Multinuclear ruthenium(II) complexes as anticancer agents

A series of dinuclear ruthenium(ii) complexes that contain labile chlorido ligands, [{Ru(tpy)Cl}2{μ-bbn}]2+ {designated Cl-Rubbn; tpy = 2,2′:6′,2′′-terpyridine, bbn = bis[4(4′-methyl-2,2′-bipyridyl)]-1,n-alkane (n = 7, 10, 12, 14 or 16)} and derivatives containing nitro substituents on the tpy ligand and/or secondary amines within the bbn linking chain have been synthesised and their potential as anticancer agents examined. Some of the Cl-Rubbn species showed good anticancer activity against MCF-7 and MDA-MB-231 breast cancer cell lines, with the Cl-Rubb12 complex being four-times more active than cisplatin. Inclusion of nitro substituents on the tpy ligands of Cl-Rubb12 resulted in significantly decreased anticancer activity. The incorporation of amine groups into the linking ligand did not increase the anticancer activity of the Cl-Rubbn complexes. The Cl-Rubbn complexes and those containing amine groups in the linking chain aquated at approximately the same rate, with 50% aquation within 120 minutes. By comparison, the complexes containing nitro substituents on the tpy ligand aquated extremely slowly, with 60% of the chlorido complex remaining 24 hours after they were dissolved in water. Cyclic voltammetry with the model mononuclear complex [Ru{(NO2)3tpy}(Me2bpy)Cl] + {(NO2)3tpy = 4,4′,4′′- trinitro-2,2′:6′,2′′-terpyridine} showed that the nitro substituents exerted a strong effect on the ruthenium centre, with the anodic peak corresponding to the Ru(iii/ii) couple shifted positively by 300 mV compared to that from the non-nitrated parent complex [Ru(tpy)(Me 2bpy)Cl]+. 1H NMR studies of the reaction of the Cl-Rubbn complexes with GMP indicated that the ruthenium complexes covalently bound the nucleotide slowly, with 33% bound in 24 hours. However, the results of this study suggest that the cytotoxicity of the dinuclear ruthenium complexes is a combination of covalent and reversible binding with DNA. © the Partner Organisations 2014

Paper and electronic versions of HM-PRO, a novel patient-reported outcome measure for hematology: an equivalence study.

© 2019 Goswami, Oliva, Ionova et al.Aim:To determine measurement equivalence of paper and electronic application of the hematologi-cal malignancy-patient-reported outcome (HM-PRO), a specific measure for the evaluation of patient-reported outcomes in HMs.Patients & methods:Following International Society of Pharmacoeconomicsand Outcomes Research ePRO Good Research Practice Task Force guidelines, a total of 193 adult patientswith different HMs were recruited into a multicenter prospective study. The paper and the electronic ver-sion of the instrument were completed in the outpatient clinics in a randomized crossover design with a30-min time interval to minimize the learning effect. Those who completed the paper version first, com-pleted the electronic version after 30 min and vice versa. Instrument version and order effects were testedon total score of the two parts of the HM-PRO (Part A: quality of life and Part B: signs & symptoms) in atwo-way ANOVA with patients as random effects. Intraclass correlation coefficients (95% CI) and Spear-man’s rank correlation coefficients were used to evaluate test–retest reliability and reproducibility. Theeffects of instrument version and order were tested on total score of the two parts of HM-PRO.Results:The questionnaire version and administration order effects were not significant at the 5% level. Therewere no interactions found between these two factors for HM-PRO (Part A [quality of life]; p=0.95); and(part B [signs and symptoms]; p=0.72]. Spearman’s rank correlation coefficients were greater than 0.9, andintraclass correlation coefficients ranged from 0.94 to 0.98; furthermore, the scores were not statisticallydifferent between the two versions, showing acceptable reliability indexes. Noteworthy, the differencebetween the completion time for both paper (mean=6:38 min) and electronic version (mean=7:29 min)was not statistically significant (n=100; p=0.11). Patients did not report any difficulty in completing theelectronic version during cognitive interviews and were able to understand and respond spontaneously.Conclusion:Measurement equivalence has been demonstrated for the paper and electronic applicationof the HM-PRO.Peer reviewe

An exploratory study of a NoSQL database for a clinical data repository

The need to implement a distributed Clinical Data Repository (CDR) at a healthcare facility, rose in large part due to the high volume of data and the discrepancy of their sources. Over the years, Relational Database Management Systems (RDBMS) began to present difficulties in responding to the needs of various organizations when it comes to manipulating a large amount of data and to its scalability. Therefore, it was necessary to explore other techniques to choose the appropriate technology to build the CDR. In this way, NoSQL emerged as a new type of database that is quite useful to work with multiple and different types of data. In addition, NoSQL introduces a number of user-friendly features such as a distributed, scalable, elastic and also fault tolerant system. In this way, Oracle NoSQL Database was the NoSQL solution chosen to develop this case study, using the key-value storage. This article was motivated to propose a CDR architecture based on Oracle NoSQL Database functionalities. A one-single node database was deployed for better comprehension, in order to enhance their features for future implementation.The work has been supported by FCT – Fundação para a Ciência e Tecnologia within the Project Scope UID/CEC/00319/2019 and DSAIPA/DS/0084/2018

Supplementation of a western diet with golden kiwifruits (Actinidia chinensis var.'Hort 16A':) effects on biomarkers of oxidation damage and antioxidant protection

<p>Abstract</p> <p>Background</p> <p>The health positive effects of diets high in fruits and vegetables are generally not replicated in supplementation trials with isolated antioxidants and vitamins, and as a consequence the emphasis of chronic disease prevention has shifted to whole foods and whole food products.</p> <p>Methods</p> <p>We carried out a human intervention trial with the golden kiwifruit, Actinidia chinensis, measuring markers of antioxidant status, DNA stability, plasma lipids, and platelet aggregation. Our hypothesis was that supplementation of a normal diet with kiwifruits would have an effect on biomarkers of oxidative status. Healthy volunteers supplemented a normal diet with either one or two golden kiwifruits per day in a cross-over study lasting 2 × 4 weeks. Plasma levels of vitamin C, and carotenoids, and the ferric reducing activity of plasma (FRAP) were measured. Malondialdehyde was assessed as a biomarker of lipid oxidation. Effects on DNA damage in circulating lymphocytes were estimated using the comet assay with enzyme modification to measure specific lesions; another modification allowed estimation of DNA repair.</p> <p>Results</p> <p>Plasma vitamin C increased after supplementation as did resistance towards H₂O₂-induced DNA damage. Purine oxidation in lymphocyte DNA decreased significantly after one kiwifruit per day, pyrimidine oxidation decreased after two fruits per day. Neither DNA base excision nor nucleotide excision repair was influenced by kiwifruit consumption. Malondialdehyde was not affected, but plasma triglycerides decreased. Whole blood platelet aggregation was decreased by kiwifruit supplementation.</p> <p>Conclusion</p> <p>Golden kiwifruit consumption strengthens resistance towards endogenous oxidative damage.</p

Case report on trial: Do you, Doctor, swear to tell the truth, the whole truth and nothing but the truth?

We are in the era of "evidence based medicine" in which our knowledge is stratified from top to bottom in a hierarchy of evidence. Many in the medical and dental communities highly value randomized clinical trials as the gold standard of care and undervalue clinical reports. The aim of this editorial is to emphasize the benefits of case reports in dental and oral medicine, and encourage those of us who write and read them

Improving NFS for the Discrete Logarithm Problem in Non-prime Finite Fields

International audienceThe aim of this work is to investigate the hardness of the discrete logarithm problem in fields GF$(p^n)$ where $n$ is a small integer greater than 1. Though less studied than the small characteristic case or the prime field case, the difficulty of this problem is at the heart of security evaluations for torus-based and pairing-based cryptography. The best known method for solving this problem is the Number Field Sieve (NFS). A key ingredient in this algorithm is the ability to find good polynomials that define the extension fields used in NFS. We design two new methods for this task, modifying the asymptotic complexity and paving the way for record-breaking computations. We exemplify these results with the computation of discrete logarithms over a field GF$(p^2)$ whose cardinality is 180 digits (595 bits) long

Tribo-induced catalytically active oxide surfaces enabling the formation of the durable and high-performance carbon-based tribofilms

Carbon-containing tribofilms have attracted significant interest in the lubrication research despite a scarcity of information on their high-temperature performance under severe boundary conditions. In this study, high-temperature lubrication of the carbon tribofilm produced from cyclopropane carboxylic acid (CPCa) and NiAl-layered double hydroxide (LDH) nanoparticles was evaluated. NiAl-LDH nanoparticles significantly enhanced the friction stability and antiwear performance of CPCa by over 90% at 50°C and 100°C, comparable to the benchmark zinc dialkyldithiophosphates (ZDDPs). The highly graphitic amorphous carbon tribofilms and the fine-grain intermediate tribolayer constructed by the thermal decomposition products of NiAl-LDH contributed to such excellent lubrication performance. This study paves a pathway in developing functional anti-wear additives for the durable and high-performance carbon-containing tribofilms at high temperatures

Quality-of-life issues and symptoms reported by patients living with haematological malignancy: a qualitative study

Background: Our aim was to identify health-related quality-of-life (HRQoL) issues and symptoms in patients with haematological malignancies (HMs) and develop a conceptual framework to reflect the inter-relation between them. / Methods: A total of 129 patients with HMs were interviewed in a UK multicentre qualitative study. All interviews were audio recorded, transcribed and analysed using NVivo-11. / Results: Overall, 34 issues were reported by patients and were grouped into two parts: quality of life (QoL) and symptoms. The most prevalent HRQoL issues were: eating and drinking habits; social life; physical activity; sleep; and psychological well-being. Furthermore, most prevalent disease-related symptoms were: tiredness; feeling unwell; breathlessness; lack of energy; and back pain. The most prevalent treatment side effects were: tiredness; feeling sick; disturbance in sense of taste; and breathlessness. / Conclusions: Both HMs and their treatments have a significant impact on patients’ HRQoL, in particular on issues such as job-role change, body image and impact on finances