Molecular profile in Paraguayan colorectal cancer patients, towards to a precision medicine strategy.

Somatic mutation analysis and evaluation of microsatellite instability (MSI) have become mandatory for selecting personalized therapy strategies for advanced colorectal cancer and are not available as routine methods in Paraguay. The aims of this study were to analyze the molecular profile as well as the microsatellite status in a series of advanced colorectal patients from two public hospitals from Paraguay, to introduce these methodologies in the routine practice to guide the therapeutic decisions. Thirty-six patients diagnosed with advanced colorectal cancer from two referent public hospitals from Paraguay were recruited from May 2017 to February 2018. Sequenom Mass spectrometry, Oncocarta Panel V.1 was applied to analyze the mutational profile from formalin-fixed paraffin-embedded samples. The microsatellite status was tested by immunohistochemistry (IHC). The mean age of the patients was 52 years with a range from 20 to 74 years. Eighty-three percent of the patients included in the study have advanced-stage tumors at the moment of the diagnosis. Sixteen patients (44.4%) were wild-type for all the oncogene regions analyzed with the Oncocarta panel. Thirty-two hot-spot pathogenic variants on seven oncogenes, among 20 patients (55.6%), were identified, including KRAS, NRAS, BRAF, PI3KCA, FGFR, epidermal growth factor receptor, and PDGFRA. Moreover, 14 (38.8%) of these patients presented pathogenic variants in KRAS/NRAS or BRAF genes that have implications in the clinical practice decisions. Five patients (14%) presented MSI. The IHC study for microsatellite status and the molecular profile analysis through Sequenom mass spectrometry are feasible and useful methods, due to identify those patient candidates for targeted therapies and for the budgetary calculations of the National Health Plans.

Ciudades saludables / ciudades enfermas / Healthy cities / sick cities

Las ciudades son el producto material más grandioso, complejo, e importante del hombre. Su proliferación y dominio como forma de asentamiento humano ha sido indetenible. Hoy día la ciudad es la principal fuerza productiva, indispensable para contar con sociedades más avanzadas. La forma contemporánea de las ciudades presenta características y problemas complejos no resueltos. En las ciudades de Asia, África y América Latina, el desempleo y el subempleo campean, las normas de habitabilidad no valen y existen zonas desprovistas de servicios urbanos, incluidos el suministro de agua potable y el saneamiento básico. Es necesario repensar la ciudad, tal como la conocemos hoy, fortaleciendo las ciudades existentes con especial énfasis en el desarrollo de las infraestructuras, el desarrollo de las áreas públicas, así como el transporte colectivo eficiente para todo el conjunto urbano. Debe lograrse la mayor calidad del medio ambiente que facilite la vida urbana al conjunto de pobladores, incluyendo desarrollar programas especiales para homologar en estas condiciones de vida a los habitantes de los desarrollos no controlados o barrios(AU)

Cities are the greatest, most complex and important achievements produced by humankind. Their growth and power as human settlements are unstoppable. Today the city is considered to be the principal productive settlement necessary for advanced societies. Contemporary cities present features as well as acute problems yet unsolved. In cities of Asia, Africa and Latin America unemployment and under-employment prevail while living standards are deprived of their value; at the same time, these cities face the problem of being constituted by large settlements which are characterized by the lack of adequate (in some cases, almost to the point of non-existence)urban services, including water supply and basic drainage. Therefore is necessary to rethink cities, as we know them today, in order to reinforce them with special emphasis on infrastructure development, the construction of public spaces as well as public transportation for the city as a whole. The best way of building a healthy environment is through the task of providing the benefits of urban life to all inhabitants. This policy must include the implementation of special upgrading programs in order to cope with the growing problem of uncontrolled settlements or squatters(AU)

Crystal structure, solid state and solution characterisation of copper(II) coordination compounds of ethyl 5-methyl-4-imidazolecarboxylate (emizco).

The synthesis and characterisation of the following compounds derived from the biological relevant compound ethyl 5-methyl-4-imidazolecarboxylate (emizco) (1): [Cu(emizco)Cl2] (2), [Cu(emizco)2Cl2] (3), [Cu(emizco)2Br2] (4), [Cu(emizco)2(H2O)2](NO3)2 (5) and [Cu(emizco)4](NO3)2 (6), is presented. These compounds were characterised by IR and UV spectroscopic techniques, in addition the crystal structures of compounds 1-5 were determined. For complexes 2-5, emizco is coordinated as a bidentate ligand, through the oxygen atom of the carboxylate moiety and the nitrogen atom of the imidazolic ring. Different geometries are stabilised: compound 2 includes a pentacoordinated square pyramidal metal centre, while 3-5 are derived from octahedral geometry. Halide compounds 3 and 4 show a cis-octahedral arrangement, which is not very common on [CuN2O2X2] systems, while 5 stabilises the trans-octahedral isomer. Compound 6 displays a square planar geometry. Finally, hydrolysis of emizco to its corresponding carboxylic acid (mizco), allowed the preparation of another square planar complex 7, identified as [Cu(mizco)2] 0.5H2O. Solution studies of these compounds indicate that emizco is not substituted from the coordination sphere, remaining as a bidentate ligand. Halides are substituted by water molecules, changing from cis octahedral to the trans-[Cu(emizco)2(H2O)2]2+ isomer.

Cobalt(II) coordination compounds of ethyl 4-methyl-5-imidazolecarboxylate: chemical and biochemical characterization on photosynthesis and seed germination.

In this work we present the synthesis, structural and spectroscopic characterization of Co(2+) coordination compounds with ethyl 4-methyl-5-imidazolecarboxylate (emizco). The effects of emizco, the metal salts CoCl(2).6H(2)O, CoBr(2), Co(NO(3))(2).6H(2)O and their metal coordination compounds [Co(emizco)(2)Cl(2)], [Co(emizco)(2) Br(2)].H(2)O, [Co(emizco)(2) (H(2)O)(2)(NO(2))(2).2H(2)O were evaluated on photosynthesis in spinach chloroplasts. Seed germination and seedling growth of the monocotyledonous species Lolium multiflorum and Triticum aestivum and the dicotyledonous species Trifolium alexandrinum and Physalis ixocarpa were also assayed under the effect of the compounds and salts. The results showed that cobalt(II) salts and their emizco coordination compounds inhibit photosynthetic electron flow and ATP-synthesis, behaving as Hill reaction inhibitors. Coordination compounds are more potent inhibitors than the salts. It was found that the salts target is at the b(6)f level while the complexes targets are at Q(B)(D1)-protein and b(6)f level. The Q(B) inhibition site was confirmed by variable chlorophyll a fluorescence yield. On the other hand, emizco inhibits seed germination, root and shoot development, in both weed and crop species. Cobalt(II) coordination compounds are the most effective photosynthesis inhibitors, but they are less potent than emizco in germination and seedling growth, while the metal salts are the least active of all.