From EU-SoilHydroGrids to HU-SoilHydroGrids: A leap forward in soil hydraulic mapping.

Spatially explicit, quantitative information on soil hydraulic properties is required in various modelling schemes. At European scale, EU-SoilHydroGrids proved its applicability in a number of studies, in ecological predictions, geological and hydrological hazard assessment, agri-environmental models, among others. Inspired by its continental antecedent, an analogous, but larger scale, national, 3D soil hydraulic database was elaborated for the territory of Hungary (HU-SoilHydroGrids) supported by various improvements (i-iv) in the computation process. Pedotransfer functions (PTFs) were built in the form of i) advanced machine learning methods and ensemble models, and trained on the ii) national soil hydrophysical dataset. The set of predictors used in PTFs was supplemented by iii) additional environmental auxiliary variables. Spatial layers of the soil hydraulic parameters were generated using iv) 100 m resolution information on primary soil properties, namely DOSoReMI.hu. HU-SoilHydroGrids provides information on the most frequently required soil hydraulic properties (water content at saturation, field capacity and wilting point, saturated hydraulic conductivity and van Genuchten parameters for the description of the moisture retention curve) with national coverage at 100 m spatial resolution down to 2 m depth for six GSM standard depth layers. The HU-SoilHydroGrids has significantly lower squared error in the case of describing the moisture retention curve and hydraulic conductivity than the EU-SoilHydroGrids. The derived 3D soil hydraulic database (ver1.0) is presently available in National Laboratory for Water Science and Water Safety for project partners in order to test its functional performance in describing hydrological and ecological processes.

Novel family of [RuCp(N,N)(P)]+ compounds with simultaneous anticancer and antibacterial activity: Biological evaluation and solution chemistry studies.

A family of ten novel ruthenium(II)-cyclopentadienyl organometallics of general formula [Ru(η5-C5H5)(N,N)(PPh2(C6H4COOR)][CF3SO3] (1-10) in which (N,N) = 4,4'-R'-2,2'-bipyridyl (R = -H or -CH2CH2OH; R' = -H, -CH3, -OCH3, -CH2OH, and -CH2-biotin) was prepared from [Ru(η5-C5H5)(PPh2(C6H4COOH))2Cl]. All compounds were fully characterized by means of several spectroscopic and analytical techniques, and the molecular structures of [Ru(η5-C5H5)(PPh2(C6H4COOH))2Cl], 1, 3 and 4 have been additionally studied by single-crystal X-ray diffraction. The anticancer activity of all compounds was evaluated in sensitive and multidrug-resistant counterpart cell lines from human colorectal cancer (Colo 205 and Colo 320) and non-small cell lung cancer NSCLC (A549, NCI-H460 versus NCI-H460/R) as well. Notably, compounds 6 and 7 (R CH2CH2OH and (N,N) = bipy or Me2bipy, respectively) showed antiproliferative effect against both cell lines with high intrinsic selectivity towards cancer cells. The antibacterial activity of all compounds was also evaluated against both Gram negative and Gram positive strains, and some compounds in the series showed potent antibacterial activity against Staphylococcus aureus strains, including the methicillin-resistant MRSA strains. Solution speciation studies revealed that the complexes bearing the PPh2(C6H4COO-) ligand are neutral at physiological pH (7.4) in contrast with their ethylene glycol derivatives that have a permanent positive charge. While all compounds are lipophilic, the difference in the distribution coefficient for neutral and charged complexes is around one order of magnitude. Complexes 6 and 7 exhibited excellent biological activity and were selected for further studies. Spectrofluorometric methods were used to investigate their interaction with biomolecules such as human serum albumin (HSA) and calf thymus DNA (ct-DNA). For these complexes, binding site II of HSA is a possible binding pocket through non-covalent interactions. The release of ethidium from the DNA adduct by the charged complexes proves their interaction with DNA in contrast to the neutral ones. In conclusion, Ru(II)-cyclopentadienyl complexes with 2,2'-bipyridyl-derivatives and an ethylene glycol moiety tethered to the phenylphosphane co-ligand are very promising from a therapeutic perspective, in particular complexes 6 and 7 that display remarkable antibacterial activity with a high anti-proliferative effect against colon and non-small cell lung cancers, both clinically challenging neoplasias in need of effective solutions.

The application of data altruism in clinical research through empirical and legal analysis lenses.

Background: The legal framework for clinical research in the EU is complex and the lack of harmonization of the relevant legal and ethical rules remains one of the main challenges for stakeholders in the field. The recently adopted Data Governance Act (DGA) and the proposal for a European Health Data Space (EHDS) promise to solve the existing challenges with respect to access to and (re)use of personal data for research, but also risk to further complexify the field. The DGA introduced a novel mechanism - data altruism. Data altruism is understood as the voluntary sharing of personal and non-personal data, based on the consent of data subjects or the permission of natural and legal persons, without seeking a reward and for objectives of general interest. This study aimed to gain insights into the opinion of clinical research stakeholders on data altruism, and to critically discuss key issues pertaining to the application of data altruism from a legal point of view. Methods: Semi-structured interviews with (1) data protection officers (DPOs) and legal experts working with commercial and academic sponsors of clinical trials, (2) investigators, and (3) members of research ethics committees. Data underwent framework analysis. The legal discussion was comprised of legal doctrinal research with focus on the DGA, EHDS proposal, and the interplay with the EU General Data Protection Regulation (GDPR). Results: Fourteen experts took part in the interviews, more than half of which were DPOs/legal experts. Interviewees were based in seven EU Member states and the United Kingdom. The majority of participants were critical towards the data altruism mechanism and pointed out challenges and risks associated with its application. Conclusion: Although data altruism holds the potential to facilitate data sharing, its application in clinical research at the moment is still riddled with uncertainties. The interplay of the DGA rules with the provisions of the GDPR and the EHDS proposal are insufficiently clear and further efforts from the legislator are required to build a working, patient-centered, and research fostering data altruism system.

A comparative study on the metal complexes of an anticancer estradiol-hydroxamate conjugate and salicylhydroxamic acid.

Hydroxamic acids bearing an (O,O) donor set are well-known metal-chelating compounds with diverse biological activities including anticancer activity. Since steroid conjugation with a pharmacophoric moiety may have the potential to improve this effect, a salicylhydroxamic acid-estradiol hybrid molecule (E2HA) was synthesized. Only minimal effect of the conjugation on the proton dissociation constants was observed in comparison to salicylhydroxamic acid (SHA). The complexation with essential metal ions (iron, copper) was characterized, since E2HA may exert its cytotoxicity through the binding of these ions in cells. UV-visible spectrophotometric and pH-potentiometric titrations revealed the formation of high-stability complexes, while the Fe(III) preference over Fe(II) was proved by cyclic voltammetry and spectroelectrochemical measurements. Complex formation with half-sandwich Rh(III)(η5-Cp*) and Ru(II)(η6-p-cymene) organometallic cations was also studied as it may improve the anticancer effect and the pharmacokinetic profile of the ligand. At equimolar concentration the speciation is complicated because of the presence of mononuclear and binuclear complexes. The complexes readily react with small molecules e.g. glutathione, 1-methylimidazole and nucleosides, having major effect on solution speciation, namely mixed-ligand complex formation and ligand displacement occur. These processes serve as models for the interactions with biomolecules in the body. E2HA exerted moderate anticancer activity (IC50 = 25-59 µM) in the tested three human cancer cell lines (Colo205, Colo320 and MCF-7), while being non-toxic on non-cancerous MRC-5 cells. Meanwhile, SHA was inactive in the same cells. Complexation with half-sandwich Rh(III) and Ru(II) cations had only a minor improvement on the cytotoxic effect of E2HA.

Half-Sandwich Rhodium Complexes with Releasable N-Donor Monodentate Ligands: Solution Chemical Properties and the Possibility for Acidosis Activation.

Cancer chemotherapeutics usually have serious side effects. Targeting the special properties of cancer and activation of the anticancer drug in the tumor microenvironment in situ may decrease the intensity of the side effects and improve the efficacy of therapy. In this study, half-sandwich Rh complexes are introduced, which may be activated at the acidic, extracellular pH of the tumor tissue. The synthesis and aqueous stability of mixed-ligand complexes with a general formula of [Rh(η5-Cp*)(N,N/O)(N)]2+/+ are reported, where (N,N/O) indicates bidentate 8-quinolate, ethylenediamine and 1,10-phenanthroline and (N) represents the releasable monodentate ligand with a nitrogen donor atom. UV-visible spectrophotometry, 1H NMR, and pH-potentiometry were used to determine the protonation constants of the monodentate ligands, the proton dissociation constants of the coordinated water molecules in the aqua complexes, and the formation constants of the mixed-ligand complexes. The obtained data were compared to those of the analogous Ru(η6-p-cymene) complexes. The developed mixed-ligand complexes were tested in drug-sensitive and resistant colon cancer cell lines (Colo205 and Colo320, respectively) and in four bacterial strains (Gram-positive and Gram-negative, drug-sensitive, and resistant) at different pH values (5-8). The mixed-ligand complexes with 1-methylimidazole displayed sufficient stability at pH 7.4, and their activation was found in cancer cells with decreasing pH; moreover, the mixed-ligand complexes demonstrated antimicrobial activity in Gram-positive and Gram-negative bacteria, including the resistant MRSA strain. This study proved the viability of incorporating releasable monodentate ligands into mixed-ligand half-sandwich complexes, which is supported by the biological assays.

Metal Coordination and Biological Screening of a Schiff Base Derived from 8-Hydroxyquinoline and Benzothiazole.

Designing new metallodrugs for anticancer therapy is a driving force in the scientific community. Aiming to contribute to this field, we hereby report the development of a Schiff base (H2L) derived from the condensation of 2-carbaldehyde-8-hydroxyquinoline with 2-hydrazinobenzothiazole and its complexation with transition metal ions. All compounds were characterised by analytical and spectroscopic techniques, which disclosed their structure: [Cu(HL)Cl], [Cu(HL)2], [Ni(HL)(acetate)], [Ni(HL)2], [Ru(HL)Cl(DMSO)], [VO(HL)2] and [Fe(HL)2Cl(H2O)]. Different binding modes were proposed, showing the ligand's coordination versatility. The ligand proton dissociation constants were determined, and the tested compounds showed high lipophilicity and light sensitivity. The stability of all complexes in aqueous media and their ability to bind to albumin were screened. Based on an antiproliferative in vitro screening, [Ni(HL)(acetate)] and [Ru(HL)Cl(DMSO)] were selected for further studies aiming to investigate their mechanisms of action and therapeutic potential towards colon cancer. The complexes displayed IC50 < 21 µM towards murine (CT-26) and human (HCT-116) colon cancer cell lines. Importantly, both complexes exhibited superior antiproliferative properties compared to the clinically approved 5-fluorouracil. [Ni(HL)(acetate)] induced cell cycle arrest in S phase in CT-26 cells. For [Ru(HL)Cl(DMSO)] this effect was observed in both colon cancer cell lines. Additionally, both compounds significantly inhibited cell migration particularly in the human colon cancer cell line, HCT-116. Overall, the therapeutic potential of both metal complexes was demonstrated.

The future regulation of artificial intelligence systems in healthcare services and medical research in the European Union.

Despite its promising future, the application of artificial intelligence (AI) and automated decision-making in healthcare services and medical research faces several legal and ethical hurdles. The European Union (EU) is tackling these issues with the existing legal framework and drafting new regulations, such as the proposed AI Act. The EU General Data Protection Regulation (GDPR) partly regulates AI systems, with rules on processing personal data and protecting data subjects against solely automated decision-making. In healthcare services, (automated) decisions are made more frequently and rapidly. However, medical research focuses on innovation and efficacy, with less direct decisions on individuals. Therefore, the GDPR's restrictions on solely automated decision-making apply mainly to healthcare services, and the rights of patients and research participants may significantly differ. The proposed AI Act introduced a risk-based approach to AI systems based on the principles of ethical AI. We analysed the complex connection between the GDPR and AI Act, highlighting the main issues and finding ways to harmonise the principles of data protection and ethical AI. The proposed AI Act may complement the GDPR in healthcare services and medical research. Although several years may pass before the AI Act comes into force, many of its goals will be realised before that.

Challenges related to data protection in clinical research before and during the COVID-19 pandemic: An exploratory study.

Background: The COVID-19 pandemic brought global disruption to health, society and economy, including to the conduct of clinical research. In the European Union (EU), the legal and ethical framework for research is complex and divergent. Many challenges exist in relation to the interplay of the various applicable rules, particularly with respect to compliance with the General Data Protection Regulation (GDPR). This study aimed to gain insights into the experience of key clinical research stakeholders [investigators, ethics committees (ECs), and data protection officers (DPOs)/legal experts working with clinical research sponsors] across the EU and the UK on the main challenges related to data protection in clinical research before and during the pandemic. Materials and methods: The study consisted of an online survey and follow-up semi-structured interviews. Data collection occurred between April and December 2021. Survey data was analyzed descriptively, and the interviews underwent a framework analysis. Results and conclusion: In total, 191 respondents filled in the survey, of whom fourteen participated in the follow-up interviews. Out of the targeted 28 countries (EU and UK), 25 were represented in the survey. The majority of stakeholders were based in Western Europe. This study empirically elucidated numerous key legal and ethical issues related to GDPR compliance in the context of (cross-border) clinical research. It showed that the lack of legal harmonization remains the biggest challenge in the field, and that it is present not only at the level of the interplay of key EU legislative acts and national implementation of the GDPR, but also when it comes to interpretation at local, regional and institutional levels. Moreover, the role of ECs in data protection was further explored and possible ways forward for its normative delineation were discussed. According to the participants, the pandemic did not bring additional legal challenges. Although practical challenges (for instance, mainly related to the provision of information to patients) were high due to the globally enacted crisis measures, the key problematic issues on (cross-border) health research, interpretations of the legal texts and compliance strategies remained largely the same.

Internet addiction: the medical challenge of the 21st century? br / Internetfüggoség: a 21. század orvosi kihívása?

As a result of digitalisation and the increasing use of the internet, its problematic use is on the rise in the 21st cen-tury, with a predominant impact on minors and a potentially increasing challenge for health care systems in the fu-ture. The main risk factors for this phenomenon are age, inadequate social and family relationships, and can be as-sociated with mental problems such as depression and anxiety, somatic illnesses, often with additional dependencies. Imaging studies can detect abnormally functioning brain areas in the affected individuals, however, there is a signifi-cant heterogeneity among them. Similar to other addictions, extensive internet use negatively affects the individual in all areas of life. We do not have a high level of evidence for treatment yet, but it appears that treatments used in other (classic) addictive diseases may be effective.

Digitizing the Informed Consent Process: A Review of the Regulatory Landscape in the European Union.

Background: Rapid technological advancements are reshaping the conduct of clinical research. Electronic informed consent (eIC) is one of these novel advancements, allowing to interactively convey research-related information to participants and obtain their consent. The COVID-19 pandemic highlighted the importance of establishing a digital, long-distance relationship between research participants and researchers. However, the regulatory landscape in the European Union (EU) is diverse, posing a legal challenge to implement eIC in clinical research. Therefore, this study takes the necessary steps forward by providing an overview of the current regulatory framework in the EU, relevant to eIC. Methods: We reviewed and analyzed the key EU regulations, such as the EU General Data Protection Regulation (GDPR) and the Clinical Trials Regulation (CTR). We investigated the legality of eIC in several EU Member States, Switzerland, and the United Kingdom. To this end, we contacted the medicines agencies of various countries to clarify the national requirements related to the implementation and use of eIC in clinical research. Our research was complemented by comparing the legal acceptance of eIC between the EU and the United States. Results: In the EU, a distinction must be made between eIC for participation in clinical research and eIC for processing the participants' personal data, complying respectively with requirements laid down by the CTR and the GDPR. On a national level, countries were classified into three groups: (1) countries accepting and regulating the use of eIC, (2) countries accepting the use of eIC without explicitly regulating it, and (3) countries not accepting the use of eIC. As a result, the regulation of eIC through laws and guidelines shows a large variety among EU Member States, while in the United States, it is harmonized through the Code of Federal Regulations. Conclusion: Various requirements must be considered when implementing eIC in clinical research. Nevertheless, requirements across the EU Member States may differ significantly, whereas, in the United States, efforts have already been made to achieve a harmonized approach.

Prevalence and Risk Factors of Problematic Internet Use among Hungarian Adult Recreational Esports Players.

Background: Esports are highly prevalent in modern culture, particularly among young people, and are a healthy hobby for the majority of users. However, there is a possible link between video gaming (including esports) and problematic internet use (so-called internet addiction, IA), mostly involving adolescents. Methods: Here we present an online survey focusing on the prevalence and risk factors of internet addiction among adult esports players. Demographics included age, gender, family type, type of work, working years and daily internet use. Medical conditions associated with IA such as smoking, alcohol and drug intake, hypertension, diabetes, ischemic heart disease, musculoskeletal pain and history of depression were also recorded. Results: Overall, 2313 players including 176 females (7.6%) and 2137 males (92.4%) participated in our online survey. Age distribution was the following: 18−25 years 90.3% (2088/2313), 26−35 years 7.95% (184/2313), 36−45 years 0.86% (20/2313), 46−55 years 0.82% (19/2313), 56−62 years 0.04% (1/2313) and 62 years or older 0.04% (1/2313). Internet addiction was detected in 19.9% of players (461/2313) based on the Problematic Internet Use Questionnaire. In a multivariate analysis internet addiction was significantly associated with age between 18 and 25 (OR: 1.675, p = 0.002), being single (OR = 1.505, p = 0.014), internet use > 6 h daily (OR = 4.338, p < 0.001), having < 3 children (OR: 2.037, p = 0.023) and having secondary employment (OR = 1.789, p = 0.037). Regular alcohol intake (OR = 18.357, p < 0.001) and history of depression (OR= 5.361, p = 0.032) were also strongly correlated with IA. Conclusion: This is the first study from Hungary investigating the prevalence and risk factors of internet addiction among adult esports players. One out of five adult gamers suffered from IA. Our study also draws attention to increased risk within this group and risk factors such as younger age, family status and type of employment.

8-Hydroxyquinoline-Amino Acid Hybrids and Their Half-Sandwich Rh and Ru Complexes: Synthesis, Anticancer Activities, Solution Chemistry and Interaction with Biomolecules.

Solution chemical properties of two novel 8-hydroxyquinoline-D-proline and homo-proline hybrids were investigated along with their complex formation with [Rh(η5-C5Me5)(H2O)3]2+ and [Ru(η6-p-cymene)(H2O)3]2+ ions by pH-potentiometry, UV-visible spectrophotometry and 1H NMR spectroscopy. Due to the zwitterionic structure of the ligands, they possess excellent water solubility as well as their complexes. The complexes exhibit high solution stability in a wide pH range; no significant dissociation occurs at physiological pH. The hybrids and their Rh(η5-C5Me5) complexes displayed enhanced cytotoxicity in human colon adenocarcinoma cell lines and exhibited multidrug resistance selectivity. In addition, the Rh(η5-C5Me5) complexes showed increased selectivity to the chemosensitive cancer cells over the normal cells; meanwhile, the Ru(η6-p-cymene) complexes were inactive, most likely due to arene loss. Interaction of the complexes with human serum albumin (HSA) and calf-thymus DNA (ct-DNA) was investigated by capillary electrophoresis, fluorometry and circular dichroism. The complexes are able to bind strongly to HSA and ct-DNA, but DNA cleavage was not observed. Changing the five-membered proline ring to the six-membered homoproline resulted in increased lipophilicity and cytotoxicity of the Rh(η5-C5Me5) complexes while changing the configuration (L vs. D) rather has an impact on HSA or ct-DNA binding.

Ischemic stroke mimics: A comprehensive review.

BACKGROUND: Ischemic stroke is the leading cause of disability and one of the leading causes of death. Ischemic stroke mimics (SMs) can account for a noteble number of diagnosed acute strokes and even can be thrombolyzed. METHODS: The aim of our comprehensive review was to summarize the findings of different studies focusing on the prevalence, type, risk factors, presenting symptoms, and outcome of SMs in stroke/thrombolysis situations. RESULTS: Overall, 61 studies were selected with 62.664 participants. Ischemic stroke mimic rate was 24.8% (15044/60703). Most common types included peripheral vestibular dysfunction in 23.2%, toxic/metabolic in 13.2%, seizure in 13%, functional disorder in 9.7% and migraine in 7.76%. Ischemic stroke mimic have less vascular risk factors, younger age, female predominance, lower (nearly normal) blood pressure, no or less severe symptoms compared to ischemic stroke patients (p < 0.05 in all cases). 61.7% of ischemic stroke patients were thrombolysed vs. 26.3% among SMs (p < 0.001). (p < 0.001). Overall intracranial hemorrhage was reported in 9.4% of stroke vs. 0.7% in SM patients (p < 0.001). Death occurred in 11.3% of stroke vs 1.9% of SM patients (p < 0.001). Excellent outcome was (mRS 0-1) was reported in 41.8% ischemic stroke patients vs. 68.9% SMs (p < 0.001). Apart from HINTS manouvre or Hoover sign there is no specific method in the identification of mimics. MRI DWI or perfusion imaging have a role in the setup of differential diagnosis, but merit further investigation. CONCLUSION: Our article is among the first complex reviews focusing on ischemic stroke mimics. Although it underscores the safety of thrombolysis in this situation, but also draws attention to the need of patient evaluation by physicians experienced in the diagnosis of both ischemic stroke and SMs, especially in vertigo, headache, seizure and conversional disorders.

Critical factors affecting the albumin binding of half-sandwich Ru(ii) and Rh(iii) complexes of 8-hydroxyquinolines and oligopyridines.

There is significant interest today in the interaction of half-sandwich anticancer organometallic complexes with proteins. It is considered as a crucial factor in the transport and mode of action of these compounds; thus it can affect their overall pharmacological and toxicological profiles. Albumin binding of high stability Ru(ii)(η6-p-cymene) and Rh(iii)(η5-C5Me5) complexes formed with 8-hydroxyquinoline, its 5-chloro-7-((proline-1-yl)methyl) substituted derivative, 2,2'-bipyridine and 1,10-phenanthroline is discussed herein. The interaction with human serum albumin in terms of kinetic aspects, binding strength and possible binding sites was studied in detail by means of various methods such as 1H NMR spectroscopy, UV-visible spectrophotometry, steady-state and time-resolved fluorometry, ultrafiltration and capillary zone electrophoresis. Ru(ii)(η6-p-cymene)(2,2'-bipyridine) and Ru(ii)(η6-p-cymene)(1,10-phenanthroline) complexes do not bind to the protein measurably, most probably due to kinetic reasons. However, other complexes bind significantly to albumin with fairly different kinetics to albumin. The binding affinity towards hydrophobic binding pockets shows correlation with lipophilicity along with the actual charge of the respective complexes. The studied complexes preserve their original structure upon interaction with albumin. Formation constants computed for the binding of these metal complexes to histidine-containing model oligopeptides demonstrated significant ternary complex formation, pointing out the importance of histidine coordination in the binding of these types of complexes.

Half-sandwich organometallic Ru and Rh complexes of (N,N) donor compounds: effect of ligand methylation on solution speciation and anticancer activity.

A series of half-sandwich polypyridyl complexes was synthesized and compared focusing on structural, cytotoxic and aqueous solution behaviour. The formula of the synthesized complexes is [M(arene)(N,N)Cl]Cl, where M: Ru or Rh, arene: p-cymene, toluene or C5Me5-, (N,N): 2,2'-bipyridine (bpy), 4,4'-dimethyl-2,2'-bipyridine (dmb), 1,10-phenanthroline (phen) or 2,9-dimethyl-1,10-phenanthroline (neo). The structures of five half-sandwich complexes were determined by X-ray crystallography. It was found that introducing methyl groups next to the coordinating nitrogen atoms of the bidentate ligand causes steric congestion around the metal centre which changes the angle between ligand planes. The ligands and the Rh complexes showed significant cytotoxicity in A2780 and MES-SA cancer cell lines (IC50 = 0.1-56 µM) and in the cisplatin-resistant A2780cis cells. Paradoxically, phen and dmb as well as their half-sandwich Rh complexes showed increased toxicity against multidrug resistant MES-SA/Dx5 cells. In contrast, coordination to Ru caused loss of toxicity. Solution equilibrium constants showed that the studied metal complexes have high stability, and no dissociation was found for Ru and Rh complexes even at micromolar concentrations in a wide pH range. However, in the case of Ru complexes a slow and irreversible decomposition, namely arene loss, was also observed, which was more pronounced in light exposure in aqueous solution. In the case of neo, the methyl groups next to the nitrogen atoms significantly decrease the stability of complexes. For Rh complexes, the order of the stability constants corrected with ligand basicity (log K*): 9.78 (phen) > 9.01 (dmb) > 8.89 (bpy) > 3.93 (neo). The coordinated neo resulted in an enormous decrease in the chloride ion affinity of Ru compounds. Based on the results, a universal model was introduced for the prediction of chloride ion capability of half-sandwich Rh and Ru complexes. It combines the effects of the bidentate ligand and the M(arene) part using only two terms, performing multilinear regression procedure.

An 8-hydroxyquinoline-proline hybrid with multidrug resistance reversal activity and the solution chemistry of its half-sandwich organometallic Ru and Rh complexes.

Herein the design and synthesis of a new 8-hydroxyquinoline derivative, (S)-5-chloro-7-((proline-1-yl)methyl)8-hydroxyquinoline (HQCl-Pro), with good water solubility and multidrug resistance reversal activity are reported. In this work the proton dissociation processes of HQCl-Pro and its complex formation with [Rh(η5-C5Me5)(H2O)3]2+, [Ru(η6-p-cymene)(H2O)3]2+ and [Ru(η6-toluene)(H2O)3]2+ were investigated by the combined use of pH-potentiometry, UV-visible spectrometry and 1H NMR spectroscopy. Our results revealed the prominent solution stability of the complexes in all cases. The lipophilicity of the complexes increased with the chloride ion concentration, and the complexes showed moderate log D values (-0.8 to +0.4) at pH 7.4 at all tested Cl- concentrations. The formation of mixed hydroxido complexes from the aqua complexes was characterized by relatively high pKa values (8.45-9.62 in chloride-free medium). Complexation processes are much slower with the Ru(η6-arene) triaqua cations than with [Rh(η5-C5Me5)(H2O)3]2+. Both the pKa values and H2O/Cl- exchange constants of the Ru-complexes are lower by 0.5-1.0 orders of magnitude than those of the Rh analogue. Arene loss (p-cymene and toluene) and oxidation were found in the case of Ru-complexes when an excess of HQCl-Pro and aromatic (N,N) bidentate ligands was added. The cytotoxicity and antiproliferative effect of HQCl-Pro and its complexes were assayed in vitro. In contrast to the structurally familiar 8-hydroxyquinoline, HQCl-Pro and its Rh(η5-C5Me5) complex were somewhat more effective against drug resistant Colo 320 adenocarcinoma human cells compared to the drug sensitive Colo 205 cells. The Ru- and Rh-complexes showed a similar metal uptake level after 4 h, while a longer incubation time resulted in higher cellular Rh concentration.

Framingham Risk Stratification of Middle-Aged Migraineurs.

Introduction. Migraine is a common primary headache disorder involving about 10-15% of the whole population. Several epidemiological and prospective studies showed a link between migraine (especially migraine with aura) and cardio- and cerebrovascular events. OBJECTIVES: We prospectively analyzed the data of vascular event-free middle-aged patients with migraine who were referred to our Headache Clinic between 01/2014 and 01/2018. Framingham 10-year risk were calculated; covariates included in the analysis were age, total cholesterol, HDL cholesterol, systolic blood pressure, antihypertensive medication use, current smoking, and diabetes status. RESULTS: Total of 1037 patients were screened and 221 were selected, 161 were women (mean age 55.5 ± 5.2 years) and 60 were men (mean age 56 ± 6 years). 25 patients (11.3%) were labelled as having low risk, 162 patients (73.3%) had moderate risk, and 34 patients (15.4%) had high or very high risk. Blood pressure and lipid targets were reached in 73% and in 49% in the moderate risk and in 53% and 12% in the high risk/very high risk groups, respectively. Migraine with aura (MA) was associated significantly higher cardiovascular risk profile compared with migraine without aura (MO). About one-third of our nondiabetic patients had fasting blood glucose above the normal levels. 24 patients (mean age 60 ± 4.9 years) were diabetic. Mean blood pressure was 149/85 Hgmm, mean choleterol was 5.11 mmol/l, and mean LDL was 2.93 mmol/l in this subgroup, respectively, which do not fall within the recommended targets. CONCLUSION: Our article draws attention to the higher cardiovascular risk profile of middle-aged migraineurs and highlights the deficiency of primary prevention. Pain physicians must be aware of the cardiovascular aspects of migraine and holistic approach is required instead of focusing only on pain and pain relief.

[Chronic orofacial pain]. / Krónikus orofacialis fájdalmak.

Orofacial pain is the common name of a variety of disorders from inflammatory diseases to neuropathic pain syndromes. This condition is quite common, it may involve 7% of the whole population. Patients (and doctors) are not aware of the origin of their complaints, therefore initial management falls among the variety of healthcare professionals. The aim of our review was to summarize the current evidence of chronic orofacial pain including diagnosis, management and pitfalls. Orv Hetil. 2019; 160(27): 1047-1056.

Comparative solution and structural studies of half-sandwich rhodium and ruthenium complexes bearing curcumin and acetylacetone.

Half-sandwich organometallic complexes of curcumin are extensively investigated as anticancer compounds. Speciation studies were performed to explore the solution stability of curcumin complexes formed with [Rh(η5-C5Me5)(H2O)3]2+. Acetylacetone (Hacac), as the simplest ß-diketone ligand bearing (O,O) donor set, was involved for comparison and its Ru(η6­p­cymene), Ru(η6­toluene) complexes were also studied. 1H NMR, UV-visible and pH-potentiometric titrations revealed a clear trend of stability constants of the acac complexes: Ru(η6­p­cymene) > Ru(η6­toluene) > Rh(η5-C5Me5). Despite this order, the highest extent of complex formation is seen for the Rh(η5-C5Me5) complexes at pH 7.4. Formation constant of [Rh(η5-C5Me5)(H2curcumin)(H2O)]+ reveals similar solution stability to that of the acac complex. Additionally, structures of two complexes were determined by X-ray crystallography. The in vitro cytotoxicity of curcumin was not improved by the complexation with these organometallic cations.

The Relationship between Body Fat Percentage and Some Anthropometric and Physical Fitness Characteristics in Pre- and Peripubertal Boys.

The main aim of this study was to compare anthropometric and physical fitness indicators of boys of the same chronical age but with different fat percentages. Subjects were Hungarian boys aged 9⁻13 years (N = 6919). Anthropometry was measured according the guidelines of the International Biological Program. Relative body fat was estimated by Drinkwater⁻Ross's method (1980); Conrad's growth type of physique was also estimated (1963). Physical fitness was tested with 30 m dash (s), standing long jump (cm), fistball throw (m), and 1200 m run (s). Subjects of each cohort were grouped into seven subgroups with fat percentage ranges of 4%. Differences between subgroups were tested by one-way ANOVA. In the case of a significant F-test, Tukey's post-hoc tests were used. The level of effective random error was set at 5% in all significance tests (p < 0.05). Except for the three groups with low fat percentages, values of body weight, stature, body mass index, and plastic and metric indexes were significantly higher; results of 30 m, 1200 m running, and standing long jump were worse in all groups with higher fat percentages. An interesting finding of the current study is that body fat percentage also influenced the physical fitness of non-overweight and obese children as well when using merely the 4% ranges in grouping by fatness. The lower the fat the better the physical fitness was in this sample of pre- and peripubertal boys.