Alstonespersen1372
This extremely broad distribution of biofilm-induced tolerance phenotypes across the clinical isolates was greatly influenced by the choice of the antibiotic. We furthermore describe cross-tolerance against ciprofloxacin and tobramycin, but not colistin, and observed an additive activity between biofilm-induced tolerance and genetically determined resistance. This became less evident when the biofilm-grown cells were exposed to very high antibiotic concentrations. Although much more remains to be learned on the molecular mechanisms underlying biofilm-induced tolerance, our data on intra-species variations in tolerance profiles provide valuable new insights. Furthermore, our observation that colistin appears to act independently of the tolerance mechanisms of individual clinical strains could make colistin a valuable therapeutic option in chronic biofilm-associated infections characterized by the presence of particularly tolerant strains.Schistosoma is a genus of parasitic trematodes that undergoes complex migration in final hosts, finally developing into adult worms, which are responsible for egg production and disease dissemination. selleck chemical Recent studies documented the importance of extracellular vesicles (EVs) in the regulation of host-parasite interactions. Herein, we investigated the microRNA (miRNA) profiles of EVs isolated from host plasma at different stages of Schistosoma japonicum infection (lung stage 3 days post-infection (dpi), and liver stages 14 and 21 dpi) to identify miRNA cargo potentially involved in the pathogenesis and immune regulation of schistosomiasis. Characterization of the isolated plasma EVs revealed their diameter to be approximately 100 nm, containing typical EV markers such as Hsp70 and Tsg101. Deep sequencing analysis indicated the presence of 811 known and 15 novel miRNAs with an increasing number of differential miRNAs from the lung stage (27 miRNAs) to the liver stages (58 and 96 miRNAs at 14 and 21 dpi, respectivtory mechanism of the host-parasite interaction. Moreover, the differentially abundant miRNA cargo in host EVs associated with S. japonicum infection may also provide valuable clues for identifying novel biomarkers for schistosomiasis diagnosis.
The objective of this article was to compare the efficiency of azacitidine (AZA) and decitabine (DAC) in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) who are not suitable for high-dose chemotherapy.
MDS and AML patients who were treated with hypomethylating agents (HMAs) between January 2005 and 2020 were evaluated retrospectively.
No statistically significant difference was found between the patients whoreceived AZA or DAC in AML patients. In MDS group, the rate of patients who achieved remission was statistically significantly higher in patients who received DAC (p=0.032).
The advantage in terms of response for MDS and no survival difference between AZA and DAC for AML and MDS patients will be an important contribution to the literature.
The advantage in terms of response for MDS and no survival difference between AZA and DAC for AML and MDS patients will be an important contribution to the literature.
During COVID-19, the management of outpatient inflammatory bowel disease (IBD) changed from face-to-face (F2F) to telephone and video consultations across the UK. We surveyed patients with IBD and IBD healthcare professionals (HCPs) to evaluate the impact of this abrupt transition on patient and HCP satisfaction outcomes, including the barriers and enablers of this service.
Patient satisfaction surveys were sent to patients who had a telephone consultation from May to July 2020. A second survey was sent to IBD HCPs across the UK. Questions from both surveys consisted of a mixture of multiple-choice options, ranking answers as well as short-answer questions.
210 patients and 114 HCPs completed the survey. During COVID-19, there was a significantly greater use of telephone, video or a mixture of consultation. F2F consultations were consistently preferred by patients, with 50% of patients indicating they did not want the option of for video consultations. Patients were more likely to prefer a telephone consultation if they were stable and needed routine review. Significantly fewer HCPs (5.3%) intend to use F2F consultations alone, preferring the use of telephone (20.2%) or combinations of telephone/F2F (22.8%), telephone/video (4.4%) or combination of all three consultation types (34.2%). 63% indicated they intend to incorporate video consultations in the future.
Telephone and video consultations need to be balanced proportionately with F2F clinics to achieve both patient and HCP satisfaction. Further research needs to be done to explore the use of video medicine in patients with IBD.
Telephone and video consultations need to be balanced proportionately with F2F clinics to achieve both patient and HCP satisfaction. Further research needs to be done to explore the use of video medicine in patients with IBD.There is an increasing demand and availability of bariatric surgery, with a range of procedures performed, some leading to altered upper gastrointestinal anatomy. The patient population undergoing bariatric surgery is also at increased risk of gallstones and biliary stone disease. Endoscopy (ie, endoscopic retrograde cholangiopancreatography) is the cornerstone of management of biliary stone disease, but may be challenging after bariatric surgery. In this review the endoscopic, surgery assisted, or percutaneous options that may be considered are discussed, based on the details of surgical anatomy and available expertise.
Debate is ongoing regarding the need for universal endoscopic follow-up to ensure gastric ulcer healing. We aimed to assess the value of follow-up oesophago-gastro-duodenoscopies (OGDs) for gastric ulcer healing and stratify patients according to risk of malignancy by developing a risk score.
All patients in National Health Service (NHS) Lothian with an index OGD and a diagnosis of gastric ulcer between 1 January 2014 and 31 December 2018 were identified. Data were analysed with logistic regression to identify factors significantly associated with a diagnosis of cancer; a risk score was derived and externally validated.
778 patients were identified and 60.3% (469/778) of patients had a follow-up OGD. 8.6% (66/778) of patients were diagnosed with cancer. No cases of cancer were found on follow-up OGD of a benign appearing ulcer with negative biopsies. Macroscopic suspicion of malignancy was present at index OGD in 100% (3/3) of those diagnosed with cancer on subsequent OGDs. Older age (p=0.014), increased ulcer size (p<0.001) and non-antral location (p=0.030) were significantly associated with malignancy. A risk score (area under the curve (AUC) 0.868, p<0.001, minimum score=0, maximum score=6) was derived from these variables. 78.0% of patients with malignant ulcers scored ≥3, only 15.8% with benign ulcers scored ≥3 (negative predictive value (NPV) 97.4%). External validation yielded an AUC of 0.862 (p<0.001) and NPV of 98.6%; 84.0% of those with malignant ulcers scored ≥3.
Ulcers with a combination of macroscopically benign appearances, at least six negative biopsies and a low risk score do not necessarily need endoscopic follow-up.
Ulcers with a combination of macroscopically benign appearances, at least six negative biopsies and a low risk score do not necessarily need endoscopic follow-up.
Autoimmune hepatitis (AIH) is a substantial UK health burden, but there is variation in care, facilities and in opinion regarding management. We conducted an audit of service provision and care of patients with AIH in 28 UK hospitals.
Centres provided information about staffing, infrastructure and patient management (measured against predefined guideline-based standards) via a web-based data collection tool.
Hospitals (14 university hospitals (UHs), 14 district general hospitals (DGHs)) had median (range) of 8 (3-23) gastroenterologists; including 3 (0-10) hepatologists. Eight hospitals (29%, all DGHs) had no hepatologist. In individual hospital departments, there were 50% (18-100) of all consultants managing AIH in DGH's 92% (20-100) vs 46% (17-100) in UHs. Specialist nurses managed AIH in only 18%. Seventeen (61%) hospitals had a histopathologist with a liver interest, these were more likely to find rosettes than those without (172/795 vs 50/368; p<0.001).Of 999 steroid-treated patients with ≥12 mot discussed with transplant teams. Care might be improved by expanding specialist input and management by fewer designated consultants.Genetic analyses of fast-evolving pathogens are frequently undertaken to test the impact of covariates on their dispersal. In particular, a popular approach consists of parameterizing a discrete phylogeographic model as a generalized linear model to identify and analyse the predictors of the dispersal rates of viral lineages among discrete locations. However, such a full probabilistic inference is often computationally demanding and time-consuming. In the face of the increasing amount of viral genomes sequenced in epidemic outbreaks, there is a need for a fast exploration of covariates that might be relevant to consider in formal analyses. We here present PhyCovA (short for 'Phylogeographic Covariate Analysis'), a web-based application allowing users to rapidly explore the association between candidate covariates and the number of phylogenetically informed transition events among locations. Specifically, PhyCovA takes as input a phylogenetic tree with discrete state annotations at the internal nodes, or reconstructs those states if not available, to subsequently conduct univariate and multivariate linear regression analyses, as well as an exploratory variable selection analysis. In addition, the application can also be used to generate and explore various visualizations related to the regression analyses or to the phylogenetic tree annotated by the ancestral state reconstruction. PhyCovA is freely accessible at https//evolcompvir-kuleuven.shinyapps.io/PhyCovA/ and also distributed in a dockerized form obtainable from https//hub.docker.com/repository/docker/timblokker/phycova. The source code and tutorial are available from the GitHub repository https//github.com/TimBlokker/PhyCovA.Mutation is the primary determinant of genetic diversity in influenza viruses. The rate of mutation, measured in an absolute time-scale, is likely to be dependent on the rate of errors in copying RNA sequences per replication and the number of replications per unit time. Conditions for viral replication are probably different among host taxa, potentially generating the host specificity of the viral mutation rate, and possibly between highly and low pathogenic (HP and LP) viruses. This study investigated whether mutation rates per year in avian influenza A viruses depend on host taxa and pathogenicity. We inferred mutation rates from the rates of synonymous substitutions, which are assumed to be neutral and thus equal to mutation rates, at four segments that code internal viral proteins (PB2, PB1, PA, NP). On the phylogeny of all avian viral sequences for each segment, multiple distinct subtrees (clades) were identified that represent viral subpopulations, which are likely to have evolved within particular host taxa.
