Targeting cancer stem cell OXPHOS with tailored ruthenium complexes as a new anti-cancer strategy.

BACKGROUND: Previous studies by our group have shown that oxidative phosphorylation (OXPHOS) is the main pathway by which pancreatic cancer stem cells (CSCs) meet their energetic requirements; therefore, OXPHOS represents an Achille's heel of these highly tumorigenic cells. Unfortunately, therapies that target OXPHOS in CSCs are lacking. METHODS: The safety and anti-CSC activity of a ruthenium complex featuring bipyridine and terpyridine ligands and one coordination labile position (Ru1) were evaluated across primary pancreatic cancer cultures and in vivo, using 8 patient-derived xenografts (PDXs). RNAseq analysis followed by mitochondria-specific molecular assays were used to determine the mechanism of action. RESULTS: We show that Ru1 is capable of inhibiting CSC OXPHOS function in vitro, and more importantly, it presents excellent anti-cancer activity, with low toxicity, across a large panel of human pancreatic PDXs, as well as in colorectal cancer and osteosarcoma PDXs. Mechanistic studies suggest that this activity stems from Ru1 binding to the D-loop region of the mitochondrial DNA of CSCs, inhibiting OXPHOS complex-associated transcription, leading to reduced mitochondrial oxygen consumption, membrane potential, and ATP production, all of which are necessary for CSCs, which heavily depend on mitochondrial respiration. CONCLUSIONS: Overall, the coordination complex Ru1 represents not only an exciting new anti-cancer agent, but also a molecular tool to dissect the role of OXPHOS in CSCs. Results indicating that the compound is safe, non-toxic and highly effective in vivo are extremely exciting, and have allowed us to uncover unprecedented mechanistic possibilities to fight different cancer types based on targeting CSC OXPHOS.

Perception of evidence-based practice and the professional environment of primary health care nurses in the Spanish context: a cross-sectional study.

BACKGROUND: The study of the factors that encourage evidence-based clinical practice, such as structure, environment and professional skills, has contributed to an improvement in quality of care. Nevertheless, most of this research has been carried out in a hospital context, neglecting the area of primary health care. The main aim of this work was to assess the factors that influence an evidence-based clinical practice among nursing professionals in Primary Health Care. METHODS: A multicentre cross-sectional study was designed, taking the 619 Primary Care staff nurses at the Balearic Islands' Primary Health Care Service, as the study population. The methodology applied consisted on a self-administered survey using the instruments Evidence-Based Practice Questionnaire (EBPQ) and Nursing Work Index (NWI). RESULTS: Three hundred and seventy seven surveys were received (60.9% response rate). Self-assessment of skills and knowledge, obtained 66.6% of the maximum score. The Knowledge/Skills factor obtained the best scores among the staff with shorter professional experience. There was a significant difference in the Attitude factor (p = 0.008) in favour of nurses with management functions, as opposed to clinical nurses.Multivariate analysis showed a significant positive relationship between NWI and level of evidence-based practice (p < 0,0001). CONCLUSIONS: Institutions ought to undertake serious reflection on the lack of skills of senior nurses about Evidence-Based Clinical Practice, even when they have more professional experience. Leadership emerge as a key role in the transferral of knowledge into clinical practice.

Self-perceived factors associated with smoking cessation among primary health care nurses: a qualitative study / Tabagismo em enfermeiras de cuidados primários à saúde: um estudo qualitativo / Tabaquismo en enfermeras de Atención Primaria: un estudio cualitativo

The aim of this work was to characterize the views of nurses about factors modulating smoking cessation. Results of this study will allow us to design helping interventions with the maximum specificity for nurses. A qualitative study through a semi-structured interview of 15 Primary Health Care nurses who were smokers was performed. In contrast with other studies in which nurses were not aware of any particular social pressure to give up smoking, 18 months after the application of the Anti-Smoking Spanish Law, this feeling was expressed. Therefore, the main reasons for giving up smoking include that smoking in public is every day worse seen, together with a sense of shame and guilt in front of their social and family environment, especially for being a professional group dedicated to health.

O objetivo deste estudo foi identificar os fatores percebidos por enfermeiras fumantes como facilitadores ao abandono do tabagismo, com o propósito de, posteriormente, elaborar intervenções de ajuda com maior especificidade para esse grupo. Foi realizado estudo qualitativo, por meio de entrevistas semiestruturadas, com 15 enfermeiras de cuidados primários à saúde, que eram fumantes. Ao contrário de outros estudos, os quais as enfermeiras não percebiam pressão social para deixar o hábito tabágico, 18 meses após a vigência da Lei de Prevenção ao Tabagismo, as enfermeiras entrevistadas expressaram sentir pressão social. Portanto, entre os principais motivos para abandonar o hábito tabágico é que, a cada dia, fumar em público é malvisto, e está aliado a sentimentos de vergonha e culpa no seu entorno social e familiar, principalmente por se tratar de um grupo profissional dedicado aos cuidados da saúde.

El objetivo de este trabajo fue identificar los factores percibidos por las enfermeras fumadoras como moduladores del cese tabáquico, con el fin de diseñar posteriormente intervenciones de ayuda con la máxima especificidad para este colectivo. Se realizó un estudio cualitativo mediante entrevista semiestructurada a 15 enfermeras fumadoras de Atención Primaria de Salud. Contrariamente a otros estudios en los que las enfermeras no percibían una especial presión social para dejar el hábito tabáquico, 18 meses después de vigencia de la Ley de Prevención del Tabaquismo sí que la expresan. Por ello, entre los principales motivos de cese figura el que cada día esté peor considerado fumar en público, unido a un sentimiento de vergüenza y de culpa ante su entorno social y familiar, especialmente por tratarse de un colectivo profesional dedicado a los cuidados de salud.

Self-perceived factors associated with smoking cessation among primary health care nurses: a qualitative study.

The aim of this work was to characterize the views of nurses about factors modulating smoking cessation. Results of this study will allow us to design helping interventions with the maximum specificity for nurses. A qualitative study through a semi-structured interview of 15 Primary Health Care nurses who were smokers was performed. In contrast with other studies in which nurses were not aware of any particular social pressure to give up smoking, 18 months after the application of the Anti-Smoking Spanish Law, this feeling was expressed. Therefore, the main reasons for giving up smoking include that smoking in public is every day worse seen, together with a sense of shame and guilt in front of their social and family environment, especially for being a professional group dedicated to health.

[Smoking among nursing and physical therapy students of the University of the Balearic Islands: opinions on regulation of smoking in public places]. / Hábito tabáquico entre los estudiantes de enfermería y fisioterapia de la Universitat de les Illes Balears: opinión ante la regulación del consumo en lugares públicos.

OBJECTIVE: To evaluate the prevalence, opinions and attitudes of nursing and physical therapy students at the University of the Balearic Islands toward smoking in public places and the influence of regulatory policies. METHOD: We performed a cross-sectional, descriptive, observational study using a self-administered questionnaire. The survey was designed to evaluate opinions on and the degree of agreement with smoking and regulatory policies on this issue. The assessment was performed using Likert scales. The survey was offered to all students attending class in the core subject with the greatest number of enrolled students on a normal academic day between February 15 and March 15, 2006. We calculated 95% confidence intervals for proportions. The Chi square test was used to compare qualitative variables and Student's t-test was used for quantitative variables. RESULTS: The sample consisted of 345 students, 82.2% of whom were women. The mean age was 21.9 years. The prevalence of regular smokers was 26.1% (26.9% among women and 22.6% among men). Almost all (93.8%) of the respondents agreed that smoking should be banned in closed spaces in educational institutions and 70.9% believed that the law should be complied with at the University of the Balearic Islands, with differences between 2003 and 2006. CONCLUSIONS: Smoking was less prevalent in our population than in the general regional and national populations, as well as in other Spanish nursing students of the same age and gender. The prevalence of occasional smokers has fallen since 2003. Most students had a favorable view of the new Smoking Prevention Act.

Intra- and intermolecular 1,3-dipolar cycloaddition of sugar ketonitrones with mono-, di-, and trisubstituted dipolarophiles.

The 1,3-dipolar cycloaddition of sugar ketonitrones is a useful synthetic procedure to build up nitrogenated quaternary centers in terms of scope (substrate, dipolarophile, inter- and intramolecular versions), yield, and regio- and stereoselectivity. The hybrid ONIOM (B3LYP/6-31G(d):AM1) theoretical method followed by single-point energy calculations at the B3LYP/6-31G(d) level adequately perform to model this cycloaddition for the relatively large ketosugar precursors commonly used.