Nitrate modulates the physiological tolerance responses of the halophytic species Sarcocornia fruticosa to copper excess.

Coexistence impact of pollutants of different nature on halophytes tolerance to metal excess has not been thoroughly examined, and plant functional responses described so far do not follow a clear pattern. Using the Cu-tolerant halophyte Sarcocornia fruticosa as a model species, we conducted a greenhouse experiment to evaluate the impact of two concentration of copper (0 and 12 mM CuSO4) in combination with three nitrate levels (2, 14 and 50 mM KNO3) on plant growth, photosynthetic apparatus performance and ROS-scavenging enzymes system. The results revealed that S. fruticosa was able to grow adequately even when exposed to high concentrations of copper and nitrate. This response was linked to the plant capacity to uptake and retain a large amount of copper in its roots (up to 1500 mg kg-1 Cu), preventing its transport to aerial parts. This control of translocation was further magnified with nitrate concentration increment. Likewise, although Cu excess impaired S. fruticosa carbon assimilation capacity, the plant was able to downregulate its light-harvesting complexes function, as indicated its lowers ETR values, especially at 12 mM Cu + 50 mM NO3. This downregulation would contribute to avoid excess energy absorption and transformation. In addition, this strategy of avoiding excess energy was accompanied by the upregulation of all ROS-scavenging enzymes, a response that was further enhanced by the increase in nitrate concentration. Therefore, we conclude that the coexistence of nitrate would favor S. fruticosa tolerance to copper excess, and this effect is mediated by the combined activation of several tolerance mechanisms.

Metabolic Dysfunction-Associated Fibrosis 5 (MAF-5) Score Predicts Liver Fibrosis Risk and Outcome in the General Population With Metabolic Dysfunction.

BACKGROUND & AIMS: There is an unmet need for noninvasive tests to improve case-finding and aid primary care professionals in referring patients at high risk of liver disease. METHODS: A metabolic dysfunction-associated fibrosis (MAF-5) score was developed and externally validated in a total of 21,797 individuals with metabolic dysfunction in population-based (National Health and Nutrition Examination Survey 2017-2020, National Health and Nutrition Examination Survey III, and Rotterdam Study) and hospital-based (from Antwerp and Bogota) cohorts. Fibrosis was defined as liver stiffness ≥8.0 kPa. Diagnostic accuracy was compared with FIB-4, nonalcoholic fatty liver disease fibrosis score (NFS), LiverRisk score and steatosis-associated fibrosis estimator (SAFE). MAF-5 was externally validated with liver stiffness measurement ≥8.0 kPa, with shear-wave elastography ≥7.5 kPa, and biopsy-proven steatotic liver disease according to Metavir and Nonalcoholic Steatohepatitis Clinical Research Network scores, and was tested for prognostic performance (all-cause mortality). RESULTS: The MAF-5 score comprised waist circumference, body mass index (calculated as kg / m2), diabetes, aspartate aminotransferase, and platelets. With this score, 60.9% was predicted at low, 14.1% at intermediate, and 24.9% at high risk of fibrosis. The observed prevalence was 3.3%, 7.9%, and 28.1%, respectively. The area under the receiver operator curve of MAF-5 (0.81) was significantly higher than FIB-4 (0.61), and outperformed the FIB-4 among young people (negative predictive value [NPV], 99%; area under the curve [AUC], 0.86 vs NPV, 94%; AUC, 0.51) and older adults (NPV, 94%; AUC, 0.75 vs NPV, 88%; AUC, 0.55). MAF-5 showed excellent performance to detect liver stiffness measurement ≥12 kPa (AUC, 0.86 training; AUC, 0.85 validation) and good performance in detecting liver stiffness and biopsy-proven liver fibrosis among the external validation cohorts. MAF-5 score >1 was associated with increased risk of all-cause mortality in (un)adjusted models (adjusted hazard ratio, 1.59; 95% CI, 1.47-1.73). CONCLUSIONS: The MAF-5 score is a validated, age-independent, inexpensive referral tool to identify individuals at high risk of liver fibrosis and all-cause mortality in primary care populations, using simple variables.

Hunting Drosophila viruses from wild populations: A novel isolation approach and characterisation of viruses.

Metagenomic studies have demonstrated that viruses are extremely diverse and abundant in insects, but the difficulty of isolating them means little is known about the biology of these newly discovered viruses. To overcome this challenge in Drosophila, we created a cell line that was more permissive to infection and detected novel viruses by the presence of double-stranded RNA. We demonstrate the utility of these tools by isolating La Jolla virus (LJV) and Newfield virus (NFV) from several wild Drosophila populations. These viruses have different potential host ranges, with distinct abilities to replicate in five Drosophila species. Similarly, in some species they cause high mortality and in others they are comparatively benign. In three species, NFV but not LJV caused large declines in female fecundity. This sterilization effect was associated with differences in tissue tropism, as NFV but not LJV was able to infect Drosophila melanogaster follicular epithelium and induce follicular degeneration in the ovary. We saw a similar effect in the invasive pest of fruit crops Drosophila suzukii, where oral infection with NFV caused reductions in the fecundity, suggesting it has potential as a biocontrol agent. In conclusion, a simple protocol allowed us to isolate new viruses and demonstrate that viruses identified by metagenomics have a large effect on the fitness of the model organism D. melanogaster and related species.

Fatty Liver (part 2): Clinical Approach and Treatment

Patients with fatty liver are almost always asymptomatic; aminotransferases are usually elevated two to five times the expected value and are an important cause of initial consultation. All images can show fatty liver, and liver biopsy remains the gold standard for diagnosis. In any patient, non-invasive tests are an excellent alternative to biopsy to determine the degree of liver fibrosis and establish the stage of fibrogenesis. Weight loss and exercise are the fundamental pillars of the indicated treatment for all patients with overweight or obesity; a weight loss between 5% and 10% and a diet with caloric restriction of 500-1000 kcal/day, low in saturated fat and rich in Mediterranean diet products such as fruit, fish, vegetables, nuts, olive oil, among others, are recommended. There are other treatments, such as pharmacological measures and endoscopic and surgical procedures.

Los pacientes con hígado graso son casi siempre asintomáticos, las aminotransferasas usualmente están elevadas dos a cinco veces el valor normal y son una causa importante de consulta inicial. Todas las imágenes pueden evidenciar el hígado graso y la biopsia hepática sigue siendo la prueba de oro para su diagnóstico. En cualquier paciente las pruebas no invasivas son una excelente alternativa a la biopsia para determinar el grado de fibrosis hepática y establecer en qué etapa de la fibrogénesis se encuentra. La pérdida de peso y el ejercicio son los pilares fundamentales del tratamiento indicado para todos los pacientes con sobrepeso u obesidad; se recomienda una pérdida de peso entre 5% y 10% del peso corporal y una dieta con restricción calórica de 500-1000 kcal/día, baja en grasas saturadas y rica en productos de la dieta mediterránea como fruta, pescado, verduras, frutos secos, aceite de oliva, entre otros. Hay otros tratamientos como las medidas farmacológicas y los procedimientos endoscópicos y quirúrgicos.

Supervivencia extendida con pembrolizumab en un paciente con cáncer de pulmón no microcítico estadio IV: Reporte de caso / Extendedsurvival with pembrolizumab in a patient with stage IV non-small cell lung cancer:A case report

Introducción:La inmunoterapia con pembrolizumab ha mejorado el pronóstico del cáncer de pulmón metastásico. En el presente caso se presenta la supervivencia extendidad y evolución de un paciente específico.Caso clínico:Hombre de 66 años, fumador. Diagnosticado de masa pulmonar en lóbulo infe-rior izquierdo de dimensiones 9 x 8 cm, con metástasis supra e infratentoriales intraaxiliares. Taller diagnóstico: Establecida como neoplasia de pulmón en estadio IVc, se comprobó el estado de PDL1 que positivo en un 80 % de la muestra de masa pulmonar. Debuta con me-tástasis cerebrales.Evolución: Se inció inmunoterapia con Pembrolizumab, el cual se mantubo hasta la presencia de un efecto secundario atribuido al pembrolizumab, cumpliendo 30meses de supervivencia hasta el cierre de esta observación no se reportó la muerte del paciente.Conclusiones:En el presente reporte, la determinación del biomarcador histológico PDL1 po-sitivo en cáncer de pulmón ayudo a prescribir un tratamiento con inmunoterpia dirigida, lo que demostró aumentar la supervivencia más allá que el tratamiento convencional con quimiote-rapia

Introduction: Immunotherapy with pembrolizumab has improved the prognosis of metastatic lung cancer. A specific patient's extended survival and evolution is presented in the present case.Clinical case: 66-year-old man, smoker. Diagnosed with a lung mass in the left lower lobe measuring 9 x 8 cm, with supra and infratentorial intra-axial metastases.Diagnostic workshop: To establisha stage IVc lung neoplasm, 80% of the lung mass sample was confirmed to be positive for PDL1.Evolution: Immunotherapy was started with Pembrolizumab, which was maintained until the presence of a side effect attributed to pembrolizumab, completing 30 months of survival until the closure of this observation, the patient's death was not reported.Conclusions: In the present report, the determination of the positive histological biomarker PDL1 in lung cancer helped prescribe treatment with targeted immunotherapy, which was shown to increase survival beyond conventional treatment with chemotherapy

Hígado graso (parte 1): aspectos generales, epidemiología, fisiopatología e historia natural / Non-alcoholic fatty liver disease part 1: general aspects, epidemiology. pathophysiology and natural history

Resumen El hígado graso no alcohólico (NAFLD) se define por la presencia de grasa o esteatosis en los hepatocitos y abarca un espectro que va desde la esteatosis simple, pasa por la esteatohepatitis no alcohólica (NASH) con inflamación y fibrosis, y finaliza en la cirrosis. Se considera una prevalencia mundial global cercana al 25% en la población general y se diagnóstica entre los 40 y 50 años, con variaciones respecto al sexo predominante y con diferencias étnicas (la población hispana es la más afectada). El hígado graso está asociado al síndrome metabólico (SM), y la obesidad se considera el principal factor de riesgo con su presencia y con su progresión. El hígado graso es un trastorno complejo y muy heterogéneo en su fisiopatología, que resulta de la interacción de múltiples elementos: factores genéticos, epigenéticos, ambientales, culturales, entre otros. Todo ello en conjunto lleva a incremento paulatino de grasa hepática, resistencia a la insulina y alteraciones hormonales y de la microbiota intestinal, lo que genera un daño hepatocelular a través de la formación de radicales libres de oxígeno y activación de la fibrogénesis hepática. La historia natural del hígado graso es dinámica: los pacientes con esteatosis simple tienen bajo riesgo de progresión a cirrosis, mientras que en los pacientes con NASH este riesgo se aumenta; sin embargo, el proceso puede ser reversible y algunas personas tendrán una mejoría espontánea. La fibrosis parece ser el determinante de la mortalidad global y de los desenlaces asociados a la enfermedad hepática; se considera que en todos los pacientes la fibrosis empeora una etapa cada 14 años y en NASH empeora en una etapa cada 7 años. Estudios previos concluyen que aproximadamente 20% de los casos de esteatosis simple progresan a NASH y que, de ellos, aproximadamente el 20% progresan a cirrosis, con presencia de hepatocarcinoma (HCC) en el 5% a 10% de ellos.

Abstract Fatty liver or NAFLD is defined by the presence of fat or steatosis in hepatocytes and covers a spectrum that goes from simple steatosis, through steatohepatitis (NASH), with inflammation and fibrosis and ending in cirrhosis. It is considered a global world prevalence close to 25% in the general population and is diagnosed between 40 and 50 years, with variations regarding the predominant sex and with ethnic differences, affecting more the Hispanic population. Fatty liver is associated with metabolic syndrome (MS), and obesity is considered the main risk factor for its presence and progression. Fatty liver is a complex and very heterogeneous disorder in its pathophysiology, resulting from the interaction of multiple elements, genetic, epigenetic, environmental, cultural factors, etc. All this together leads to an accumulation of hepatic fat, insulin resistance, hormonal and intestinal microbiota alterations, generating hepatocellular damage through the formation of free oxygen radicals and activation of hepatic fibrogenesis. The natural history of fatty liver is dynamic, patients with simple steatosis have a low risk of progression to cirrhosis, in patients with NASH this risk is increased, however, the process may be reversible, and some people will have spontaneous improvement. Fibrosis seems to be the determinant of overall mortality and outcomes associated with liver disease, it is considered that in all patients fibrosis worsens one stage every 14 years, in NASH it worsens one stage every seven years. Previous studies conclude that approximately 20% of cases of simple steatosis progress to NASH and that approximately 20% of them progress to cirrhosis, with the presence of hepatocellular carcinoma (HCC) in 5 to 10% of them.

Humanización en la comunicación de malas noticias en el paciente oncológico y paliativo / Humanization in the communication of bad news in cancer and palliative patients

La comunicación de malas noticias, si bien supone un momento de importante vulnerabilidad para el paciente y sus allegados, es un acto necesario para una atención de calidad. Se trata de una habilidad transversal que, sin embargo, suele carecer de una formación específica en las facultades de Medici-na. Existen numerosos protocolos que establecen las bases de una comunicación eficiente. No obs-tante, lo que marca la diferencia en términos de humanidad es el toque personal que cada médico ofrece. En este artículo ofrecemos una reflexión sobre la visión predominante en el Servicio de Onco-logía Médica de Fuenlabrada del proceso de comunicación de malas noticias. Exponemos conceptos metafísicos, psicológicos y sociales sobre los cuales impera la necesidad de reflexionar para, desde una compresión profunda de la dificultad que la comunicación de malas noticias entraña, ser capa-ces de mejorar. Así mismo, sugerimos elementos fácilmente incorporables a la práctica clínica diaria.

Although the communication of bad news is a moment of great vulnerability for the patient and his or her relatives, it is necessary for quality care. However, it is a cross-cutting skill that often needs more specific training in medical schools. Numerous protocols lay the groundwork for efficient communication. However, each physician's personal touch makes a difference in terms of humanity. In this article, we reflect on the predominant vision of communicating bad news in the Medical On-cology Service of Fuenlabrada. We expose metaphysical, psychological, and social concepts on which there is a need to reflect to be able to improve from a deep understanding of the difficulty that the communication of bad news entails. Finally, we suggest elements that can be easily incorporated into daily clinical practice.

Adjuvant chemotherapy after curative D2 gastrectomy in Latin American patients with gastric cancer.

Background: Gastric cancer (GC) is the fourth most common cause of cancer deaths around the world and the first cause of cancer deaths in Peru; however, there are no prospective trials for adjuvant chemotherapy in GC after curative gastrectomy in this country. The objective of this study was to evaluate the effectiveness of adjuvant chemotherapy in stage II-III gastric cancer patients who underwent D2 gastrectomy. Methods: We included patients with stage II-III gastric cancer who underwent radical gastrectomy and D2 dissection between 2014 and 2016 at our institution. Patients received 3-week cycles of capecitabine (1,000 mg/m2 twice daily on days 1-14) plus oxaliplatin (130 mg/m2 on day 1) for 6 months. Survival curves were estimated with the Kaplan-Meier method, and the Cox proportional hazards model was used to identify prognostic factors for survival. Results: In total, 173 patients were included: 100 (57.8%) patients received adjuvant chemotherapy and surgery (AChS) and 73 (42.2%) surgery alone (SA). Three-year disease-free survival (DFS) was higher in the AChS groups (69%) than in the SA group (52.6%) (p = 0.034). Regarding overall survival (OS), 31 patients (31%) died in the AChS group compared with 34 (46.6%) in the SA group (p = 0.027). In the multivariate analysis, adjuvant chemotherapy was an independent prognostic factor for DFS (HR = 0.60; 95% CI = 0.37-0.97; p = 0.036) and OS (HR = 0.58; 95% CI = 0.36-0.95; p = 0.029). ACh showed consistent benefit in DFS and OS for patients with albumin >3.5 g/dL, lymphovascular and perineural invasion, pT4, pN2-3, pathologic stage (PS) IIIA and IIIB and lymph node ratio (LNR) > 13.1. Conclusion: These data suggest that adjuvant capecitabine and oxaliplatin reduce the recurrence and mortality in patients with stage II-III gastric cancer who underwent D2 gastrectomy. PS IIIA and IIIB and LNR > 13.1 benefited more from receiving adjuvant chemotherapy and poorly cohesive gastric carcinoma did not significantly reduce the rates of survival.

EGFRAP encodes a new negative regulator of the EGFR acting in both normal and oncogenic EGFR/Ras-driven tissue morphogenesis.

Activation of Ras signaling occurs in ~30% of human cancers. However, activated Ras alone is insufficient to produce malignancy. Thus, it is imperative to identify those genes cooperating with activated Ras in driving tumoral growth. In this work, we have identified a novel EGFR inhibitor, which we have named EGFRAP, for EGFR adaptor protein. Elimination of EGFRAP potentiates activated Ras-induced overgrowth in the Drosophila wing imaginal disc. We show that EGFRAP interacts physically with the phosphorylated form of EGFR via its SH2 domain. EGFRAP is expressed at high levels in regions of maximal EGFR/Ras pathway activity, such as at the presumptive wing margin. In addition, EGFRAP expression is up-regulated in conditions of oncogenic EGFR/Ras activation. Normal and oncogenic EGFR/Ras-mediated upregulation of EGRAP levels depend on the Notch pathway. We also find that elimination of EGFRAP does not affect overall organogenesis or viability. However, simultaneous downregulation of EGFRAP and its ortholog PVRAP results in defects associated with increased EGFR function. Based on these results, we propose that EGFRAP is a new negative regulator of the EGFR/Ras pathway, which, while being required redundantly for normal morphogenesis, behaves as an important modulator of EGFR/Ras-driven tissue hyperplasia. We suggest that the ability of EGFRAP to functionally inhibit the EGFR pathway in oncogenic cells results from the activation of a feedback loop leading to increase EGFRAP expression. This could act as a surveillance mechanism to prevent excessive EGFR activity and uncontrolled cell growth.

Assessment of Registration Methods for Thermal Infrared and Visible Images for Diabetic Foot Monitoring.

This work presents a revision of four different registration methods for thermal infrared and visible images captured by a camera-based prototype for the remote monitoring of diabetic foot. This prototype uses low cost and off-the-shelf available sensors in thermal infrared and visible spectra. Four different methods (Geometric Optical Translation, Homography, Iterative Closest Point, and Affine transform with Gradient Descent) have been implemented and analyzed for the registration of images obtained from both sensors. All four algorithms' performances were evaluated using the Simultaneous Truth and Performance Level Estimation (STAPLE) together with several overlap benchmarks as the Dice coefficient and the Jaccard index. The performance of the four methods has been analyzed with the subject at a fixed focal plane and also in the vicinity of this plane. The four registration algorithms provide suitable results both at the focal plane as well as outside of it within 50 mm margin. The obtained Dice coefficients are greater than 0.950 in all scenarios, well within the margins required for the application at hand. A discussion of the obtained results under different distances is presented along with an evaluation of its robustness under changing conditions.

Segmentation Approaches for Diabetic Foot Disorders.

Thermography enables non-invasive, accessible, and easily repeated foot temperature measurements for diabetic patients, promoting early detection and regular monitoring protocols, that limit the incidence of disabling conditions associated with diabetic foot disorders. The establishment of this application into standard diabetic care protocols requires to overcome technical issues, particularly the foot sole segmentation. In this work we implemented and evaluated several segmentation approaches which include conventional and Deep Learning methods. Multimodal images, constituted by registered visual-light, infrared and depth images, were acquired for 37 healthy subjects. The segmentation methods explored were based on both visual-light as well as infrared images, and optimization was achieved using the spatial information provided by the depth images. Furthermore, a ground truth was established from the manual segmentation performed by two independent researchers. Overall, the performance level of all the implemented approaches was satisfactory. Although the best performance, in terms of spatial overlap, accuracy, and precision, was found for the Skin and U-Net approaches optimized by the spatial information. However, the robustness of the U-Net approach is preferred.

A new species of Pseudosinella Schäffer, 1897 (Collembola, Entomobryidae) from Altamira Caves (Cantabria, Spain).

This paper describes Pseudosinella altamirensis sp. nov. from the Altamira Caves, municipal district of Santillana del Mar (Cantabria, Spain), and five other caves near the coast of Cantabria (northern Spain). Its taxonomic position is discussed and differences and similarities among morphologically and geographically close species are highlighted. The new species can be identified by its five eyes, the basal and small inner paired teeth on the claw, and the length of the uncrenulated part of the distal dens.

Disentangling elevation, annual flooding regime and salinity as hydrochemical determinants of halophyte distribution in non-tidal saltmarsh.

BACKGROUND AND AIMS: Hydrological disconnection, especially in a Mediterranean climate, creates coastal saltmarshes with an annual cycle of flooding that are unlike tidally inundated systems. Winter rainfall produces long, continuous hydroperiods, alternating with continuous exposure caused by evaporation in warm, rain-free summers. We aimed to distinguish the effects of elevation, hydroperiod and salinity on annual and perennial halophytes in such a system. METHODS: We recorded vegetation and sediment salinity in permanent quadrats on a marsh in the Doñana National Park, Spain, over seven consecutive years with widely differing rainfall. Elevation was determined from LIDAR data and the duration of the annual hydroperiod from satellite imagery. The independent effects of collaterally varying elevation, hydroperiod and salinity on species distribution were examined using generalized linear models and hierarchical partitioning. KEY RESULTS: Both hydroperiod and salinity were inversely related to elevation but interannual fluctuations in rainfall facilitated discrimination of independent effects of the three collaterally varying factors on halophyte distribution. Perennial distribution was strongly structured by elevation, whereas many annual species were more sensitive to hydroperiod. The independent effects of salinity varied according to individual species' salt tolerance from positive to negative. Thus life-history and, in the case of annuals, phenology were important in determining the relative impact of elevation and hydroperiod. CONCLUSIONS: The consequences of elevation for halophyte distribution in seasonally flooded saltmarshes are fundamentally different from those in tidal marshes, because protracted and frequent flooding regimes require different adaptations, and because of the unpredictability of flooding from year to year. These differences could explain greater species diversity in non-tidal marshes and the absence of key saltmarsh species prominent in tidal marshes. The vegetation of non-tidal marshes will be particularly susceptible to the more extreme annual cycles of temperature and rainfall predicted for Mediterranean climates.

First description of a giant manta ray fetus Mobula birostris (Walbaum 1792) from Tumbes, Peru (Southeast Pacific).

The population of Mobula birostris ("giant manta ray") found in the waters of northern Peru and Ecuador is believed to be the largest in the world (Harding Beirwagen, 2009). This species is considered to be the largest within the group of manta rays, as they attains at least 670 cm disc width (reported to 910 cm) (White et al., 2006) and there is a record of an individual weighing 2000 kg (Kunjipalu Boopendranath, 1981). This species is ovoviviparous (matrotrophic viviparious) (Herbert, 2012). A single pup follows a gestation period of approximently one year, (Marshall et al., 2008, Mendonça et al., 2012). Sucessive pregnancies are speculated to be separated by a refactory period of two or more years (Mendonça et al., 2012). The objective of this study is to record the measurements of a M. birostris fetus of a female caught accidentally in the region of Tumbes, Peru. This is the first record of morphological and morphometric data regarding a manta fetus in Peru.

Affordable Custom Three-Dimensional Anatomy Atlases.

In this paper, we present methodology and tools for creating custom three-dimensional anatomical atlases for medical education based on web technologies and open-source software. Traditional medical anatomy education has relied on printed anatomical atlases, in-person lectures, and anatomical dissection. This traditional approach underserves populations in need due to high cost, lack of availability of materials, and a limited of trained educators. Open and free online anatomical atlases developed by an international community of experts help remedy these shortcomings, more fully addressing the sustainable development goals of quality education and good health at a global scale. We have developed a web application, the Atlas Assembly Tool, that assists medical professionals in assembling atlases for open dissemination throughout the world. Our tool aims to complement existing open source medical projects such as 3D Slicer and the Open Anatomy Browser to provide a pipeline from original medical image data to web-browsable atlases suitable for medical education. Our development is an integral part of the European INTERREG MACbioIDi project, promoting sustainable development through technology-based medical education and training in close collaboration with partners in Europe, Africa and the United States.

Hepatocellular carcinoma surgery outcomes in the developing world: A 20-year retrospective cohort study at the National Cancer Institute of Peru.

In the developing world, most patients with hepatocellular carcinoma present with advanced-stage disease, considered to be incurable based on current therapeutic algorithms. Here, we demonstrate that curative liver resection is achievable in a portion of Peruvian patients not addressed by these treatment algorithms. We conducted a retrospective cohort study of 253 hepatocellular carcinoma patients that underwent a curative hepatectomy between 1991 and 2011 at the National Cancer Institute of Peru. The median age of the cohort was 36 years, and merely 15.4% of the patients displayed cirrhosis. The average tumor size was over 14 cm in diameter, resulting in 76.3% of major hepatectomies performed. The 5- and 10-year survival probability estimates were 37.5% and 26.2%, respectively. Age (>44 vs. ≤44 years old; P = 0.005), tumor size (>10 cm vs. ≤10 cm in diameter; P = 0.009), cirrhosis (P < 0.001), satellite lesions (P < 0.001), macroscopic vascular invasion (P < 0.001), allogeneic blood transfusion (P = 0.011), and spontaneous rupture of the tumor (P = 0.006) were independent predictive factors for prognosis. Hepatocellular carcinomas in Peru are characterized by a distinct clinical presentation with notable features compared with those typically described throughout relevant literature. Despite a large number of advanced-stage hepatocellular carcinomas, the outcomes of liver resection observed in the present study were in good standing with the results previously described in other series. It thus appears that staging systems and associated therapeutic algorithms designed for use in the developed world remain inadequate in certain populations, especially in the context of Peruvian patients. Our findings suggest that clinicians in the developing world should reconsider management guidelines pertaining to hepatocellular carcinoma. Indeed, we hypothesize that, in developing countries, a strict adherence to these therapeutic algorithms might create a selection bias resulting in the dismissal of patients who could eventually be treated.

Split liver transplantation: Report of right and left graft outcomes from a multicenter Argentinean group.

Grafts from split livers (SLs) constitute an accepted approach to expand the donor pool. Over the last 5 years, most Argentinean centers have shown significant interest in increasing the use of this technique. The purpose of this article is to describe and analyze the outcomes of right-side grafts (RSGs) and left-side grafts (LSGs) from a multicenter study. The multicenter retrospective study included data from 111 recipients of SL grafts from between January 1, 2009 and December 31, 2013. Incidence of surgical complications, patient and graft survival, and factors that affected RSG and LSG survival were analyzed. Grafts types were 57 LSG and 54 RSG. Median follow-up times for LSG and RSG were 46 and 42 months, respectively. The 36-month patient and graft survivals for LSG were 83% and 79%, respectively, and for RSG were 78% and 69%, respectively. Retransplantation rates for LSG and RSG were 3.5% and 11%, respectively. Arterial complications were the most common cause of early retransplantation (less than 12 months). Cold ischemia time (CIT) longer than 10 hours and the use of high-risk donors (age ≥ 40 years or body mass index ≥ 30 kg/m2 or ≥ 5 days intensive care unit stay) were independent factors for diminished graft survival in RSG. None of the analyzed variables were associated with worse graft survival in LSG. Biliary complications were the most frequent complications in both groups (57% in LSG and 33% in RSG). Partial grafts obtained from liver splitting are an excellent option for patients in need of liver transplantation and have the potential to alleviate the organ shortage. Adequate donor selection and reducing CIT are crucial for optimizing results.

Radionuclides transfer into halophytes growing in tidal salt marshes from the Southwest of Spain.

Estuaries are sinks of materials and substances which are released directly into them or transported from rivers that drain the basin. It is usual to find high organic matter loads and fine particles in the sediments. We analyzed radionuclide concentrations ((210)Po, (230)Th, (232)Th, (234)U, (238)U, (226)Ra, (228)Th, (228)Ra, (40)K) in sediments and three different organs (roots, stems and leaves) of three species of halophytes plants (Spartina maritima, Spartina densiflora and Sarcocornia perennis). The study was carried out in two tidal salt marshes, one polluted by U-series radionuclides and another nearby that was unpolluted and was used as a control (or reference) area. The Tinto River salt marsh shows high levels of U-series radionuclides coming from mining and industrial discharges. On the contrary, the unperturbed Piedras River salt marsh is located about 25 km from the Tinto marsh, and shows little presence of contaminants and radionuclides. The results of this work have shown that natural radionuclide concentrations (specially the U-isotopes) in the Tinto salt marsh sediments are one order of magnitude higher than those in the Piedras marsh. These radionuclide enhancements are reflected in the different organs of the plants, which have similar concentration increases as the sediments where they have grown. Finally, the transfer factor (TF) of the most polluted radionuclides (U-isotopes and (210)Po) in the Tinto area are one order of magnitude higher than in the Piedras area, indicating that the fraction of each radionuclide in the sediment originating from the pollution is more available for the plants than the indigenous fraction. This means that the plants of the salt marshes are unhelpful as bioindicators or for the phytoremediation of radionuclides.

GTP exchange factor Vav regulates guided cell migration by coupling guidance receptor signalling to local Rac activation.

Guided cell migration is a key mechanism for cell positioning in morphogenesis. The current model suggests that the spatially controlled activation of receptor tyrosine kinases (RTKs) by guidance cues limits Rac activity at the leading edge, which is crucial for establishing and maintaining polarized cell protrusions at the front. However, little is known about the mechanisms by which RTKs control the local activation of Rac. Here, using a multidisciplinary approach, we identify the GTP exchange factor (GEF) Vav as a key regulator of Rac activity downstream of RTKs in a developmentally regulated cell migration event, that of the Drosophila border cells (BCs). We show that elimination of the vav gene impairs BC migration. Live imaging analysis reveals that vav is required for the stabilization and maintenance of protrusions at the front of the BC cluster. In addition, activation of the PDGF/VEGF-related receptor (PVR) by its ligand the PDGF/PVF1 factor brings about activation of Vav protein by direct interaction with the intracellular domain of PVR. Finally, FRET analyses demonstrate that Vav is required in BCs for the asymmetric distribution of Rac activity at the front. Our results unravel an important role for the Vav proteins as signal transducers that couple signalling downstream of RTKs with local Rac activation during morphogenetic movements.