Unveiling the tartrazine binding mode with ds-DNA by UV-visible spectroscopy, electrochemical, and QM/MM methods.

Here, we studied the interaction between the food colorant tartrazine (TZ) and double stranded DNA (dsDNA), using spectroscopic, electrochemical, and computational methods such as QM/MM combined with TD-DFT. Despite the UV-vis spectroscopy is widely used to study the interaction between molecules, for the case of TZ there are discrepancies in the analyses presented in the literature available, presenting both hyperchromic and hypochromic effects and consequently different rationalizations for their results. Herein we propose the combination of UV-vis experiments with the design of high-level computational models capable of reproducing the experimental behavior to finally define the proper binding mode at the molecular scale together with the rationalization of the experimental optical response due to the complex formation. To complement the UV-vis experiments, we propose the use of electrochemical measurements, to support the results obtained through UV-vis spectroscopy, as it has been successfully used for the determination of interaction modes between small molecules and biomolecules in any condition. Our UV-vis spectroscopy experiments showed only a hypochromic effect of the absorption spectra of TZ after interaction with DNA, indicative of TZ being deeply buried in the DNA structure. The effect of ionic strength in the experimental procedures led to the dissociation of TZ, thus indicating that the interaction mode was groove binding. On the other hand, the electrochemical studies showed an irreversible reduction peak of TZ, which after the interaction with DNA exhibited a positive shift in potential that can be attributed to groove binding. The binding constant for TZ-DNA was calculated as 4.45x104M-1 (UV-vis) and 5.75x104M-1 (electrochemistry), in line with other groove binder azo dyes. Finally, through the QM/MM calculations we found that the minor-groove binding mode interacting in zones rich in adenine and thymine was the model best suited to reproduce the experimental UV-vis response.

Detection of incident breast and colorectal cancer cases from an administrative healthcare database in Catalonia, Spain.

OBJECTIVE: To validate the Catalan minimum basic data set (MBDS) of hospital discharges as an information source for detecting incident breast (BC) and colorectal cancer (CRC), against the Hospital del Mar Cancer Registry (RTHMar) in Barcelona (Spain) as the gold standard. METHODS: Using ASEDAT software (Analysis, Selection and Extraction of Tumour Data), we identified Catalan public hospital discharge abstracts in patients with a first-time diagnosis of BC and CRC in the years 2005, 2008, and 2011, aggregated by unique patient identifiers and sorted by date. Once merged with the RTHMar database and anonymized, tumour-specific algorithms were validated to extract data on incident cases, tumour stage, surgical treatment, and date of incidence. RESULTS: MBDS had a respective sensitivity and positive predictive value (PPV) of 78.0% (564/723) and 90.5% (564/623) for BC case detection; and 83.9% (387/461) and 94.9% (387/408) for CRC case detection. The staging algorithms overestimated the proportion of local-stage cases and underestimated the regional-stage cases in both cancers. When loco-regional stage and surgery were combined, sensitivity and PPV reached 98.3% and 99.8%, respectively, for BC and 96.4% and 98.4% for CRC. The differences between dates of incidence between RTHMar and MBDS were greater for BC cases without initial surgery, whereas they were generally smaller and homogeneous for CRC cases. CONCLUSIONS: The MBDS is a valid and efficient instrument to improve the completeness of a hospital-based cancer registry (HBCR), particularly in BC and CRC, which require hospitalization and are predominantly surgical.

Reoperations after primary breast conserving surgery in women with invasive breast cancer in Catalonia, Spain: a retrospective study.

BACKGROUND: Although complete tumor resection is accepted as the best means to reduce recurrence, reoperations after lumpectomy are a common problem in breast cancer. The aim of this study was to assess the reoperation rates after primary breast conserving surgery in invasive breast cancer cases diagnosed in Catalonia, Spain, between 2005 and 2011 and to identify variations based on patient and tumour characteristics. METHODS: Women with invasive incident breast cancer identified from the Patient's Hospital Discharge Database [174.0-174.9 codes of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) as the primary diagnosis] and receiving primary breast conserving surgery were included in the study and were followed up to 3 and 12 months by collecting information about repeat breast cancer surgery. RESULTS: Reoperation rates after primary breast conserving surgery decreased from 13.0 % in 2005 to 11.7 % in 2011 at 3 months and from 14.2 % in 2005 to 12.9 % in 2011 at 12 months' follow-up. While breast conservation reoperations saw a slight, non-significant increase in the same period (from 5.7 to 7.3 % at 3 months, and from 6.0 to 7.5 % at 12 months), there was a significant decrease in radical reoperation (from 7.3 to 4.4 % at 3 months and from 8.2 to 5.4 % at 12 months). Overall, additional breast surgeries decreased among younger women. CONCLUSIONS: Despite the rise of breast conserving surgery, reoperation rates following initial lumpectomy in Catalonia decreased by 10 % at 3 and 12 months' follow-up, remaining low and almost unchanged. Ultimately, there was also a significant decrease in mastectomies.

Mejorando la respuesta patológica completa con tres esquemas diferentes de antraciclinas en densidad de dosis como primera línea en el tratamiento preoperatorio del cáncer de mama localmente avanzado / Improving the complete pathological response with three different schemes anthracyclines dose density as the first line in the preoperative treatment locally advanced breast cancer

Es un estudio prospectivo multiinstitucional que conlleva, a su vez, tres subestudios y luego se hace el metaanalisis de estos estudios piloto en pacientes con cáncer de mama localmente avanzado que reciben quimioterapia preoperatoria con antraciclinas en densidad de dosis seguido de tres esquemas diferentes, teniendo como objetivo llegar a la respuesta patológica completa (pCR). MATERIAL Y METODOS. Participaron 150 pacientes, 28 pacientes en el primer grupo (4AC+4AT), 57 pacientes en el segundo grupo (4AC+4CptT) y 65 pacientes en el tercer grupo (4AC+ 12 TXe), todos de inicio cánceres inoperables no metastásicos. RESULTADOS. En el primer grupo la RPC fue de 28 %, en el segundo grupo 20 % y en el tercer grupo 24 %, que se incrementó a 35 %, 19 %y 30 %, respectivamente, cuando solo se tabulo los datos de las pacientes que culminaron todo el tratamiento y que no presentaron progresión de enfermedad. CONCLUSIONES. En pacientes con tumores gigantes y en mds de 90 % EC III, las respuestas obtenidas son muy significativas solo con uso de quimioterapia, además de un ahorro económico importante al no usar biológicos. Con esto no se pretende ignorar la gran ayuda de los biológicos, simplemente que, para la realidad peruana, se proponen nuevas alternativas...

Is a prospective multi-institutional study involved three substudies in turn and then the meta-analysis of these pilot studies in patients with breast cancer with locally advanced receiving preoperative chemotherapy with anthracycline dose density followed by 3 different schemes, taking aim to reach the pCR. MATERIAL AND PATIENTS METHODS. 150 patients, 28 patients in the first group (4AC + 4AT), 57 patients in the second group (4CptT 4AC +) and 65 patients in the third group (4AC + I2TXe), all of them with inoperable cancers with nonmetastatic disease. RESULTS. The pCR In the first group was 28 %, in the second group 20% and in the third group 24 %, which increased to 35 %, 19 % and 30 % respectively when only the data of the patients culminating all treatment and no progression of disease was tabulated. CONCLUSIONS. Whereas these patients with giant tumors and in 90 % EC III responses obtained are significant only with use of chemotherapy, in addition to significant cost savings by not using biological agents. We not pretended ignore the evidence that the biological products help in excellent manner, but for our country this is an alternative good way...

Biallelic HERC1 mutations in a syndromic form of overgrowth and intellectual disability.

We report two Colombian siblings affected by overgrowth, intellectual disability and facial dysmorphism. Exome (via NGS) and Sanger sequencing revealed that biallelic sequence variants in a novel gene (HERC1) might be related to the disease pathogenesis. These results provide useful data for future genotype-phenotype correlations and for a molecular diagnosis of overgrowth.

Evidence of an association between 10/10 genotype of DAT1 and endophenotypes of attention deficit/hyperactivity disorder.

INTRODUCTION: Genetic variance of attention deficit-hyperactivity disorder (ADHD) is a strong determinant of this disorder. The 40 base pairs (bp) variable number tandem repeat (VNTR) located in the 3' untranslated region (UTR) of DAT1 gene increases the expression of the dopamine transporter. Therefore, DAT1 has been associated with susceptibility to ADHD. OBJECTIVE: To determine the association between the VNTR of DAT1 and the phenotype of ADHD or its endophenotypes in a sample of children aged between 6 and 15 years from Bogotá. SUBJECTS AND METHODS: We selected 73 patients with ADHD and 54 controls. WISC test was applied in all subjects and executive functions were assessed. The VNTR of DAT1 was polymerase chain reaction-amplified. Data regarding population genetics and statistical analysis were obtained. Correlation and association tests between genotype and neuropsychological testing were performed. RESULTS: The DAT1 polymorphism was not associated with ADHD (P=.85). Nevertheless, the 10/10 genotype was found to be correlated with the processing speed index (P<.05). In the hyperactivity subtype, there was a genotypic correlation with some subtests of executive function (cognitive flexibility) (P≤.01). In the combined subtype, the 10/10 genotype was associated with verbal comprehension index of WISC (P<.05). CONCLUSIONS: A correlation was found between DAT1 VNTR and the subtest "processing speed index" of WISC and the subtest "cognitive flexibility" of executive functions. To our knowledge, this is the first report to assess DAT1 gene in a Colombian population.

Event-based criteria in GT-STAF information indices: theory, exploratory diversity analysis and QSPR applications.

Versatile event-based approaches for the definition of novel information theory-based indices (IFIs) are presented. An event in this context is the criterion followed in the "discovery" of molecular substructures, which in turn serve as basis for the construction of the generalized incidence and relations frequency matrices, Q and F, respectively. From the resultant F, Shannon's, mutual, conditional and joint entropy-based IFIs are computed. In previous reports, an event named connected subgraphs was presented. The present study is an extension of this notion, in which we introduce other events, namely: terminal paths, vertex path incidence, quantum subgraphs, walks of length k, Sach's subgraphs, MACCs, E-state and substructure fingerprints and, finally, Ghose and Crippen atom-types for hydrophobicity and refractivity. Moreover, we define magnitude-based IFIs, introducing the use of the magnitude criterion in the definition of mutual, conditional and joint entropy-based IFIs. We also discuss the use of information-theoretic parameters as a measure of the dissimilarity of codified structural information of molecules. Finally, a comparison of the statistics for QSPR models obtained with the proposed IFIs and DRAGON's molecular descriptors for two physicochemical properties log P and log K of 34 derivatives of 2-furylethylenes demonstrates similar to better predictive ability than the latter.

Human-threatened ecosystem: new signs of groundwater connection between Yacyreta reservoir and Ibera wetland (South America).

Ibera wetland is one of the most pristine and singular ecosystems of South America. Satellite-derived thermal analysis of its lacustrine system supported the existence of a groundwater connection with the Yacyreta reservoir through basaltic fractures located along the ancient river bed of the Parana. The groundwater outflow would be located on the geological discontinuity of the eastern border of Ibera wetland, concretely Laguna Ibera and Laguna Luna-Disparo. This new sign of connection comes on top of the hydrological signs which already exist. A call to prudence recommends not extending the recently projected increase of the water level of Yacyreta reservoir. Deeper hydrogeological studies should analyze the hypothesis emerged from this study before modifying the water level of Yacyreta.

Structural invariants for the prediction of relative toxicities of polychloro dibenzo-p-dioxins and dibenzofurans.

Multivariate models are reported that can predict the relative toxicity of compounds with severe environmental impact, namely polychloro dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs). Multiple linear regression analysis (MLR) and partial least square projections of latent variables (PLS) show the usefulness of graph-theoretical descriptors, mainly topological charge indices (TCIs), in these series. The general trends of the group are correctly reproduced and better results are presented than have previously been published. In general, the more toxic compounds exhibit more symmetric molecular structures.

Definition of a novel atomic index for QSAR: the refractotopological state.

PURPOSE: In this work, a novel descriptor of atoms in molecules is introduced. The Refractotopological State Index for atoms (R-state,R), rectifies the atomic refractivity values reported by Crippen et al with the atomic refractivity values of the topological environment of each skeletal atom in the molecule. METHOD: The R-state (R(i)), for atom i is an hybrid index that is defined as the intrinsic refractivity value of the atom i (AR(i)) plus a perturbation term Delta AR(i) in the non-hydrogen depleted graph. RESULTS: The variations of the R values in different molecules are showed. QSAR examples previously reported by other authors are given for benzimidazole inhibition of Lee strain flu virus and receptor binding affinity of beta-carbolines. CONCLUSIONS: The index does not only describe the representation of the atomic dispersive forces related to the molar refractivity but also the influence of bounded and unbounded atoms as a measure of the distance-effect of the other groups in the molecule. The R-state index has proved a good performance, either alone or combined with the electro topological (E)-state index. This implies that in those cases this representation of dispersive forces between the molecule and the active site is a valid approach to the biological problem

Gangrena de Fournier: presentación de dos casos clínicos / Fournier's gangrene: two clinical cases presentation

A partir de la presentación de dos casos clínicos de gangrena de Fournier, hospitalizados en el servicio de ginecología y obstetricia del Hospital San Juan de Dios, se realizó una revisión de esta entidad clínica llamando la atención los pocos reportes existentes en la literatura. La gangrena de Fournier es una enfermedad infecciosa de los tejidos blandos, causada por la acción sinérgica de varios microorganismos aerobios y anaerobios. Su mortalidad es alta (21 por ciento), con oscilaciones de 7 a 75 por ciento. La incidencia actual es baja, no obstante cuando se presenta constituye a una urgencia quirúrgica. Entre los factores determinantes y con valor pronóstico destaca la diabetes, la inmunosupresión y las infecciones urinarias o rectales.

Topological virtual screening: a way to find new anticonvulsant drugs from chemical diversity.

A topological virtual screening (tvs) test is presented, which is capable of identifying new drug leaders with anticonvulsant activity. Molecular structures of both anticonvulsant-active and non active compounds, extracted from the Merck Index database, were represented using topological indexes. By means of the application of a linear discriminant analysis to both sets of structures, a topological anticonvulsant model (tam) was obtained, which defines a connectivity function. On the basis of this model, 41 new structures with anticonvulsant activity have been identified by a topological virtual screening.

Study of the action of flavonoids on xanthine-oxidase by molecular topology.

A study was performed on xanthine-oxidase inhibition by 22 flavonoids, including flavones, flavonols, flavanones, and chalcones, using UV spectroscopy for experimental data and molecular topology to establish the structure-activity relationship (SAR) model. The flavonoids were classified into four groups according to their activity on xanthine-oxidase (inactive, low, significant, or high), and linear discriminant analysis was used to classify each compound within a group. The results led to a very good model, which was able to classify correctly as xanthine oxidase inhibitors, along with a test set of molecules including a variety of different compounds such as allopurinol, caffeic acid, esculetin, and alloxantin.

Valor del Ultrasonido en el Diagnósitco de la Hemorragia Suprarenal en el Neonato

La hemorragia suprarenal es una alteración no poco frecuente en el recién nacido. Generalmente, la sospecha diagnóstica ocurre en aquellos niños que presentan una masa abdominal con ictericia y anemia o sin ellas. Su causa más común es el trauma del parto y la asfixia

Binuclear Copper(II) Chelates of Amide-Based Cyclophanes.

A chelating cyclophane has been synthesized by cyclocondensation of two ethylenediaminetetraacetic (EDTA) units with two p-phenylenediamine units: the resulting cyclophane is 2,9,18,25-tetraoxo-4,7,20,23-tetrakis(carboxymethyl)-1,4,7,10,17,20,23,26-octaaza[10.10]paracyclophane, abbreviated as (bis-edtapdn)H(4). Cyclocondensation of two EDTA and two 1,5-diaminonaphthalene units has given the naphthalenophane, 2,9,22,29-tetraoxo-4,7,24,27-tetrakis(carboxymethyl)-1,4,7,10,21,24,27,30-octaaza[10.10](1,5)naphthalenophane, (bis-edtanap)H(4). Studies of electronic and EPR spectra have been carried out on the binuclear Cu(2+) complexes of these new ligands and of related chelating cyclophanes, 2,9,25,32-tetraoxo-4,7,27,30-tetrakis(carboxymethyl)-1,4,7,10,24,27,30,33-octaaza[10.1.10.1]paracyclophane, abbreviated as (bis-edtabpm)H(4), and 2,9,25,32-tetraoxo-4,7,27,30-tetrakis(carboxymethyl)-1,4,7,10,24,27,30,33-octaaza-17,40-dioxa[10.1.10.1]paracyclophane, abbreviated as (bis-edtabpe)H(4). Common features of these chelating cyclophanes are as follows: (1) amino, amide, and pendant carboxymethyl donor groups are substituents in the cyclophane ring, and (2) the amide groups are directly bound to the aromatic groups. These ligands formed neutral binuclear Cu(2+) chelates [Cu(2)L](0) that are water-insoluble. In alkaline solutions, these Cu(2+) complexes were converted to anionic chelates [Cu(2)(LH(-)(4))](4)(-) in which deprotonated amide nitrogens coordinated Cu(2+) ions. These anionic metal chelates of (bis-edtapdn)H(4), (bis-edtabpm)H(4), and (bis-edtabpe)H(4) exhibited three pi-pi transition bands in the spectral range 240-340 nm, in contrast to the uncoordinated cyclophanes, which showed a single band in this spectral range. The unusual pi-pi transition spectra of the [Cu(2)(LH(-)(4))](4)(-) complexes originate from the combined effect of metal-ligand charge transfer and proximity of the pi systems. The absorption and emission spectra of (bis-edtanap)H(4) were also influenced by coordination with copper. The EPR spectrum of [Cu(2)(bis-edtanapH(-)(4))](4)(-) in a methanol glass matrix showed a hyperfine structure due to the spin exchange between two Cu(2+) ions. These unusual spectral and magnetic properties arise from the strong coordination between Cu(2+) ions and deprotonated amide nitrogens that are bound to the pi systems.

[Systematic echography in the first trimester of pregnancy]. / Ecografía sistemática en el primer trimestre del embarazo.

The purpose of this prospective study was to ascertain the usefulness of routine first trimester ultrasonography in 872 consecutive patients. A high incidence of abnormalities was noted: 35% A significant discrepancy between ultrasonography and menstrual dating was frequently noted: in 24% of all patients, and in 14% of patients with optimum menstrual history. These data suggest that routine obstetric ultrasonography should be considered for all patients at the first trimester, and that ultrasonometry in this period is the gold standard to estimate the true gestational age.

[Prevalence of viral hepatitis B in a group of prostitutes living in Chimbote (Peru)]. / Prevalencia de hepatitis viral B en un grupo de meretrices residentes en Chimbote (Perú).

We have studied HBV markers in 56 sera from 56 prostitutes who were registered to the Health Ministry Zonal Hospital of Chimbote on October, 1987. We used micro-Elisa solid phase technics to study the HBs Ag, HBs Ab, HBc Ab (Total IgG) and HBe Ag markers. From them, 89.3% were positive to any marker: 5.4% were asypmtomatic carriers and 83.9% had markers related to past HBV (immunity). In conclusion, this data shows clearly, that the prostitutes represent an important risk group for the transmission of the Hepatitis Type B virus to people who maintains sexual relations with them. The HBc Ab was the best marker to detect HBV antibodies, that did it in 95.7%.

Nuevas formas de presentación de los residuos sólidos urbanos en una gran ciudad (conteinerización y recogida hermética); ejemplo; ciudad de Madrid

Explica la organización del servicio de recolección de residuos para llegar a una rentabilización, entendiendo por ello un mínimo de costos y beneficios sociales. Se eligió un lugar para el vertido sanitario y se puso el acento en la recolección. Analiza los volúmenes de residuos sólidos, volúmenes totales por año, por día y kg por habitante. Evalúa las condiciones de pre-recolección e instalación de contenedores y describe el sistema de recogida mecanizada