72 ± 0.52] × 104 M–1⋅s–1). Whole-genome sequencing demonstrated that the aac(2′)-If gene was located on the chromosome with a relatively unique genetic environment. Identification of a novel aminoglycoside resistance gene in a strain of a novel Providencia species will help us find ways to elucidate the complexity of resistance mechanisms in the microbial population. [ABSTRACT FROM AUTHOR]

Objectives: To describe a novel chromosomal aminoglycoside phosphotransferase named APH(3')-IId identified in an MDR Brucella intermedia ZJ499 isolate from a cancer patient.Methods: Species identity was determined by PCR and MALDI-TOF MS analysis. WGS was performed to determine the genetic elements conferring antimicrobial resistance. Gene cloning, transcriptional analysis and targeted gene deletion, as well as protein purification and kinetic analysis, were performed to investigate the mechanism of resistance.Results: APH(3')-IId consists of 266 amino acids and shares the highest identity (48.25%) with the previously known APH(3')-IIb. Expression of aph(3')-IId in Escherichia coli decreased susceptibility to kanamycin, neomycin, paromomycin and ribostamycin. The aph(3')-IId gene in ZJ499 was transcriptionally active under laboratory conditions and the relative abundance of this transcript was unaffected by treatment with the above four antibiotics. However, deletion of aph(3')-IId in ZJ499 results in decreased MICs of these drugs. The purified APH(3')-IId showed phosphotransferase activity against kanamycin, neomycin, paromomycin and ribostamycin, with catalytic efficiencies (kcat/Km) ranging from ∼105 to 107 M-1 s-1. Genetic environment and comparative genomic analyses suggested that aph(3')-IId is probably a ubiquitous gene in Brucella, with no mobile genetic elements detected in its surrounding region.Conclusions: APH(3')-IId is a novel chromosomal aminoglycoside phosphotransferase and plays an important role in the resistance of B. intermedia ZJ499 to kanamycin, neomycin, paromomycin and ribostamycin. To the best of our knowledge, APH(3')-IId represents the fourth characterized example of an APH(3')-II enzyme. [ABSTRACT FROM AUTHOR]

A novel plasmid-encoded aminoglycoside 3''-nucleotidyltransferase ANT(3")-IId, was discovered in Acinetobacter lwoffi strain H7 isolated from a chick on an animal farm in Wenzhou, China. The whole-genome of A. lwoffii H7 consisted of one chromosome and five plasmids (pH7-250, pH7-108, pH7-68, pH7-48, and pH7-11). ant(3")-IId was identified as being encoded on pH7-250, sharing the highest amino acid identity of 50.64% with a function-known resistance gene, ant(3")-IIb (KB849358.1). Susceptibility testing and enzyme kinetic parameter analysis were conducted to determine the function of the aminoglycoside 3"-nucleotidyltransferase. The ant(3")-IId gene conferred resistance to spectinomycin and streptomycin [the minimum inhibitory concentration (MIC) levels of both increased 16-fold compared with the control strain]. Consistent with the MIC data, kinetic analysis revealed a narrow substrate profile including spectinomycin and streptomycin, with K cat/ K m ratios of 4.99 and 4.45×103M−1 S−1, respectively. Sequencing analysis revealed that the ant(3")-IId gene was associated with insertion sequences (IS) element [ΔIS Aba14 -ΔIS Aba14 -hp-orf-orf-orf1- ant(3")-IId ], and ant(3")-IId were identified in plasmids from various Acinetobacter species. This study of the novel aminoglycoside 3"-nucleotidyltranferase ANT(3")-IId helps us further understand the functional and sequence characteristics of aminoglycoside 3"-nucleotidyltranferases, highlights the risk of resistance gene transfer among Acinetobacter species and suggests that attention should be given to the emergence of new aminoglycoside 3"-nucleotidyltranferase genes. [ABSTRACT FROM AUTHOR]

Coagulase-negative Staphylococcus warneri is an opportunistic pathogen that is capable of causing several infections, especially in patients with indwelling medical devices. Here, we determined the complete genome sequence of a clinical S. warneri strain isolated from the blood culture of a 1-year-old nursling patient with acute upper respiratory infection. Genome-wide phylogenetic analysis confirmed the phylogenetic relationships between S. warneri and other Staphylococcus species. Using comparative genomics, we identified three cell wall-anchored (CWA) proteins at the same locus (sdr), named SdrJ, SdrK, and SdrL, on the chromosome sequences of different S. warneri strains. Structural predictions showed that SdrJ/K/L have structural features characteristic of Sdr proteins but exceptionally contained an unusual N-terminal repeat region. However, the C-terminal repetitive (R) region of SdrJ contains a significantly larger proportion of alanine (142/338, 42.01%) than the previously reported SdrI (37.00%). Investigation of the genetic organization revealed that the sdrJ/K/L genes were always followed by one or two glycosyltransferase genes, gtfA and gtfB and were present in an ∼56 kb region bordered by a pair of 8 bp identical direct repeats, named Sw-Sdr. This region was further found to be located on a 160-kb region subtended by a pair of 160-bp direct repeats along with other virulence genes and resistance genes. Sw-Sdr contained a putative integrase that was probably a remnant of a functional integrase. Evidence suggests that Sw-Sdr is improbably an efficient pathogenicity island. A large-scale investigation of Staphylococcus genomes showed that sdr loci were a potential hotspot of insertion sequences (ISs), which could lead to intraspecific diversity at these loci. Our work expanded the repository of Staphylococcus Sdr proteins, and for the first time, we established the connection between sdr loci and phylogenetic relationships and compared the sdr loci in different Staphylococcus species, which provided large insights into the genetic environment of CWA genes in Staphylococcus. [ABSTRACT FROM AUTHOR]

Florfenicol is widely used to control respiratory diseases and intestinal infections in food animals. However, there are increasing reports about florfenicol resistance of various clinical pathogens. floR is a key resistance gene that mediates resistance to florfenicol and could spread among different bacteria. Here, we investigated the prevalence of floR in 430 Pseudomonas aeruginosa isolates from human clinical samples and identified three types of floR genes (designated floR , floR-T1 and floR-T2) in these isolates, with floR-T1 the most prevalent (5.3%, 23/430). FloR-T2 was a novel floR variant identified in this study, and exhibited less identity with other FloR proteins than FloRv. Moreover, floR-T1 and floR-T2 identified in P. aeruginosa strain TL1285 were functionally active and located on multi-drug resistance region of a novel incomplete Tn 4371 -like integrative and conjugative elements (ICE) in the chromosome. The expression of the two floR variants could be induced by florfenicol or chloramphenicol. These results indicated that the two floR variants played an essential role in the host's resistance to amphenicol and the spreading of these floR variants might be related with the Tn 4371 family ICE. [ABSTRACT FROM AUTHOR]

Aminoglycosides are important options for treating life-threatening infections. However, high levels of aminoglycoside resistance (HLAR) among Klebsiella pneumoniae isolates have been observed to be increasing frequently. In this study, a total of 292 isolates of the K. pneumoniae complex from a teaching hospital in China were analyzed. Among these isolates, the percentage of HLAR strains was 13.7% (40/292), and 15 aminoglycoside resistance genes were identified among the HLAR strains, with rmtB being the most dominant resistance gene (70%, 28/40). We also described an armA -carrying Klebsiella variicola strain KP2757 that exhibited a high-level resistance to all aminoglycosides tested. Whole-genome sequencing of KP2757 demonstrated that the strain contained one chromosome and three plasmids, with all the aminoglycoside resistance genes (including two copies of armA and six AME genes) being located on a conjugative plasmid, p2757-346, belonging to type IncHI5. Comparative genomic analysis of eight IncHI5 plasmids showed that six of them carried two copies of the intact armA gene in the complete or truncated Tn 1548 transposon. To the best of our knowledge, for the first time, we observed that two copies of armA together with six AME genes coexisted on the same plasmid in a strain of K. variicola with HLAR. Comparative genomic analysis of eight armA -carrying IncHI5 plasmids isolated from humans and sediment was performed, suggesting the potential for dissemination of these plasmids among bacteria from different sources. These results demonstrated the necessity of monitoring the prevalence of IncHI5 plasmids to restrict their worldwide dissemination. [ABSTRACT FROM AUTHOR]

Purpose: An increasing frequency of antibiotic resistance has been observed in both clinical and environmental Aeromonas hydrophila isolates in recent years. However, there are still very few in-depth studies regarding the role of plasmids in the antibiotic resistance of A. hydrophila. Hence, we investigated the molecular and functional characterization of a multidrug-resistant plasmid encoding an NDM-like metallo-β-lactamase, AFM-1, in the clinical A. hydrophila isolate SS332. Methods: The minimum inhibitory concentrations (MICs) of 24 antibiotics against A. hydrophila SS332 were measured by the agar dilution method. The genome of A. hydrophila SS332 was sequenced with PacBio and Illumina platforms. Six plasmid-borne antimicrobial resistance genes were chosen for cloning, including blaAFM-1, blaOXA-1, msr(E), mph(E), aac(6ʹ)-Ib10, and aph(3ʹ)-Ia. Phylogenetic analysis, amino acid sequence alignment, and comparative genomic analysis were performed to elucidate the active site requirements and genetic context of the blaAFM-1 gene. Results: A. hydrophila SS332 showed high levels of resistance to 15 antibiotics, especially those with MIC levels at or above 1024 μg/mL, including ampicillin, cefazolin, ceftriaxone, aztreonam, spectinomycin, and roxithromycin. Six plasmid-borne resistance genes from A. hydrophila were verified to be functional in E. coli DH5α. AFM-1 shared 86% amino acid identity with NDM-1 and showed resistance to ampicillin, cefazolin, cefoxitin, and ceftazidime. In addition, the blaAFM-1 gene was associated with three different novel ISCR19-like elements, designated ISCR19-1, ISCR19-2 and ∆ISCR19-3, which may be involved in the acquisition and mobilization of the blaAFM-1 gene. Conclusion: Our investigation showed that plasmid-borne resistance genes can contribute to antibiotic resistance in A. hydrophila SS332. A novel blaNDM-like gene, blaAFM-1, was verified to be functional and associated with novel ISCR19-like elements. This fact indicated the risk of spread of blaAFM-1 genes and ISCR19-like elements. [ABSTRACT FROM AUTHOR]

Introduction: Human adenovirus (HAdV) is a common pathogen in children with acute respiratory infections (ARIs). The aim was to describe the epidemiology, molecular, and clinical characteristics of HAdV among children hospitalized with ARIs in Wenzhou in southeastern China. Methodology: From January 2018 to December 2019, nasopharyngeal swab or sputum specimens were prospectively collected from hospitalized children with ARIs. HAdV was detected using direct immunofluorescence. We used a multiplex PCR assay combined with capillary electrophoresis targeting the hexon gene's hypervariable region to identify HAdV types 1, 2, 3, 4, 5, 7, 14, 21, 37, 40, 41, and 55. We analyzed the epidemiological, molecular, and clinical data according to the HAdV type. Results: HAdVs were detected in 1,059 (3.5%) of the total of 30,543 children tested. A total of 947 cases with monotype HAdV identified by the PCR assay were included in the analysis. HAdV-3 (415/947, 43.8%), HAdV-7 (318/947, 33.6%), HAdV-2 (108/947, 11.4%), and HAdV-1 (70/947, 7.4%) were the predominant types. Of the 550 (58.1%) cases detected from December 2018 to August 2019, HAdV-3, and HAdV-7 were the main types. The main diagnoses included 358 cases of pneumonia, 232 cases of tonsillitis, 198 cases of bronchitis, and 159 cases of upper respiratory tract infection (URTI). Among children with pneumonia the main types were HAdV-7 (51.1%), HAdV-3 (36.9%), and HAdV-1 (2.2%). Among children with bronchitis, the main types were HAdV-3 (48.0%), HAdV-7 (28.3%), and HAdV-2 (10.6%). Among children with URTIs, the main types were HAdV-3 (49.7%), HAdV-7 (22.6%), and HAdV-2 (13.2%). Among children with tonsillitis, the main types were HAdV-3 (47.4%), HAdV-2 (22.4%), and HAdV-7 (18.5%). In total, 101 (55.2%) patients required supplemental oxygen, 15 (8.2%) required critical care, and 1 child (0.5%) with HAdV-7 pneumonia died. Conclusion: HAdV-3 -7, -2, and -1 were the predominant types identified in hospitalized children with ARIs in Wenzhou. From December 2018 to August 2019, there were outbreaks of HAdV-3 and -7. There were significant differences in HAdV types among children with pneumonia, tonsillitis, bronchitis, and URTI. HAdV-7 can cause more severe pneumonia in children than HAdV-3. [ABSTRACT FROM AUTHOR]

Background: This study was designed to characterize the dissemination mechanism and genetic context of Klebsiella pneumoniae carbapenemase (KPC) genes in carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates. Methods: A retrospective analysis was performed on CRKP strains isolated from a teaching hospital of Wenzhou Medical University during 2015– 2017. Polymerase chain reaction (PCR)-based amplification and whole-genome sequencing (WGS) were used to analyze the genetic context of the blaKPC-2 gene. Conjugation experiments were performed to evaluate the transferability of blaKPC-2-bearing plasmids. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were performed to investigate the clonal relatedness of blaKPC-2-producing strains. Results: The blaKPC-2 gene was identified from 13.61% (40/294) of clinical K. pneumoniae isolates. Three different sequence types (ST11, ST15 and ST656) and 5 PFGE subtypes (A to E) were classified among them. ST11 was the dominant sequence type (92.50%, 37/40). Plasmid-oriented antibiotic resistance genes, such as extended spectrum-β-lactamases (ESBLs) and other antimicrobial resistance genes, were also found in KPC-positive K. pneumoniae (KPC-Kp) isolates. Mapping PCR and genomic sequencing revealed that the blaKPC-2-bearing sequence regions, which are related to different mobile elements, including Tn1721- and IS26-based transposons, were mainly located in but not restricted to IncFII-like plasmids and were structurally divergent. Conclusion: The blaKPC-2 genes related to divergent mobile genetic elements encoded on transferable plasmids may transfer widely, facilitating the spread of carbapenem resistance among bacteria with different genetic backgrounds. The dissemination of blaKPC-bearing plasmids that collectively carry additional multidrug resistance genes has caused widespread public concern, further limiting the antibiotics available to treat infections caused by KPC-producing pathogens. [ABSTRACT FROM AUTHOR]

Yokenella regensburgei , a member of the family Enterobacteriaceae, is usually isolated from environmental samples and generally resistant to early generations of cephalosporins. To characterize the resistance mechanism of Y. regensburgei strain W13 isolated from the sewage of an animal farm, whole genome sequencing, comparative genomics analysis and molecular cloning were performed. The results showed that a novel chromosomally encoded class C β-lactamase gene with the ability to confer resistance to β-lactam antibiotics, designated bla YOC –1, was identified in the genome of Y. regensburgei W13. Kinetic analysis revealed that the β-lactamase YOC-1 has a broad spectrum of substrates, including penicillins, cefazolin, cefoxitin and cefotaxime. The two functionally characterized β-lactamases with the highest amino acid identities to YOC-1 were CDA-1 (71.69%) and CMY-2 (70.65%). The genetic context of the bla YOC –1 -ampR -encoding region was unique compared with the sequences in the NCBI nucleotide database. The plasmid pRYW13-125 of Y. regensburgei W13 harbored 11 resistance genes (bla OXA –10, bla LAP –2, dfrA14 , tetA , tetR , cmlA5 , floR , sul2 , ant(3″)-IIa , arr-2 and qnrS1) within an ∼34 kb multidrug resistance region; these genes were all related to mobile genetic elements. The multidrug resistance region of pYRW13-125 shared the highest identities with those of two plasmids from clinical Klebsiella pneumoniae isolates, indicating the possibility of horizontal transfer of these resistance genes between bacteria of various origins. [ABSTRACT FROM AUTHOR]

Staphylococcus caprae, Staphylococcus capitis , and Staphylococcus epidermidis belong to the "Epidermidis Cluster Group" (ECG) and are generally opportunistic pathogens. In this work, whole genome sequencing, molecular cloning and pan-genome analysis were performed to investigate the genetic characteristics of the resistance, virulence and genome structures of 69 ECG strains, including a clinical isolate (S. caprae SY333) obtained in this work. Two resistance genes (blaZ and aadD2) encoded on the plasmids pSY333-41 and pSY333-45 of S. caprae SY333 were confirmed to be functional. The bla region in ECG exhibited three distinct structures, and these chromosome- and plasmid-encoded bla operons seemed to follow two different evolutionary paths. Pan-genome analysis revealed their pan-genomes tend to be "open." For the virulence-related factors, the genes involved in primary attachment were observed almost exclusively in S. epidermidis , while the genes associated with intercellular aggregation were observed more frequently in S. caprae and S. capitis. The type VII secretion system was present in all strains of S. caprae and some of S. epidermidis but not in S. capitis. Moreover, the isd locus (iron regulated surface determinant) was first found to be encoded on the genomes of S. caprae and S. capitis. These findings suggested that the plasmid and chromosome encoded bla operons of ECG species underwent different evolution paths, as well as they differed in the abundance of virulence genes associated with adherence, invasion, secretion system and immune evasion. Identification of isd loci in S. caprae and S. capitis indicated their ability to acquire heme as nutrient iron during infection. [ABSTRACT FROM AUTHOR]

Thrombosis has been recognized as one of the most significant risk factors of high mortality and disability in patients with Philadelphia (Ph) chromosome negative myeloproliferative neoplasms (MPNs). However, the risk factors of thrombotic events in these patients have not been completely understood. In this study, the clinical data of 58 patients with Ph-MPNs were obtained and analyzed, including 34 cases of essential thrombocytopenia (ET), 23 thrombotic events happened in 21 (36%) patients, among which 60% (14 of 23) with cerebral infarction, 17% (4 of 23) with coronary heart disease and 23% (5 of 23) with venous thrombosis. There were no significant differences in age, sex, and blood cell count between polycythemia vera (PV) and ET patients who have experienced thrombotic events and those who have not. In ET patients, the incidence of thrombotic events in plasminogen activator inhibitor-1 (PAI-1) genotype 4G4G was significantly higher than that in genotype 4G5G and genotype 5G5G (P <.05). The incidence of thrombotic events in PV and ET patients with infection was higher than those without infection (P <.05). Using logistic regression analysis, we found that PAI-1 genotype 4G4G and infection were associated with thrombotic events (odds ratio 6.744, 95% CI: 1.195-38.056 and 15.641 95% CI: 3.327-73.522). The 4G/4G polymorphism of PAI-1 gene and infection are independent risk factors of thrombotic events in patients with Ph-MPNs. PAI-1 gene 4G4G and infection in ET and PV patients with Janus kinase 2 (JAK2) V617F mutation were shown to be high risk of thrombotic events. Therefore, clinical doctors should put more attention on PAI-1 genotype 4G4G and infection in JAK2 V617F mutated patients with Ph-MPNs to prevent the thrombosis. [ABSTRACT FROM AUTHOR]

Background: Notch signaling pathway is critically involved in the differentiation of T helper (Th) cells, key players in the pathogenesis of allergic diseases. Objective: The study is to explore whether Th17/Treg dysregulation in children with allergic asthma (AA) is associated with alteration of Notch expression. Methods: Thirty-five patients with AA and thirty-five healthy control children were selected. Flow cytometry was used to detect Th17 and Treg cells. Quantitative real-time polymerase chain reaction (QRT-PCR) was used to measure the expression of Notch1 mRNA. The correlations among Notch1 mRNA expression, the percentage of Th17 cells, and Th17/Treg ratio were calculated. Results: Th17 and Treg cells were significantly increased and decreased, respectively, in children with AA than in healthy control (p < 0.001). mRNA level of Notch1 was elevated in children with AA comparing to healthy controls (p < 0.001). The mRNA expression of Notch1 was positively correlated with the percentage of Th17 cells (r = 0.775, p < 0.001) and Th17/Treg ratio (r = 0.698, p < 0.001). Conclusion: Children with AA showed dysregulation of Th17/Treg cells in peripheral blood. Such change is accompanied with overexpression of Notch1, indicating Th17/Treg dysregulation in children with AA is associated with elevated Notch expression. [ABSTRACT FROM AUTHOR]

The Philadelphia (Ph) chromosome formed by the translocation of chromosomes 9 and 22, which result in I BCR-ABL1 i fusion gene, is seen in more than 95% of chronic myeloid leukemia (CML) and 5-20% acute lymphoblastic leukemia (ALL) [[1]]. Due to little is known about characteristic clinical features of I BCR/ABL1 i positive AML, the distinction between I BCR/ABL1 i positive AML and CML in primary myeloid blast crisis can be difficult. Furthermore, the presence of common AML mutations, such as I CEBPA i double mutations, is more conducive to the diagnosis of I BCR/ABL1 i positive AML [[3]]. [Extracted from the article]