Neurostatus e-Scoring improves consistency of Expanded Disability Status Scale assessments: A proof of concept study.

BACKGROUND: To improve the consistency of standardized Expanded Disability Status Scale (EDSS) assessments, an electronic data capture tool and analysis tool was developed, Neurostatus e-Scoring (NESC). This tool allows real-time feedback by comparing entries with established scoring rules. OBJECTIVE: To test whether using NESC reduces inconsistencies as compared to the paper-and-pencil version of the Expanded Disability Status Scale (pEDSS). METHODS: In all, 100 multiple sclerosis (MS) patients were assessed in random order on the same day by pairs of neurologists, one using pEDSS and one NESC. We compared inter-rater reliability and frequency of inconsistencies in Neurostatus subscores, functional system (FS) scores, ambulation and EDSS steps. RESULTS: Inconsistencies of any type were more likely to occur when using pEDSS (mean odds ratio (95% confidence interval (CI)) = 2.93 (1.62; 5.29)). This was also the case for FS score inconsistencies (2.54 (1.40; 4.61)) and more likely for patients in the lower EDSS range (⩽3.5 vs >3.5) (5.32 (1.19; 23.77)). Overall, inter-rater agreement for the assessed Neurostatus subscores was high (median and inter-quartile range = 0.84 (0.73, 0.81)). CONCLUSION: Our data provide class II evidence that the use of NESC increases consistency of standardized EDSS assessments, and may thus have the potential to decrease noise and increase power of MS clinical trials.

Synthesis, structure, spectroscopic properties, and antiproliferative activity in vitro of novel osmium(III) complexes with azole heterocycles.

Reactions of (H 2azole) 2[OsCl 6], where Hazole = pyrazole, Hpz, ( 1), indazole, Hind, ( 2), imidazole, Him, ( 3) and benzimidazole, Hbzim, ( 4) with the corresponding azole heterocycle in 1:4 molar ratio in boiling isoamyl alcohol or hexanol-1 afforded novel water-soluble osmium(III) complexes of the type trans-[OsCl 2(Hazole) 4]Cl, where Hazole = Hpz ( 5a), Hind ( 6a), Him ( 7a), and Hbzim ( 9a) in 50-70% ( 5a, 7a, 9a) and 5% ( 6a) yields. The synthesis of 7a was accompanied by a concurrent reaction which led to minor formation (<4%) of cis-[OsCl 2(Him) 4]Cl ( 8). The complexes were characterized by elemental analysis, IR spectroscopy, UV-vis spectroscopy, ESI mass spectrometry, cyclic voltammetry, and X-ray crystallography. 5a, 7a, and 9a were found to possess remarkable antiproliferative activity in vitro against A549 (non-small cell lung carcinoma), CH1 (ovarian carcinoma), and SW480 (colon carcinoma) cells, which was compared with that of related ruthenium compounds trans-[RuCl 2(Hazole) 4]Cl, where Hazole = Hpz (5b), Hind (6b), Him (7b), and Hbzim (9b).

Metal-based paullones as putative CDK inhibitors for antitumor chemotherapy.

Paullones constitute a class of potent cyclin-dependent kinase inhibitors. To overcome the insufficient solubility and bioavailability, which hamper their potential medical application, we aim at the development of metal-based derivatives. Two types of paullone ligands, L (1) - L (3) and L (4) , with different locations of metal-binding sites, were prepared. They were found to form organometallic complexes of the general formula [M (II)Cl(eta (6)- p-cymene)L]Cl ( 1- 4, L = L (1) - L (4) ; a, M = Ru; b, M = Os). The complexes were characterized by X-ray crystallography, one- and two-dimensional NMR spectroscopy and other physical methods. Complexes 1- 3, with a coordinated amidine unit, were found to undergo E/ Z isomerization in solution. The reaction was studied by NMR spectroscopy, and activation parameters Delta H (double dagger) and Delta S (double dagger) were determined. Antiproliferative activity in the low micromolar range was observed in vitro in three human cancer cell lines by means of MTT assays. (3)H-Thymidine incorporation assays revealed the compounds to lower the rate of DNA synthesis, and flow cytometric analyses showed cell cycle arrest mainly in G 0/ G 1 phase.

Landscape of Research on Older Adults' Health in the Arab Region: Is It Demography-Driven or Development-Dependent?

OBJECTIVES: To describe the quantity, methods, themes, and collaboration profiles of research on older adults' health in the Arab world, and map research productivity against demographic, economic, and development indicators. METHODS: A scoping review of research on older adults' health drawing from 7 databases and covering the period 1994-2013. RESULTS: Aging research output has increased 6-fold over the study period, with middle-income countries showing the sharpest rise. The majority of the reviewed publications are descriptive in nature, oriented toward examining the extent of disease or factors associated with various morbidity and mortality outcomes (88.5%). Despite the increasing regional instability, there is a dearth of studies on "seniors in emergencies." Collaboration with international coauthors (16.0%) has been more frequent than with regional coauthors (4.2%). Correlation analysis suggests that research production has been more strongly influenced by literacy rates than by population aging indicators, Gross Domestic Product, or government investment in research and development. DISCUSSION: This study lays the basis for a "roadmap" for research on older adults' health in the Arab region. It calls for cooperation among various stakeholders to produce a targeted and well-informed research agenda that is more responsive to emerging and context-specific needs of older adults in the region.

Thoracic metastasectomy for thyroid malignancies.

OBJECTIVE: To better define early and long-term outcomes of patients undergoing thoracic metastasectomy for thyroid cancer. METHODS: We identified, reviewed, and analyzed the medical records of all patients who underwent thoracic metastasectomy for thyroid cancer in our institution from 1971 to 2006. RESULTS: There were 48 patients (25 men, 23 women). A complete resection (R0) of all known disease was performed in 33 (69%) patients, while 15 (31%) underwent incomplete resection (R1 or R2). By histology, the majority were papillary 31 (65%), follicular 8 (17%), medullary 5 (10%), and Hürthle cell 4 (8%). Ninety percent were confined to a single side of the chest, with 10% presenting with bilateral metastases. Thoracotomy was performed in 28 (58%), sternotomy in 12 (25%), and thoracoscopy was used in 8 (17%). Operative mortality was zero and postoperative complications occurred in 8 patients (17%). There are currently 18 surviving patients from the cohort (37%) with a median follow-up of 10 years (range, 1 month to 17 years). The overall 5-year survival after thoracic metastasectomy was 60%. Based on histology, 5-year survival for papillary cancer was 64% compared to 37% for follicular and Hürthle cell neoplasms (p=0.03). All five medullary thyroid cancer patients were alive at 5 years. Five-year survival was also improved for patients less than 45 years old at the time of diagnosis of their initial thyroid malignancy (94% vs 49%; p=0.03). Disease-free interval of >3 years between initial thyroid malignancy diagnosis and thoracic metastasectomy demonstrated improved 5-year survival (67% vs 52%; p=0.01). CONCLUSION: Pulmonary resection for thyroid metastasis is safe with low morbidity and mortality. Retrospective analysis demonstrates improved long-term survival in patients with papillary histology, longer disease-free interval (>3 years) and younger age at diagnosis of initial thyroid malignancy. Excellent long-term survival was also achievable in selected patients with medullary thyroid metastasis.

In vitro anticancer activity and biologically relevant metabolization of organometallic ruthenium complexes with carbohydrate-based ligands.

The synthesis and in vitro anticancer activity of dihalogenido(eta6-p-cymene)(3,5,6-bicyclophosphite-alpha-D-glucofuranoside)ruthenium(II) complexes are described. The compounds were characterized by NMR spectroscopy and ESI mass spectrometry, and the molecular structures of dichlorido-, dibromido- and diiodido(eta6-p-cymene)(3,5,6-bicyclophosphite-1,2-O-isopropylidene-alpha-D-glucofuranoside)ruthenium(II) were determined by X-ray diffraction analysis. The complexes were shown to undergo aquation of the first halido ligand in aqueous solution, followed by hydrolysis of a P--O bond of the phosphite ligand, and finally formation of dinuclear species. The hydrolysis mechanism was confirmed by DFT calculations. The aquation of the complexes was markedly suppressed in 100 mM NaCl solution, and notably only very slow hydrolysis of the P--O bond was observed. The complexes showed affinity towards albumin and transferrin and monoadduct formation with 9-ethylguanine. In vitro studies revealed that the 3,5,6-bicyclophosphite-1,2-O-cyclohexylidene-alpha-D-glucofuranoside complex is the most cytotoxic compound in human cancer cell lines (IC50 values from 30 to 300 microM depending on the cell line).

The first ruthenium-based paullones: syntheses, X-ray diffraction structures, and spectroscopic and antiproliferative properties in vitro.

Two novel paullone derivatives, namely, 6-(alpha-picolylamino)-7,12-dihydroindolo[3,2-d][1]benzazepine (L1) and 9-bromo-6-(alpha-picolylamino)-7,12-dihydroindolo[3,2-d][1]benzazepine (L2), have been prepared. The reaction of cis-[RuCl2(DMSO)4] (DMSO=dimethyl sulfoxide) with L1 and L2 in a 1:1 molar ratio in dry ethanol at 50 degrees C afforded the complexes trans-[RuIICl2(DMSO)2L1] (1a) and trans-[RuIICl2(DMSO)2L2] (1b) in 26 and 30% yield, respectively. The reaction carried out from the same starting compounds in a 1:2 molar ratio at 75 degrees C led to the formation of [RuIICl(DMSO)(L1)2]Cl (2a) and [RuIICl(DMSO)(L2)2]Cl (2b) in 16 and 23% yield, correspondingly. The products were characterized by elemental analysis, one- and two-dimensional NMR spectroscopy, electrospray ionization mass spectrometry, IR spectroscopy, electronic spectra, cyclic voltammetry, and X-ray crystallography (L1, L2, 1a, and 2b). Complexes 2a and 2b exhibit remarkable antiproliferative activity in three human carcinoma cell lines, A549 (non-small cell lung carcinoma), CH1 (ovarian carcinoma), and SW480 (colon carcinoma). The novel complexes show an intercalative mode of interaction with DNA, which may render them attractive alternatives to metal compounds with a coordinative mode of interaction.