Ruthenium(II) Polypyridyl Complexes as FRET Donors: Structure- and Sequence-Selective DNA-Binding and Anticancer Properties

Ruthenium(II) polypyridyl complexes (RPCs) that emit from metal-to-ligand charge transfer (MLCT) states have been developed as DNA probes and are being examined as potential anticancer agents. Here, we report that MLCT-emissive RPCs that bind DNA undergo Förster resonance energy transfer (FRET) with Cy5.5-labeled DNA, forming mega-Stokes shift FRET pairs. Based on this discovery, we developed a simple and rapid FRET binding assay to examine DNA-binding interactions of RPCs with diverse photophysical properties, including non-“light switch” complexes [Ru(dppz)2(5,5′dmb)]2+ and [Ru(PIP)2(5,5′dmb)]2+ (dppz = dipyridophenazine, 5,5′dmb = 5,5′-dimethyl-2,2′-bipyridine, PIP = 2-phenyl-imidazo[4,5-f][1,10]phenanthroline). Binding affinities toward duplex, G-quadruplex, three-way junction, and mismatch DNA were determined, and derived FRET donor–acceptor proximities provide information on potential binding sites. Molecules characterized by this method demonstrate encouraging anticancer properties, including synergy with the PARP inhibitor Olaparib, and mechanistic studies indicate that [Ru(PIP)2(5,5′dmb)]2+ acts to block DNA replication fork progression

QUALICOPC – az alapellátás minőségének, költségének és méltányosságának vizsgálata Európa országaiban: magyarországi ág = QUALICOPC – Primary Care Study on Quality, Costs and Equity in European Countries: The Hungarian Branch

Az alapellátás fontosságát már évtizedekkel ezelőtt felismerték és sok fejlett ország egészségügyében prioritást kapott. Európában igen eltérő keretek és feltételek között működnek az egyes országok alapellátási rendszerei. A QUALICOPC vizsgálat során 31 európai és három tengerentúli országban hasonlítják össze az alapellátás költségét, minőségét és méltányosságát. Hasonlóan a többi részt vevő országhoz, Magyarországon is a reprezentativitásra törekedve, országos koordináció alapján, 222 háziorvosi körzetben történt kérdőíves felmérés, a praxisokban dolgozó háziorvosok munkakörülményei, működési feltételei, megengedett és gyakorolt kompetenciája, érdekeltségi rendszere irányában. Minden körzetben 10 betegnek az ellátással kapcsolatos tapasztalatait, igényét és véleményét is kikérték a független kérdezőbiztos munkatársak. A szerzők a résztvevők és a metodika leírása mellett a vizsgálat kezdeti tapasztalatait mutatják be. A vizsgálat befejezését követően a részt vevő országokban nyert eredmények megismerése segítheti a politikai döntéshozókat és az egészségügy tervezőit. The importance of primary care has already been recognized in the developed countries, where the structure and function of primary care is very heterogeneous. In the QUALICOPC study, the costs, quality and equity of primary care systems will be compared in the 34 participating countries. Representative samples of primary care practices were recruited in Hungary. An evaluation with questionnaire was performed in 222 practices on the work circumstances, conditions, competency and fi nancial initiatives. Ten patients in each practice were also questioned by independent fieldworkers. In this work, the methodology and Hungarian experience are described. The final results of the international evaluation will be analyzed and published later. It is expected that data obtained from the QUALICOPC study may prove to be useful in health service planning and may be shared with policy makers

Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine

In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown

Primary care obesity management in Hungary: evaluation of the knowledge, practice and attitudes of family physicians

BACKGROUND: Obesity, a threatening pandemic, has an important public health implication. Before proper medication is available, primary care providers will have a distinguished role in prevention and management. Their performance may be influenced by many factors but their personal motivation is still an under-researched area. METHOD: The knowledge, attitudes and practice were reviewed in this questionnaire study involving a representative sample of 10% of all Hungarian family physicians. In different settings, 521 practitioners (448 GPs and 73 residents/vocational trainees) were questioned using a validated questionnaire. RESULTS: The knowledge about multimorbidity, a main consequence of obesity, was balanced.Only 51% of the GPs were aware of the diagnostic threshold for obesity; awareness being higher in cities (60%) and the highest among residents (90%). They also considered obesity an illness rather than an aesthetic issue.There were wider differences regarding attitudes and practice, influenced by the the doctors' age, gender, known BMI, previous qualification, less by working location.GPs with qualification in family medicine alone considered obesity management as higher professional satisfaction, compared to physicians who had previously other board qualification (77%vs68%). They measured their patients' waist circumference and waist/hip ratio (72%vs62%) more frequently, provided the obese with dietary advice more often, while this service was less frequent among capital-based doctors who accepted the self-reported body weight dates by patients more frequently / commonly. Similar reduced activity and weight-measurement in outdoor clothing were more typical among older doctors.Diagnosis based on BMI alone was the highest in cities (85%). Consultations were significantly shorter in practices with a higher number of enrolled patients and were longer by female providers who consulted longer with patients about the suspected causes of developing obesity (65%vs44%) and offered dietary records for patients significantly more frequently (65%vs52%). Most of the younger doctors agreed that obesity management was a primary care issue.Doctors in the normal BMI range were unanimous that they should be a model for their patients (94%vs81%). CONCLUSION: More education of primary care physicians, available practical guidelines and higher community involvement are needed to improve the obesity management in Hungary

Feel4Diabetes healthy diet score: Development and evaluation of clinical validity

Background: The aim of this paper is to present the development of the Feel4Diabetes Healthy Diet Score and to evaluate its clinical validity. Methods: Study population consisted of 3268 adults (63% women) from high diabetes risk families living in 6 European countries. Participants filled in questionnaires at baseline and after 1 year, reflecting the dietary goals of the Feel4Diabetes intervention. Based on these questions the Healthy Diet Score was constructed, consisting of the following components: breakfast, vegetables, fruit and berries, sugary drinks, whole-grain cereals, nuts and seeds, low-fat dairy products, oils and fats, red meat, sweet snacks, salty snacks, and family meals. Maximum score for each component was set based on its estimated relative importance regarding T2DM risk, higher score indicating better quality of diet. Clinical measurements included height, weight, waist circumference, heart rate, blood pressure, and fasting blood sampling, with analyses of glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides. Analysis of (co) variance was used to compare the Healthy Diet Score and its components between countries and sexes using baseline data, and to test differences in clinical characteristics between score categories, adjusted for age, sex and country. Pearson''s correlations were used to study the association between changes from baseline to year 1 in the Healthy Diet Score and clinical markers. To estimate reproducibility, Pearson''s correlations were studied between baseline and 1 year score, within the control group only. Results: The mean total score was 52.8 ± 12.8 among women and 46.6 ± 12.8 among men (p < 0.001). The total score and its components differed between countries. The change in the Healthy Diet Score was significantly correlated with changes in BMI, waist circumference, and total and LDL cholesterol. The Healthy Diet Score as well as its components at baseline were significantly correlated with the values at year 1, in the control group participants. Conclusion: The Feel4Diabetes Healthy Diet Score is a reproducible method to capture the dietary information collected with the Feel4Diabetes questionnaire and measure the level of and changes in the adherence to the dietary goals of the intervention. It gives a simple parameter that associates with clinical risk factors in a meaningful manner

Časově průměrované a časově rozlišené toky iontů v reaktivní HiPIMS depozici vrstev Ti–Al–N

Práce se zabývá časově průměrovanou i časově rozlišenou analýzou toku ionů v reaktivní HiPIMS depozici pro přípravu tenkých vrstev Ti–Al–N z kompozitních Ti–Al terčů. Hmotnostní spektroskopie odhalila, že zvýšení obsahu Al v terči nebo snížení podílu N2 v reaktivní atmosféře vede k proporčnímu zvýšení podílu Al+ iontů v toku na substrát. Za zkoumaných depozičních podmínek byly připraveny kubické Ti–Al–N vrstvy vykazující vysokou tvrdost až ~36 GPa a zároveň nízké tlakové pnutí.Time-averaged and time-resolved ion fluxes during reactive HiPIMS deposition of Ti–Al–N thin films are thoroughly investigated for the usage of Ti–Al composite targets. Ion mass spectroscopy analysis revealed, that increasing Al content in the target material or reducing the N2 flow-rate ratio leads to a proportional increase of the Al+-ion count fraction. The deposition conditions allowed for the growth of cubic Ti–Al–N coatings exhibiting high indentation hardness of up to ~36 GPa at a low compressive stress level

QUALICOPC: az alapellátás minőségének, költségének és méltányosságának vizsgálata Európa országaiban: magyarországi ág = QUALICOPC: primary care study on quality, costs and equity in European countries: the Hungarian branch.

The importance of primary care has already been recognized in the developed countries, where the structure and function of primary care is very heterogeneous. In the QUALICOPC study, the costs, quality and equity of primary care systems will be compared in the 34 participating countries. Representative samples of primary care practices were recruited in Hungary. An evaluation with questionnaire was performed in 222 practices on the work circumstances, conditions, competency and financial initiatives. Ten patients in each practice were also questioned by independent fieldworkers. In this work, the methodology and Hungarian experience are described. The final results of the international evaluation will be analyzed and published later. It is expected that data obtained from the QUALICOPC study may prove to be useful in health service planning and may be shared with policy makers. (aut. ref.