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

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

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

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

Flower vs. Leaf Feeding by Pieris brassicae: Glucosinolate-Rich Flower Tissues are Preferred and Sustain Higher Growth Rate

Interactions between butterflies and caterpillars in the genus Pieris and plants in the family Brassicaceae are among the best explored in the field of insect–plant biology. However, we report here for the first time that Pieris brassicae, commonly assumed to be a typical folivore, actually prefers to feed on flowers of three Brassica nigra genotypes rather than on their leaves. First- and second-instar caterpillars were observed to feed primarily on leaves, whereas late second and early third instars migrated via the small leaves of the flower branches to the flower buds and flowers. Once flower feeding began, no further leaf feeding was observed. We investigated growth rates of caterpillars having access exclusively to either leaves of flowering plants or flowers. In addition, we analyzed glucosinolate concentrations in leaves and flowers. Late-second- and early-third-instar P. brassicae caterpillars moved upward into the inflorescences of B. nigra and fed on buds and flowers until the end of the final (fifth) instar, after which they entered into the wandering stage, leaving the plant in search of a pupation site. Flower feeding sustained a significantly higher growth rate than leaf feeding. Flowers contained levels of glucosinolates up to five times higher than those of leaves. Five glucosinolates were identified: the aliphatic sinigrin, the aromatic phenyethylglucosinolate, and three indole glucosinolates: glucobrassicin, 4-methoxyglucobrassicin, and 4-hydroxyglucobrassicin. Tissue type and genotype were the most important factors affecting levels of identified glucosinolates. Sinigrin was by far the most abundant compound in all three genotypes. Sinigrin, 4-hydroxyglucobrassicin, and phenylethylglucosinolate were present at significantly higher levels in flowers than in leaves. In response to caterpillar feeding, sinigrin levels in both leaves and flowers were significantly higher than in undamaged plants, whereas 4-hydroxyglucobrassicin leaf levels were lower. Our results show that feeding on flower tissues, containing higher concentrations of glucosinolates, provides P. brassicae with a nutritional benefit in terms of higher growth rate. This preference appears to be in contrast to published negative effects of volatile glucosinolate breakdown products on the closely related Pieris rapae

A terminal assessment of stages theory : introducing a dynamic states approach to entrepreneurship

Stages of Growth models were the most frequent theoretical approach to understanding entrepreneurial business growth from 1962 to 2006; they built on the growth imperative and developmental models of that time. An analysis of the universe of such models (N=104) published in the management literature shows no consensus on basic constructs of the approach, nor is there any empirical confirmations of stages theory. However, by changing two propositions of the stages models, a new dynamic states approach is derived. The dynamic states approach has far greater explanatory power than its precursor, and is compatible with leading edge research in entrepreneurship

Towards an international language for incontinence-associated dermatitis (IAD): design and evaluation of psychometric properties of the Ghent Global IAD Categorization Tool (GLOBIAD) in 30 countries

Background Incontinence-associated dermatitis (IAD) is a specific type of irritant contact dermatitis with different severity levels. An internationally accepted instrument to assess the severity of IAD in adults, with established diagnostic accuracy, agreement and reliability, is needed to support clinical practice and research. Objectives To design the Ghent Global IAD Categorization Tool (GLOBIAD) and evaluate its psychometric properties. Methods The design was based on expert consultation using a three-round Delphi procedure with 34 experts from 13 countries. The instrument was tested using IAD photographs, which reflected different severity levels, in a sample of 823 healthcare professionals from 30 countries. Measures for diagnostic accuracy (sensitivity and specificity), agreement, interrater reliability (multirater Fleiss kappa) and intrarater reliability (Cohen’s kappa) were assessed. Results The GLOBIAD consists of two categories based on the presence of persistent redness (category 1) and skin loss (category 2), both of which are subdivided based on the presence of clinical signs of infection. The agreement for differentiating between category 1 and category 2 was 0 86 [95% confidence interval (CI) 0 86–0 87], with a sensitivity of 90% and a specificity of 84%. The overall agreement was 0 55 (95% CI 0 55–0 56). The Fleiss kappa for differentiating between category 1 and category 2 was 0 65 (95% CI 0 65–0 65). The overall Fleiss kappa was 0 41 (95% CI 0 41–0 41). The Cohen’s kappa for differentiating between category 1 and category 2 was 0 76 (95% CI 0 75–0 77). The overall Cohen’s kappa was 0 61 (95% CI 0 59–0 62). Conclusions The development of the GLOBIAD is a major step towards a better systematic assessment of IAD in clinical practice and research worldwide. However, further validation is needed.info:eu-repo/semantics/acceptedVersio

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

Topological and Functional Characterization of an Insect Gustatory Receptor

Insect gustatory receptors are predicted to have a seven-transmembrane structure and are distantly related to insect olfactory receptors, which have an inverted topology compared with G-protein coupled receptors, including mammalian olfactory receptors. In contrast, the topology of insect gustatory receptors remains unknown. Except for a few examples from Drosophila, the specificity of individual insect gustatory receptors is also unknown. In this study, the total number of identified gustatory receptors in Bombyx mori was expanded from 65 to 69. BmGr8, a silkmoth gustatory receptor from the sugar receptor subfamily, was expressed in insect cells. Membrane topology studies on BmGr8 indicate that, like insect olfactory receptors, it has an inverted topology relative to G protein-coupled receptors. An orphan GR from the bitter receptor family, BmGr53, yielded similar results. We infer, from the finding that two distantly related BmGrs have an intracellular N-terminus and an odd number of transmembrane spans, that this is likely to be a general topology for all insect gustatory receptors. We also show that BmGr8 functions independently in Sf9 cells and responds in a concentration-dependent manner to the polyalcohols myo-inositol and epi-inositol but not to a range of mono- and di-saccharides. BmGr8 is the first chemoreceptor shown to respond specifically to inositol, an important or essential nutrient for some Lepidoptera. The selectivity of BmGr8 responses is consistent with the known responses of one of the gustatory receptor neurons in the lateral styloconic sensilla of B. mori, which responds to myo-inositol and epi-inositol but not to allo-inositol