Worldwide dissemination of extended-spectrum -lactamase (ESBL)-producing
Escherichia coli
constitutes an emerging global health issue, with animal food products contributing as potential reservoirs. ...ESBL
E. coli
infection is associated with the high mortality and mobility rate in developing countries due to less susceptibility to antibiotics. The present study aimed to elucidate the molecular characteristics and sequence-based analysis of ESBL
E. coli
in the Gujarat state of India. This study included 108
E. coli
strains were isolated from different poultry farms (broiler and layer) in the Banaskantha District. PCR was employed to identify genotypic ESBL-producing antimicrobial resistance genes. Overall, a high occurrence of ESBL genes was found in poultry farms due to the high usage of antimicrobials. The PCR analysis revealed that 79.62% of isolates were detected positive with one or more ESBL genes. Among them,
bla
TEM
(63.88%) was found to be the predominant genotype, followed by
bla
SHV
(30.55%) and
bla
OXA
(28.70%). In the
bla
CTX-M
group, a higher occurrence was observed in
bla
CTX-M-9
(23.14%), followed by
bla
CTX-M-2
(24.07%) and
bla
CTX-M-1
(22.22%). We used the whole-genome sequencing (WGS) method to evaluate the antimicrobial resistance genes, virulence factors, single nucleotide polymorphisms (SNPs), plasmid replicons, and plasmid-mediated AMR genes of one ESBL
E. coli
isolated. We examined the genetic relatedness of a human pathogenic
E. coli
strain by comparing its sequence with the broad geographical reference
E. coli
sequences.
Escherichia coli
ST 681 was determined using multi-locus sequence typing. We compared our findings to the reference sequence of
Escherichia coli
str. K- 12 substr. MG1655. We found 24,937 SNPs with 21,792 in the genic region, 3,145 in the intergenic region, and six InDels across the genome. The WGS analysis revealed 46 antimicrobial resistance genes and seven plasmid-mediated AMR genes
viz.
,
tetA
,
qnrS1, dfrA14
,
sul2
,
aph(3”)-lb
,
aph(6)-ld
, and
Aph(3’)-la
. The ST 681 was found to have
Cib
,
traT
, and
terC
virulence factors and two plasmid replicons, IncFII(pHN7A8) and IncI1-I(Alpha). This study revealed a higher occurrence of ESBL
E. coli
detected in poultry.
The spin-phonon interaction in spin density wave (SDW) systems often determines the free energy landscape that drives the evolution of the system. When a passing energy flux, such as photoexcitation, ...drives a crystalline system far from equilibrium, the resulting lattice displacement generates transient vibrational states. Manipulating intermediate vibrational states in the vicinity of the critical point, where the SDW order parameter changes dramatically, would then allow dynamical control over functional properties. Here we combine double photoexcitation with an X-ray free-electron laser (XFEL) probe to control and detect the lifetime and magnitude of the intermediate vibrational state near the critical point of the SDW in chromium. We apply Landau theory to identify the mechanism of control as a repeated partial quench and sub picosecond recovery of the SDW. Our results showcase the capabilities to influence and monitor quantum states by combining multiple optical photoexcitations with an XFEL probe. They open new avenues for manipulating and researching the behaviour of photoexcited states in charge and spin order systems near the critical point.
Type I interferons (IFN-Is) are a group of potent inflammatory and antiviral cytokines. They induce IFN stimulated genes (ISGs), which act as proinflammatory mediators, antiviral effectors, and ...negative regulators of the IFN-I signaling cascade itself. One such regulator is interferon stimulated gene 15 (ISG15). Humans with complete ISG15 deficiency express persistently elevated levels of ISGs, and consequently, exhibit broad spectrum resistance to viral infection. Here, we demonstrate that IFN-I primed fibroblasts derived from ISG15-deficient individuals are more resistant to infection with single-cycle HIV-1 compared to healthy control fibroblasts. Complementation with both wild-type (WT) ISG15 and ISG15ΔGG (incapable of ISGylation while retaining negative regulation activity) was sufficient to reverse this phenotype, restoring susceptibility to infection to levels comparable to WT cells. Furthermore, CRISPR-edited ISG15ko primary CD4+ T cells were less susceptible to HIV-1 infection compared to cells treated with non-targeting controls. Transcriptome analysis of these CRISPR-edited ISG15ko primary CD4+ T cells recapitulated the ISG signatures of ISG15 deficient patients. Taken together, we document that the increased broad-spectrum viral resistance in ISG15-deficiency also extends to HIV-1 and is driven by a combination of T-cell-specific ISGs, with both known and unknown functions, predicted to target HIV-1 replication at multiple steps.
Patel S. The use of cone beam computed tomography in the conservative management of dens invaginatus: a case report. International Endodontic Journal.
Aim To report the use of cone beam computed ...tomography (CBCT) in the assessment of dens invaginatus.
Summary Chronic periradicular periodontitis associated with an infected invagination was diagnosed in an immature mandibular lateral incisor tooth. A CBCT scan revealed essential information for the management of the tooth. There was no communication between the invagination and the main root canal. Endodontic treatment was carried out on the invagination. The root canal with a vital pulp was left untreated, thus allowing the tooth to mature and continue to develop.
Key learning points
•
The true nature of dens invaginatus cannot always be estimated from conventional radiographs.
•
Cone beam computed tomography is a useful diagnostic tool in the management of dens invaginatus.
Interferons establish an antiviral state through the induction of hundreds of interferon-stimulated genes (ISGs). The mechanisms and viral specificities for most ISGs remain incompletely understood. ...To enable high-throughput interrogation of ISG antiviral functions in pooled genetic screens while mitigating potentially confounding effects of endogenous interferon and antiproliferative/proapoptotic ISG activities, we adapted a CRISPR-activation (CRISPRa) system for inducible ISG expression in isogenic cell lines with and without the capacity to respond to interferons. We used this platform to screen for ISGs that restrict SARS-CoV-2. Results included ISGs previously described to restrict SARS-CoV-2 and novel candidate antiviral factors. We validated a subset of these by complementary CRISPRa and cDNA expression experiments. OAS1, a top-ranked hit across multiple screens, exhibited strong antiviral effects against SARS-CoV-2, which required OAS1 catalytic activity. These studies demonstrate a high-throughput approach to assess antiviral functions within the ISG repertoire, exemplified by identification of multiple SARS-CoV-2 restriction factors.
Rapid diagnostic tests, which accurately distinguish bacterial from viral infections, are being heralded as the solution to antibiotic overuse, which is a key driver of antimicrobial resistance. We ...have concerns that this approach is oversimplistic. Rapid diagnostic tests are complex interventions, with clinical context, patient flow, access and timing affecting their impact. There is little robust evidence that they reduce antibiotic prescribing in real-world settings. We suggest that prior to introducing these costly tests, emphasis should be placed on optimizing the implementation of efficient evidence-based antimicrobial stewardship interventions, such as increasing the use of proven automated clinical infection syndrome prediction tools by clinicians, supporting patients to self-care by providing them with high-quality safety-netting resources, providing front-line clinicians with individual prescribing data to facilitate peer benchmarking and setting specific and purposeful antibiotic prescribing targets to improve the quality of antimicrobial prescribing. The stakes are high and time is running out; let's start by getting the basics right.
Lymph node density (LND) has previously been reported to reliably predict recurrence risk and survival in oral cavity squamous cell carcinoma (OSCC). This multicenter international study was designed ...to validate the concept of LND in OSCC.
The study included 4254 patients diagnosed as having OSCC. The median follow-up was 41 months. Five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional control and distant metastasis rates were calculated using the Kaplan-Meier method. Lymph node density (number of positive lymph nodes/total number of excised lymph nodes) was subjected to multivariate analysis.
The OS was 49% for patients with LND0.07 compared with 35% for patients with LND>0.07 (P<0.001). Similarly, the DSS was 60% for patients with LND0.07 compared with 41% for those with LND>0.07 (P<0.001). Lymph node density reliably stratified patients according to their risk of failure within the individual N subgroups (P=0.03). A modified TNM staging system based on LND ratio was consistently superior to the traditional system in estimating survival measures.
This multi-institutional study validates the reliability and applicability of LND as a predictor of outcomes in OSCC. Lymph node density can potentially assist in identifying patients with poor outcomes and therefore for whom more aggressive adjuvant treatment is needed.
This Position Statement represents a consensus of an expert committee convened by the European Society of Endodontology (ESE) on the use of Cone Beam Computed Tomography (CBCT) in Endodontics. This ...paper is an update of the ESE CBCT position statement which was published in 2014 (European Society of Endodontology 2014, https://doi.org/10.1111/iej.12267). Recent review articles provide more detailed background information and the basis for this position statement. It is intended that this position statement will be updated at least every 4-5 years to keep abreast of relevant research. The aim of this paper is to provide clinicians with evidence-based guidance on the application of CBCT in Endodontics. Since 2014, there has been an increase in the number of clinical studies confirming the positive impact of CBCT on treatment planning, decision-making when reviewing cases and reduced practitioner stress levels.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic that is a serious global health problem. Evasion of ...IFN-mediated antiviral signaling is a common defense strategy that pathogenic viruses use to replicate and propagate in their host. In this study, we show that SARS-CoV-2 is able to efficiently block STAT1 and STAT2 nuclear translocation in order to impair transcriptional induction of IFN-stimulated genes (ISGs). Our results demonstrate that the viral accessory protein Orf6 exerts this anti-IFN activity. We found that SARS-CoV-2 Orf6 localizes at the nuclear pore complex (NPC) and directly interacts with Nup98-Rae1 via its C-terminal domain to impair docking of cargo-receptor (karyopherin/importin) complex and disrupt nuclear import. In addition, we show that a methionine-to-arginine substitution at residue 58 impairs Orf6 binding to the Nup98-Rae1 complex and abolishes its IFN antagonistic function. All together our data unravel a mechanism of viral antagonism in which a virus hijacks the Nup98-Rae1 complex to overcome the antiviral action of IFN.
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