Subcutaneous infliximab cut-off points in patients with inflammatory bowel disease. Data from the ENEIDA registry.

BACKGROUND AND AIMS: Switching from the intravenous to the subcutaneous biosimilar infliximab (SC-IFX) has been shown to safely maintain clinical remission and increase drug levels in patients with Crohn's disease (CD) and ulcerative colitis (UC). The aim of this study was to evaluate long-term outcomes after switching from intravenous IFX (IV-IFX) to SC-IFX, the drug concentration thresholds for maintaining remission and other predictors for loss of response after the switch. METHODS: Multicenter observational study involving CD and UC patients who were in clinical remission for at least 24 weeks and scheduled to switch from IV-IFX to SC-IFX. RESULTS: Two hundred and twenty patients were included [74 UC (34%) and 146 (66%) CD]. IV-IFX was administered for 52.5 months [range 25-89]. Pre-switch, 106 (49%) patients were receiving intensified IV-IFX. While SC-IFX levels significantly increased following the switch from IV to SC-IFX, clinical parameters, C-reactive protein and faecal calprotectin remained unchanged during follow-up. SC-IFX levels were significantly higher between patients receiving the standard IV-IFX dose than those with the intensified dose. Immunomodulator therapy at baseline and perianal disease had no effect on IFX trough levels, whereas higher body mass index was associated with increased levels. The suggested optimal SC-IFX cut-off concentration for clinical and biochemical remission based on ROC analysis was 12.2 µg/mL (AUC: 0.62) at week 12 and 13.2 µg/mL (AUC: 0.57) at week 52. Drug persistence was 92% at week 52, with a good safety profile. CONCLUSION: Switching from IV-IFX to SC-IFX safely maintains long-term remission in patients with CD and UC. In maintenance, the optimal cut-off point associated with remission was 12-13 µg/mL.

The detrimental role of galectin-3 and endoplasmic reticulum stress in the cardiac consequences of myocardial ischemia in the context of obesity.

The association between cardiac fibrosis and galectin-3 was evaluated in patients with acute myocardial infarction (MI). The role of galectin-3 and its association with endoplasmic reticulum (ER) stress activation in the progression of cardiovascular fibrosis was also evaluated in obese-infarcted rats. The inhibitor of galectin-3 activity, modified citrus pectin (MCP; 100 mg/kg/day), and the inhibitor of the ER stress activation, 4-phenylbutyric acid (4-PBA; 500 mg/kg/day), were administered for 4 weeks after MI in obese rats. Overweight-obese patients who suffered a first MI showed higher circulating galectin-3 levels, higher extracellular volume, and LV infarcted size, as well as lower E/e'ratio and LVEF compared with normal-weight patients. A correlation was observed between galectin-3 levels and extracellular volume. Obese-infarcted animals presented cardiac hypertrophy and reduction in LVEF, and E/A ratio as compared with control animals. They also showed an increase in galectin-3 gene expression, as well as cardiac fibrosis and reduced autophagic flux. These alterations were associated with ER stress activation characterized by enhanced cardiac levels of binding immunoglobulin protein, which were correlated with those of galectin-3. Both MCP and 4-PBA not only reduced cardiac fibrosis, oxidative stress, galectin-3 levels, and ER stress activation, but also prevented cardiac functional alterations and ameliorated autophagic flux. These results show the relevant role of galectin-3 in the development of diffuse fibrosis associated with MI in the context of obesity in both the animal model and patients. Galectin-3 in tandem with ER stress activation could modulate different downstream mechanisms, including inflammation, oxidative stress, and autophagy.

Methodology for the induction of myocardial infarction and cardiac function evaluation.

Cardiovascular disease (CVD) is the main cause of death worldwide, with myocardial infarction (MI) being the most prevalent pathology involved in CVD. MI is characterized by a deficiency in oxygen supply to the myocardium, thereby promoting ventricular remodeling of the ischemic and remote zone of the heart. Cardiac remodeling associated with MI could promote the development of heart failure and finally death. For these reasons, it is important to develop animal models that mimic human cardiac disease which could help to identify new mechanisms involved in the pathology and, consequently, develop new therapeutic strategies. We herein describe in detail a protocol for MI induction with low mortality rate (<15%) in rats by ligation of the left anterior descending artery. In addition, we also describe two imaging techniques which allow to evaluate cardiac structure and function-including deformation parameters in rats such as transthoracic echocardiography and cardiac magnetic resonance. This animal model could be useful for acute and chronic studies and for evaluating the potential usefulness of different treatments.

Mechanical Determinants of Sprinting and Change of Direction in Elite Female Field Hockey Players.

Profile determination in field hockey is critical to determining athletes' physical strengths and weaknesses, and is key in planning, programming, and monitoring training. This study pursued two primary objectives: (i) to provide descriptive data on sprinting, deceleration, and change of direction (COD) abilities and (ii) to elucidate the mechanical variables that influence sprint and COD performance in elite female field hockey players. Using radar and time-gate technology, we assessed performance and mechanical data from 30 m sprinting, deceleration, and COD tests for 26 elite female hockey players. A machine learning approach identified mechanical variables related to sprint and COD performance. Our findings offer a framework for athlete categorization and the design of performance-enhancing training strategies at the international level. Two pivotal mechanical variables-relative maximum horizontal force (F0) and maximum velocity (Vmax)-predominantly influence the times across all tested distances. However, the force-velocity profile (FVP) and horizontal deceleration do not influence the variance in the COD test outcomes. These insights can guide the design, adjustment, and monitoring of training programs, assisting coaches in decision making to optimize performance and mitigate injury risks for female hockey players.

Negative effects of the spatial clumping of thermal resources on lizard thermoregulation in a fragmented habitat.

In ecosystems threatened by the expansion of croplands, habitat fragmentation and climate change, two of the main extinction drivers, may have thermoregulation-mediated interacting effects on demographic trends of terrestrial ectotherms. We studied the thermal biology of a metapopulation of the widespread Mediterranean lacertid Psammodromus algirus in ten fragments of evergreen or deciduous oak forests interspersed among cereal fields. We obtained thermoregulation statistics (selected temperature range, body and operative temperatures, thermal quality of the habitat, and precision, accuracy, and effectiveness of thermoregulation) that could be compared among fragments and with conspecific populations living in unfragmented habitat. We also measured the selection (use vs. availability) and spatial distribution of sunlit and shaded patches used for behavioral thermoregulation in fragments, and we estimated operative temperatures and thermal habitat quality in the agricultural matrix surrounding the fragments. Variation of the thermal environment was much larger within fragments than among them, and thermoregulation was accurate, precise, and efficient throughout the fragmented landscape; its effectiveness was similar to that of previously studied unfragmented populations. The average distance between sunlit and shaded patches was shorter in deciduous than in evergreen fragments, producing a more clumped distribution of the mosaic of thermal resources. Consequently, in evergreen habitat the cost of thermoregulation was higher, because lizards were more selective in their choice of sunlit sites (i.e. they used sunlit patches closer to shade and refuge than expected at random, and the extent of such selection was larger than at deciduous habitat). Temperatures available in croplands were too high to allow lizard dispersal, at least in the post-breeding season. This result confirms the role of croplands as a thermal barrier that promotes inbreeding and associated fitness losses in isolated fragments, and it forecasts a dark future for populations of forest lizards in agricultural landscapes under the combined effects of habitat fragmentation and global warming.

Data mining assessment of Poaceae pollen influencing factors and its environmental implications.

Poaceae pollen is highly allergenic, with a marked contribution to the pollen worldwide allergy prevalence. Pollen counts are defined by the species present in the considered area, although year-to-year oscillations may be triggered by different parameters, among which are weather conditions. Due to the predominant role of Poaceae pollen in the allergenicity in urban green areas, the aim of this study was the analysis of pollen trends and the influence of meteorology to forecast relevant variations in airborne pollen levels. The study was carried out during the 1993-2020 period in Ourense, in NW Iberian Peninsula. We used a volumetric Lanzoni VPPS 2000 trap for recording Poaceae airborne pollen grains, and meteorological daily data were obtained from the Galician Institute for Meteorology and Oceanography. The main indexes of the pollen season and their trends were calculated. A correlation analysis and 'C5.0 Decision Trees and Rule-Based Models' data mining algorithm were applied to determine the influence of meteorological conditions on pollen levels. We detected atmospheric Poaceae pollen during 139 days on average, mainly from April to August. The mean pollen grains amount recorded during the pollen season was 4608 pollen grains, with the pollen maximum peak of 276 pollen/m3 on 27 June. We found no statistically significant trends and slight slopes for the seasonal indexes, similarly to previous Poaceae studies in the same region. The calculated C5.0 model offered defined results, indicating that the combination of mean temperature above 17.46 °C and sunlight exposure higher than 12.7 h is conductive to significantly high pollen levels. The obtained results make possible the identification of risk moments during the pollen season for the activation of protective measures for sensitized population to grass pollen.

Changes in the Mechanical Properties of the Horizontal Force-Velocity Profile during a Repeated Sprint Test in Professional Soccer Players.

The objective was to analyze the changes in the horizontal force-velocity profile (HFVP) during the execution of repeated sprinting. Methods: Seventeen first-division Chilean soccer players completed a repeated sprint protocol consisting of eight sprints of 30 m with 25-s pauses between repetitions. The behavior of HFVP variables in each attempt was recorded from video recordings and analysis in the MySprint® application. Results: Differences (p < 0.05) were found between sprints in the following: time (T), starting from sprint 5 (F = 35.6; η2p = 0.69); theoretical maximum speed (V0), starting from sprint 4 (F = 29.3; η2p = 0.51); maximum power (PM), starting from sprint 5 (F = 17; η2p = 0.52); rate of decrease in force index produced at each step (DRF), starting from sprint 1 (F = 3.20; η2p = 0.17); and RF10, starting from sprint 1 (F = 15.5; η2p = 0.49). In comparison, F0 and RFpeak did not present any differences (p > 0.05). Conclusion: The HFVP variables more sensitive to the effects of fatigue induced by an RSA protocol are those associated with the production of force at high speeds, being V0, DRF, and Pmax, while those that contribute to the generation of force at the beginning of the sprint, F0 and RFpeak, do not present essential variations.

Environmental association modelling with loci under divergent selection predicts the distribution range of a lizard.

During the historical building of a species range, individual colonizers have to confront different ecological challenges, and the capacity of the species to broaden its range may depend on the total amount of adaptive genetic variation supplied by evolution. We set out to increase our understanding of what defines a range and the role of underlying genetics by trying to predict an entire species' range from the geographical distribution of its genetic diversity under selection. We sampled five populations of the western Mediterranean lizard Psammodromus algirus that inhabit a noticeable environmental gradient of temperature and precipitation. We correlated the genotypes of 95 individuals (18-20 individuals per population) for 21 SNPs putatively under selection with environmental scores on a bioclimatic gradient, using 1 × 1 km2  grid cells as sampling units. By extrapolating the resulting model to all possible combinations of alleles, we inferred all the geographic cells that were theoretically suitable for a given amount of genetic variance under selection. The inferred distribution range overlapped to a large extent with the realized range of the species (77.46% of overlap), including an accurate prediction of internal gaps and range borders. Our results suggest an adaptability threshold determined by the amount of genetic variation available that would be required to warrant adaptation beyond a certain limit of environmental variation. These results support the idea that the expansion of a species' range can be ultimately linked to the arising of new variants under selection (either newly selected variants from standing genetic variation or innovative mutations under selection).

Adaptive Divergence under Gene Flow along an Environmental Gradient in Two Coexisting Stickleback Species.

There is a general and solid theoretical framework to explain how the interplay between natural selection and gene flow affects local adaptation. Yet, to what extent coexisting closely related species evolve collectively or show distinctive evolutionary responses remains a fundamental question. To address this, we studied the population genetic structure and morphological differentiation of sympatric three-spined and nine-spined stickleback. We conducted genotyping-by-sequencing and morphological trait characterisation using 24 individuals of each species from four lowland brackish water (LBW), four lowland freshwater (LFW) and three upland freshwater (UFW) sites in Belgium and the Netherlands. This combination of sites allowed us to contrast populations from isolated but environmentally similar locations (LFW vs. UFW), isolated but environmentally heterogeneous locations (LBW vs. UFW), and well-connected but environmentally heterogenous locations (LBW vs. LFW). Overall, both species showed comparable levels of genetic diversity and neutral genetic differentiation. However, for all three spatial scales, signatures of morphological and genomic adaptive divergence were substantially stronger among populations of the three-spined stickleback than among populations of the nine-spined stickleback. Furthermore, most outlier SNPs in the two species were associated with local freshwater sites. The few outlier SNPs that were associated with the split between brackish water and freshwater populations were located on one linkage group in three-spined stickleback and two linkage groups in nine-spined stickleback. We conclude that while both species show congruent evolutionary and genomic patterns of divergent selection, both species differ in the magnitude of their response to selection regardless of the geographical and environmental context.

Low genome-wide divergence between two lizard populations with high adaptive phenotypic differentiation.

Usually, adaptive phenotypic differentiation is paralleled by genetic divergence between locally adapted populations. However, adaptation can also happen in a scenario of nonsignificant genetic divergence due to intense gene flow and/or recent differentiation. While this phenomenon is rarely published, findings on incipient ecologically driven divergence or isolation by adaptation are relatively common, which could confound our understanding about the frequency at which they actually occur in nature. Here, we explore genome-wide traces of divergence between two populations of the lacertid lizard Psammodromus algirus separated by a 600 m elevational gradient. These populations seem to be differentially adapted to their environments despite showing low levels of genetic differentiation (according to previously studies of mtDNA and microsatellite data). We performed a search for outliers (i.e., loci subject to selection) trying to identify specific loci with FST statistics significantly higher than those expected on the basis of overall, genome-wide estimates of genetic divergence. We find that local phenotypic adaptation (in terms of a wide diversity of characters) was not accompanied by genome-wide differentiation, even when we maximized the chances of unveiling such differentiation at particular loci with FST-based outlier detection tests. Instead, our analyses confirmed the lack of genome-wide differentiation on the basis of more than 70,000 SNPs, which is concordant with a scenario of local adaptation without isolation by environment. Our results add evidence to previous studies in which local adaptation does not lead to any kind of isolation (or early stages of ecological speciation), but maintains phenotypic divergence despite the lack of a differentiated genomic background.

Comparative Metagenomics of Palearctic and Neotropical Avian Cloacal Viromes Reveal Geographic Bias in Virus Discovery.

Our understanding about viruses carried by wild animals is still scarce. The viral diversity of wildlife may be best described with discovery-driven approaches to the study of viral diversity that broaden research efforts towards non-canonical hosts and remote geographic regions. Birds have been key organisms in the transmission of viruses causing important diseases, and wild birds are threatened by viral spillovers associated with human activities. However, our knowledge of the avian virome may be biased towards poultry and highly pathogenic diseases. We describe and compare the fecal virome of two passerine-dominated bird assemblages sampled in a remote Neotropical rainforest in French Guiana (Nouragues Natural Reserve) and a Mediterranean forest in central Spain (La Herrería). We used metagenomic data to quantify the degree of functional and genetic novelty of viruses recovered by examining if the similarity of the contigs we obtained to reference sequences differed between both locations. In general, contigs from Nouragues were significantly less similar to viruses in databases than contigs from La Herrería using Blastn but not for Blastx, suggesting that pristine regions harbor a yet unknown viral diversity with genetically more singular viruses than more studied areas. Additionally, we describe putative novel viruses of the families Picornaviridae, Reoviridae and Hepeviridae. These results highlight the importance of wild animals and remote regions as sources of novel viruses that substantially broaden the current knowledge of the global diversity of viruses.

Diez años de incidentes críticos pediátricos declarados en el Sistema Español de Notificación en Seguridad en Anestesia y Reanimación / Ten years of pediatric critical incidents reported in the Spanish Anesthesia Safety Notification System

OBJETIVES: The aim of this study is to analyze all the pediatric critical incidents (PCI) reported in the Spanish Anesthesiology and Reanimation Safety Notification System in ten years time. MATERIALS AND METHODS: We reviewed all the critical incidents (CI) reported between the years 2009 and 2018 in SEN- SAR online database and we selected those related to newborns and children up to 16 years. RESULTS: 9480 CI were declared; 474 were pediatrics. Infants accounted for the 36% of the PCI, of whom the 44% were children under the age of one. Most of them affected to healthy patients (the 66%) and took place in the operating room (the 49%), during general pediatric surgery (the 19%), otorhinolaryngology (the 15%), orthopedic (the 13%) and radiology procedures (the 5%). The majority of them were medications errors (the 24%), followed by clinical incidents (the 18%) and equipment-related events (14%). Human factor accounted for the 42% of reports ­ both of them in its individual characteristics (the 25%) and in team performance (the 15%). Up to the 30% of the children suffered consequences derived from the incidents. Two fatal events were recorded, both airway related. Improvement measures were de- signed and implemented in the 93% of them. CONCLUSIONS: Designing studies that shed light on the causes of the relative inefficiency of CI Reporting Systems and the factors that condition a lower rate of CI communication in the pediatric setting in comparison with the adult population is necessary.

OBJETIVOS: Realizar un análisis retrospectivo de todos los incidentes críticos pediátricos (ICP) declarados en el Sistema Español de Notificación en Seguridad en Anestesia y Reanimación en sus primeros diez años. MATERIAL Y MÉTODOS: Se realizó una revisión de los incidentes críticos (IC) declarados entre el 1 de enero de 2009 y el 31 de diciembre de 2018. Se seleccionaron los IC acontecidos en pacientes de 0 a 16 años de edad. RESULTADOS: De los 9.480 IC declarados en ese período, 474 fueron ICP. El 36% ocurrió en lactantes menores de dos años, de los que el 44% fueron menores de un año. La mayoría (66%) ocurrieron en pacientes sanos y tuvieron lugar en quirófano (49%), durante procedimientos de cirugía general pediátrica (19%), de otorrinolaringología (15%), de traumatología (13%) y de radiología (5%). El tipo de IC más declarado fueron los errores de medicación (24%), seguidos de los incidentes clínicos (18%) y de los errores de equipamiento (14%). El factor humano estuvo implicado en el 42% de los IC, tanto en su faceta del individuo (25%) como en las relaciones en equipo (15%). El 30% de los pacientes sufrieron daño. Se registraron dos fallecimientos derivados del incidente, ambos relacionados con la vía aérea. Se implementaron medidas de mejora en un 93% de los casos. CONCLUSIONES: Es necesario profundizar en las causas de la ineficiencia relativa de los Sistemas de Declaración de IC y en las que condicionan una menor tasa de comunicación de IC en el ámbito pediátrico respecto al adulto.

Imaging the Human Immunological Synapse.

The purpose of the method is to generate an immunological synapse (IS), an example of cell-to-cell conjugation formed by an antigen-presenting cell (APC) and an effector helper T lymphocyte (Th) cell, and to record the images corresponding to the first stages of the IS formation and the subsequent trafficking events (occurring both in the APC and in the Th cell). These events will eventually lead to polarized secretion at the IS. In this protocol, Jurkat cells challenged with Staphylococcus enterotoxin E (SEE)-pulsed Raji cells as a cell synapse model was used, because of the closeness of this experimental system to the biological reality (Th cell-APC synaptic conjugates). The approach presented here involves cell-to-cell conjugation, time-lapse acquisition, wide-field fluorescence microscopy (WFFM) followed by image processing (post-acquisition deconvolution). This improves the signal-to-noise ratio (SNR) of the images, enhances the temporal resolution, allows the synchronized acquisition of several fluorochromes in emerging synaptic conjugates and decreases fluorescence bleaching. In addition, the protocol is well matched with the end point cell fixation protocols (paraformaldehyde, acetone or methanol), which would allow further immunofluorescence staining and analyses. This protocol is also compatible with laser scanning confocal microscopy (LSCM) and other state-of-the-art microscopy techniques. As a main caveat, only those T cell-APC boundaries (called IS interfaces) that were at the right 90° angle to the focus plane along the Z-axis could be properly imaged and analyzed. Other experimental models exist that simplify imaging in the Z dimension and the following image analyses, but these approaches do not emulate the complex, irregular surface of an APC, and may promote non-physiological interactions in the IS. Thus, the experimental approach used here is suitable to reproduce and to confront some biological complexities occurring at the IS.

The combined use of raw and phylogenetically independent methods of outlier detection uncovers genome-wide dynamics of local adaptation in a lizard.

Local adaptation is a dynamic process by which different allele combinations are selected in different populations at different times, and whose genetic signature can be inferred by genome-wide outlier analyses. We combined gene flow estimates with two methods of outlier detection, one of them independent of population coancestry (CIOA) and the other one not (ROA), to identify genetic variants favored when ecology promotes phenotypic convergence. We analyzed genotyping-by-sequencing data from five populations of a lizard distributed over an environmentally heterogeneous range that has been changing since the split of eastern and western lineages ca. 3 mya. Overall, western lizards inhabit forest habitat and are unstriped, whereas eastern ones inhabit shrublands and are striped. However, one population (Lerma) has unstriped phenotype despite its eastern ancestry. The analysis of 73,291 SNPs confirmed the east-west division and identified nonoverlapping sets of outliers (12 identified by ROA and 9 by CIOA). ROA revealed ancestral adaptive variation in the uncovered outliers that were subject to divergent selection and differently fixed for eastern and western populations at the extremes of the environmental gradient. Interestingly, such variation was maintained in Lerma, where we found high levels of heterozygosity for ROA outliers, whereas CIOA uncovered innovative variants that were selected only there. Overall, it seems that both the maintenance of ancestral variation and asymmetric migration have counterbalanced adaptive lineage splitting in our model species. This scenario, which is likely promoted by a changing and heterogeneous environment, could hamper ecological speciation of locally adapted populations despite strong genetic structure between lineages.

Trends in Mortality From Diabetes Mellitus in Spain: 1998-2013.

INTRODUCTION AND OBJECTIVES: Diabetes mellitus (DM) is a leading causes of death, mainly due to cardiovascular complications. The aim of this study was to describe DM mortality in Spain from 1998 to 2013 and to compare it between distinct provinces. METHODS: Ecological time-trend study. Data sources consisted of the population register and the death rate figures, by cause of death, from Spain's National Statistics Institute. Rates were age-standardized by the direct method. Standardized mortality rates were calculated for each province every 5 years (1998-2013). Time trends in mortality were established by joint point regression models. RESULTS: The standardized mortality rate for DM fell markedly, by 25.3% in men and by 41.4% in women from 1998 to 2013. At the beginning of the study period, mortality rates were higher in southern than in northern regions, but this difference gradually disappeared in later years. The highest mortality rates were consistently found in the Canary Islands. CONCLUSIONS: Mortality from DM fell substantially from 1998 to 2013. The marked geographical clustering showing higher mortality in the south and southeastern areas of the country was significantly reduced during the study period, except in the Canary Islands, where mortality remains strikingly high.

In-house validation of a multiplex real-time PCR method for simultaneous detection of Salmonella spp., Escherichia coli O157 and Listeria monocytogenes.

A wide variety of qPCR methods currently exist for Salmonella spp., Escherichia coli O157 and Listeria monocytogenes detection. These methods target several genes and use different detection chemistries, either in simplex or in multiplex formats. However, the majority of these methods have not been carefully validated, and the number of validated methods that use multiplex qPCR is even lower. The aim of the present study was to develop and validate a multiplex qPCR method from previously validated simplex qPCR primers and probes. A modified broth medium was selected and primary and secondary enrichment times were further optimized. Efficiency of the newly combined qPCR system was comprised between 91% and 108%, for simplex and multiplex analyses. A total of 152 food and environmental, natural and spiked samples, were analyzed for the evaluation of the method obtaining values above 91% that were reached for all the quality parameters analyzed. A very low limit of detection (5 cfu/25 g after enrichment) for simultaneous identification of these 3 pathogens was obtained.

In vitro approaches to evaluate toxicity induced by organotin compounds tributyltin (TBT), dibutyltin (DBT), and monobutyltin (MBT) in neuroblastoma cells.

The toxic effects of the organotin compounds (OTCs) monobutyltin (MBT), dibutyltin (DBT), and tributyltin (TBT) were evaluated in vitro in a neuroblastoma human cell line. Mechanisms of cell death, apoptosis versus necrosis, were studied by using several markers: inhibition of cell viability and proliferation, F-actin, and mitochondrial membrane potential changes as well as reactive oxygen species (ROS) production and DNA fragmentation. The most toxic effects were detected with DBT and TBT even at very low concentrations (0.1-1 µM). In contrast, MBT induced lighter cytotoxic changes at the higher doses tested. None of the studied compounds stimulated propidium iodide uptake, although the most toxic chemical, TBT, caused lactate dehydrogenase release at the higher concentrations tested. These findings suggest that in neuroblastoma, OTC-induced cytotoxicity involves different pathways depending on the compound, concentration, and incubation time. A screening method for DBT and TBT quantification based on cell viability loss was developed, allowing a fast detection alternative to complex methodology.

Uso de bevacizumab en pacientes con cáncer de colon metastásico en el Instituto Nacional de Cancerología: una serie de casos / Bevacizumab in patients with metastatic colorectal cancer at the Colombian National Cancer Institute: a case series study

Objetivos: Describir las características clínicas y epidemiológicas de los pacientes con cáncer de colon metastásico a quienes se les administró bevacizumab en el Instituto Nacional de Cancerología (INC). Métodos: Se revisaron 38 historias clínicas de pacientes atendidos en la consulta de Oncología Clínica del INC con diagnóstico de cáncer colorrectal metastásico entre 2010 y 2011. Resultados: La edad promedio de los pacientes que recibieron bevacizumab fue de 57 años; los principales sitios de metástasis fueron el hígado y el peritoneo. Los esquemas de quimioterapia utilizados más a menudo con bevacizumab fueron 5 fluoruracilo/leucovorina y FOLFOX. En relación con los eventos adversos por el uso de bevacizumab, este fue, en general, bien tolerado; la supervivencia mediana global de los pacientes tratados con bevacizumab fue de 17,5 meses. Conclusiones: Esta serie de casos describe las características generales de pacientes en la consulta externa del INC con cáncer colorrectal metastásico, los cuales tuvieron una buena adherencia al tratamiento con bevacizumab, y su uso estuvo asociado a una baja toxicidad con los diferentes esquemas de quimioterapia utilizados en cáncer colorrectal metastásico.

Objectives: To describe the clinical and epidemiolgical features of patients with metastatic colon cancer treated with bevacizumab at the National Cancer Institute of Colombia (NCI). Methods: Review was undertaken on 38 clinical cases of patients diagnosed for metastatic colorectal cancer and treated at the NCI Oncology Clinic from 2010 to 2011. Results: Median patient age when treated with bevacizumab was 57 years; most frequent metastatic sites were the liver and peritoneum. Most commonly used chemotherapy regimen with bevacizumab included 5 fluoruracil/leucovorin and FOLFOX. Bevacizumab was generally well tolerated, with few adverse events reported; median survival rate for patients treated with bevacizumab was 17.5 months. Conclusions: Analysis on this series of medical cases describes the general characteristics of patients treated at the NCI for metastatic colorrectal cancer whose favorable adherence to treatment with bevacizumab was linked to the low toxicity of diverse chemotherapy regimens used for metastatic colorectal cancer.

Cytotoxic activity of extracts of marine sponges from NW Spain on a neuroblastoma cell line.

Six species of marine sponges collected at intertidal and sublittoral sites of the coast of Galicia (NW Spain) were screened for potential cytotoxic properties on Neuroblastoma BE(2)-M17 cell line. Exposure to Halichondria panicea, Pachymatisma johnstonia, Ophlitaspongia seriata and Haliclona sp. aqueous extracts strongly affected cell appearance, inducing loss of neuron-like morphology and the formation of clumps. Extracts from these species also caused significant rates of cell detachment and decrease of mitochondrial membrane potential. Incubation with P. johnstonia, O. seriata and Suberites massa extracts also decreased the rate of cell proliferation. The increase of incubation time enhanced propidium iodide uptake by neuroblastoma cells. Toxic responses triggered by sponge extracts are compatible with apoptotic phenomena in neuroblastoma cells, even though increasing propidium uptake at long periods of exposure might indicate the induction of secondary necrosis. The cytotoxic properties of the tested extracts suggest the presence of compounds with potential pharmacological or biotechnological applications in the screened sponge species.

Comparison between a TaqMan polymerase chain reaction assay and a culture method for ctx-positive Vibrio cholerae detection.

The main objective of the present work was to evaluate a real-time polymerase chain reaction (PCR) method to detect toxigenic Vibrio cholerae in Pangasius hypophthalmus, a freshwater fish cultured mainly in South East Asia. A FDA traditional culture method and a real-time PCR method of the ctx gene were used for detection of V. cholerae in spiked samples of pangasius fish. After an overnight enrichment of samples at 37 degrees C in alkaline peptone water, 2 cfu/25 g of fish was detected with both methods. Although both methods were very sensitive, obtaining results with culture methods may take several days, while real-time PCR takes only a few hours. Furthermore, with traditional methods, complementary techniques such as serotyping, although not available for all serogroups, are needed to identify toxigenic V. cholerae. However, with real-time PCR, toxigenic serogroups are detected in only one step after overnight enrichment.