Escherichia (E.) coli is the main causative pathogen of neonatal and post-weaning diarrhea and edema disease in swine production. There is a significant health concern due to an increasing number of ...human infections associated with food and/or environmental-borne pathogenic and multidrug-resistant E. coli worldwide. Monitoring the presence of pathogenic and antimicrobial-resistant E. coli isolates is essential for sustainable disease management in livestock and human medicine. A total of 102 E. coli isolates of diseased pigs were characterized by antimicrobial and biocide susceptibility testing. Antimicrobial resistance genes, including mobile colistin resistance genes, were analyzed by PCR and DNA sequencing. The quinolone resistance-determining regions of gyrA and parC in ciprofloxacin-resistant isolates were analyzed. Clonal relatedness was investigated by two-locus sequence typing (CH clonotyping). Phylotyping was performed by the Clermont multiplex PCR method. Virulence determinants were analyzed by customized DNA-based microarray technology developed in this study for fast and economic molecular multiplex typing. Thirty-five isolates were selected for whole-genome sequence-based analysis. Most isolates were resistant to ampicillin and tetracycline. Twenty-one isolates displayed an ESBL phenotype and one isolate an AmpC β-lactamase-producing phenotype. Three isolates had elevated colistin minimal inhibitory concentrations and carried the mcr-1 gene. Thirty-seven isolates displayed a multi-drug resistance phenotype. The most predominant β-lactamase gene classes were blaTEM-1 (56%) and blaCTX-M-1 (13.71%). Mutations in QRDR were observed in 14 ciprofloxacin-resistant isolates. CH clonotyping divided all isolates into 51 CH clonotypes. The majority of isolates belonged to phylogroup A. Sixty-four isolates could be assigned to defined pathotypes wherefrom UPEC was predominant. WGS revealed that the most predominant sequence type was ST100, followed by ST10. ST131 was detected twice in our analysis. This study highlights the importance of monitoring antimicrobial resistance and virulence properties of porcine E. coli isolates. This can be achieved by applying reliable, fast, economic and easy to perform technologies such as DNA-based microarray typing. The presence of high-risk pathogenic multi-drug resistant zoonotic clones, as well as those that are resistant to critically important antibiotics for humans, can pose a risk to public health. Improved protocols may be developed in swine farms for preventing infections, as well as the maintenance and distribution of the causative isolates.
Background
In patients with severe pulmonary arterial hypertension, subcutaneous or catheter-based intravenous application of prostanoids carries a risk of local side effects or systemic infections, ...which limits their use and acceptance. Recently, a fully implantable pump for continuous application of intravenous treprostinil was approved in Germany. However, surgery is a major risk for patients with severe pulmonary arterial hypertension. The purpose of this study was to investigate the safety of a fully implantable pump inserted under local or general anesthesia in patients with severe pulmonary hypertension.
Methods
All patients with pulmonary hypertension undergoing pump implantation for the continuous application of intravenous treprostinil were included from two German centers. Surgery was performed under local or general anesthesia according to the protocol of the recruiting center. Intra-operative safety and in-hospital complications were analyzed for the two different implantation regimens.
Results
In total, 51 patients were included. No major intra-operative complications were recorded. During the observation period, two patients died of progressive right heart failure, and two patients required treatment in the intensive care unit for acute right heart decompensation and respiratory failure. In total, major complications occurred in 8 out of 51 patients.
Conclusions
Our observational study provides preliminary evidence supporting the procedural safety of a fully implantable pump inserted under local or general anesthesia for patients with severe pulmonary hypertension. The observation of major complications in a subset of patients requires extensive pre- and post-operative assessments. Future trials are required to provide further evidence for the long-term safety and efficacy of the pump using this approach.
The preparation and use of bispidine derivatives (3,7-diazabicyclo3.3.1nonane) as chelate ligands for radioactive copper isotopes for diagnosis (64Cu) or therapy (67Cu) are reported. Starting from ...the hexadentate bispidine-based bis(amine)tetrakis(pyridine) ligand 1 with a keto and two ester substituents, the corresponding mono-ol 2 and two dicarboxylic acid derivatives 3 and 5 have been synthesized. A range of techniques, including single-crystal X-ray structure analysis, UV/vis spectroscopy, cyclic voltammetry, thin-layer- (TLC), and high-performance liquid chromatography (HPLC), have been used to characterize the structure and stability of the copper(II)-bispidine complexes. A rapid formation (within 1 min) of stable copper(II)-bispidine complexes under mild conditions (ambient temperature, aqueous solution) has been observed. Challenge experiments of these complexes in the presence of a high excess of competing ligands, such as glutathione, cyclam, or superoxide dismutase (SOD), as well as in rat plasma, gave no evidence of demetalation or transchelation. The bifunctional bispidine derivative 5 can be readily functionalized with biologically active molecules at the pendant carboxylate groups. The coupling of a bombesin analogue βhomo-Glu-βAla-βAla-Cha13,Nle14BBN(7−14), by condensation of a carboxylate of the bispidine backbone with the N-terminus of the peptide produced the bifunctional ligand 6. The radiocopper(II) complex of this bombesin−bispidine conjugate has a considerable hydrophilicity (log D o/w < −2.4), and this leads to a very fast blood clearance (blood: 0.28 ± 0.02 SUV, 1 h p.i.), low liver tissue accumulation (liver: 1.20 ± 0.27 SUV, 1 h p.i.), and rapid renal-urinary excretion (kidneys: 6.06 ± 2.96 SUV, 1 h p.i.) as shown by biodistribution studies of 64 Cu-6 in Wistar rats. Preliminary in vivo studies of 64 Cu-6 in NMRI nu/nu mice, bearing the human prostate tumor PC-3 showed an accumulation of the conjugate in the tumor (2.25 ± 0.13 SUV, 12.5 min p.i.; 0.94 ± 0.05 SUV, 55 min p.i.) and allowed a clear visualization of the gastrin-releasing peptide receptor distribution by positron emission tomography (PET).
is a versatile pathogen that does not only occur in humans but also in various wild and domestic animals, including several avian species. When characterizing
isolates from waterfowl, isolates were ...identified as atypical CC133 by DNA microarray analysis. They differed from previously sequenced CC133 strains in the presence of the collagen adhesin gene
; some also showed a different capsule type and a deviant
type. Thus, they were subjected to whole-genome sequencing. This revealed multiple insertions of large regions of DNA from other
lineages into a CC133-derived backbone genome. Three distinct strains were identified based on the size and extent of these inserts. One strain comprised two small inserts of foreign DNA up- and downstream of
; one of about 7000 nt or 0.25% originated from CC692 and the other, at ca. 38,000 nt or 1.3% slightly larger one was of CC522 provenance. The second strain carried a larger CC692 insert (nearly 257,000 nt or 10% of the strain's genome), and its CC522-derived insert was also larger, at about 53,500 nt or 2% of the genome). The third strain carried an identical CC692-derived region (in which the same mutations were observed as in the second strain), but it had a considerably larger CC522-like insertion of about 167,000 nt or 5.9% of the genome. Both isolates of the first, and two out of four isolates of the second strain also harbored a hemolysin-beta-integrating prophage carrying "bird-specific" virulence factors, ornithine cyclodeaminase D0K6J8 and a putative protease D0K6J9. Furthermore, isolates had two different variants of SCC elements that lacked
genes. These findings highlight the role of horizontal gene transfer in the evolution of
facilitated by SCC elements, by phages, and by a yet undescribed mechanism for large-scale exchange of core genomic DNA.
Abstract Background and purpose Induction chemotherapy is associated with anemia in non-small cell lung cancer (NSCLC) patients undergoing radiotherapy. This randomized, open-label study compared the ...effect of sequential radiochemotherapy (RCHT) versus RCHT + epoetin alfa (RCHT + EPO), with respect to 2-year overall survival (OS). Material and methods Patients ⩾ 18 years received sequential RCHT; one arm also received EPO (chemotherapy day 1, when Hb < 12 g/dL). Kaplan–Meier analysis with log-rank test, and Cox-regression methods were performed. Results Of the 385 patients randomized (RCHT + EPO: n = 195; RCHT: n = 190), 78 (RCTH + EPO: 46 23.6%; RCHT: 32 16.8%) were anemic at baseline. Two-year OS was higher in RCHT + EPO-treated versus RCHT-treated (28.5% 95% CI: 22.2–35.1% versus 20.6% 95% CI: 15.1–26.8% p = 0.2278), and requirement for RBC transfusion was lower (24/195 12.3% versus 61/190 32.1%). In anemic (baseline) patients (post hoc analysis), median survival was shorter in RCTH-treated (212 days) versus RCHT + EPO-treated (343 days) (Hazard ratio = 1.62 95% CI: 0.99–2.63, p = 0.0525). Adverse events were documented in 72.7% (RCHT + EPO: 75.0%; RCHT: 70.5%) patients, and thrombovascular events (TVEs) in 45 patients (RCHT + EPO: 16.7%; RCHT: 7.9%; p = 0.0099). Conclusions A statistically non-significant trend for 2-year OS was observed in a sub-group of EPO-treated NSCLC-patients with baseline anemia, although this trend was not maintained in the overall population with inoperable NSCLC.
Electron-beam-induced grafting of hydrophilic polymers was applied to modify PVDF membranes for biomedical applications. Grafting was performed by immersing the membrane in an aqueous solution of ...different hydrophilic polymers followed by electron-beam irradiation. The two polymer types are able to cross-link by recombination of adjacent radicals formed viathe irradiation. Although the untreated membrane was already quite hydrophilic, the modification resulted in even lower water contact angles at the membrane surface indicating improved water wettability. The presence of different functional groups originating from the hydrophilic polymers was detected on the membrane surface by electrokinetic measurements. SEM investigations as well as porosimetry experiments showed that the grafted hydrophilic polymer layer is very thin; therefore, the membrane pore structure is not negatively affected. Soxhlet extraction revealed the stability of the modification for selected polymers: surface contact angles were comparable after extraction, and total organic carbon investigation of the extraction water revealed no significant loss of organic material. Investigated mechanical properties confirmed an increased stability due to cross-linking of the polymers. Undesired hemolysis was not detected with hemocompatibility tests, and coagulation was decreased with selected hydrophilic polymers. Because of the absence of any toxic material during surface modification and the high stability of the product, this method is believed to be suitable for the modification of membranes for medical applications, e.g. for improving the hemo- or biocompatibility.
ABSTRACT Objective To investigate the effect of perioperative complications involving artificial urinary sphincter (AUS) implantation on rates of explantation and continence as well as health-related ...quality of life (HRQOL). Materials and methods Inclusion criteria encompassed non-neurogenic, moderate-to-severe stress urinary incontinence (SUI) post radical prostatectomy and primary implantation of an AUS performed by a high-volume surgeon (>100 previous implantations). Reporting complications followed the validated Clavien-Dindo scale and Martin criteria. HRQOL was assessed by the validated IQOL score, continence by the validated ICIQ-SF score. Statistical analysis included Chi (2) test, Mann-Whitney-U test, and multivariate regression models (p <0.05). Results 105 patients from 5 centers met the inclusion criteria. After a median follow-up of 38 months, explantation rates were 27.6% with a continence rate of 48.4%. In the age-adjusted multivariate analysis, perioperative urinary tract infection was confirmed as an independent predictor of postoperative explantation rates OR 24.28, 95% CI 2.81-209.77, p=0.004). Salvage implantation (OR 0.114, 95% CI 0.02-0.67, p=0.016) and non-prostatectomy related incontinence (OR 0.104, 95% CI 0.02-0.74, p=0.023) were independent predictors for worse continence outcomes. Low visual analogue scale scores (OR 9.999, 95% CI 1,42-70.25, p=0.021) and ICIQ-SF scores, respectively (OR 0.674, 95% CI 0.51-0.88, p=0.004) were independent predictors for increased HRQOL outcomes. Perioperative complications did not significantly impact on continence and HRQOL outcomes. Conclusion Findings show postoperative infections adversely affect device survival after AUS implantation. However, if explantation can be avoided, the comparative long-term functional results and HRQOL outcomes are similar between patients with or without perioperative complications.
Charge formation within surface-confined polyelectrolyte layers (PL)—including biopolymer films—is of highest importance in the application of biomedical materials in demanding products. However, due ...to the lack of adequate analytical tools the impact of electrical charging on the intra- and intermolecular structure of surface-confined PL so far remained poorly understood. The traditional characterization of hard surfaces by electrokinetic (zeta potential) measurements cannot be applied for the characterization of the internal structure of thick PL, although the traditional electrokinetics remains important for characterizing PL/electrolyte interfaces. Systematic investigations revealed that surface conductivity (SC) measurements provide a unique opportunity for the characterization of PL, including the determination of Donnan and surface potentials, maximal PL charge at complete dissociation, fractional PL charge, counterion condensation, and even PL thickness. This was achieved through advanced electrokinetic measurements in microchannels and an extension of the related theoretical modeling. A serious restriction in modeling as well as in the quantitative interpretation of experimental data is the assumption of a uniform segment distribution within the PL while the gradual decay of the segment concentration with the distance to the solid surface is rather abundant. Recently, we showed that the concept of local Donnan potentials holds true for cases of a nonuniform segment concentration if the characteristic length
h of the segment concentration decay exceeds the Debye length
κ
m
−1
of the PL. We demonstrate that the incorporation of the concept of local Donnan potentials into the SC theory permits us to derive an analytical equation for the fractional charge of PL and for the SC at nonuniform segment distribution. In addition, the measurement of the fractional PL charge can provide information about layer thickness, the length of the segment concentration decay, and concentration values near the solid surface and near the PL/electrolyte interface.
A concept for the characterization of charging and structural features of nonuniform polyelectrolyte layers is presented and discussed.
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