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Abstract Background The demographic structure has a significant influence on the use of healthcare services, as does the size of the population denominators. Very few studies have been published on methods for estimating the real population such as tourist resorts. The lack of information about these problems means there is a corresponding lack of information about the behaviour of populational denominators (the floating population or tourist load) and the effect of this on the use of healthcare services. The objectives of the study were: a) To determine the Municipal Solid Waste (MSW) ratio, per person per day, among populations of known size; b) to estimate, by means of this ratio, the real population in an area where tourist numbers are very significant; and c) to determine the impact on the utilisation of hospital emergency healthcare services of the registered population, in comparison to the non-resident population, in two areas where tourist numbers are very significant. Methods An ecological study design was employed. We analysed the Healthcare Districts of the Costa del Sol and the island of Menorca. Both are Spanish territories in the Mediterranean region. Results In the two areas analysed, the correlation coefficient between the MSW ratio and admissions to hospital emergency departments exceeded 0.9, with p < 0.001. On the basis of MSW generation ratios, obtained for a control zone and also measured in neighbouring countries, we estimated the real population. For the summer months, when tourist activity is greatest and demand for emergency healthcare at hospitals is highest, this value was found to be double that of the registered population. Conclusion The MSW indicator, which is both ecological and indirect, can be used to estimate the real population in areas where population levels vary significantly during the year. This parameter is of interest in planning and dimensioning the provision of healthcare services.

α-Arylated alanine derivatives were made enantioselectively by migratory rearrangement of a urea derivative using (R,R)-pseudoephedrine as a chiral auxiliary. Incorporation of a single residue of the product α-methyl phenylglycine into an otherwise achiral oligomer of aminoisobutyric acid oligomer induced a preferred screw sense, detectable by a NMR reporter located at the remote terminus of the oligomer. The magnitude of the screw sense induction was greater when the chiral residue was located at the N-terminus of the foldamer, and in some cases the sense of induction was opposite to that of related α-methylated amino acids with α-substituents other than aryl.

Lithiation reactions of tertiary benzylic esters and carbamates have been studied. Kinetic methodology revealed that a two-step reaction pathway should be considered for these reactions, where either the lithium precomplexation and/or the proton transfer steps can be rate determining. Kinetic isotopic effects were evaluated by comparison of the lithiations of the corresponding protio/deutero substrates, and the results obtained support the notion that lithium precomplexation is taking place on the reaction pathway and that it is the rate-determining step in this transformation.

Palladium(II) trifluoroacetate (5 mol %) catalyzes the C-arylation of N,N-disubstituted hydantoins by aryl iodides in good yield. The reaction proceeds through base-promoted enolization of the amino acid derived hydantoins, and the resulting 5,5-disubstituted hydantoins may be deprotected at one or both N atoms to yield biologically active structures or alternatively hydrolyzed to the parent α-aryl α-amino acids. The reaction is successful with a variety of parent amino acids and a range of electron-rich and electron-poor aryl iodides.

Available α-amino acids undergo arylation at their α position in an enantioselective manner on treatment with base of N'-aryl urea derivatives ligated to pseudoephedrine as a chiral auxiliary. In situ silylation and enolization induces diastereoselective migration of the N'-aryl group to the α position of the amino acid, followed by ring closure to a hydantoin with concomitant explulsion of the recyclable auxiliary. The hydrolysis of the hydantoin products provides derivatives of quaternary amino acids. The arylation avoids the use of heavy-metal additives, and is successful with a range of amino acids and with aryl rings of varying electronic character., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A two-step, stereoselective procedure for the synthesis of nine- and ten-membered carbocycles from readily available phthalates is described. A variety of dialkyl phthalates have been transformed into [6,n]-fused bicyclo systems (n = 5, 6, 7) by a dearomatization/cyclization process and then converted into cyclonona- and cyclodecadienes through a bond cleavage reaction, whereby both processes are promoted by alkaline metals in THF.

Alzheimer's disease is a neurodegenerative pathology with unmet clinical needs. A highly desirable approach to this syndrome would be to find a single lead that could bind to some or all of the selected biomolecules that participate in the amyloid cascade, the most accepted route for Alzheimer disease genesis. In order to circumvent the challenge posed by the sizable differences in the binding sites of the molecular targets, we propose a computer-assisted protocol based on a pharmacophore and a set of required interactions with the targets that allows for the automated screening of candidates. We used a combination of docking and molecular dynamics protocols in order to discard nonbinders, optimize the best candidates, and provide a rationale for their potential as inhibitors. To provide a proof of concept, we proceeded to screen the literature and databases, a task that allowed us to identify a set of carbazole-containing compounds that initially showed affinity only for the cholinergic targets in our experimental assays. Two cycles of design based on our protocol led to a new set of analogues that were synthesized and assayed. The assay results revealed that the designed inhibitors had improved affinities for BACE-1 by more than 3 orders of magnitude and also displayed amyloid aggregation inhibition and affinity for AChE and BuChE, a result that led us to a group of multitarget amyloid cascade inhibitors that also could have a positive effect at the cholinergic level.

The complexation of an anionic guest by a cationic water-soluble pillararene is reported. Isothermal titration calorimetry (ITC), (1)H NMR, (1)H and (19)F DOSY, and STD NMR experiments were performed to characterize the complex formed under aqueous neutral conditions. The results of ITC and (1)H NMR analyses showed the inclusion of the guest inside the cavity of the pillar[5]arene, with the binding constant and thermodynamic parameters influenced by the counter ion of the macrocycle. NMR diffusion experiments showed that although a fraction of the counter ions are expelled from the host cavity by exchange with the guest, a complex with both counter ions and the guest inside the pillararene is formed. The results also showed that at higher concentrations of guest in solution, in addition to the inclusion of one guest molecule in the cavity, the pillararene can also form an external complex with a second guest molecule., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A series of dibenzo [n.2.2] bicyclic compounds (n = 2-20) were prepared in one step and good yields starting from dimethyl anthracene-9,10-dicarboxylate. Reduction of the aromatic diester using lithium/naphthalene led to a bis-enolate that was cyclized with a variety of bis-electrophiles. The ease of the cyclization is probably due to the puckered conformation of the intermediate formed after the first alkylation step, in which the newly introduced chain that will become the bridge portion occupies a pseudoaxial position, positioning the leaving group close to the enolate nucleophile in the macrocyclization step.

Kinetic study of the α-lithiation of benzyl methyl ether (BME) by nBuLi has revealed that increasing the concentration of the organolithium compound does not necessarily increase the reactivity, and this is a consequence of the reactivities of the different nBuLi aggregates present in solution. We propose a dimer-based mechanism, in which a pre-complexation step is a key process for substrates bearing a donor oxygen atom that can interact with the lithium cation to form mixed dimers. For these studies, we have developed a system based on UV/Vis spectroscopy that allows kinetic measurements to be conducted at -80 °C under argon., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)