Extended pleurectomy decortication and chemotherapy versus chemotherapy alone for pleural mesothelioma (MARS 2): a phase 3 randomised controlled trial.

BACKGROUND: Extended pleurectomy decortication for complete macroscopic resection for pleural mesothelioma has never been evaluated in a randomised trial. The aim of this study was to compare outcomes after extended pleurectomy decortication plus chemotherapy versus chemotherapy alone. METHODS: MARS 2 was a phase 3, national, multicentre, open-label, parallel two-group, pragmatic, superiority randomised controlled trial conducted in the UK. The trial took place across 26 hospitals (21 recruiting only, one surgical only, and four recruiting and surgical). Following two cycles of chemotherapy, eligible participants with pleural mesothelioma were randomly assigned (1:1) to surgery and chemotherapy or chemotherapy alone using a secure web-based system. Individuals aged 16 years or older with resectable pleural mesothelioma and adequate organ and lung function were eligible for inclusion. Participants in the chemotherapy only group received two to four further cycles of chemotherapy, and participants in the surgery and chemotherapy group received pleurectomy decortication or extended pleurectomy decortication, followed by two to four further cycles of chemotherapy. It was not possible to mask allocation because the intervention was a major surgical procedure. The primary outcome was overall survival, defined as time from randomisation to death from any cause. Analyses were done on the intention-to-treat population for all outcomes, unless specified. This study is registered with ClinicalTrials.gov, NCT02040272, and is closed to new participants. FINDINGS: Between June 19, 2015, and Jan 21, 2021, of 1030 assessed for eligibility, 335 participants were randomly assigned (169 to surgery and chemotherapy, and 166 to chemotherapy alone). 291 (87%) participants were men and 44 (13%) women, and 288 (86%) were diagnosed with epithelioid mesothelioma. At a median follow-up of 22·4 months (IQR 11·3-30·8), median survival was shorter in the surgery and chemotherapy group (19·3 months [IQR 10·0-33·7]) than in the chemotherapy alone group (24·8 months [IQR 12·6-37·4]), and the difference in restricted mean survival time at 2 years was -1·9 months (95% CI -3·4 to -0·3, p=0·019). There were 318 serious adverse events (grade ≥3) in the surgery group and 169 in the chemotherapy group (incidence rate ratio 3·6 [95% CI 2·3 to 5·5], p<0·0001), with increased incidence of cardiac (30 vs 12; 3·01 [1·13 to 8·02]) and respiratory (84 vs 34; 2·62 [1·58 to 4·33]) disorders, infection (124 vs 53; 2·13 [1·36 to 3·33]), and additional surgical or medical procedures (15 vs eight; 2·41 [1·04 to 5·57]) in the surgery group. INTERPRETATION: Extended pleurectomy decortication was associated with worse survival to 2 years, and more serious adverse events for individuals with resectable pleural mesothelioma, compared with chemotherapy alone. FUNDING: National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (15/188/31), Cancer Research UK Feasibility Studies Project Grant (A15895).

The Impact on Survival of Neoadjuvant Treatment Interruptions in Locally Advanced Rectal Cancer Patients.

The standard oncologic treatment of locally advanced rectal cancer is long-course radio-chemotherapy followed by surgery and adjuvant chemotherapy. This can result in a lengthy total treatment duration, sometimes up to one year from the diagnosis. Interruptions to neoadjuvant treatment can occur for a variety of reasons, forced or unforced. The main purpose of this study is to analyze the survival data of locally advanced rectal cancer patients who received neoadjuvant treatment and to find a cut-off point showing exactly how many days of interruption of neoadjuvant treatment the risk of death or disease relapse increases. We conducted a retrospective study on 299 patients with locally advanced rectal cancer using survival analysis (Kaplan-Meier curve and Cox regression) to determine survival probabilities for overall survival, local control, and disease-free survival. Patients with 0 to 3 days of neoadjuvant therapy interruption had a higher overall survival probability compared to patients with 4 or more days (90.2% compared to 57.9%, p-value < 0.001), hazard ratio 5.89 (p < 0.001). Local control and disease-free survival had a higher probability in patients with 0-2 days of interruption compared to people with 3 or more days (94% vs. 75.4%, and 82.2% vs. 50.5%, respectively, both p-values < 0.001). Patients with tumoral or nodal downstaging experienced fewer days of interruption than patients with no downstage. These findings reinforce the need for radiation oncologists to be well-organized when starting neoadjuvant treatment for rectal cancer, in order to anticipate and prevent potential treatment interruptions and achieve the best therapeutic results.

Inflammatory appearance of the parietal pleura at thoracoscopy - What does it hide?

BACKGROUND: Medical thoracoscopy (MT) is a well-established diagnostic procedure in cases of unexplained exudative pleural effusions. Despite the advantages of MT, challenges remain since occasionally malignancies mimic pleural inflammation. OBJECTIVES: To assess the relationship between the macroscopic appearance of the pleura at MT, the histology of the pleural biopsy and the final diagnosis after follow up. METHODS: Data was prospectively collected on patients undergoing MT over 8 years, using a standardised electronic thoracoscopy report. We report the sensitivity, specificity, positive and negative predictive values (PPV, NPV) of the macroscopic changes, the sensitivity of computer tomographic (CT) appearances and final outcome. RESULTS: A total of 228 thoracoscopies and biopsy were performed, 70 reports described benign macroscopic changes; of these 15.7% had malignant histology. When the final outcome was taken into account, the sensitivity of macroscopic appearance at MT was 91.5%, specificity 76.0%, PPV 88.6% and the NPV 81.4%. Nodular changes were more likely to be associated with malignancy (Chi2 75.5, p < 0.05). The CT scans performed prior to thoracoscopy had a poor sensitivity for the diagnosis of malignant pleural effusion (50%) and a good specificity in the diagnosis of benign disease (90.5%). CONCLUSION: A standardised structured report allows reliable evaluation of the macroscopic findings at MT. The PPV of the macroscopic findings for malignancy is relatively high; however, in a significant minority of cases despite benign-looking macroscopic changes the final diagnosis was malignancy. Careful consideration must be given in cases with benign histology to either monitoring or further diagnostic tests based on clinical suspicion.

Cytotoxicity of Alizarine versus Tetrabromocathecol Cyclometalated Pt(II) Theranostic Agents: A Combined Experimental and Computational Investigation.

Platinum compounds cytotoxicity is strictly related to their ability to be converted into active mono- and di-aquated species and consequently to the replacement of labile ligands by water molecules. This activation process makes the platinum center prone to nucleophilic substitution by DNA purines. In the present work, quantum mechanical density functional theory (DFT) computations and experimental investigations were carried out in order to shed light on the relationship between the internalization, aquation, and DNA binding of two isostructural anionic theranostic complexes previously reported by our group, NBu4[(PhPy)Pt(Aliz)], 1 (IC50 1.9 ± 1.6 µM), and NBu4[(PhPy)Pt(BrCat)], 2 (IC50 52.8 ± 3.9 µM). Cisplatin and a neutral compound [(NH3)2Pt(Aliz)], 3, were also taken as reference compounds. The computed energy barriers and the endergonicity of the hydrolysis reactions showed that the aquation rates are comparable for 1 and 2, with a slightly higher reactivity of 1. The second hydrolysis process was proved to be the rate-determining step for both 1 and 2, unlike for compound 3. The nucleophilic attack by the N7 site of guanine to both mono- and di-aquated forms of the complexes was computationally investigated as well, allowing to rationalize the observed different cytotoxicity. Computational results were supported by photostability data and biological assays, demonstrating DNA as the main target for compound 1.

Health anxiety, perceived risk and perceived control in following recommended preventive measures during early COVID-19 response in Romania.

BACKGROUND: Compliance with government-recommended preventive measures represents a key factor in mitigating the negative consequences of coronavirus disease 2019 (COVID-19). AIMS: The study investigated the relation between health anxiety, perceived risk and perceived control as predictors of coronavirus disease 2019 (COVID-19)-related anxiety and preventive behaviours (both adaptive and dysfunctional/excessive) during the early pandemic response in Romania. METHOD: Data were collected in April-May 2020, and the sample comprised 236 participants, 192 women, mean age 31.44 (s.d. = 10.30, age range 16-67). RESULTS: Our results showed that health anxiety and perceived control, but not perceived risk predicted adaptive preventive behaviours, whereas dysfunctional behaviours were predicted by health anxiety alone. COVID-19-related anxiety was predicted by health anxiety and perceived risk, with perceived control emerging as a non-significant predictor. Also, we found that the effect of health anxiety on COVID-19-related anxiety was mediated by perceived risk, and that perceived control acted as a moderator in the relation between health anxiety and dysfunctional (but not adaptive) preventive behaviours. CONCLUSIONS: Our results suggest health anxiety is a significant predictor of COVID-19-related anxiety and preventive behaviours. Also, adaptive, but not dysfunctional, preventive behaviours were additionally predicted by perceived control, pointing to the important role of control and self-efficacy in explaining adherence to recommendations.

Photoconductive Properties and Electronic Structure in 3,5-Disubstituted 2-(2'-Pyridyl)Pyrroles Coordinated to a Pd(II) Salicylideneiminate Synthon.

The synthesis and the electrochemical, photophysical, structural, and photoconductive properties of three new heteroleptic Pd(II) complexes with various 3',5'- disubstituted-2-(2'-pyridil) pyrroles H(N^N) as coordinated ligands are reported. The coordination of the metal center was completed by a functionalized Schiff base H(O^N) used as an ancillary ligand. The [(N^N)Pd(O^N)] complexes showed highly interesting photoconductive properties which have been correlated to their electronic and molecular structures. Theoretical density functional theory (DFT) and time-dependent DFT calculations were performed, and the results were confronted with the organization in crystalline phase, allowing to point out that the photoconductive properties are mainly a consequence of an efficient intramolecular ligand-to-metal charge transfer, combined to the proximity between the central metal and the donor moieties in the solid-state molecular stacks. The reported results confirm that these new Pd(II) complexes form a novel class of organometallic photoconductors with intrinsic characteristics suitable for molecular semiconductors applications.

Mesothelioma and Radical Surgery 2 (MARS 2): protocol for a multicentre randomised trial comparing (extended) pleurectomy decortication versus no (extended) pleurectomy decortication for patients with malignant pleural mesothelioma.

INTRODUCTION: Mesothelioma remains a lethal cancer. To date, systemic therapy with pemetrexed and a platinum drug remains the only licensed standard of care. As the median survival for patients with mesothelioma is 12.1 months, surgery is an important consideration to improve survival and/or quality of life. Currently, only two surgical trials have been performed which found that neither extensive (extra-pleural pneumonectomy) or limited (partial pleurectomy) surgery improved survival (although there was some evidence of improved quality of life). Therefore, clinicians are now looking to evaluate pleurectomy decortication, the only radical treatment option left. METHODS AND ANALYSIS: The MARS 2 study is a UK multicentre open parallel group randomised controlled trial comparing the effectiveness and cost-effectiveness of surgery-(extended) pleurectomy decortication-versus no surgery for the treatment of pleural mesothelioma. The study will test the hypothesis that surgery and chemotherapy is superior to chemotherapy alone with respect to overall survival. Secondary outcomes include health-related quality of life, progression-free survival, measures of safety (adverse events) and resource use to 2 years. The QuinteT Recruitment Intervention is integrated into the trial to optimise recruitment. ETHICS AND DISSEMINATION: Research ethics approval was granted by London - Camberwell St. Giles Research Ethics Committee (reference 13/LO/1481) on 7 November 2013. We will submit the results for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBERS: ISRCTN-ISRCTN44351742 and ClinicalTrials.gov-NCT02040272.

Electrochromic behaviour of Ir(iii) bis-cyclometalated 1,2-dioxolene tetra-halo complexes: fully reversible catecholate/semiquinone redox switches.

Neutral cyclometalated Ir(iii) complexes of general formula [Ir(ppy)2(O^O)squi], where ppy = 2-phenylpyridine and (O^O)squi = TBC (tetrabromocatechol) or TCC (tetrachlorocatechol) in their semiquinone (squi) monoanionic redox state, were synthesized by chemically oxidizing the anionic parent complexes NBu4[Ir(ppy)2(O^O)cat], in which (O^O)cat represents the corresponding ancillary dioxolene ligand in its dianionic catecholate (cat) redox state. This chemical oxidation leads to the modification of both the photophysical and the magnetic properties of the complexes. While the NBu4[Ir(ppy)2(O^O)cat] complexes are diamagnetic (D) and yellow-orange solids, the corresponding oxidized complexes [Ir(ppy)2(O^O)squi] display paramagnetic (P) properties and are characterized by a dark-green color. The conversion between the two forms (squi vs. cat) is electrochemically and chemically fully reversible. Indeed, the anionic NBu4[Ir(ppy)2(O^O)cat] complexes are quantitatively restored by chemical reduction of the neutral [Ir(ppy)2(O^O)squi] parents. These complexes therefore represent interesting redox based switches between multi-parameter states since they allow switching from a neutral paramagnetic to an anionic diamagnetic form together with a significant change in chromicity. Taking advantage of the significant color difference between the oxidized and the reduced form, an electrochromic cell was prepared with [Ir(ppy)2(TBC)squi] and its spectroelectrochemical properties are reported.

Anionic versus neutral Pt(II) complexes: The relevance of the charge for human serum albumin binding.

The focus of this work is pointing out the different behavior of two structurally related Pt(II) complexes, the anionic cyclometalated NBu4[(Bzq)Pt(Thio)], 1 and the neutral [(Phen)Pt(Thio)], 2, (Bzq = benzo[h]quinoline, Phen = 1,10-phenantroline, Thio = 1,2-benzenedithiolate), on the interaction with human serum albumin (HSA), a key drug-delivery protein in the bloodstream. Being very limited the number of anionic Pt(II) complexes reported to date, this is a pioneering example of report on a protein-ligand interaction involving a negatively charged platinum compound. The study was carried out by using fluorescence spectroscopy, differential scanning calorimetry and molecular docking simulations. The results revealed a strong binding affinity between the anionic compound and the protein, whereas a weak/moderate binding interaction was highlighted for the neutral one. Comparative studies with site specific ligands (warfarin and ibuprofen), allowed us to identify the protein binding sites of the two compounds. The work aims to shed light on the relevance of the charge in designing new drugs with a favorable binding affinity for HSA, which strongly contributes to influence their pharmacological and toxicological profile.

Adsorption of Nile Red Self-Assembled Monolayers on Au(111).

The ability of Nile Red to self-assemble into supramolecular packings on Au(111) was studied using scanning tunneling microscopy and modeled through theoretical semiempirical calculations. At both submonolayer (sub-ML) and ML coverages, two distinct molecular packings, that is, four-leaf clover and dense chain, were observed, both weakly interacting with the underlying metal surface. Theoretical calculations suggested that the dipole moment plays a subtle role in both molecular assemblies, held together by hydrogen bonds between the Nile Red molecules. Furthermore, although both molecular assemblies were observed in as-deposited samples, a mild thermal annealing caused the transition from the four-leaf clover to the dense-chain packing, pointing out the greater stability of the dense-chain configuration. The study further emphasized how the established interactions between the Nile Red molecules are strongly influenced by the surrounding environment.

Histone hyperacetylation and DNA methylation interplay during murine spermatogenesis.

Male germ cell development is a critical period during which epigenetic patterns are established and maintained. The progression from diploid spermatogonia to haploid spermatozoa involves the incorporation of testis-specific histone variants, mitotic and meiotic divisions, haploid gene expression, histone-protamine transitions and massive epigenetic reprogramming. Understanding the protein players and the epigenetic mark network involved in the setting of the epigenetic programme in spermatogenesis is an exciting new clue in the field of reproductive biology with translational outcomes. As information in the existing literature regarding cross-talk between DNA methylation and histone hyperacetylation in the advanced stages of murine spermatogenesis is still scarce and controversial we have investigated the effect of a DNA-methyltransferase inhibitor, 5-aza-2'-deoxycytidine, at the cytological and molecular level (by transmission electron microscopy, immunocytochemistry and immunoprecipitation methods). Our results revealed an important role for regulation of DNA methylation in controlling histone hyperacetylation and chromatin remodelling during spermatogenesis.

Electropolymerizable IrIII Complexes with ß-Ketoiminate Ancillary Ligands.

A series of electropolymerizable cyclometallated IrIII complexes were synthesized and their electrochemical and photophysical properties studied. The triphenylamine electropolymerizable fragment was introduced by using triphenylamine-2-phenylpyridine and, respectively, triphenylamine-benzothiazole as cyclometalated ligands. The coordination sphere was completed by two differently substituted ß-ketoiminate ligands deriving from the condensation of acetylacetone or hexafluoroacetylacetone with para-bromoaniline. The influence of the -CH3 /-CF3 substitution to the electrochemical and photophysical properties was investigated. Both complexes with CH3 substituted ß-ketoiminate were emissive in solution and in solid state. Highly stable films were electrodeposited onto ITO coated glass substrates. Their emission was quenched by electron trapping within the polymeric network as proven by electrochemical studies. The -CF3 substitution of the ß-ketoiminate leads instead to the quenching of the emission and inhibits electropolymerization.

Anionic cyclometalated Pt(ii) and Pt(iv) complexes respectively bearing one or two 1,2-benzenedithiolate ligands.

Novel anionic cyclometalated Pt(ii) square-planar complexes NBu4[(C^N)PtII(S^S)], containing 2-phenylpyridine H(PhPy), 2-(2,4-difluorophenyl)-pyridine H(F2PhPy) and benzo[h]quinoline H(Bzq), respectively, as a cyclometalated ligand and the dianionic 1,2-benzenedithiolate (Thio)2- fragment as an (S^S) ligand, were synthesised. By the simple addition of an equivalent of (Thio)2- to the NBu4[(C^N)PtII(Thio)] complexes, octahedral anionic NBu4[(C^N)PtIV(Thio)2] analogues were obtained, representing, to the best of our knowledge, the first examples of Pt(iv) anionic cyclometalated complexes. The molecular structures of the obtained complexes in the case of the NBu4[(Bzq)PtII(Thio)] and the NBu4[(Bzq)PtIV(Thio)2] complexes were confirmed by single crystal X-ray diffraction analysis. Furthermore, the electrochemical and photophysical properties of the two series of Pt(ii) and Pt(iv) newly synthesised complexes were studied and DFT and TD-DFT calculations were performed in order to comprehensively investigate the displayed behaviour. All Pt(ii) and Pt(iv) complexes show intense luminescence in the solid state, with remarkable enhancement of the emission quantum yields, proving to be excellent examples of aggregation-induced emission systems.

Anionic cyclometallated Pt(ii) square-planar complexes: new sets of highly luminescent compounds.

Two series of novel NBu4+ salts of anionic cyclometallated Pt(ii) complexes were synthesized and fully characterized. These highly luminescent compounds (NBu4[(C^N)Pt(O^N)] and NBu4[(C^N)Pt(O^O)]) are incorporated as testing examples of cyclometallating ligands 2-phenylpyridine (PhPy), 2-(2,4-difluorophenyl)-pyridine (F2PhPy) and 2-thienylpyridine (ThPy), and a benzo[h]quinoline (Bzq) fragment. All complexes display a square-planar coordination sphere, wherein the "(C^N)Pt" fragment is completed either by an O^N orotate (Ort) or an O^O tetrabromocatecholate (Cat) ligand. The HOMO and LUMO levels of all complexes were estimated by cyclic voltammetry and a comprehensive electrochemical and photophysical study was performed. The new complexes are emissive in solution at 298 K and the NBu4[(ThPy)Pt(Ort)] complex displays good photosensitizing properties (Φ = 28% in deaerated solution vs. Φ = 1.4% in the presence of O2). Both series of NBu4[(C^N)Pt(Ort)] and NBu4[(C^N)Pt(Cat)] complexes are highly luminescent in the solid state (emission quantum yields from 10 to 85%). Remarkably, the square-planar Pt(ii) anionic complexes showed an important increase in luminescence quantum yields on changing from the dilute solution to the solid state (the most significant from 0.13% to 85% for the NBu4[(PhPy)Pt(Ort)] complex, an ideal candidate as an active species for LEECs).

High Order in a Self-Assembled Iridium(III) Complex Gelator Towards Nanostructured IrO2 Thin Films.

The preparation and characterization of a new metallogelator based on the IrIII discrete cyclometalated complex [(ppy)2 Ir(bpy)](CH3 CH2 OCH2 CO2 ) are reported, where H(ppy) is 2-phenylpiridine and bpy is 2,2'-bipyridine, which is used as an ancillary ligand. The compound is able to self-assemble in water in a range of concentrations between 3 % and 6 % w/w, creating a luminescent ordered supramolecular gel. The gel and xerogel architectures were investigated through polarized optical microscopy (POM), SEM and TEM microscopies coupled with powder X-ray diffraction. The gel supramolecular organization is characterized by columnar tetragonal strands, already present at high dilution conditions, of cations surrounded by counteranions. These strands, in turn, are self-assembled in an oblique columnar cell upon gelification. The xerogel thin films obtained upon complete dehydration maintained the gel supramolecular order and can be used as a precursor for the preparation of nanostructured IrO2 thin films.

A novel route towards water-soluble luminescent iridium(iii) complexes via a hydroxy-bridged dinuclear precursor.

The synthesis and photophysical characterization of a new family of luminescent water-soluble ionic iridium(iii) complexes of the general formula [(ppy)2Ir(bpy)]X are reported. The Ir(iii) complexes incorporate a cyclometalated 2-phenylpyridine (ppy), the ancillary ligand 2,2'-bipyridyl (bpy) and different counterions (X- = EtO-, OH-, EtOCH2CO2-, MeOCH2CO2-). These complexes were obtained starting from the cyclometalated Ir(iii) chloro-bridged dimer [(ppy)2Ir(µ-Cl)]2, for the first time synthesized through a new microwave assisted synthetic procedure, and subsequently converted into the corresponding hydroxy-bridged dimer [(ppy)2Ir(µ-OH)]2. The latter was eventually used as a sole reagent for the synthesis of all the reported complexes by simply varying the nature of the reaction solvent from water to alcohols and glycol ethers. This study demonstrates the versatility of the [(ppy)2Ir(µ-OH)]2 complex as a precursor to water soluble ionic Ir(iii) complexes. Indeed, [(ppy)2Ir(µ-OH)]2 has shown its peculiar chemical reactivity due to both a strong base character and an unexpected oxidative ability towards the alcoholic function of glycol ethers. All the synthesized complexes exhibit, in water solution, an orange emission centred at 606 nm. Moreover, all complexes display the ability to give rise to gel phases in water upon increasing their concentration, and the photophysical study evidenced the various interactions governing the gelification process. The water-solubility of these new luminescent Ir(iii) complexes makes them potentially useful in bio-related systems.

Near-IR Electrochromism in Electrodeposited Thin Films of Cyclometalated Complexes.

Homogeneous thin films of controlled thickness obtained from cyclometalated complexes of general formula [(C(∧)N)M(O(∧)N)], where M = Pd(II) or Pt(II), H(C(∧)N) = 2-phenylpyridine and, respectively, 2-thienylpyridine and H(O(∧)N) = a triphenylamine functionalized Schiff base, have been deposited by oxidative electropolymerization. The films have been electrochemically and morphologically characterized. The metallopolymeric thin films present stable reversible redox behavior and typical cauliflower-like textures in agreement with a nucleation-growth electropolymerization mechanism. However, the film growth is greatly influenced by the nature of the metal center, with a higher tendency of the Pt complexes to promote the 3D growth. Furthermore, a complete spectroelectrochemical study has been performed on electrodeposited films showing near-IR absorption in the oxidized state, high contrast ratios (up to 65%) and low response times.

Electropolymerized highly photoconductive thin films of cyclopalladated and cycloplatinated complexes.

The complete characterization of novel electropolymerizable organometallic complexes is presented. These are newly synthesized cyclometalated complexes of general formula (PPy)M(O ∧ N)(n) (H(PPy) = 2-phenylpyridine, M = Pd(II) or Pt(II), H(O ∧ N)(n) = Schiff base). Polymeric thin films have been obtained from these complexes by electropolymerization of the triphenylamino group grafted onto the H(O ∧ N)(n) ancillary ligand. The redox behavior and the photoconductivity of both of the monomers (PPy)M(O ∧ N)(n) and the electropolymerized species have been investigated. The polymeric films of (PPy)M(O ∧ N)(n) have shown a very significant enhancement of photoconductivity when compared to their monomeric amorphous counterparts. The high stability of the obtained films strongly suggests that electropolymerization of cyclometalated complexes represents a viable deposition technique of quality thin films with improved photoconduction properties, hence opening the door to a new class of materials with suitable properties for optoelectronic applications.

Cerebrovascular complications in patients with inflammatory bowel disease.

UNLABELLED: Cerebrovascular complications in 9 patients with inflammatory bowel disease (IBD) are presented, 6 with Crohn's disease (CD) and 3 with ulcerative colitis (UC), 7 men and 2 women, mean age 36.5 +/- 3.5 years, 4 of them during acute disease. Cerebrovascular complications were: cerebral venous thrombosis (CVT)--7 cases (5 CD and 2 UC) and ischemic stroke--2 cases (1 CD and 1 UC). Out of 7 cases with CVT 5 were superior sagittal sinus thrombosis (SSS), 2 SSS and transverse and sigmoid sinus thrombosis. Both ischemic strokes were infarctions in the middle cerebral artery area. No correlation between high doses of corticosteroids or their lowering, IBD activity, duration of the disease, and the appearance of cerebrovascular complications was observed. Tendency to hypercoagulation even in the inactive stage of the IBD was revealed. Investigations for thrombophilia were negative. Significantly high levels of homocysteine were observed in all patients. CONCLUSION: Neurovascular complications may be observed in IBD, both of venous and arterial type. Pathogenic mechanisms of these vascular complications are complex, low serum folate levels, of vitamin B6 and B12 being associated with elevation of homocysteine levels, high activation of platelets and microvascular endothelial dysfunction. A guide for the orientation of prophylaxis of cerebrovascular complications in IBD patients is necessary.

Orotate containing anionic luminescent iridium(III) complexes and their use in soft salts.

Two anionic iridium complexes [(R-ppy)2Ir(O^N)]TBA with R-ppy = 2-phenylpyridine or 4,5'-dimethyl-2-phenylpyridine, O^N = dianionic form of orotic acid and TBA = tetrabutylammonium have been synthesised and fully characterised by UV-Vis, emission, IR, NMR and cyclic voltammetric studies. These cyclometallated luminescent complexes containing a dianionic bidentate ancillary ligand show bright emission (60-70% PLQY) with maxima in the green region of the visible spectrum. Coupled with the ionic iridium complexes [(ppy)2Ir(N^N)]X, where N^N = 2-picolylamine or 2,2'-bipyridyl, and X = Cl(-) or CH3CO2(-), a series of new soft salts of general formula [(ppy)2Ir(N^N)][(R-ppy)2Ir (O^N)] have been obtained and fully characterized, with enhanced luminescent properties up to ca. 80% of phosphorescence quantum yields.