Filamentous bacteriophage delays healing of Pseudomonas-infected wounds.

Chronic wounds infected by Pseudomonas aeruginosa (Pa) are characterized by disease progression and increased mortality. We reveal Pf, a bacteriophage produced by Pa that delays healing of chronically infected wounds in human subjects and animal models of disease. Interestingly, impairment of wound closure by Pf is independent of its effects on Pa pathogenesis.

Burnout, Depression, Career Satisfaction, and Work-Life Integration by Physician Race/Ethnicity.

Importance: Previous research suggests that the prevalence of occupational burnout varies by demographic characteristics, such as sex and age, but the association between physician race/ethnicity and occupational burnout is less well understood.

Objective: To investigate possible differences in occupational burnout, depressive symptoms, career satisfaction, and work-life integration by race/ethnicity in a sample of US physicians.

Design, Setting, And Participants: In this cross-sectional study, data for this secondary analysis of 4424 physicians were originally collected from a cross-sectional survey of US physicians between October 12, 2017, and March 15, 2018.

Resilience and Burnout Among Physicians and the General US Working Population.

Importance: The prevalence of physician burnout is well documented, and resilience training has been proposed as an option to support physician well-being. However, the resilience of physicians compared with that of the US working population is not established, and the association between resilience and physician burnout is not well understood.

Objectives: To evaluate resilience among physicians and US workers, and to determine the association between resilience and burnout among US physicians.

Association of Perceived Electronic Health Record Usability With Patient Interactions and Work-Life Integration Among US Physicians.

This cross-sectional survey assesses the association of perceived electronic health record usability with patient interaction and work-life integration among US physicians.

The Association Between Perceived Electronic Health Record Usability and Professional Burnout Among US Physicians.

Objective: To describe and benchmark physician-perceived electronic health record (EHR) usability as defined by a standardized metric of technology usability and evaluate the association with professional burnout among physicians.

Participants And Methods: This cross-sectional survey of US physicians from all specialty disciplines was conducted between October 12, 2017, and March 15, 2018, using the American Medical Association Physician Masterfile. Among the 30,456 invited physicians, 5197 (17.

Filamentous bacteriophages are associated with chronic lung infections and antibiotic resistance in cystic fibrosis.

Filamentous bacteriophage (Pf phage) contribute to the virulence of infections in animal models, but their relevance to human disease is unclear. We sought to interrogate the prevalence and clinical relevance of Pf phage in patients with cystic fibrosis (CF) using sputum samples from two well-characterized patient cohorts. Bacterial genomic analysis in a Danish longitudinal cohort of 34 patients with CF revealed that 26.

D-propranolol attenuates lysosomal iron accumulation and oxidative injury in endothelial cells.

The influence of selected beta-receptor blockers on iron overload and oxidative stress in endothelial cells (ECs) was assessed. Confluent bovine ECs were loaded with iron dextran (15 muM) for 24 h and then exposed to dihydroxyfumarate (DHF), a source of reactive oxygen species, for up to 2 h. Intracellular oxidant formation, monitored by fluorescence of 2',7'-dichlorofluorescin (DCF; 30 microM), increased and peaked at 30 min; total glutathione decreased by 52 +/- 5% (p < 0.

Pro-oxidant properties and cytotoxicity of AZT-monophosphate and AZT.

The effects of zidovudine (AZT) and AZT-monophosphate (AZT-MP) on lipid peroxidation and oxidative cell injury were studied. When microsomal membranes from rat livers were peroxidized by a superoxide-driven, Fe-catalyzed oxy-radical system (ORS), both AZT-MP and, to a lesser extent AZT, but not thymidine, concentration dependently (2-100 microM) enhanced lipid peroxidation (TBARS formation) up to 51% above control. Significance (p < 0.

11 beta-amidoalkyl estradiols, a new series of pure antiestrogens.

In order to find new antiestrogens, devoid of any agonistic activity, a series of 11 beta-amidoalkyl estradiols were prepared. These compounds have been studied in comparison with tamoxifen (TAM): in vitro, for their relative binding affinities (RBA) for mouse and MCF-7 estrogen receptors (ER) and for their antiproliferative effect on MCF-7 (estradiol or EGF/PDGF stimulated) and Ly2 human breast cancer cell lines; in vivo, for their uterotrophic/antiuterotrophic activities in the mouse and for their antitumoral activities on MCF-7 tumors implanted in nude mice. The most representative compounds are N-methyl-N-isopropyl-(3,17 beta-dihydroxy-estra-1,3,5(10)-trien-11 beta-yl)- undecanamide (RU 51625) and its 17 alpha-ethynyl derivative (RU 53637).

New analogues of mifepristone with more dissociated antiprogesterone activities.

Mifepristone (RU 486 or RU 38486) possesses strong antiprogesterone and antiglucocorticoid along with moderate antiandrogen properties, which would limit its use in some therapeutic applications. In a search for more dissociated derivatives, the hydroxy substituent and the propynyl group in position 17 of the RU 486 series was replaced by a spiroether group, which is known to induce specific affinity for the progestin receptor in steroid series. The substituents in the para position of the 11 beta-phenyl group, leading to the most potent derivatives in the RU 486 series, were retained.

Synthesis of new fluorescent spirolactone derivatives: determination of their affinities for aldosterone receptors.

Fluorescent spirolactone derivatives are obtained by coupling 3-carboxylic coumarins to a spirolactone bearing a 3-hydroxypropyl chain in the 7 alpha position. The two esters prepared by this method are highly fluorescent (emission 383 and 408 nm).

Antiandrogenic activity of a series of des-A-steroid derivatives.

In the search for new antiandrogens, a number of des-A-steroids were prepared by condensation of Grignard reagents with lactone 3. From the resulting key intermediates 5, various structural modifications were performed such as the introduction of an additional unsaturation to afford dienones 8 and aromatic derivatives 10 or the introduction of an alkyl substituent mostly in position 10 (11-13) but also in some cases in position 16 (22). In addition, 13-ethyl analogues were also prepared from lactone 4.

Synthesis and central dopaminergic activities of (+/-)-hexahydro-7H-indolo[3,4-gh][1,4]benzoxazine derivatives [(+/-)-9-oxaergolines].

The synthesis and biological activities of a series of (+/-)-hexahydro-7H-indolo[3,4-gh][1,4]benzoxazine derivatives [(+/-)-trans-9-oxaergolines] with central dopamine (DA) agonist properties are described. The compounds were prepared from [2aRS-(2a alpha,4 beta,5 alpha)]-4-amino-1,2,2a,3,4, 5-hexahydro-1-(phenylmethyl)benz[cd]indol-5-ol (6b) by alkaline cyclization of the corresponding N-chloracetamide 7b, followed by reduction of the amido group [5aRS-(5a alpha, 6a beta, 10a alpha)]-4,5,5a,6,6a,7,9, 10a-octahydro-4-(phenylmethyl)-7H-indolo[3,4-gh][1,4]benzoxazin-8-one (8b) with LiAlH4. After debenzylation of the resulting amine 9a, the indoline ring of [5aRS-(5a alpha, 6a beta, 10a alpha)]-4,5,5a,6,6a,8,9, 10a-octahydro-7H-indolo[3,4-gh][1,4 ]benzoxazine (10a) was dehydrogenated with MnO2 to give (+/-)-trans-9-oxaergoline (11a), which can be alkylated on the nitrogen (11b,c and 12) and brominated in position 2 (13a,b).