Mask-Guided Convolutional Neural Network for Breast Tumor Prognostic Outcome Prediction on 3D DCE-MR Images

Journal of Digital Imaging - In this proof-of-concept work, we have developed a 3D-CNN architecture that is guided by the tumor mask for classifying several patient-outcomes in breast cancer from...     

Morpholinium-based ionic liquids show antimicrobial activity against clinical isolates of Pseudomonas aeruginosa

Pseudomonas aeruginosa is a multi-drug resistant (MDR) pathogen. It is classified by WHO as one of the most life-threatening pathogens causing nosocomial infections. Some of its clinical isolates and their subpopulations show high persistence to many antibiotics that are recommended by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Thus, there is a need for non-traditional classes of antibiotics to fight the increasing threat of MDR P. aeruginosa. Ionic liquids (IL) are one such promising class of novel antibiotics. We selected four strains of P. aeruginosa and studied the growth inhibition and other effects of 12 different ILs. We used the well-characterized P. aeruginosa PAO1 (ATCC 15692) as model strain and compared it to three other isolates from chronic lung infection (LES B58), skin burn infection (UCBPP-PA14) and keratitis infection (39016), respectively. The ILs consisted of either 4,4-didecylmorpholinium [Dec₂Mor]⁺ or 4-decyl-4-ethylmorpholinium [DecEtMor]⁺ cations combined with different anions. We found that the ILs with 4,4-didecylmorpholinium [Dec₂Mor]⁺ cations most effectively inhibited bacterial growth as well as reduced strain fitness and virulence factor production. Our results indicate that these ILs could be used to treat P. aeruginosa infections.     

In Vitro Selection of Ceftazidime-Avibactam Resistance in Enterobacteriaceae with KPC-3 Carbapenemase

Ceftazidime-avibactam is active against most Enterobacteriaceae isolates with KPC carbapenemases. We investigated whether this activity could be compromised by mutation. Single-step and multistep selections were attempted using ceftazidime-avibactam (avibactam fixed at 1 or 4 μg/ml) versus two strains each of Enterobacter cloacae and Klebsiella pneumoniae, all with the KPC-3 enzyme. Mutant bla_KPC alleles were sequenced, and their parentage was confirmed by typing. Ceftazidime-avibactam selected mutants at up to 16× MIC, with frequencies of ca. 10⁻⁹. This contrasted with previous experience for ceftaroline-avibactam, where mutant frequencies under similar conditions were <10⁻⁹. The MICs of ceftazidime with 1 μg/ml avibactam for the ceftazidime-avibactam-selected mutants rose from 1 to 8 μg/ml to 16 to >256 μg/ml and those of ceftazidime with 4 μg/ml avibactam from 0.25 to 1 μg/ml to 4 to 128 μg/ml; ceftaroline-avibactam MICs rose less, typically from 0.5 to 1 μg/ml to 1 to 8 μg/ml. The MICs of carbapenems and cephalosporins except ceftazidime and piperacillin-tazobactam were reduced for many mutants. Sequencing of bla_KPC revealed point and insertion changes in 12/13 mutants investigated, representing all four parents; one mutant lacked bla_KPC changes and possibly had reduced permeability. Amino acid changes commonly involved Ω loop alterations or 1 to 6 amino acid insertions immediately C-terminal to this loop. The most frequent change, seen in four mutants from three strains, was Asp179Tyr, replacing a residue that ordinarily forms a salt bridge to stabilize the Ω loop. Since ceftaroline-avibactam was less affected than ceftazidime-avibactam, we postulate that these mutations increase ceftazidimase specificity rather than conferring avibactam resistance. The clinical relevance remains uncertain.     

Prenatal Sonographic Diagnosis of Premature Constriction of the Fetal Ductus Arteriosus After Maternal Self‐Medication With Benzydamine Hydrochloride

We report 3 cases of prenatal diagnosis of premature constriction of the ductus arteriosus after maternal benzydamine hydrochloride therapy (3‐mg lozenges) in third‐trimester pregnancies. In each case, fetal echocardiography revealed a dilated, hypocontractile right ventricle with severe tricuspid regurgitation and constriction of the ductus arteriosus. Although the effect of indomethacin and other nonsteroidal anti‐inflammatory drugs on prenatal ductal constriction is well known, readily available over‐the‐counter nonsteroidal anti‐inflammatory drugs such as benzydamine can have an equally deleterious effect and are best avoided in the third trimester of pregnancy.     

Factors associated with preservation of C-peptide levels at the diagnosis of type 1 diabetes

Aims

The level of C-peptide can identify individuals most likely to respond to immune interventions carried out to prevent pancreatic β-cell damage.The aim of the study was to evaluate factors associated with C-peptide levels at type 1 diabetes (T1D) diagnosis.

Does aspirin-induced oxidative stress cause asthma exacerbation?

Aspirin-induced asthma (AIA) is a distinct clinical syndrome characterized by severe asthma exacerbations after ingestion of aspirin or other non-steroidal anti-inflammatory drugs. The exact pathomechanism of AIA remains unknown, though ongoing research has shed some light. Recently, more and more attention has been focused on the role of aspirin in the induction of oxidative stress, especially in cancer cell systems. However, it has not excluded the similar action of aspirin in other inflammatory disorders such as asthma. Moreover, increased levels of 8-isoprostanes, reliable biomarkers of oxidative stress in expired breath condensate in steroid-naïve patients with AIA compared to AIA patients treated with steroids and healthy volunteers, has been observed. This review is an attempt to cover aspirin-induced oxidative stress action in AIA and to suggest a possible related pathomechanism.