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There is growing recognition across broad sectors of the scientific community that use of genomic biomarkers has the potential to reduce the need for conventional rodent carcinogenicity studies of industrial chemicals, agrochemicals, and pharmaceuticals through a weight-of-evidence approach. These biomarkers fall into 2 major categories: (1) sets of gene transcripts that can identify distinct tumorigenic mechanisms of action; and (2) cancer driver gene mutations indicative of rapidly expanding growth-advantaged clonal cell populations. This call-to-action article describes a collaborative approach launched to develop and qualify biomarker gene expression panels that measure widely accepted molecular pathways linked to tumorigenesis and their activation levels to predict tumorigenic doses of chemicals from short-term exposures. Growing evidence suggests that application of such biomarker panels in short-term exposure rodent studies can identify both tumorigenic hazard and tumorigenic activation levels for chemical-induced carcinogenicity. In the future, this approach will be expanded to include methodologies examining mutations in key cancer driver gene mutation hotspots as biomarkers of both genotoxic and nongenotoxic chemical tumor risk. Analytical, technical, and biological validation studies of these complementary genomic tools are being undertaken by multisector and multidisciplinary collaborative teams within the Health and Environmental Sciences Institute. Success from these efforts will facilitate the transition from current heavy reliance on conventional 2-year rodent carcinogenicity studies to more rapid animal- and resource-sparing approaches for mechanism-based carcinogenicity evaluation supporting internal and regulatory decision-making.

This study evaluated the effect of different protocols for Ca(OH)2 removal on the bond strength (BS) of epoxy resin-based sealer in long oval root canals. Forty-eight mandibular incisors with long oval root canals were selected by CBCT. Biomechanical preparation was performed, the samples were filled with Ca(OH)2 paste and distributed in four groups (n = 12): G-without Ca(OH)2 paste (C); G2-syringe/needle (SN); G3-SN + XP-Endo® Finisher (XPF); G4-SN + passive ultrasonic irrigation (PUI). After 7 days, Ca(OH)2 was removed and teeth were filled using AHPlus and guttapercha. In four samples from each group, the sealer was manipulated with 0.1% rhodamine to assess sealer penetration by fluorescent laser confocal microscopy (FLCM). Samples were sectioned in slices for BS, scanning electron microscopy, and FLCM analysis. The BS data were analyzed by ANOVA and Tukey tests (α = 0.05). The lowest BS values were found for the SN group (12.89 ± 4.36) compared to C (35.55 ± 10.05), while PUI group presented intermediate values (28.57 ± 9.35) and the XPF group (31.34 ± 9.8) showed values that were sometimes similar to C group and sometimes similar to PUI group (p > .05). The analysis of the adhesive interface showed evident gaps, with the presence of residues between the dentin and the filling material for the SN group, and for C, XPF and PUI groups juxtaposed adhesive interface. FLCM images showed sealer penetration in the dentinal tubules along the entire perimeter for C, XPF, and PUI groups. Ca(OH)2 removal with XPF and PUI from long oval root canals resulted in higher bond strength values compared to SN, besides better sealer penetration on dentinal tubules and juxtaposed adhesive interface.

La extensión universitaria implica siempre poner en juego, al menos, dos elementos centrales: sinergia y multiplicidad de voces. Por consiguiente, el presente artículo tiene por objetivo socializar de manera crí-tica la presencia de nuestros “socios” en la co-cons-trucción de saberes relevando para ello las diferen-tes voces durante diversos proyectos de extensión dinamizados por el Programa Educación y Sociedad: hacia una mayor inclusión educativa dependiente de la Secretaría de Extensión Social y Cultural de la UNL. Dividiremos este trabajo en tres apartados relacio-nados cada uno de ellos con proyectos anclados en el Programa. Estamos haciendo referencia a las prác-ticas de voluntariado social universitario, a los pro-yectos de enseñanza y aprendizaje de las Ciencias Experimentales y, finalmente, a los proyectos sobre educación rural. Volver hacia ellos resaltando las mi-radas de los actores nos permite repensarnos y ajus-tar la mirada propia.

To determine the influence of periapical lesions on the repeatability of two electronic apex locators (EALs), Root ZX II, and RomiApex A-15, in maxillary anterior teeth, in vivo. After approval by the local ethics committee, 43 maxillary anterior teeth scheduled for root canal therapy were assigned to two groups. The periapical lesion (PAL) group included 21 teeth with necrotic pulps and radiographically visible periapical lesion, and the normal periapex (NPA) group consisted of 22 teeth with vital pulps and no periapical lesion. In each canal, Root ZX II and RomiApex A-15 were used to determine working length defined as the “zero” reading on the display. Two consecutive measurements were performed with each EAL on each tooth and a second operator measured the endodontic file with a digital caliper without knowledge of the EAL being used or the tooth diagnosis. The absolute value of the difference between the first and second measurement (measurement pairs) was calculated. Repeatability was evaluated by the Bland-Altman method, and an aligned ranks transformation ANOVA was conducted to compare the EALs. The median absolute difference between measurement pairs was significantly lower (p < 0.001) and the limits of agreement were narrower in the NPA group. Among the EALs, median absolute differences were significantly smaller for Root ZX (p < 0.001). Measurements were more repeatable when no periapical lesion was present. Root ZX showed better repeatability than RomiApex. Periapical lesions seem to influence successive in vivo measurements with EALs.

Under ICH M7, impurities are assessed using the bacterial reverse mutation assay (i.e., Ames test) when predicted positive using in silico methodologies followed by expert review. N-Nitrosamines (NAs) have been of recent concern as impurities in pharmaceuticals, mainly because of their potential to be highly potent mutagenic carcinogens in rodent bioassays. The purpose of this analysis was to determine the sensitivity of the Ames assay to predict the carcinogenic outcome with curated proprietary Vitic (n = 131) and Leadscope (n = 70) databases. NAs were selected if they had corresponding rodent carcinogenicity assays. Overall, the sensitivity/specificity of the Ames assay was 93-97% and 55-86%, respectively. The sensitivity of the Ames assay was not significantly impacted by plate incorporation (84-89%) versus preincubation (82-89%). Sensitivity was not significantly different between use of rat and hamster liver induced S9 (80-93% versus 77-96%). The sensitivity of the Ames is high when using DMSO as a solvent (87-88%). Based on the analysis of these databases, the Ames assay conducted under OECD 471 guidelines is highly sensitive for detecting the carcinogenic hazards of NAs.

La gulupa (Passiflora edulis Sims) es una fruta exótica de sabor dulce y ligeramente ácido, aroma agradable y de gran aceptación principalmente en mercados europeos. En Colombia, una parte de las cosechas producidas está conformada por frutos que no cumplen con los estándares de calidad para la exportación, por lo que se destinan para el consumo nacional, y son comercializados a precios muy bajos; por eso, es necesario proponer alternativas para su aprovechamiento y potencial mercado. El objetivo del presente trabajo fue evaluar la influencia del grado de madurez de gulupa sobre la aceptación sensorial en productos alimenticios. Se elaboraron yogur y barras de cereal endulzados con salsa de gulupa proveniente de frutos con diferentes estados de madurez (T1: 30 %, T2: 50 %, T3: 70 % y T4: 100 %). Estos productos fueron evaluados sensorialmente por un panel de 101 consumidores, de edades entre los 18 y 54 años, por medio de la escala hedónica facial de 5 puntos. Los resultados obtenidos mostraron que el 56.44% de los consumidores mencionaron que les encantó el tratamiento T4 (yogur), y el 51.49% de los consumidores que les gustó el tratamiento T3 (barras de cereal). Lo anterior permite concluir que para el yogur, lo más recomendable es endulzar con frutas maduras, o incluso sobremaduras, mientras que para las barras de cereal lo ideal es usar gulupas con menor estado de maduración (70%).

The metabolic syndrome (MS) is a constellation of related factors that increases the risk of developing cardiovascular diseases. Vaccinium meridionale Swartz contains polyphenols that could modulate some components of MS. Epidemiological and intervention studies have shown differences between men and women in MS components and antioxidant capacity. The objective of this study is to compare between men and women with MS the effects of agraz consumption on insulin resistance, antioxidant capacity, and markers of oxidation and inflammation. Men and women diagnosed with MS according to the Adult Treatment Panel III criteria were recruited in a double-blind, crossover study of 12 weeks. Participants were assigned to consume agraz nectar or placebo over 4 weeks. After 4 weeks of washout, they were switched to the alternative treatment. At the end of each period, the components of the MS, insulin resistance, antioxidant capacity, and some oxidative (oxidized low-density lipoprotein [oxLDL]; thiobarbituric acid reactive substances) and inflammatory (high-sensitive C-reactive protein [hs-CRP]) markers were evaluated. After consuming agraz, there was a tendency to increase the levels of antioxidants and to reduce the levels of hs-CRP in both genders. In addition, women who increased their serum phenols after consuming agraz had a significant reduction in insulin resistance, which was different from the results in men. Regarding men, those who increased their serum antioxidant capacity after consuming agraz had a better effect on the reduction of oxLDL levels that was significant compared to women. There are important differences between genders in the effects of agraz consumption in adults with MS.

Given the interest in the conservation of the Mesoamerican scarlet macaw (Ara macao cyanoptera), the Xcaret Park formed an initial reproductive population about 30 years ago, which has progressively grown to a considerable population in captivity. In this work, we focus on the evaluation of the genetic diversity of the captive population, taking two groups into account: its founding (49) and the current breeding individuals (166). The genetic analysis consisted of genotyping six nuclear microsatellite loci that are characterized by their high variability. Tests for all loci revealed a Hardy–Weinberg equilibrium in four loci of the founders and in no loci of the breeding groups. The results showed that the genetic variation in the Xcaret population was relatively high (founders He = 0.715 SE = 0.074, breeding pairs He = 0.763 SE = 0.050), with an average polymorphism of 7.5 (4–10) alleles per locus in founders and 8.3 (4–14) in breeding pairs. No significant differences in the evaluated genetic diversity indexes were found between both groups. This indicates that the genetic variability in Xcaret has been maintained, probably due to the high number of pairs and the reproductive management strategy. Bayesian analysis revealed five different genetic lineages present in different proportions in the founders and in the breeding pairs, but no population structure was observed between founders and breeding individuals. The analyzed captive individuals showed levels of genetic diversity comparable to reported values from Ara macao wild populations. These data indicate that the captive population has maintained a similar genetic diversity as the metapopulation in the Mayan Forest and is an important resource for reintroduction projects, some of which began more than five years ago and are still underway.

Objective:To know the anti-infective effectiveness of ascorbic acid, after a linear incision in the mucosa of the mandibular antero-inferior segment of the oral cavity of the guinea pigs, housed in the vivarium of the Biology Center of the Central University of Ecuador. Materials and methods:This study is experimental in-vivo and longitudinal, where an incision was made in the mucosa of the mandibular anteroinferior segment of the oral cavity in guinea pigs, three groups of 10 guinea pigs were formed, Group C, received mega doses ( 1.42 ml / 214.2 mg) which contained high amounts of ascorbic acid, Group B received normal doses (0.095 ml / 14.25 mg) and group Aor control group did not receive ascorbic acid, this dose was applied one day before, during, and one day after the incision. The clinical evaluation was performed at 24 and 72 hours post incision, a sample was taken by swab from the wounded area at 72 hours for the planting of bacterial cultivation. Results: The clinical examination shows that at 24 hours in group C, 0% bleeding, edema, and erythema, and 100% epithelial junction, while in group B, 30% bleeding, 50% edema, 50% erythema and 100% epithelial junction and in group A50% bleeding, 40% edema, 40% erythema and 20% epithelial junction; at 72 hours the results in group C and B showed better healing percentages in relation to group A, in this group some guinea pigs still showed bleeding edema and erythema in the wounded area. Conclusion: It is determined that the guinea pigs who received mega doses of ascorbic acid presented a better result in the process of healing after clinical examination at 24 and 72 hours and the swab exam shows a lower amount of bacterial colonization, thus demonstrating the effectiveness of ascorbic acid in mega doses of infectious processes.

Introducción: La mayoría de los estudios han evaluado y comparado la exactitud de los localizadores apicales electrónicos pero pocos evaluaron la repetibilidad del método de medición; de estos casi todos son ex vivo. Objetivo: Comparar la repetibilidad in vivo de tres localizadores apicales electrónicos en dientes antero-superiores permanentes. Métodos: Se realizó un estudio observacional analítico de corte transversal en 14 pacientes adultos sanos de ambos sexos con indicación de tratamiento de conductos en una pieza dentaria antero-superior. La selección fue por casos consecutivos. Se utilizaron tres localizadores apicales electrónicos ( Root ZX II, Canal Pro y RomiApex A-15) para realizar las mediciones de los conductos. Dos operadores independientes realizaron dos mediciones con cada localizador apical electrónico. Los datos se analizaron por medio de la prueba de Bland-Altman para la repetibilidad y la prueba de Friedman para comparar los localizadores apicales. Resultados: La edad media (desviación estándar) de los pacientes fue 28,79 (± 9,12) años; 8 (57,1 %) pacientes fueron del sexo femenino. La media de las diferencias (límites de concordancia) de las mediciones para Root ZX, Canal Pro y RomiApex A-15 fueron 0,13 mm (± 0,42), 0,12 mm (± 0,88), y 0,18 (± 0,76) mm, respectivamente. Conclusiones: El Root ZX presentó el mayor grado de repetibilidad, seguido por el RomiApex. No se encontraron diferencias estadísticamente significativas entre los localizadores en cuanto a las diferencias absolutas entre la 1ra y 2da mediciones.

The in vitro MultiFlow® DNA Damage Assay multiplexes γH2AX, p53, phospho-histone H3, and polyploidization biomarkers into a single flow cytometric analysis. The current report describes a tiered sequential data analysis strategy based on data generated from exposure of human TK6 cells to a previously described 85 chemical training set and a new pharmaceutical-centric test set (n = 40). In each case, exposure was continuous over a range of closely spaced concentrations, and cell aliquots were removed for analysis following 4 and 24 hr of treatment. The first data analysis step focused on chemicals' genotoxic potential, and for this purpose, we evaluated the performance of a machine learning (ML) ensemble, a rubric that considered fold increases in biomarkers against global evaluation factors (GEFs), and a hybrid strategy that considered ML and GEFs. This first tier further used ML output and/or GEFs to classify genotoxic activity as clastogenic and/or aneugenic. Test set results demonstrated the generalizability of the first tier, with particularly good performance from the ML ensemble: 35/40 (88%) concordance with a priori genotoxicity expectations and 21/24 (88%) agreement with expected mode of action (MoA). A second tier applied unsupervised hierarchical clustering to the biomarker response data, and these analyses were found to group certain chemicals, especially aneugens, according to their molecular targets. Finally, a third tier utilized benchmark dose analyses and MultiFlow biomarker responses to rank genotoxic potency. The relevance of these rankings is supported by the strong agreement found between benchmark dose values derived from MultiFlow biomarkers compared to those generated from parallel in vitro micronucleus analyses. Collectively, the results suggest that a tiered MultiFlow data analysis pipeline is capable of rapidly and effectively identifying genotoxic hazards while providing additional information that is useful for modern risk assessments-MoA, molecular targets, and potency. Environ. Mol. Mutagen. 60:513-533, 2019. © 2019 Wiley Periodicals, Inc.

This paper presents the results obtained in the use of the Automated Driving Toolbox of MATLAB to detect moving and static objects in a virtual simulation environment of autonomous driving. The objective of this research is to configure different scenarios related to autonomous driving systems (ADAS - Advanced Driver Assistance Systems), in order to obtain information about the behavior of cameras and radars in the presence of different objects placed on the road. The results obtained show that the best performance is achieved when side cameras and a frontal sensor are placed. In addition, the size of the object under study does not affect the objetcs detection rate on the road.

Resumen La criptococosis meníngea presenta alta mortalidad mundial, especialmente en población VIH/sida. La OMS recomienda detectar el antígeno capsular de Crypto coccus como estrategia para un diagnóstico temprano y poder minimizar complicaciones. Objetivo: realizar antigenemia temprana de Cryptococcus mediante in munocromatografía/ensayo de flujo lateral en pacientes asintomáticos VIH+. Material y método: estudio descriptivo observacional; entre julio-2016 y mayo-2019 se procesaron mediante ensayo de flujo lateral, muestras de suero de 169 pacientes asintomáticos VIH+, con CD4 ≤120 cel/μL en Barranquilla, Colombia. Ante resultado positivo, se indicó profilaxis con fluconazol; se hizo seguimiento a todos los casos. Resultados: la antigenemia fue positiva en cinco pacientes (2,96%); uno falleció, cuatro recibieron profilaxis y la prueba se negativizó en dos. Los pacientes con resultado negativo inicial no desarrollaron durante el estudio sinto matología compatible con esta micosis. Discusión: el ensayo de flujo lateral de Cryptococcus está recomendado para el diagnóstico temprano de la criptococosis en población VIH/sida. Conclusión: detectar tempranamente el antígeno circulante de Cryptococcus mediante ensayo de flujo lateral en pacientes asintomáticos VIH+, permitió instaurar profilaxis oportuna, hacer seguimiento y control para reducir la mortalidad asociada con la criptococosis meníngea. Abstract Meningeal cryptococcosis presents high levels of global mortality, especially in the HIV/AIDS population. The WHO recommends detecting the capsular antigen as an important strategy for early diagnosis and be able to minimize complications. Objective: Perform early cryptococcal antigenemia by immunochromatographic/ lateral flow assay in asymptomatic HIV+ patients. Material and method: descriptive observational study; between July-2016 and May-2019, serum samples from 169 asymptomatic HIV+ patients with CD4 ≤120 cells/μL were processed by lateral flow assay in Barranquilla, Colombia. Given a positive result, prophylaxis with fluconazole was indicated; all cases were followed up. Results: antigenemia was positive in five (2.96%) patients; one died; four received prophylaxis, and the test turned negative in two. The patients with an initial negative result, did not developed symptoms compatible with this mycosis during the study period. Discussion: lateral flow assay for Cryptococcus is recommended for the early diagnosis of cryptococcosis in the HIV/AIDS population. Conclusion: early detection of circulating Cryptococcus antigen by lateral flow assay in HIV+ patients allowed the establishment of timely prophylaxis, follow-up, and control to reduce mortality associated with meningeal cryptococcosis.

Objectives The aim of this study was to investigate the feasibility of saliva sampling as a non-invasive and safer tool to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to compare its reproducibility and sensitivity with nasopharyngeal swab samples (NPS). The use of sample pools was also investigated. Methods A total of 2107 paired samples were collected from asymptomatic healthcare and office workers in Mexico City. Sixty of these samples were also analyzed in two other independent laboratories for concordance analysis. Sample processing and analysis of virus genetic material were performed according to standard protocols described elsewhere. A pooling analysis was performed by analyzing the saliva pool and the individual pool components. Results The concordance between NPS and saliva results was 95.2% (kappa 0.727, p = 0.0001) and 97.9% without considering inconclusive results (kappa 0.852, p = 0.0001). Saliva had a lower number of inconclusive results than NPS (0.9% vs 1.9%). Furthermore, saliva showed a significantly higher concentration of both total RNA and viral copies than NPS. Comparison of our results with those of the other two laboratories showed 100% and 97% concordance. Saliva samples are stable without the use of any preservative, and a positive SARS-CoV-2 sample can be detected 5, 10, and 15 days after collection when the sample is stored at 4 °C. Conclusions The study results indicate that saliva is as effective as NPS for the identification of SARS-CoV-2-infected asymptomatic patients. Sample pooling facilitates the analysis of a larger number of samples, with the benefit of cost reduction.

Introducción. El uso de cuestionarios de predicción clínica para el diagnóstico de la enfermedad pulmonar obstructiva crónica (EPOC) en atención primaria en salud podría mejorar el subdiagnóstico de esta enfermedad. Hoy en día existen varios instrumentos de este tipo; sin embargo, hay poca información sobre su rendimiento diagnóstico. Objetivo. Determinar la validez del uso de los diferentes cuestionarios de predicción clínica para el diagnóstico de la EPOC. Materiales y métodos. Se realizó una revisión sistemática con metaanálisis de prueba diagnóstica en las bases de datos PubMed, EMBASE y LILACS a partir de la estrategia PICO y utilizando términos MeSH y DeCS. Se incluyeron los estudios publicados entre julio 1 de 1997 y junio 30 de 2019. Dos revisores seleccionaron los artículos para análisis completo con base en los criterios de inclusión y exclusión. La calidad de los artículos se evaluó con el instrumento QUADAS. Resultados. Se incluyeron 19 artículos para el análisis. En cuanto a la evaluación global de los cuestionarios se obtuvieron los siguientes datos: sensibilidad: 68.1% (IC95%: 66.7-69.4); especificidad: 64.9% (IC95%: 64.3-65.5); razón de verosimilitud positiva: 2.024 (IC95%: 1.715-2.388); razón de verosimilitud negativa: 0.407 (IC95%: 0.289-0.573) y el área bajo la curva de características del receptor (ACOR): 0.75. El cuestionario COPD-PS reportó el mayor rendimiento —sensibilidad: 0.673 (IC95%: 0.653-0.692), especificidad: 0.663 (IC95%: 0.655-0.671) y ACOR: 0.750—; seguido de LFQ —sensibilidad: 0.840 (IC95%: 0.806-0.871), especificidad: 0.312 (IC95%: 0.289-0.336) y ACOR: 0,730—, y CDQ —sensibilidad: 0.798 (IC95%: 0.764-0.829), especificidad: 0.517 (IC95%: 0.495-0.538) y ACOR: 0.727—. Conclusión. Los instrumentos de predicción clínica para el diagnóstico de EPOC tienen un rendimiento aceptable, pues los valores de sensibilidad obtenidos a través de estos son superiores a los de la evaluación individual de la sintomatología respiratoria que se puede hacer a través de la historia clínica habitual.

COVID-19 morbidity is highest in Black and Latino older adults. These racial and ethnic groups initially had lower vaccination uptake than others, and rates in Black adults continue to lag.To evaluate the effect of outreach via electronic secure messages and mailings from primary care physicians (PCPs) on COVID-19 vaccination uptake among Black and Latino older adults and to compare the effects of culturally tailored and standard PCP messages.This randomized clinical trial was conducted from March 29 to May 20, 2021, with follow-up surveys through July 31, 2021. Latino and Black individuals aged 65 years and older from 4 Kaiser Permanente Northern California (KPNC) service areas were included. Data were analyzed from May 27, 2021, to September 28, 2021.Individuals who had not received COVID-19 vaccination after previous outreach were randomized to electronic secure message and/or mail outreach from their PCP, similar outreach with additional culturally tailored content, or usual care. Outreach groups were sent a secure message or letter in their PCP's name, followed by a postcard to those still unvaccinated after 4 weeks.The primary outcome was time to receipt of COVID-19 vaccination during the 8 weeks after initial study outreach. KPNC data were supplemented with state data from external sources. Intervention effects were evaluated via proportional hazards regression.Of 8287 included individuals (mean [SD] age, 72.6 [7.0] years; 4665 [56.3%] women), 2434 (29.4%) were Black, 3782 (45.6%) were Latino and preferred English-language communications, and 2071 (25.0%) were Latino and preferred Spanish-language communications; 2847 participants (34.4%) had a neighborhood deprivation index at the 75th percentile or higher. A total of 2767 participants were randomized to culturally tailored PCP outreach, 2747 participants were randomized to standard PCP outreach, and 2773 participants were randomized to usual care. Culturally tailored PCP outreach led to higher COVID-19 vaccination rates during follow-up compared with usual care (664 participants [24.0%] vs 603 participants [21.7%]; adjusted hazard ratio (aHR), 1.22; 95% CI, 1.09-1.37), as did standard PCP outreach (635 participants [23.1%]; aHR, 1.17; 95% CI, 1.04-1.31). Individuals who were Black (aHR, 1.19; 95% CI, 1.06-1.33), had high neighborhood deprivation (aHR, 1.17; 95% CI, 1.03-1.33), and had medium to high comorbidity scores (aHR, 1.19; 95% CI, 1.09-1.31) were more likely to be vaccinated during follow-up.This randomized clinical trial found that PCP outreach using electronic and mailed messages increased COVID-19 vaccination rates among Black and Latino older adults.ClinicalTrials.gov Identifier: NCT05096026.

Purple passionfruit (Passiflora edulis Sims) is an exotic, sweet and slighty acid flavored fruit with a pleasant aroma. It is also widely accepted in European markets. In Colombia, a part of the yield crop is comprised of fruit that does not meet quality standards for export and is intended for national consumption, and marketed at very low prices. Therefore, it is necessary to propose alternatives for its use and potential market. The aim of this study was to assess the influence of the degree of ripeness for purple passionfruit on the sensory acceptance in food products. Yogurt and cereal bars sweetened with purple passionfruit sauce from fruit with different stages of ripeness (T1: 30 %, T2: 50 %, T3: 70 % and T4: 100 %) were prepared. By a panel of 101 consumers aged 18-54 years old, using a 5-point facial hedonic scale, said products were sensorially assessed. The results obtained showed that 56.44% of consumers preferred T4 treatment (yogurt) and 51.49% of consumers preferred T3 treatment (cereal bars). The above mentioned leads to conclude that, for yogurt preparations, it is best to sweeten with ripe or even overripe fruit, while for cereal bars it is ideal to use purple passionfruit with a lower stage of ripeness (70%)., La gulupa (Passiflora edulis Sims) es una fruta exótica de sabor dulce y ligeramente ácido, aroma agradable y de gran aceptación principalmente en mercados europeos. En Colombia, una parte de las cosechas producidas está conformada por frutos que no cumplen con los estándares de calidad para la exportación, por lo que se destinan para el consumo nacional, y son comercializados a precios muy bajos; por eso, es necesario proponer alternativas para su aprovechamiento y potencial mercado. El objetivo del presente trabajo fue evaluar la influencia del grado de madurez de gulupa sobre la aceptación sensorial en productos alimenticios. Se elaboraron yogur y barras de cereal endulzados con salsa de gulupa proveniente de frutos con diferentes estados de madurez (T1: 30 %, T2: 50 %, T3: 70 % y T4: 100 %). Estos productos fueron evaluados sensorialmente por un panel de 101 consumidores, de edades entre los 18 y 54 años, por medio de la escala hedónica facial de 5 puntos. Los resultados obtenidos mostraron que el 56.44% de los consumidores mencionaron que les encantó el tratamiento T4 (yogur), y el 51.49% de los consumidores que les gustó el tratamiento T3 (barras de cereal). Lo anterior permite concluir que para el yogur, lo más recomendable es endulzar con frutas maduras, o incluso sobremaduras, mientras que para las barras de cereal lo ideal es usar gulupas con menor estado de maduración (70%).

To determine the influence of periapical lesions on the repeatability of two electronic apex locators (EALs), Root ZX II, and RomiApex A-15, in maxillary anterior teeth, in vivo.After approval by the local ethics committee, 43 maxillary anterior teeth scheduled for root canal therapy were assigned to two groups. The periapical lesion (PAL) group included 21 teeth with necrotic pulps and radiographically visible periapical lesion, and the normal periapex (NPA) group consisted of 22 teeth with vital pulps and no periapical lesion. In each canal, Root ZX II and RomiApex A-15 were used to determine working length defined as the "zero" reading on the display. Two consecutive measurements were performed with each EAL on each tooth and a second operator measured the endodontic file with a digital caliper without knowledge of the EAL being used or the tooth diagnosis. The absolute value of the difference between the first and second measurement (measurement pairs) was calculated. Repeatability was evaluated by the Bland-Altman method, and an aligned ranks transformation ANOVA was conducted to compare the EALs.The median absolute difference between measurement pairs was significantly lower (p0.001) and the limits of agreement were narrower in the NPA group. Among the EALs, median absolute differences were significantly smaller for Root ZX (p0.001).Measurements were more repeatable when no periapical lesion was present. Root ZX showed better repeatability than RomiApex.Periapical lesions seem to influence successive in vivo measurements with EALs.

Pharmaceutic products designed to perturb the function of epigenetic modulators have been approved by regulatory authorities for treatment of advanced cancer. While the predominant effort in epigenetic drug development continues to be in oncology, non-oncology indications are also garnering interest. A survey of pharmaceutical companies was conducted to assess the interest and concerns for developing small molecule direct epigenetic effectors (EEs) as medicines. Survey themes addressed (1) general levels of interest and activity with EEs as therapeutic agents, (2) potential safety concerns, and (3) possible future efforts to develop targeted strategies for nonclinical safety assessment of EEs. Thirteen companies contributed data to the survey. Overall, the survey data indicate the consensus opinion that existing ICH guidelines are effective and appropriate for nonclinical safety assessment activities with EEs. Attention in the framework of study design should, on a case by case basis, be considered for delayed or latent toxicities, carcinogenicity, reproductive toxicity, and the theoretical potential for transgenerational effects. While current guidelines have been appropriate for the nonclinical safety assessments of epigenetic targets, broader experience with a wide range of epigenetic targets will provide information to assess the potential need for new or revised risk assessment strategies for EE drugs.

In a previously reported CD-1 mouse 2-year carcinogenicity study with the sodium glucose cotransporter-2 inhibitor empagliflozin, an increased incidence of renal tubular adenomas and carcinomas was identified only in the male high-dose group. Follow-up investigative studies have shown that the renal tumors in male high-dose mice were preceded by a number of renal degenerative/regenerative findings. Prior cross-species in vitro metabolism studies using microsomes identified an oxidative metabolite (M466/2) predominantly formed in the male mouse kidney and which spontaneously degrades to a metabolite (M380/1) and reactive 4-OH crotonaldehyde (CTA). In order to further evaluate potential modes of action for empagliflozin-associated male mouse renal tumors, we report here a series of in vitro investigative toxicology studies conducted to evaluate the cytotoxic and genotoxic potential of empagliflozin and M466/2. To assess the cytotoxic potential of empagliflozin and M466/2, a primary mouse renal tubular epithelial (mRTE) cell model was used. In mRTE cells, M466/2-derived in vitro 4-OH CTA exposure was cytotoxic, while empagliflozin was not cytotoxic or mitogenic. Empagliflozin and M466/2 were not genotoxic, supporting an indirect mode of action for empagliflozin-associated male mouse renal tumorigenesis. In conclusion, these in vitro data show that M466/2-derived 4-OH CTA exposure is associated with cytotoxicity in renal tubule cells and may be involved in promoting compound-related in vivo renal metabolic stress and chronic low-level renal injury, in turn supporting a nongenotoxic mode of tumor pathogenesis specific to the male mouse.

In May 2017, the Health and Environmental Sciences Institute's Genetic Toxicology Technical Committee hosted a workshop to discuss whether mode of action (MOA) investigation is enhanced through the application of the adverse outcome pathway (AOP) framework. As AOPs are a relatively new approach in genetic toxicology, this report describes how AOPs could be harnessed to advance MOA analysis of genotoxicity pathways using five example case studies. Each of these genetic toxicology AOPs proposed for further development includes the relevant molecular initiating events, key events, and adverse outcomes (AOs), identification and/or further development of the appropriate assays to link an agent to these events, and discussion regarding the biological plausibility of the proposed AOP. A key difference between these proposed genetic toxicology AOPs versus traditional AOPs is that the AO is a genetic toxicology endpoint of potential significance in risk characterization, in contrast to an adverse state of an organism or a population. The first two detailed case studies describe provisional AOPs for aurora kinase inhibition and tubulin binding, leading to the common AO of aneuploidy. The remaining three case studies highlight provisional AOPs that lead to chromosome breakage or mutation via indirect DNA interaction (inhibition of topoisomerase II, production of cellular reactive oxygen species, and inhibition of DNA synthesis). These case studies serve as starting points for genotoxicity AOPs that could ultimately be published and utilized by the broader toxicology community and illustrate the practical considerations and evidence required to formalize such AOPs so that they may be applied to genetic toxicity evaluation schemes. Environ. Mol. Mutagen. 61:114-134, 2020. © 2019 Wiley Periodicals, Inc.

The International Workshop on Genotoxicity Testing (IWGT) meets every four years to obtain consensus on unresolved issues associated with genotoxicity testing. At the 2017 IWGT meeting in Tokyo, four sub-groups addressed issues associated with the Organization for Economic Cooperation and Development (OECD) Test Guideline TG471, which describes the use of bacterial reverse-mutation tests. The strains sub-group analyzed test data from >10,000 chemicals, tested additional chemicals, and concluded that some strains listed in TG471 are unnecessary because they detected fewer mutagens than other strains that the guideline describes as equivalent. Thus, they concluded that a smaller panel of strains would suffice to detect most mutagens. The laboratory proficiency sub-group recommended (a) establishing strain cell banks, (b) developing bacterial growth protocols that optimize assay sensitivity, and (c) testing "proficiency compounds" to gain assay experience and establish historical positive and control databases. The sub-group on criteria for assay evaluation recommended that laboratories (a) track positive and negative control data; (b) develop acceptability criteria for positive and negative controls; (c) optimize dose-spacing and the number of analyzable doses when there is evidence of toxicity; (d) use a combination of three criteria to evaluate results: a dose-related increase in revertants, a clear increase in revertants in at least one dose relative to the concurrent negative control, and at least one dose that produced an increase in revertants above control limits established by the laboratory from historical negative controls; and (e) establish experimental designs to resolve unclear results. The in silico sub-group summarized in silico utility as a tool in genotoxicity assessment but made no specific recommendations for TG471. Thus, the workgroup identified issues that could be addressed if TG471 is revised. The companion papers (a) provide evidence-based approaches, (b) recommend priorities, and (c) give examples of clearly defined terms to support revision of TG471.

espanolIntroduccion: Las sustancias relacionadas con los microorganismos involucrados en la enfermedad periodontal puedan llegar a la interfaz materno-fetal por via hematogena y estimular la contractilidad uterina. Objetivo: Determinar la asociacion entre enfermedad periodontal con nacimiento pretermino. Metodo: Estudio de casos y controles de 343 embarazadas pretermino y 686 de termino. Se calculo la edad gestacional por fecha de ultimo periodo menstrual y se confirmo con los metodos de Capurro y Ballard. La enfermedad periodontal se diagnostico por la profundidad del espacio entre la raiz dental y la encia. La asociacion fue medida con regresion logistica. Resultados: La edad de las madres en los casos fue de 23.8 ± 6.7 anos y en los controles de 23.2 ± 6.7 anos. La enfermedad periodontal estuvo presente en 66.8 % de los casos y 40.5 % de los controles. Los factores asociados con nacimiento pretermino fueron enfermedad periodontal (RM = 2.26), antecedente de nacimiento pretermino (RM = 4.96), embarazo no planeado (RM = 2.15), control prenatal deficiente (RM = 2.53), infeccion de vias urinarias (RM = 2.22), preeclampsia (RM = 4.49), ruptura prematura de membranas amnioticas (RM = 2.59) y nacer por cesarea (RM = 9.15). Conclusion: La enfermedad periodontal en el embarazo constituyo un factor de riesgo independiente para nacimiento pretermino. EnglishIntroduction: Substances related to microorganisms involved in periodontal disease can reach the maternal-fetal interface via the hematogenous route and stimulate uterine contractility. Objective: To determine the association between periodontal disease and preterm birth. Method: Case-control study in 343 preterm and 686 full-term pregnant women. Gestational age was calculated based on the date of the last menstrual period and confirmed with Capurro and Ballard methods. Periodontal disease was diagnosed according to the depth of the space between the tooth root and the gum. The association was measured with logistic regression. Results: Maternal age of the cases was 23.8 ± 6.7 years, and 23.2 ± 6.7 in the controls. Periodontal disease was present in 66.8% of cases and 40.5% of controls. The factors associated with preterm birth were periodontal disease (Odds ratio [OR] = 2.26), history of preterm birth (OR = 4.96), unplanned pregnancy (OR = 2.15) poor prenatal control (OR = 2.53), urinary tract infection (OR = 2.22), preeclampsia (OR = 4.49), premature rupture of membranes (OR = 2.59) and caesarean section delivery (OR = 9.15). Conclusion: Periodontal disease in pregnancy was an independent risk factor for preterm birth.

Arylboronic acids and esters (referred to collectively as arylboronic compounds) are commonly used intermediates in the synthesis of pharmaceuticals but pose a challenge for chemical syntheses because they are often positive for bacterial mutagenicity in vitro. As such, arylboronic compounds are then typically controlled to levels that are acceptable for mutagenic impurities, that is, the threshold of toxicological concern (TTC). This study used ICH M7 guidance to design and conduct a testing strategy to investigate the in vivo relevance of the in vitro positive findings of arylboronic compounds. Eight arylboronic compounds representing a variety of chemical scaffolds were tested in Sprague Dawley and/or Wistar rats in the in vivo Pig-a (peripheral blood reticulocytes and mature red blood cells) and/or comet assays (duodenum and/or liver). Five of the eight compounds were also tested in the micronucleus (peripheral blood) assay. The arylboronic compounds tested orally demonstrated high systemic exposure; thus the blood and bone marrow were adequately exposed to test article. One compound was administered intravenously due to formulation stability issues. This investigation showed that arylboronic compounds that were mutagenic in vitro were not found to be mutagenic in the corresponding in vivo assays. Therefore, arylboronic compounds similar to the scaffolds tested in this article may be considered non-mutagenic and managed in accordance with the ICH Q3A/Q3B guidelines. Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc.

The bacterial reverse mutation test is a mainstay for evaluation of mutagenicity predicting the carcinogenic potential of a test substance and is recommended by regulatory agencies across the globe. The popularity of the test is due, in part, to the relatively low cost, rapid results and small amount of test material required compared to most other toxicological tests as well as the near universal acceptance of the toxicological significance of a clear positive or negative result. Most laboratories follow the Organization for Economic Cooperation and Development Test Guideline 471 (TG471) or national guidelines based on TG471. Regulatory agencies in most countries are obligated to consider results from tests which meet the recommendations laid out in TG471. Nonetheless, laboratories unfamiliar with the test sometimes have trouble generating reliable, reproducible results. TG471 is a test guideline, not a detailed test protocol. A group of experts from regulatory agencies and laboratories which use the assay has assembled here a set of recommendations which if followed, will allow an inexperienced laboratory to acquire proficiency in assay conduct. These include recommendations for how to create a cell bank for the 5 Salmonella typhimurium/Escherichia coli strains and develop a laboratory protocol to reliably culture each strain to ensure each culture has the characteristics which allow adequate sensitivity for detection of mutagens using the test as described in TG471. By testing compounds on the provided lists of positive and negative test substances, the laboratory will have surmounted many of the problems commonly encountered during routine testing of unknown chemicals and will have gained the experience necessary to prepare the detailed protocol needed for performing the test under Good Laboratory Procedures and the laboratory will have generated the historical positive and negative control databases which are needed for test reports which adhere to TG471.

A database of 91 chemicals with published data from both transgenic rodent mutation (TGR) and rodent comet assays has been compiled. The objective was to compare the sensitivity of the two assays for detecting genotoxicity. Critical aspects of study design and results were tabulated for each dataset. There were fewer datasets from rats than mice, particularly for the TGR assay, and therefore, results from both species were combined for further analysis. TGR and comet responses were compared in liver and bone marrow (the most commonly studied tissues), and in stomach and colon evaluated either separately or in combination with other GI tract segments. Overall positive, negative, or equivocal test results were assessed for each chemical across the tissues examined in the TGR and comet assays using two approaches: 1) overall calls based on weight of evidence (WoE) and expert judgement, and 2) curation of the data based on a priori acceptability criteria prior to deriving final tissue specific calls. Since the database contains a high prevalence of positive results, overall agreement between the assays was determined using statistics adjusted for prevalence (using AC1 and PABAK). These coefficients showed fair or moderate to good agreement for liver and the GI tract (predominantly stomach and colon data) using WoE, reduced agreement for stomach and colon evaluated separately using data curation, and poor or no agreement for bone marrow using both the WoE and data curation approaches. Confidence in these results is higher for liver than for the other tissues, for which there were less data. Our analysis finds that comet and TGR generally identify the same compounds (mainly potent mutagens) as genotoxic in liver, stomach and colon, but not in bone marrow. However, the current database content precluded drawing assay concordance conclusions for weak mutagens and non-DNA reactive chemicals.

This case report describes a technique in which endodontic treatment and permanent indirect restoration were completed in the same clinical appointment with the aid of a computer-aided design/computer-aided manufacturing (CAD/CAM) system. Two patients were diagnosed with irreversible pulpitis of the mandibular first molar. After access preparation, root canals were located, irrigation was performed until bleeding ceased, and the coronal tooth structure was prepared for indirect restoration. Then, utilizing an interim 3-mm build-up of the endodontic access cavity, a hemi-arch digital scan was performed with an intraoral scanner. Subsequent to digital scanning, restoration design was performed simultaneously with the endodontic procedure. The root canals were shaped using the Race system under irrigation with 2.5% sodium hypochlorite followed by root canal filling. The pulp chamber was subsequently filled with a 3-mm-thick composite resin restoration mimicking the interim build-up previously utilized to facilitate block milling in the CAD/CAM system. Clinical try-in of the permanent onlay restoration was followed by acid etching, application of a 5th generation adhesive, and cementation of the indirect restoration. Once the restoration was cemented, rubber dam isolation was removed, followed by occlusal adjustment and polishing. After 2 years of follow-up, the restorations were esthetically and functionally satisfactory, without complications.

BACKGROUND Health information technology (IT) tools are increasingly used to improve patient care. However, implementation of English-only health IT tools could potentially worsen health disparities for non-English speakers. OBJECTIVE We aim to describe the “trans-creation” process of developing linguistically and culturally appropriate health IT tools through a detailed case analysis of a waiting room health mobile app designed to help Spanish-speaking Latino people prepare for primary care visits. METHODS We adapted the English-language Visit Planner mobile app for Spanish-speaking Latino patients. We applied culturally defined themes derived from prior published research and input by both skilled linguists and potential end users. Initial changes were iteratively reviewed and edited by a team of writers, health care educators, subject matter experts, patients, and providers. RESULTS The trans-creation process resulted in the following key culturally mediated changes to the tool: replacing the “provider” actors with “patient” actors; changing the choice of “Stress at Home or Work” (represented by an icon of a house) to “Mi Familia” (translation: my family; icon is an outline of family members holding hands); replacing the English terms “anxiety” and “depression” with “Me siento desanimado”(translation: I am feeling down) to avoid mental health stigma; and using more concise text translation to ensure the wording fit the available on-screen space. CONCLUSIONS The trans-creation process of cultural and linguistic adaptation led to several design changes that would not have been implemented if we had simply translated the words from English to Spanish.

As a part of the 6th IWGT, an expert working group on the comet assay evaluated critical topics related to the use of the in vivo comet assay in regulatory genotoxicity testing. The areas covered were: identification of the domain of applicability and regulatory acceptance, identification of critical parameters of the protocol and attempts to standardize the assay, experience with combination and integration with other in vivo studies, demonstration of laboratory proficiency, sensitivity and power of the protocol used, use of different tissues, freezing of samples, and choice of appropriate measures of cytotoxicity. The standard protocol detects various types of DNA lesions but it does not detect all types of DNA damage. Modifications of the standard protocol may be used to detect additional types of specific DNA damage (e.g., cross-links, bulky adducts, oxidized bases). In addition, the working group identified critical parameters that should be carefully controlled and described in detail in every published study protocol. In vivo comet assay results are more reliable if they were obtained in laboratories that have demonstrated proficiency. This includes demonstration of adequate response to vehicle controls and an adequate response to a positive control for each tissue being examined. There was a general agreement that freezing of samples is an option but more data are needed in order to establish generally accepted protocols. With regard to tissue toxicity, the working group concluded that cytotoxicity could be a confounder of comet results. It is recommended to look at multiple parameters such as histopathological observations, organ-specific clinical chemistry as well as indicators of tissue inflammation to decide whether compound-specific toxicity might influence the result. The expert working group concluded that the alkaline in vivo comet assay is a mature test for the evaluation of genotoxicity and can be recommended to regulatory agencies for use.

Lesser toe deformities are one of the most common conditions faced by orthopedic surgeons. Knowledge of the anatomy of the lesser toes is important for ensuring correct diagnosis and treatment of deformities, which are caused by factors such as muscle imbalance between the extensor apparatus and flexor tendons. However, this apparatus has not received sufficient attention in the literature. In addition, the large number of inaccurate and erroneous descriptions means that gaining an understanding of these structures is problematic. The objective of the present article is to clarify the anatomy of the extensor apparatus by means of a pictorial essay, in which the structures involved will be grouped and discussed in detail. The most relevant clinical implications will be addressed. Level of Evidence: Level V, expert opinion.

A committee was constituted within the International Workshop on Genetic Toxicology Testing (IWGT) to evaluate the current criteria for a valid Ames test and to provide recommendations for interpretation of test results. Currently, determination of a positive vs. a negative result is made by applying various data evaluation procedures for comparing dosed plates with the concurrent solvent control plates. These evaluation procedures include a requirement for a specific fold increase (2- or 3-fold, specific to the bacterial strain), formal statistical procedures, or subjective (expert judgment) evaluation. After extensive discussion, the workgroup was not able to reach consensus recommendations in favor of any of these procedures. There was a consensus that combining additional evaluation criteria to the comparison between dosed plates and the concurrent solvent control plates improves test interpretation. The workgroup recommended using these additional criteria because the induction of mutations is a continuum of responses and there is no biological relevance to a strict dividing line between a positive (mutagenic) and not-positive (nonmutagenic) response. The most useful additional criteria identified were a concentration-response relationship and consideration of a possible increase above the concurrent control in the context of the laboratory’s historical solvent control values for the particular tester strain. The workgroup also emphasized the need for additional testing to resolve weak or inconclusive responses, usually with altered experimental conditions chosen based on the initial results. Use of these multiple criteria allowed the workgroup to reach consensus on definitions of “clear positive” and “clear negative” responses which would not require a repeat test for clarification. The workgroup also reached consensus on recommendations to compare the responses of concurrent positive and negative controls to historical control distributions for assay acceptability, and the use of control charts to determine the validity of the individual test.

Este trabajo tiene por objetivo mostrar cómo se han tejido algunos entramados sociales, culturales y académicos alrededor de la conformación de una nueva sociedad, la sociedad de la información, mediada por lo informacional y generada principalmente por la aparición de la internet. Destaca el artículo los apuntes de referencia al uso de la web con fines académicos a partir del manejo de los rastreos bibliográficos. Se pretende, además, que los maestros pongan la mirada en algunos principios propios del quehacer docente como son la enseñanza, la puesta en práctica del currículo oculto y el manejo de la didáctica para el uso de la información virtual en el aula.Palabras clave: rastreo bibliográfico, ciberespacio, autopista electrónica, investigación, realidad virtual.

The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) Project Committee on the Relevance and Follow-up of Positive Results in In Vitro Genetic Toxicity (IVGT) Testing established an Emerging Technologies and New Strategies Workgroup to review the current State of the Art in genetic toxicology testing. The aim of the workgroup was to identify promising technologies that will improve genotoxicity testing and assessment of in vivo hazard and risk, and that have the potential to help meet the objectives of the IVGT. As part of this initiative, HESI convened a workshop in Washington, DC in May 2008 to discuss mature, maturing, and emerging technologies in genetic toxicology. This article collates the abstracts of the New and Emerging Technologies Workshop together with some additional technologies subsequently considered by the workgroup. Each abstract (available in the online version of the article) includes a section addressed specifically to the strengths, weaknesses, opportunities, and threats associated with the respective technology. Importantly, an overview of the technologies and an indication of how their use might be aligned with the objectives of IVGT are presented. In particular, consideration was given with regard to follow-up testing of positive results in the standard IVGT tests (i.e., Salmonella Ames test, chromosome aberration assay, and mouse lymphoma assay) to add weight of evidence and/or provide mechanism of action for improved genetic toxicity risk assessments in humans.

Las macrófitas acuáticas han sido utilizadas en procesos de biorremediación, ya que pueden absorber algunas sustancias disueltas y producir oxígeno mediante fotosíntesis. Con base en los estudios de remoción de compuestos tóxicos por parte de plantas acuáticas que permitan la depuración de aguas residuales, la presente investigación tuvo como propósito principal buscar la disminución de la contaminación por cianuro y la toxicidad de las aguas residuales del lavado de arena del proceso de cianuración de oro de la mina La Coqueta, mediante la utilización de macrófitas acuáticas flotantes (Eichhornia crassipes,Pistia stratiotesSalvinia auriculata); además, de acuerdo con los resultados de pruebas cualitativas, encontrar el destino final del cianuro en las plantas al ser absorbidos por éstas. El tratamiento de agua cianurada se realizó mediante un sistema de acuarios, los cuales contenían el agua proveniente de la mina, en ellos se depositaron las plantas para el tratamiento, se tomaron parámetros fisicoquímicos de control (pH, porcentaje de saturación de oxígeno y conductividad), además de la determinación de cianuro y toxicidad en el agua, pruebas cualitativas de compuestos nitrogenados en las plantas y bioensayos conDaphnia pulexen las plantas y en el agua tratada. Con base en los resultados de las pruebas cualitativas, se evidenció que las macrófitas pueden cambiar su metabolismo en condiciones de estrés y este cambio de metabolismo induce también a que se produzcan otro tipo de metabolitos secundarios no presentes naturalmente (e. g. glicósidos cianogénicos y alcaloides) en las plantas sometidas al tratamiento.La remoción de cianuro por parte de estas especies fue hasta del 86% al final del tratamiento, demostrando gran eficiencia para remover compuestos tóxicos del agua cianurada proveniente de la mina La Coqueta, ya que en los bioensayos realizados conDaphnia pulexindicaron que estos organismos podían resistir a las características del agua después del tratamiento con las plantas. Señalando que se puede realizar un tratamiento natural, ambientalmente seguro y económicamente viable que permita descontaminar el agua cianurada proveniente del lavado de las arenas del beneficio del oro a través del proceso de cianuración. Aquatic macrophytes have been used in bioremediation processes, as they can absorb some dissolved substances and produce oxygen through photosynthesis. Based on the studies of toxic compounds removal by aquatic plants that allow wastewater treatment, this research had as main purpose to search the reduction of cyanide contamination and toxicity of waste water from sand washing in the cyanidation process inLa Coquetagold mine by means of the use of floating aquatic macrophytes (Eichhornia crassipes, Salvinia auriculata, Pistiastratiotes). Similarly, according to the results of qualitative tests, a goal was to find the final destiny of cyanide afterplants had absorbed it. Treatment of cyanide water was conducted through a system of tanks containing water from the mine in which plants for treatment were included and physicochemical control parameters (pH, oxygen saturation percentage and conductivity) were taken. Besides determination of cyanide and water toxicity, qualitative testsof nitrogenous compounds in plants and bioassays withDaphnia pulexin plants and in the treated water were determined. Based on the results of qualitative tests ti was evidenced that macrophytes can change their metabolism under stress conditions and this change in metabolism also induces the production of other types of secondary metabolites not present naturally (e.g. cyanogenic glycosides and alkaloids) in plants subjected to treatment. The removal of cyanide by these species was up to 86% at end of treatment, showing high efficiency for removal of toxic compounds of cyanide water fromLa Coquetamine, as bioassays conducted usingDaphnia pulexindicated that these organism could resist water characteristics after treatment with plants, noting that natural treatment environmentally safe and economically feasible can be made to decontaminate cyanide water from the washing of sands resulting from cyanide gold processing.

Acute myeloid leukaemia (AML) is associated with exposure to benzene and treatment with chemotherapeutic agents. It is thought to arise from damage to specific regions of DNA, resulting in chromosome rearrangements or loss. For instance, a deletion on the long arm of chromosome 5 [e.g. del(5q31)] is common in AML patients previously treated with alkylating agents, such as melphalan, or exposed to benzene. Translocations of the MLL gene at 11q23 are frequently observed in AML arising from treatment with topoisomerase II inhibitors, such as etoposide. Our goal was to determine whether or not breakage at 5q31 and 11q23 is selectively induced by these chemical agents. To address this question, the comet assay combined with fluorescence in situ hybridization (comet-FISH) was used to detect DNA breakage in the specific chromosomal regions in an in vitro model. TK6 lymphoblastoid cells were exposed to melphalan, etoposide or the benzene metabolite, hydroquinone (HQ), at various concentrations. HQ, melphalan and etoposide induced DNA breaks at both 5q31 and 11q23 chromosome regions in a dose-dependant manner. However, HQ produced significantly more DNA damage at 5q31 than at 11q23. Etoposide produce slightly more DNA damage at 11q23 and melphalan had a somewhat greater effect at 5q31, but not significantly so. Thus, HQ and melphalan act similarly, perhaps explaining some similarities between benzene- and alkylating agent-induced AML. Comet-FISH also appears to be a useful approach for detecting and comparing damage to specific chromosome regions of significance in leukaemogenesis.

As part of the Fourth International Workshop on Genotoxicity Testing (IWGT), held 9-10 September 2005 in San Francisco, California, an expert working group on the Comet assay was convened to review and discuss some of the procedures and methods recommended in previous documents. Particular attention was directed at the in vivo rodent, alkaline (pH >13) version of the assay. The aim was to review those protocol areas which were unclear or which required more detail in order to produce a standardized protocol with maximum acceptability by international regulatory agencies. The areas covered were: number of dose levels required, cell isolation techniques, measures of cytotoxicity, scoring of comets (i.e., manually or by image analysis), and the need for historical negative/positive control data. It was decided that a single limit dose was not sufficient although the required number of dose levels was not stipulated. The method of isolating cells was thought not to have a qualitative effect on the assay but more data were needed before a conclusion could be drawn. Concurrent measures of cytotoxicity were required with histopathological examination of tissues for necrosis or apoptosis as the "Gold Standard". As for analysing the comets, the consensus was that image analysis was preferred but not required. Finally, the minimal number of studies required to generate a historical positive or negative control database was not defined; rather the emphasis was placed on demonstrating the stability of the negative/positive control data. It was also agreed that a minimum reporting standard would be developed which would be consistent with OECD in vivo genotoxicity test method guidelines.

The genotoxicity of zidovudine (AZT) based treatments was investigated in human H9 lymphoblastoid cells in an in vitro study and in red blood cells (RBCs) from perinatally exposed HIV-1-infected mothers and their infants in an observational cohort study. Exposure of H9 cells for 24 hr to AZT produced dose-dependent increases in Comet assay tail moment (TM) when electrophoresed at pH 13.0, but not at pH 12.1 or pH 8.0, suggesting that DNA damage was via alkali-labile lesions and not double-stranded DNA strand breaks. The TM dose response at pH 13.0 correlated directly with AZT-DNA incorporation determined by AZT-radioimmunoassay. Levels of DNA damage in utero, measured by Comet assay TM, were similar in cord blood mononuclear cells of nucleoside analog-exposed newborns (n = 43) and unexposed controls (n = 40). In contrast, the glycophorin A (GPA) somatic cell mutation assay (which screens for large-scale DNA damage in RBCs) showed clear evidence that GPA N/N variants, arising from chromosome loss and duplication, somatic recombination, and gene conversion, were significantly elevated in mother–child pairs receiving prepartum AZT plus lamivudine (3TC). Cord blood from newborns exposed to AZT-3TC had GPA N/N variant frequencies of 4.7 ± 0.7 (mean ± SE) × 10−6 RBCs (n = 26 infants) compared with 2.2 ± 0.3 × 10−6 RBCs for unexposed controls (n = 30 infants; P < 0.001). Elevations in GPA N/N variants generally persisted through 1 year of age in nucleoside analog-exposed children. Overall, the mutagenic effects found in mother–child pairs receiving AZT-based treatments justify their surveillance for long-term genotoxic consequences. Environ. Mol. Mutagen., 2007. © 2007 Wiley-Liss, Inc.

Cuando hablamos de las “rebeldías de los maestros”, lo hacemos desde el proceso interior del ser educador, nos referimos a aquellas posturas crí-ticas y reveladoras, exigiéndonos transitar por varios escenarios: nuestras autobiografías que han develado las huellas epocales y rebeldías que de una u otra forma se conectan con diferentes historias de maestros; y de acontecimientos transcurridos a partir de la década de los 60, en donde se manifiesta una realidad política, económica, educativa, y religiosa, trans-versalidas por el desarrollo y las experiencias como maestros; el exilio, el silencio, las rebeldías, el revelarse, la desesperanza y el poder, aspectos que marcan el camino recorrido y por recorrer, levantando códigos y ca-tegorías que influyen en el quehacer docente; la innovación, pertinencia y utilidad de la investigación, partiendo del sujeto en relación con los otros, transformándose a sí mismo y a los demás, pero sobre todo, donde surgen nuevas posturas que rompen el silencio, el aquietamiento y la tranquilidad; permitiéndonos a través de nuevos códigos, rebelarnos.

La investigación es realizada en el restaurante de comidas rápidas FRISBY S.A de la ciudad de Pereira durante el año 2015, para conocer sus dinámicas de endomarketing y la construcción de marca. Va dirigida a los colaboradores de los restaurantes FRISBY S.A de Pereira de forma cualitativa. El endomarketing ha sido estudiado desde hace más de 25 años; Berry es una de las mayores referencias y un pionero del endomarketing; pues, en 1981 fue el primero en llamar a los empleados clientes internos. Este enfoque surgió por la necesidad de mejorar la gestión de personas y la atención a los clientes. El tratamiento empírico incentivó diversas interpretaciones y conceptualizaciones sobre el tema; como consecuencia surgieron distintas aplicaciones en la forma de desarrollo de metodologías con algunos puntos en común como la satisfacción del empleado y el cliente. Elendomarketing, es un conjunto de estrategias que se han empezado a implementar en un gran número de empresas alrededor del mundo. Estas estrategias están orientadas a “vender” la empresa a los propios empleados que la conforman y tengan sentido de pertenencia. Los recursos humanos son una de las mayores bases para una organización y la obtención de una ventaja competitiva aplicada en uno de los modelos de marketing interno como lo es el modelo de Berry. De esta dinámica, se genera la importancia del análisis de la gestión de recursos. Por ello; en el restaurante de comidas rápidas pereirano, FRISBY S.A, se analiza la evolución, desarrollo y dinámicas del marketing interno. The research is conducted in the fast food restaurant FRISBY SA City Pereira during the year 2015 to meet the dynamics of endomarketing and brand building. It is intended for employees of restaurants FRISBY SA de Pereira qualitatively. The endomarketing has been studied for over 25 years; Berry is one of the major references and a pioneer of endomarketing; So in 1981 he was the first to call internal clients to employees. This approach arose from the need to improve people management and customer service. Empirical treatment stimulated different interpretations and conceptualizations on the subject; as a result different applications emerged in the form of development methodologies with some points in common as employee satisfaction and customer. The endomarketing, is a set of strategies that have begun to implement a large number of companies around the world. These strategies are intended to "sell" the company to the employees that form and make sense of belonging. Human resources are one of the largest bases for an organization and gaining a competitive advantage applied to one of the internal marketing models such as the model of Berry. In this dynamic, the importance of analyzing the management of resources is generated. Thus; Pereira, in fast food restaurant, FRISBY SA, evolution, development and marketing of the internal dynamics is analyzed.

The in vivo rodent alkaline comet assay (comet assay) is used internationally to investigate the in vivo genotoxic potential of test chemicals. This assay, however, has not previously been formally validated. The Japanese Center for the Validation of Alternative Methods (JaCVAM), with the cooperation of the U.S. NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM)/the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), the European Centre for the Validation of Alternative Methods (ECVAM), and the Japanese Environmental Mutagen Society/Mammalian Mutagenesis Study Group (JEMS/MMS), organized an international validation study to evaluate the reliability and relevance of the assay for identifying genotoxic carcinogens, using liver and stomach as target organs. The ultimate goal of this validation effort was to establish an Organisation for Economic Co-operation and Development (OECD) test guideline. The purpose of the pre-validation studies (i.e., Phase 1 through 3), conducted in four or five laboratories with extensive comet assay experience, was to optimize the protocol to be used during the definitive validation study.

The in vivo rodent alkaline comet assay (comet assay) is used internationally to investigate the in vivo genotoxic potential of test chemicals. This assay, however, has not previously been formally validated. The Japanese Center for the Validation of Alternative Methods (JaCVAM), with the cooperation of the U.S. NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM)/the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), the European Centre for the Validation of Alternative Methods (ECVAM), and the Japanese Environmental Mutagen Society/Mammalian Mutagenesis Study Group (JEMS/MMS), organized an international validation study to evaluate the reliability and relevance of the assay for identifying genotoxic carcinogens, using liver and stomach as target organs. The ultimate goal of this exercise was to establish an Organisation for Economic Co-operation and Development (OECD) test guideline. The study protocol was optimized in the pre-validation studies, and then the definitive (4th phase) validation study was conducted in two steps. In the 1st step, assay reproducibility was confirmed among laboratories using four coded reference chemicals and the positive control ethyl methanesulfonate. In the 2nd step, the predictive capability was investigated using 40 coded chemicals with known genotoxic and carcinogenic activity (i.e., genotoxic carcinogens, genotoxic non-carcinogens, non-genotoxic carcinogens, and non-genotoxic non-carcinogens). Based on the results obtained, the in vivo comet assay is concluded to be highly capable of identifying genotoxic chemicals and therefore can serve as a reliable predictor of rodent carcinogenicity.

Este artículo describe y analiza el desarrollo de la formación continua de la Pontificia Universidad Católica del Perú (PUCP) entre los años 2007 y 2013. Es un estudio descriptivo en el que se utilizan datos estadísticos del crecimiento económico del Perú en la última década (2001-2013), del aumento en el número de universidades del país y del desarrollo de la oferta formativa de la PUCP, tanto del pregrado como de la formación continua. La información estadística es comparada y analizada junto con una descripción de la regulación y el ordenamiento interno de la formación continua de la PUCP, para proponer que el cuidado por la calidad académica no está necesariamente en contradicción con el crecimiento cuantitativo de la oferta en materia de formación continua.

Alterations in matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) have been implicated in adverse left ventricular (LV) remodeling after myocardial infarction (MI). However, the direct mechanistic role of TIMPs in the post-MI remodeling process has not been completely established. The goal of this project was to define the effects of altering endogenous MMP inhibitory control through combined genetic and pharmacological approaches on post-MI remodeling in mice. This study examined the effects of MMP inhibition (MMPi) with PD-166793 (30 mg·kg−1·day−1) on LV geometry and function (conductance volumetry) after MI in wild-type (WT) mice and mice deficient in the TIMP-1 gene [TIMP-1 knockout (TIMP1-KO)]. At 3 days after MI (coronary ligation), mice were randomized into four groups: WT-MI/MMPi ( n = 10), TIMP1-KO-MI/MMPi ( n = 10), WT-MI ( n = 22), and TIMP1-KO-MI ( n = 23). LV end-diastolic volume (EDV) and ejection fraction were determined 14 days after MI. Age-matched WT ( n = 20) and TIMP1-KO ( n = 28) mice served as reference controls. LVEDV was similar under control conditions in WT and TIMP1-KO mice (36 ± 2 and 40 ± 2 μl, respectively) but was greater in TIMP1-KO-MI than in WT-MI mice (48 ± 2 vs. 61 ± 5 μl, P < 0.05). LVEDV was reduced from MI-only values in WT-MI/MMPi and TIMP1-KO-MI/MMPi mice (42 ± 2 and 36 ± 2 μl, respectively, P < 0.05) but was reduced to the greatest degree in TIMP1-KO mice ( P < 0.05). LV ejection fraction was reduced in both groups after MI and increased in TIMP1-KO-MI/MMPi, but not in WT-MI/MMPi, mice. These unique results demonstrated that myocardial TIMP-1 plays a regulatory role in post-MI remodeling and that the accelerated myocardial remodeling induced by TIMP-1 gene deletion can be pharmacologically “rescued” by MMP inhibition. These results define the importance of local endogenous control of MMP activity with respect to regulating LV structure and function after MI.