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1.
Gastroenterology ; 167(2): 357-367.e9, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38513745

RESUMEN

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.


Asunto(s)
Diagnóstico por Imagen de Elasticidad , Cirrosis Hepática , Valor Predictivo de las Pruebas , Humanos , Masculino , Femenino , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/epidemiología , Cirrosis Hepática/patología , Cirrosis Hepática/etiología , Persona de Mediana Edad , Medición de Riesgo , Anciano , Pronóstico , Índice de Masa Corporal , Factores de Riesgo , Circunferencia de la Cintura , Encuestas Nutricionales , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/patología , Adulto , Aspartato Aminotransferasas/sangre , Recuento de Plaquetas , Hígado/patología , Hígado/diagnóstico por imagen , Países Bajos/epidemiología , Biopsia , Curva ROC , Reproducibilidad de los Resultados
2.
PLoS Pathog ; 19(3): e1010883, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36996192

RESUMEN

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.


Asunto(s)
Drosophila , Virus , Animales , Femenino , Drosophila melanogaster , Insectos
3.
PLoS Genet ; 17(8): e1009738, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34411095

RESUMEN

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.


Asunto(s)
Receptores ErbB/antagonistas & inhibidores , Genes ras/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Ciclo Celular , Proliferación Celular/genética , Proteínas de Drosophila/antagonistas & inhibidores , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Expresión Génica/genética , Regulación Neoplásica de la Expresión Génica/genética , Genes ras/fisiología , Discos Imaginales/metabolismo , Morfogénesis , Fosforilación , Receptores de Péptidos de Invertebrados/antagonistas & inhibidores , Receptores de Péptidos de Invertebrados/genética , Receptores de Péptidos de Invertebrados/metabolismo , Transducción de Señal/genética , Proteínas ras/genética
4.
Sensors (Basel) ; 21(3)2021 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-33573296

RESUMEN

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.


Asunto(s)
Aprendizaje Profundo , Diabetes Mellitus , Pie Diabético , Enfermedades del Pie , Pie Diabético/diagnóstico por imagen , Diagnóstico Precoz , Pie/diagnóstico por imagen , Humanos , Termografía
5.
Sensors (Basel) ; 21(7)2021 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-33804926

RESUMEN

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.


Asunto(s)
Diabetes Mellitus , Pie Diabético , Algoritmos , Pie Diabético/diagnóstico por imagen , Pie , Humanos , Monitoreo Fisiológico , Termografía
6.
Ann Bot ; 126(2): 277-288, 2020 07 24.
Artículo en Inglés | MEDLINE | ID: mdl-32320466

RESUMEN

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.


Asunto(s)
Salinidad , Plantas Tolerantes a la Sal , Inundaciones , España , Humedales
7.
Liver Transpl ; 22(1): 63-70, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26369269

RESUMEN

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.


Asunto(s)
Trasplante de Hígado/mortalidad , Complicaciones Posoperatorias/epidemiología , Adolescente , Adulto , Anciano , Argentina/epidemiología , Niño , Femenino , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
8.
J Cell Sci ; 126(Pt 10): 2285-93, 2013 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-23525006

RESUMEN

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.


Asunto(s)
Drosophila melanogaster/fisiología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-vav/metabolismo , Animales , Animales Modificados Genéticamente , Movimiento Celular/genética , Extensiones de la Superficie Celular/genética , Células Cultivadas , Drosophila melanogaster/citología , Embrión no Mamífero/citología , Embrión no Mamífero/metabolismo , Represión Enzimática/genética , Femenino , Morfogénesis/genética , Proteínas Proto-Oncogénicas c-vav/genética , ARN Interferente Pequeño/genética , Eliminación de Secuencia/genética , Técnicas del Sistema de Dos Híbridos
9.
Plant Physiol Biochem ; 210: 108569, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38552261

RESUMEN

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.


Asunto(s)
Cobre , Nitratos , Plantas Tolerantes a la Sal , Cobre/metabolismo , Cobre/toxicidad , Nitratos/metabolismo , Nitratos/farmacología , Plantas Tolerantes a la Sal/metabolismo , Plantas Tolerantes a la Sal/efectos de los fármacos , Fotosíntesis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Aizoaceae/metabolismo , Aizoaceae/efectos de los fármacos , Aizoaceae/fisiología , Raíces de Plantas/metabolismo , Raíces de Plantas/efectos de los fármacos
10.
Nat Rev Dis Primers ; 10(1): 47, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38992031

RESUMEN

Biliary atresia (BA) is a progressive inflammatory fibrosclerosing disease of the biliary system and a major cause of neonatal cholestasis. It affects 1:5,000-20,000 live births, with the highest incidence in Asia. The pathogenesis is still unknown, but emerging research suggests a role for ciliary dysfunction, redox stress and hypoxia. The study of the underlying mechanisms can be conceptualized along the likely prenatal timing of an initial insult and the distinction between the injury and prenatal and postnatal responses to injury. Although still speculative, these emerging concepts, new diagnostic tools and early diagnosis might enable neoadjuvant therapy (possibly aimed at oxidative stress) before a Kasai portoenterostomy (KPE). This is particularly important, as timely KPE restores bile flow in only 50-75% of patients of whom many subsequently develop cholangitis, portal hypertension and progressive fibrosis; 60-75% of patients require liver transplantation by the age of 18 years. Early diagnosis, multidisciplinary management, centralization of surgery and optimized interventions for complications after KPE lead to better survival. Postoperative corticosteroid use has shown benefits, whereas the role of other adjuvant therapies remains to be evaluated. Continued research to better understand disease mechanisms is necessary to develop innovative treatments, including adjuvant therapies targeting the immune response, regenerative medicine approaches and new clinical tests to improve patient outcomes.


Asunto(s)
Atresia Biliar , Atresia Biliar/fisiopatología , Atresia Biliar/diagnóstico , Atresia Biliar/terapia , Atresia Biliar/epidemiología , Atresia Biliar/complicaciones , Humanos , Portoenterostomía Hepática/métodos , Trasplante de Hígado/métodos , Trasplante de Hígado/estadística & datos numéricos
11.
Nature ; 448(7151): 362-5, 2007 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-17637670

RESUMEN

Although directed migration is a feature of both individual cells and cell groups, guided migration has been studied most extensively for single cells in simple environments. Collective guidance of cell groups remains poorly understood, despite its relevance for development and metastasis. Neural crest cells and neuronal precursors migrate as loosely organized streams of individual cells, whereas cells of the fish lateral line, Drosophila tracheal tubes and border-cell clusters migrate as more coherent groups. Here we use Drosophila border cells to examine how collective guidance is performed. We report that border cells migrate in two phases using distinct mechanisms. Genetic analysis combined with live imaging shows that polarized cell behaviour is critical for the initial phase of migration, whereas dynamic collective behaviour dominates later. PDGF- and VEGF-related receptor and epidermal growth factor receptor act in both phases, but use different effector pathways in each. The myoblast city (Mbc, also known as DOCK180) and engulfment and cell motility (ELMO, also known as Ced-12) pathway is required for the early phase, in which guidance depends on subcellular localization of signalling within a leading cell. During the later phase, mitogen-activated protein kinase and phospholipase Cgamma are used redundantly, and we find that the cluster makes use of the difference in signal levels between cells to guide migration. Thus, information processing at the multicellular level is used to guide collective behaviour of a cell group.


Asunto(s)
Movimiento Celular , Drosophila melanogaster/citología , Drosophila melanogaster/metabolismo , Transducción de Señal , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras del Transporte Vesicular/genética , Proteínas Adaptadoras del Transporte Vesicular/metabolismo , Animales , Proteínas del Citoesqueleto , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Genes Esenciales/genética , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Mutación/genética , Fosfolipasa C gamma/metabolismo , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , Receptores de Péptidos de Invertebrados/genética , Receptores de Péptidos de Invertebrados/metabolismo , Receptores del Factor de Crecimiento Derivado de Plaquetas/metabolismo , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Proteínas Adaptadoras de la Señalización Shc , Proteínas de Unión al GTP rac/metabolismo , Quinasas raf/genética , Quinasas raf/metabolismo
12.
Rev Gastroenterol Peru ; 32(1): 32-43, 2012.
Artículo en Español | MEDLINE | ID: mdl-22476176

RESUMEN

OBJECTIVES: Identify prognostic factors associated to total or proximal gastrectomy with or without splenectomy and / or distal pancreatectomy in patient with proximal gastric cancer. Evaluate the frequency of lymph node metastasis to the hilum and splenic artery, postoperative morbidity and mortality and the impact of lymphadenectomy of group 10 and 11 on long term survival. MATERIALS AND METHODS: We performed an observational, descriptive, longitudinal and retrospective study analyzing patients with diagnostic of proximal third gastric adenocarcinoma subjected to total or proximal gastrectomy with or without splenectomy or distal pancreatectomy in the service of Abdomen of the Instituto Nacional de Enfermedades Neoplásicas between 1990 and 2005. Overall survival for each of the groups was calculated using the Kaplan-Meier method, prognostic factors were evaluated using univariate and multivariate analysis. RESULTS: We studied 219 patients with proximal third gastric adenocarcinoma (cardias and bottom), of wich, according to inclusion criteria, only qualify 129 (N=129): 22 (17.1%) were treated by gastrectomy alone, 79 (61.2%) gastrectomy associated witch splenectomy and 28 (21.7%) gastrectomy with distal pancreatosplenectomy, constituting three treatment groups. We compared the survival of each group and each factor analyzed, determining the following prognostic factors: lymph node metastasis (N2-N3), degree of differentiation, undifferentiated tumors and Borrmann III and IV tumors. Neither splenectomy or distal pancreatectosplenectomy improved survival compared to the gastrectomy alone. The morbidity and mortality was higher in patients with more aggressive but more aggressive surgery without significant value. CONCLUSIONS: The number of nodes removed in patients who had pancreatosplenectomy and /or splenectomy was higher, however, had no impact on survival at 5 years.


Asunto(s)
Adenocarcinoma/cirugía , Gastrectomía , Pancreatectomía , Esplenectomía , Neoplasias Gástricas/cirugía , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Pronóstico , Estudios Retrospectivos , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Análisis de Supervivencia
13.
Ecancermedicalscience ; 16: 1387, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35919233

RESUMEN

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.

14.
Dev Cell ; 9(2): 197-207, 2005 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16054027

RESUMEN

Guidance receptors detect extracellular cues and instruct migrating cells how to orient in space. Border cells perform a directional invasive migration during Drosophila oogenesis and use two receptor tyrosine kinases (RTKs), EGFR and PVR (PDGF/VEGF Receptor), to read guidance cues. We find that spatial localization of RTK signaling within these migrating cells is actively controlled. Border cells lacking Cbl, an RTK-associated E3 ubiquitin ligase, have delocalized guidance signaling, resulting in severe migration defects. Absence of Sprint, a receptor-recruited, Ras-activated Rab5 guanine exchange factor, gives related defects. In contrast, increasing the level of RTK signaling by receptor overexpression or removing Hrs and thereby decreasing RTK degradation does not perturb migration. Cbl and Sprint both regulate early steps of RTK endocytosis. Thus, a physiological role of RTK endocytosis is to ensure localized intracellular response to guidance cues by stimulating spatial restriction of signaling.


Asunto(s)
Movimiento Celular/fisiología , Proteínas de Drosophila/fisiología , Endocitosis/fisiología , Receptores ErbB/fisiología , Proteínas Quinasas/fisiología , Proteínas Tirosina Quinasas Receptoras/fisiología , Receptores de Péptidos de Invertebrados/fisiología , Transducción de Señal/fisiología , Animales , Proteínas Portadoras/genética , Proteínas Portadoras/fisiología , Drosophila , Proteínas de Drosophila/genética , Complejos de Clasificación Endosomal Requeridos para el Transporte , Receptores ErbB/genética , Femenino , Factores de Intercambio de Guanina Nucleótido , Mutación , Oocitos/fisiología , Fosfoproteínas/genética , Fosfoproteínas/fisiología , Proteínas Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/fisiología , Proteínas Proto-Oncogénicas c-cbl , Proteínas Tirosina Quinasas Receptoras/genética , Receptores de Péptidos de Invertebrados/genética , Receptores del Factor de Crecimiento Derivado de Plaquetas/genética , Receptores del Factor de Crecimiento Derivado de Plaquetas/fisiología , Receptores de Factores de Crecimiento Endotelial Vascular/genética , Receptores de Factores de Crecimiento Endotelial Vascular/fisiología , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/fisiología
15.
Zookeys ; 989: 39-54, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33223894

RESUMEN

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.

16.
Dev Cell ; 7(1): 73-84, 2004 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15239955

RESUMEN

The Drosophila PDGF/VEGF receptor (PVR) has known functions in the guidance of cell migration. We now demonstrate that during embryonic hematopoiesis, PVR has a role in the control of antiapoptotic cell survival. In Pvr mutants, a large fraction of the embryonic hemocyte population undergoes apoptosis, and the remaining blood cells cannibalistically phagocytose their dying peers. Consequently, total hemocyte numbers drop dramatically during embryogenesis, and large aggregates of engorged macrophages carrying multiple apoptotic corpses form. Hemocyte-specific expression of the pan-caspase inhibitor p35 in Pvr mutants eliminates hemocyte aggregates and restores blood cell counts and morphology. Additional rescue experiments suggest involvement of the Ras pathway in PVR-mediated blood cell survival. In cell culture, we demonstrate that PVR directly controls survival of a hemocyte cell line. This function of PVR shows striking conservation with mammalian hematopoiesis and establishes Drosophila as a model to study hematopoietic cell survival in development and disease.


Asunto(s)
Células Sanguíneas/metabolismo , Supervivencia Celular/genética , Proteínas de Drosophila/fisiología , Drosophila melanogaster/embriología , Embrión no Mamífero/embriología , Hematopoyesis/genética , Proteínas Tirosina Quinasas Receptoras/fisiología , Proteínas Virales , Animales , Apoptosis/genética , Células Sanguíneas/citología , Agregación Celular/genética , Células Cultivadas , Proteínas de Drosophila/genética , Drosophila melanogaster/citología , Drosophila melanogaster/metabolismo , Embrión no Mamífero/citología , Embrión no Mamífero/metabolismo , Regulación del Desarrollo de la Expresión Génica/genética , Macrófagos/fisiología , Modelos Animales , Mutación/genética , Fagocitosis/genética , Proteínas/genética , Proteínas/metabolismo , Proteínas Tirosina Quinasas Receptoras/genética , Transducción de Señal/genética , Proteínas ras/genética , Proteínas ras/metabolismo
17.
Genetics ; 178(1): 307-23, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18202376

RESUMEN

The Drosophila wing primordium is subdivided into a dorsal (D) and a ventral (V) compartment by the activity of the LIM-homeodomain protein Apterous in D cells. Cell interactions between D and V cells induce the activation of Notch at the DV boundary. Notch is required for the maintenance of the compartment boundary and the growth of the wing primordium. Beadex, a gain-of-function allele of dLMO, results in increased levels of dLMO protein, which interferes with the activity of Apterous and results in defects in DV axis formation. We performed a gain-of-function enhancer-promoter (EP) screen to search for suppressors of Beadex when overexpressed in D cells. We identified 53 lines corresponding to 35 genes. Loci encoding for micro-RNAs and proteins involved in chromatin organization, transcriptional control, and vesicle trafficking were characterized in the context of dLMO activity and DV boundary formation. Our results indicate that a gain-of-function genetic screen in a sensitized background, as opposed to classical loss-of-function-based screenings, is a very efficient way to identify redundant genes involved in a developmental process.


Asunto(s)
Tipificación del Cuerpo/genética , Drosophila melanogaster/embriología , Drosophila melanogaster/genética , Genes de Insecto , Genes Supresores , Alas de Animales/embriología , Alas de Animales/metabolismo , Animales , Transporte Biológico , Cromatina/metabolismo , Proteínas de Drosophila/química , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citología , Hibridación in Situ , Fusión de Membrana , Fenotipo , Fosforilación , Estructura Terciaria de Proteína , Receptores Notch/metabolismo , Homología de Secuencia de Aminoácido , Supresión Genética , Transcripción Genética , Vesículas Transportadoras/metabolismo , Alas de Animales/citología
18.
Artículo en Inglés | MEDLINE | ID: mdl-37528900

RESUMEN

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.

19.
Zootaxa ; 4603(2): zootaxa.4603.2.12, 2019 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-31717236

RESUMEN

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.


Asunto(s)
Elasmobranquios , Rajidae , Animales , Ecuador , Femenino , Feto , Perú
20.
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1535893

RESUMEN

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.

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