Another step toward DNA selective targeting: NiII and CuII complexes of a Schiff base ligand able to bind gene promoter G-quadruplexes

DNA G-rich sequences are able to form four-stranded structures organized in stacked guanine tetrads. These structures, called G-quadruplexes, were found to have an important role in the regulation of oncogenes expression and became, for such a reason, appealing targets for anticancer drugs. Aiming at finding selective G-quadruplex binders, we have designed, synthesized and characterized a new water soluble Salen-like Schiff base ligand and its NiII and CuII metal complexes. UV-Vis, circular dichroism and FRET measurements indicated that the nickel complex can stabilize oncogene promoter G-quadruplexes with high selectivity, presenting no interactions with duplex DNA at all. The same compound exhibited dose-dependent cytotoxic activity in MCF-7 breast cancer cells when combined with lipofectamine as lipophilic carrier

Low-value home-based nursing care:A national survey study

Aims: To explore potential areas of low-value home-based nursing care practices, their prevalence and related influencing factors of nurses and nursing assistants working in home-based nursing care. Design: A quantitative, cross-sectional design. Methods: An online survey with questions containing scaled frequencies on five-point Likert scales and open questions on possible related influencing factors of low-value nursing care. The data collection took place from February to April 2022. Descriptive statistics and linear regression were used to summarize and analyse the results. Results: A nationwide sample of 776 certified nursing assistants, registered nurses and nurse practitioners responded to the survey. The top five most delivered low-value care practices reported were: (1) ‘washing the client with water and soap by default’, (2) ‘application of zinc cream, powders or pastes when treating intertrigo’, (3) ‘washing the client from head to toe daily’, (4) ‘re-use of a urinary catheter bag after removal/disconnection’ and (5) ‘bladder irrigation to prevent clogging of urinary tract catheter’. The top five related influencing factors reported were: (1) ‘a (general) practitioner advices/prescribes it’, (2) ‘written in the client's care plan’, (3) ‘client asks for it’, (4) ‘wanting to offer the client something’ and (5) ‘it is always done like this in the team’. Higher educational levels and an age above 40 years were associated with a lower provision of low-value care. Conclusion: According to registered nurses and certified nursing assistants, a number of low-value nursing practices occurred frequently in home-based nursing care and they experienced multiple factors that influence the provision of low-value care such as (lack of) clinical autonomy and handling clients' requests, preferences and demands. The results can be used to serve as a starting point for a multifaceted de-implementation strategy. Reporting Method: STROBE checklist for cross-sectional studies. Patient or Public Contribution: No Patient or Public Contribution. Implications for the Profession and/or Patient Care: Nursing care is increasingly shifting towards the home environment. Not all nursing care that is provided is effective or efficient and this type of care can therefore be considered of low-value. Reducing low-value care and increasing appropriate care will free up time, improve quality of care, work satisfaction, patient safety and contribute to a more sustainable healthcare system.</p

Low-value home-based nursing care:A national survey study

Aims: To explore potential areas of low-value home-based nursing care practices, their prevalence and related influencing factors of nurses and nursing assistants working in home-based nursing care. Design: A quantitative, cross-sectional design. Methods: An online survey with questions containing scaled frequencies on five-point Likert scales and open questions on possible related influencing factors of low-value nursing care. The data collection took place from February to April 2022. Descriptive statistics and linear regression were used to summarize and analyse the results. Results: A nationwide sample of 776 certified nursing assistants, registered nurses and nurse practitioners responded to the survey. The top five most delivered low-value care practices reported were: (1) ‘washing the client with water and soap by default’, (2) ‘application of zinc cream, powders or pastes when treating intertrigo’, (3) ‘washing the client from head to toe daily’, (4) ‘re-use of a urinary catheter bag after removal/disconnection’ and (5) ‘bladder irrigation to prevent clogging of urinary tract catheter’. The top five related influencing factors reported were: (1) ‘a (general) practitioner advices/prescribes it’, (2) ‘written in the client's care plan’, (3) ‘client asks for it’, (4) ‘wanting to offer the client something’ and (5) ‘it is always done like this in the team’. Higher educational levels and an age above 40 years were associated with a lower provision of low-value care. Conclusion: According to registered nurses and certified nursing assistants, a number of low-value nursing practices occurred frequently in home-based nursing care and they experienced multiple factors that influence the provision of low-value care such as (lack of) clinical autonomy and handling clients' requests, preferences and demands. The results can be used to serve as a starting point for a multifaceted de-implementation strategy. Reporting Method: STROBE checklist for cross-sectional studies. Patient or Public Contribution: No Patient or Public Contribution. Implications for the Profession and/or Patient Care: Nursing care is increasingly shifting towards the home environment. Not all nursing care that is provided is effective or efficient and this type of care can therefore be considered of low-value. Reducing low-value care and increasing appropriate care will free up time, improve quality of care, work satisfaction, patient safety and contribute to a more sustainable healthcare system.</p

Acquired nintedanib resistance in FGFR1-driven small cell lung cancer: Role of endothelin-A receptor-activated ABCB1 expression

Genomically amplified fibroblast growth factor receptor 1 (FGFR1) is an oncogenic driver in defined lung cancer subgroups and predicts sensibility against FGFR1 inhibitors in this patient cohort. The FGFR inhibitor nintedanib has recently been approved for treatment of lung adenocarcinoma and is currently evaluated for small cell lung cancer (SCLC). However, tumor recurrence due to development of nintedanib resistance might occur. Hence, we aimed at characterizing the molecular mechanisms underlying acquired nintedanib resistance in FGFR1-driven lung cancer. Chronic nintedanib exposure of the FGFR1-driven SCLC cell line DMS114 (DMS114/ NIN) but not of two NSCLC cell lines induced massive overexpression of the multidrug-resistance transporter ABCB1. Indeed, we proved nintedanib to be both substrate and modulator of ABCB1-mediated efflux. Importantly, the oncogenic FGFR1 signaling axis remained active in DMS114/NIN cells while bioinformatic analyses suggested hyperactivation of the endothelin-A receptor (ETAR) signaling axis. Indeed, ETAR inhibition resensitized DMS114/NIN cells against nintedanib by downregulation of ABCB1 expression. PKC and downstream NFκB were identified as major downstream players in ETAR-mediated ABCB1 hyperactivation. Summarizing, ABCB1 needs to be considered as a factor underlying nintedanib resistance. Combination approaches with ETAR antagonists or switching to non-ABCB1 substrate FGFR inhibitors represent innovative strategies to manage nintedanib resistance in lung cancer

Review on pharmacological pain management in trauma patients in (pre-hospital) emergency medicine in the Netherlands

Abstract Pain is one of the main complaints of trauma patients in (pre-hospital) emergency medicine. Significant deficiencies in pain management in emergency medicine have been identified. No evidence-based protocols or guidelines have been developed so far, addressing effectiveness and safety issues, taking the specific circumstances of pain management of trauma patients in the chain of emergency care into account. The aim of this systematic review was to identify effective and safe initial pharmacological pain interventions, available in the Netherlands, for trauma patients with acute pain in the chain of emergency care. Up to December 2011, a systematic search strategy was performed with MeSH terms and free text words, using the bibliographic databases CINAHL, PubMed and Embase. Methodological quality of the articles was assessed using standardized evaluation forms. Of a total of 2328 studies, 25 relevant studies were identified. Paracetamol (both orally and intravenously) and intravenous opioids (morphine and fentanyl) proved to be effective. Non-steroidal anti-inflammatory drugs (NSAIDs) showed mixed results and are not recommended for use in pre-hospital ambulance or (helicopter) emergency medical services [(H)EMS]. These results could be used for the development of recommendations on evidence-based pharmacological pain management and an algorithm to support the provision of adequate (pre-hospital) pain management. Future studies should address analgesic effectiveness and safety of various drugs in (pre-hospital) emergency care. Furthermore, potential innovative routes of administration (e.g., intranasal opioids in adults) need further exploration

Orientacion del mejoramiento de frijol en los climas calidos

The main priority of efforts in genetic improvement of beans is to increase the production in areas where it is currently cultivated. The environment in those areas has unfavorable climatic conditions for the crop and instead, favorable for the disease- insect complex attacking it. Through the collaboration of technicians in pathology, entomology and plant breeding, the material existing in CIATs germplasm bank was evaluated in a sequential order. A list is presented of the factors limiting productivity and production in warm climates such as BCMV, bacterioses, Empoasca, rust, BGMV, web blight, rots, excess or shortage of moisture, low fertility of the soil and the adaptation to high temp. A description is given on the characters desired for improvement, the dificulties for their attainment and the progress made up to 1979 on the obtainment of multiple resistance for warm climates. A frequency table is included on the characters selected from materials proceeding from the germplasm bank and hybrids, evaluated according to the different disciplines. (CIAT

Landomycins as glutathione-depleting agents and natural fluorescent probes for cellular Michael adduct-dependent quinone metabolism

Landomycins are angucyclines with promising antineoplastic activity produced by Streptomyces bacteria. The aglycone landomycinone is the distinctive core, while the oligosaccharide chain differs within derivatives. Herein, we report that landomycins spontaneously form Michael adducts with biothiols, including reduced cysteine and glutathione, both cell-free or intracellularly involving the benz[a]anthraquinone moiety of landomycinone. While landomycins generally do not display emissive properties, the respective Michael adducts exerted intense blue fluorescence in a glycosidic chain-dependent manner. This allowed label-free tracking of the short-lived nature of the mono-SH-adduct followed by oxygen-dependent evolution with addition of another SH-group. Accordingly, hypoxia distinctly stabilized the fluorescent mono-adduct. While extracellular adduct formation completely blocked the cytotoxic activity of landomycins, intracellularly it led to massively decreased reduced glutathione levels. Accordingly, landomycin E strongly synergized with glutathione-depleting agents like menadione but exerted reduced activity under hypoxia. Summarizing, landomycins represent natural glutathione-depleting agents and fluorescence probes for intracellular anthraquinone-based angucycline metabolism

Delirium prediction in the intensive care unit: comparison of two delirium prediction models

Background: Accurate prediction of delirium in the intensive care unit (ICU) may facilitate efficient use of early preventive strategies and stratification of ICU patients by delirium risk in clinical research, but the optimal delirium prediction model to use is unclear. We compared the predictive performance and user convenience of the prediction model for delirium (PRE-DELIRIC) and early prediction model for delirium (E-PRE-DELIRIC) in ICU patients and determined the value of a two-stage calculation. Methods: This 7-country, 11-hospital, prospective cohort study evaluated consecutive adults admitted to the ICU who could be reliably assessed for delirium using the Confusion Assessment Method-ICU or the Intensive Care Delirium Screening Checklist. The predictive performance of the models was measured using the area under the receiver operating characteristic curve. Calibration was assessed graphically. A physician questionnaire evaluated user convenience. For the two-stage calculation we used E-PRE-DELIRIC immediately after ICU admission and updated the prediction using PRE-DELIRIC after 24 h. Results: In total 2178 patients were included. The area under the receiver operating characteristic curve was significantly greater for PRE-DELIRIC (0.74 (95% confidence interval 0.71-0.76)) compared to E-PRE-DELIRIC (0.68 (95% confidence interval 0.66-0.71)) (z score of -2.73 (p < 0.01)). Both models were well-calibrated. The sensitivity improved when using the two-stage calculation in low-risk patients. Compared to PRE-DELIRIC, ICU physicians (n = 68) rated the E-PRE-DELIRIC model more feasible. Conclusions: While both ICU delirium prediction models have moderate-to-good performance, the PRE-DELIRIC model predicts delirium better. However, ICU physicians rated the user convenience of E-PRE-DELIRIC superior to PRE-DELIRIC. In low-risk patients the delirium prediction further improves after an update with the PRE-DELIRIC model after 24 h

Low-value home-based nursing care: A national survey study

AIMS: To explore potential areas of low-value home-based nursing care practices, their prevalence and related influencing factors of nurses and nursing assistants working in home-based nursing care. DESIGN: A quantitative, cross-sectional design. METHODS: An online survey with questions containing scaled frequencies on five-point Likert scales and open questions on possible related influencing factors of low-value nursing care. The data collection took place from February to April 2022. Descriptive statistics and linear regression were used to summarize and analyse the results. RESULTS: A nationwide sample of 776 certified nursing assistants, registered nurses and nurse practitioners responded to the survey. The top five most delivered low-value care practices reported were: (1) 'washing the client with water and soap by default', (2) 'application of zinc cream, powders or pastes when treating intertrigo', (3) 'washing the client from head to toe daily', (4) 're-use of a urinary catheter bag after removal/disconnection' and (5) 'bladder irrigation to prevent clogging of urinary tract catheter'. The top five related influencing factors reported were: (1) 'a (general) practitioner advices/prescribes it', (2) 'written in the client's care plan', (3) 'client asks for it', (4) 'wanting to offer the client something' and (5) 'it is always done like this in the team'. Higher educational levels and an age above 40 years were associated with a lower provision of low-value care. CONCLUSION: According to registered nurses and certified nursing assistants, a number of low-value nursing practices occurred frequently in home-based nursing care and they experienced multiple factors that influence the provision of low-value care such as (lack of) clinical autonomy and handling clients' requests, preferences and demands. The results can be used to serve as a starting point for a multifaceted de-implementation strategy. REPORTING METHOD: STROBE checklist for cross-sectional studies. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Nursing care is increasingly shifting towards the home environment. Not all nursing care that is provided is effective or efficient and this type of care can therefore be considered of low-value. Reducing low-value care and increasing appropriate care will free up time, improve quality of care, work satisfaction, patient safety and contribute to a more sustainable healthcare system

Mitochondrial disease: Needs and problems of children, their parents and family. A systematic review and pilot study into the need for information of parents during the diagnostic phase

Contains fulltext : 51979.pdf (publisher's version ) (Closed access)OBJECTIVE: Firstly, this paper aims to systematically review the mitochondrial disease literature to identify studies assessing the needs and problems in the daily life of children with a mitochondrial disease and of their parents and family. The second aim is to provide more insight into the need for information by the parents of these children during the diagnostic process while in hospital. DESIGN: A systematic review and a pilot study, using a qualitative (focus group interviews; n = 7) and a quantitative (questionnaire; n = 37) design. RESULTS: Mothers reported great socioeconomic and psychoaffective strain and showed psychopathological symptoms in the two studies published with respect to this topic. The pilot study showed that parents considered an honest and interested attitude of the person who is giving the information as most important. Furthermore they wanted oral and written information and a central point where they could go with their questions at any time they felt the need. The need for information increased during the four phases of the diagnostic process and was highest in the fourth phase. CONCLUSIONS: The few studies found in the review, combined with expectations that having a mitochondrial disease must have a great impact on these children and their parents and family, call for more research in their needs and problems. Furthermore, there are gaps in the current information provision to parents of these children. A better understanding of the needs and problems of these children and their family is essential for effective care planning and might result in an improved quality of life