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The MET gene, known as MET proto-oncogene receptor tyrosine kinase, was first identified to induce tumor cell migration, invasion, and proliferation/survival through canonical RAS-CDC42-PAK-Rho kinase, RAS-MAPK, PI3K-AKT-mTOR, and β-catenin signaling pathways, and its driver mutations, such as MET gene amplification (METamp) and the exon 14 skipping alterations (METex14), activate cell transformation, cancer progression, and worse patient prognosis, principally in lung cancer through the overactivation of their own oncogenic and MET parallel signaling pathways. Because of this, MET driver alterations have become of interest in lung adenocarcinomas since the FDA approval of target therapies for METamp and METex14 in 2020. However, after using MET target therapies, tumor cells develop adaptative changes, favoring tumor resistance to drugs, the main current challenge to precision medicine. Here, we review a link between the resistance mechanism and MET signaling pathways, which is not only limited to MET. The resistance impacts MET parallel tyrosine kinase receptors and signals shared hubs. Therefore, this information could be relevant in the patient’s mutational profile evaluation before the first target therapy prescription and follow-up to reduce the risk of drug resistance. However, to develop a resistance mechanism to a MET inhibitor, patients must have access to the drugs. For instance, none of the FDA approved MET inhibitors are registered as such in Chile and other developing countries. Constant cross-feeding between basic and clinical research will thus be required to meet future challenges imposed by the acquired resistance to targeted therapies.

We present an Oblique Plane Microscope that uses a bespoke glass-tipped tertiary objective to improve the resolution, field of view, and usability over previous variants. Owing to its high numerical aperture optics, this microscope achieves lateral and axial resolutions that are comparable to the square illumination mode of Lattice Light-Sheet Microscopy, but in a user friendly and versatile format. Given this performance, we demonstrate high-resolution imaging of clathrin-mediated endocytosis, vimentin, the endoplasmic reticulum, membrane dynamics, and Natural Killer-mediated cytotoxicity. Furthermore, we image biological phenomena that would be otherwise challenging or impossible to perform in a traditional light-sheet microscope geometry, including cell migration through confined spaces within a microfluidic device, subcellular photoactivation of Rac1, diffusion of cytoplasmic rheological tracers at a volumetric rate of 14 Hz, and large field of view imaging of neurons, developing embryos, and centimeter-scale tissue sections.

Climate change is introducing new stressors into already stressed ecosystems. Among these, extreme events such as heat waves play a crucial role in determining the structure of ecosystems. We tested single and combined effects of overgrazing, burial and heat waves on the seedlings of the habitat-forming species Posidonia oceanica. At current heat wave temperatures, overgrazing in isolation had more deleterious effects than seed burial, and effects were synergistic and additive when both factors co-occurred. The combined effect of overgrazing and seed burial with current heat waves could hamper P. oceanica seedling development, with similar or even higher levels than the sole effect of heat waves in the near future (29 °C). The effects of overgrazing and seed burial are expected to be overridden if heat waves temperatures exceed 29 °C. These results suggest that co-occurring environmental stressors, in combination with current heat waves, could compromise the sexual recruitment of this seagrass. This work was carried out as part of Research Project NEREIDAS (Project Code: 2012-ES-92177- S), funded by the European Commission. C.S. was funded by the University of Alicante (Ref. UATALENTO 17-11).

RESUMEN Las metastasis cerebrales son los tumores cerebrales mas frecuentes y son un desafio medico. Los tumores tienen una capacidad diferente de metastatizarse en el cerebro y deben tener la capacidad de penetrar la barrera hematoencefalica, interactuar con las celulas residentes y sobrevivir. La clinica es variada dependiendo del sitio afectado, asi como los riesgos asociados de convulsion. Genomicamente se ha documentado cada vez mas que las metastasis cerebrales cambian la expresion de sus mutaciones. Por lo tanto, la eleccion del tratamiento es compleja, considerando la primaria, el numero de metastasis y los sitios afectados. La radioterapia ha sido durante mucho tiempo la eleccion de los pacientes que no son candidatos a la cirugia, y se espera que los avances reduzcan especialmente la toxicidad cognitiva. El conocimiento genomico de las metastasis cerebrales y la presencia de terapias dirigidas e inmunoterapias modificadas que penetran la barrera hematoencefalica han sido clave, se espera que en el futuro se realicen mas estudios de combinaciones de tratamientos de radioterapia con terapias de inmunoterapia y dirigidas.

The adequate handling of central venous catheters is a key element in the management of patients with cancer. Catheter-associated deep vein thrombosis is frequently observed in patients with malignant diseases; however, despite being a common complication among these patients, objective information concerning its epidemiology, clinical course, prophylaxis and treatment strategies is very limited. The reported incidence of catheter-related thrombosis (CRT) is highly variable, depending on symptomatic events, or if patients are screened for asymptomatic thrombosis. Several factors have been identified as potential predisposing factors for CRT, both technical and pathological aspects. The anticoagulant of choice is still unclear; while low-molecular-weight heparin is most commonly used, recent studies assessing the role of direct oral anticoagulants in the treatment of CRT show promise as an alternative, but the evidence remains insufficient and the decision must be made on a case-by-case basis.

INTRODUCTION Mesenteric and portal venous thromboses are rare diseases with high mortality rates and are strongly associated with hepatic cirrhosis, and abdominal inflammatory or tumoral processes, but in some cases can be the first sign of myeloproliferative neoplasm (MPN) or hereditary thrombophilia. JAK2V617F mutation detection is an important diagnostic tool for MPN patients. The aim of this study was to describe the JAK2V617F mutation prevalence on Chilean patients suffering from a primary splanchnic venous thrombosis (SVT), in order to assess how it relates to primary MVT and PVT in our specific population. METHODS A retrospective observational study was conducted in patients referred to the University of Chile Clinical Hospital with mesenteric and/or portal venous thrombosis diagnosis over a 7-year period. Patients with primary thrombosis underwent hereditary thrombophilia study and JAK2V617F mutation screening. RESULTS A total of 123 patients had splanchnic venous thrombosis (mesenteric and/or portal) as their main discharge diagnosis. Sixty patients (49%) had primary mesenteric or portal venous thrombosis (no attributable secondary cause). Hereditary thrombophilia and MPN were diagnosed in 21.6% and 43.3% of SVT patients, respectively. Twenty SVT patients remained without an etiologic diagnosis. In MPN patients, almost all had the JAK2V617F mutation (92.3%). About 16% of patients who had positive JAK2V617F mutation did not meet diagnostic criteria for MPN. CONCLUSIONS In this Chilean cohort, half of mesenteric or portal venous thrombosis showed no secondary cause. In this group, the main causes were MPN and hereditary thrombophilia. Nearly, all MPN patients had JAK2V617F mutation, but there was a group of patients having JAK2V617F mutation but did not meet MPN criteria.

Therapy for submassive pulmonary embolism (intermediate risk), remains controversial. New evidence has appeared that may help us in the process of decision making. We review the relevant literature, outline prognostic factors, and discuss current recommendations and controversies regarding the available alternatives such as systemic and catheter-directed thrombolytic use.

Extreme weather events are major drivers of ecological change, and their occurrence is likely to increase due to climate change. The transient increases in atmospheric temperatures are leading to a greater occurrence of heat waves, extreme events that can produce a substantial warming of water, especially in enclosed basins such as the Mediterranean Sea. Here, we tested the effects of current and predicted heat waves on the early stages of development of the seagrass Posidonia oceanica. Temperatures above 27 °C limited the growth of the plant by inhibiting its photosynthetic system. It suffered a reduction in leaf growth and faster leaf senescence, and in some cases mortality. This study demonstrates that the greater frequency of heat waves, along with anticipated temperature rises in coming decades, are expected to negatively affect the germination of P. oceanica seedlings. This workwas carried out within the research project NEREIDAS (project code: 2012-ES-92177- S), funded by the European Commission under the Trans-European Transport Network Programme (TEN-T).

The aim of this work was to study the dispersion of particulate wastes derived from marine fish farming and correlate the data with the impact on the seabed. Carbon and nutrients were correlated with the physico-chemical parameters of the sediment and the benthic community structure. The sedimentation rates in the benthic system were 1.09, 0.09 and 0.13 g m−2 day−1 for particulate organic carbon (POC), particulate organic nitrogen (PON) and total phosphorus (TP), respectively. TP was a reliable parameter for establishing the spatial extent of the fish farm particulate wastes. Fish farming was seen to influence not only physico-chemical and biological parameters but also the functioning of the ecosystem from a trophic point of view, particularly affecting the grazers and the balance among the trophic groups. POC, PON and TP sedimentation dynamics reflected the physico-chemical status of the sediment along the distance gradient studied, while their impact on the benthic community extended further. Therefore, the level of fish farm impact on the benthic community might be underestimated if it is assessed by merely taking into account data obtained from waste dispersion rates. The benthic habitat beneath the fish farm, Maërl bed, was seen to be very sensitive to aquaculture impact compared with other unvegetated benthic habitats, with an estimated POC-carrying capacity to maintain current diversity of 0.087 g C m−2 day−1 (only 36% greater than the basal POC input). Environmental protection agencies should define different aquaculture waste load thresholds for different benthic communities affected by finfish farming, according to their particular degree of sensitivity, in order to maintain natural ecosystem functions. This work was funded by the project AGL2004-08350-C02-01/ACU and the research programme CICYT-FEDER (project 1FD97-1128) from the Ministerio de Ciencia y Tecnología from Spain, and two predoctoral grants, one to C. S. from the Ministerio de Educación y Ciencia and one to F. N. from the ALBAN programme (EU).

Behavioural responses are linked to complex biochemical and physiologic changes and may act as sensitive indicators of the sublethal effects of pollutants. This article investigates changes in the locomotor activity rhythms of the amphipod Gammarus aequicauda exposed to cadmium (Cd) as a model to study the effect of pollutants on an ecologically important species. Under a 12:12 h light-to-dark cycle, G. aequicauda showed a strict nocturnal rhythm, with 90.2±0.4% of their total daily activity occurring during the night. Under constant darkness, circadian rhythms persisted for 10 days, with a mean periodicity of 24.32 h, thus confirming endogenous control. Exposure to sublethal concentrations of Cd (0.16, 0.20, 0.24, and 0.28 mg l(-1)) did not change the nocturnal activity patterns of G. aequicauda, although their swimming activity during the night was significantly decreased by exposure to concentrations of 0.24 and 0.28 mg Cd l(-1). In conclusion, locomotor activity bioassays using the amphipod G. aequicauda appeared to be a sensitive indicator of Cd contamination, and sensitivity and tolerance to Cd in short-term bioassays may depend on the time of the day tests are carried out. These results provide further support for the idea that behavioural end points in amphipods are useful indicators of pollutant exposure and that future studies should take circadian rhythms into consideration.

We examined the effect of organic enrichment on diatom and bacterial assemblages of marine epilithic biofilms on two locations in the Mediterranean, one situated in Spain and the other in Greece. Total organic carbon, total organic nitrogen, stable isotopes (δ(13)C and δ(15)N) and chlorophyll a indicated significant incorporation of organic wastes, increased primary production and trophic niche modifications on the biofilms close to the organic enrichment source. In Spain, where the organic load was higher than in Greece, diatom and, to some extent, bacterial assemblages varied following the organic enrichment gradient. The taxonomic richness of diatom and bacterial communities was not influenced by organic enrichment. Classical community parameters showed consistent patterns to organic pollution in both locations, whereas community assemblages were only influenced when organic pollution was greatest. The successional patterns of these communities were similar to other epilithic communities. The modification of community assemblages induced by organic pollution may affect ecological functions.

We report a 40 year-old male presenting in the emergency room with headache, vertigo and left hemiparesis. A magnetic resonante imaging reported a left cerebellar infarction with occlusion of the basilar artery and a dissection of the right vertebral artery. The patient experienced a clinical deterioration with the appearance of a right hemiparesis. Therefore a brain angiography was performed along with a mechanical thrombolysis using a Solitaire FR® revascularization device. A thrombus located in the distal third of the artery was eliminated obtaining a complete perfusion of the artery. The patient had a satisfactory evolution.

The changes in the biofilm community due to organic matter enrichment, eutrophication and metal contamination derived from fish farming were studied. The biofilm biomass, polysaccharide content, trophic niche and element accumulation were quantified along an environmental gradient of fish farm wastes in two seasons. Biofilm structure and trophic diversity was influenced by seasonality as well as by the fish farm waste load. Fish farming enhanced the accumulation of organic carbon, nutrients, selenium and metals by the biofilm community. The accumulation pattern of these elements was similar regardless of the structure and trophic niche of the community. This suggests that the biofilm communities can be considered a reliable tool for assessing dissolved aquaculture wastes. Due to the ubiquity of biofilms and its wide range of consumers, its role as a sink of dissolved wastes may have important implications for the transfer of aquaculture wastes to higher trophic levels in coastal systems. This work was funded by the project AGL2004-08350-C02-01/ACU from the Ministerio de Ciencia y Tecnología, a predoctoral grant to C. S. from the Ministerio de Educación y Ciencia (Spain) and another predoctoral grant to F. N. from the ALBAN programme (EU).

Background: Waist to height ratio and ultrasensitive C-reactive protein are predictors of the presence of the metabolic syndrome in children. Aim: To determine the proportional risk of metabolic syndrome component clustering in children, using waist to height ratio and ultrasensitive C-reactive protein. Material and Methods: Anthropometric measures, blood pressure, fasting serum lipid profle, blood glucose and ultrasensitive C-reactive protein were determined in 209 children aged 11.5 ± 2 years (50% females). The presence of the metabolic syndrome as a function of waist to height ratio and C-reactive protein was modeled using logistic regression equations. The risk of clustering one, two or more components of the metabolic syndrome was calculated. Results: Metabolic syndrome was present in 5% of all children and 18% of those that were obese. The cut off points for waist to hip ratio and ultrasensitive C-reactive protein were 0.55 and 0.61 mg/L, respectively. For each 0.01 increment in waist to height ratio, the odds ratio of increasing one component of the metabolic syndrome was 1.2 (1.15-1.25) or 15 to 25%. The odds ratio for log-transformed ultrasensitive C-reactive protein was 1.62 (1.26-2.09). Excluding waist circumference, the odds ratio of adding one or more components of the metabolic syndrome was 1.05 (1.01-1.09) per 0.01 increment in waist to height ratio, but the odds ratio for C-reactive protein was no longer significant. Conclusions: Waist to height ratio and ultrasensitive C-reactive protein predict the risk of clustering components of the metabolic syndrome in these children.

Background: A cardiovascular risk score for children, that includes traditional risk factors, obesity, sedentary habits and a family history of cardiovascular disease, has been recently proposed by Spanish researchers. Aim: To apply this score in school age children in Santiago de Chile and correlate its results with markers of subclinical atherosclerotic disease. Material and Methods: Retrospective analysis of data obtained from 209 children, aged 11.5 ± 2 years, studied between 2005 and 2006. Weight, height, blood pressure, ultrasound measurement of carotid intima-media thickness and flow mediated dilatation of brachial artery and ultrasensible C reactive protein (us PCR) were measured. The Spanish cardiovascular risk score was calculated and correlated with ultrasound parameters and C reactive protein. Results: According to the score, 173 children (83%) had a low cardiovascular risk, 28 (13%) an intermediate risk and 8 (4%) a high risk. There was no association between the cardiovascular risk score and carotid intima-media thickness, flow mediated arterial dilatation and us PCR. Conclusions: No significant association was observed between the proposed cardiovascular risk score and early markers of atherosclerotic disease in this group of children

Portman Bay, southeast Spain, contains the most seriously metal-contaminated sediments of the Mediterranean Sea. From 1958 to 1991, approximately 50 million tons of mine tailings were dumped into the bay, completely filling up the bay and dispersing over an extensive area of the continental platform and continental slope. The objective of our study was to characterize the nature and extent of metal contamination and the responses of natural communities to it and to assess the toxicity of the sediment deposits 10 years after mining had ceased. We studied the physical and chemical characteristics of the sediments and toxicity (of the porewater and sediment–water interface) using two sea urchin species ( Arbacia lixula and Paracentrotus lividus ). Metal bioavailability and patterns of macroinvertebrate community composition along the contamination gradient were also studied. Univariate and multivariate analyses showed positive correlation between the sediment metal concentrations associated to the all biological effects (sea urchins toxicity tests and benthic indices). The effects of sediment contamination on the benthic community structure are visible among sampling stations.

Fish farming is an important source of organic matter input in coastal waters, which contributes to eutrophication. In this study, the macrofaunal benthic community was studied after the cessation of fish farming with the aim of improving our understanding of benthic succession and sediment recovery in a marine ecosystem. The results showed that the best environmental variables for assessing organic pollution were acid-volatile sulfides (AVS) and redox potential. Succession and recovery was best explained by macrofaunal analysis based on community composition as well as on trophic groups. The patterns of recovery differed between each impacted station. For this reason, succession could not be accurately predicted due to the unique environmental parameters and the singular community functional structure of each location. The Azti Marine Benthic Index (AMBI) proved its validity for assessing pollution but did not distinguish between successional stages. This work was financially supported by the Project AGL2004-08350-C02-01 from Ministerio de Educación y Ciencia and Culmarex S.A. Company. During the writing of the manuscript C.S. was granted a Pre-doctoral FPU scholarship from the Ministerio de Educación y Ciencia.