The relationship between truncation and phosphorylation at the C-terminus of tau protein in the paired helical filaments of Alzheimer's disease

Acknowledgements: Authors want to express their gratitude to Dr. P. Davies (Albert Einstein College of Medicine, Bronx, NY, USA) and Lester I. Binder (NorthWestern, Chicago, IL, USA) for the generous gift of mAbs (TG-3, Alz-50, and MC1), and (TauC-3), respectively, and to M. en C. Ivan J. Galván-Mendoza for his support in confocal microscopy, and Ms. Maricarmen De Lorenz for her secretarial assistance. We also want to express our gratitude to the Mexican Families who donate the brain of their loved ones affected with Alzheimer's disease, and made possible our research. This work was financially supported by CONACyT grant, No. 142293 (For R.M).Peer reviewedPublisher PD

Proyectos finales integradores : una alternativa para enseñar y aprender activamente

Este número de Reflexiones Pedagógicas busca presentar los proyectos finales integradores (PFI) como una opción de enseñanza y aprendizaje activo. Se explica qué son los PFI, así como las ventajas que se obtienen al hacer uso de estos en una o más asignaturas. Por otro lado, se relatan las experiencias que el programa de Ingeniería Biomédica ha encontrado en la implementación de PFI en algunas de sus asignaturas. Por último, se exponen algunos retos y desafíos inherentes a la implementación de esta alternativa pedagógica. Esperamos que lo compartido en este número sea de utilidad para continuar en la ruta del aprendizaje activo y significativo, el cual implica retos tanto para los docentes como para los estudiantes. Luego de lo vivido como equipo de profesores, consideramos que esta experiencia es altamente transferible a otros campos de conocimiento. Los resultados son gratificantes, así lo hemos evidenciado en cada momento con los estudiantes

Early Science with the Large Millimetre Telescope: Molecules in the Extreme Outflow of a proto-Planetary Nebula

Extremely high velocity emission likely related to jets is known to occur in some proto-Planetary Nebulae. However, the molecular complexity of this kinematic component is largely unknown. We observed the known extreme outflow from the proto-Planetary Nebula IRAS 16342-3814, a prototype water fountain, in the full frequency range from 73 to 111 GHz with the RSR receiver on the Large Millimetre Telescope. We detected the molecules SiO, HCN, SO, and $^{13}$CO. All molecular transitions, with the exception of the latter are detected for the first time in this source, and all present emission with velocities up to a few hundred km s$^{-1}$. IRAS 16342-3814 is therefore the only source of this kind presenting extreme outflow activity simultaneously in all these molecules, with SO and SiO emission showing the highest velocities found of these species in proto-Planetary Nebulae. To be confirmed is a tentative weak SO component with a FWHM $\sim$ 700 km s$^{-1}$. The extreme outflow gas consists of dense gas (n$_{\rm H_2} >$ 10$^{4.8}$--10$^{5.7}$ cm$^{-3}$), with a mass larger than $\sim$ 0.02--0.15 M$_{\odot}$. The relatively high abundances of SiO and SO may be an indication of an oxygen-rich extreme high velocity gas.Comment: Accepted for publication in Monthly Notices of the Royal Astronomical Society Letter

Please mind the gap—about equity and access to care in oncology

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Circulating Cell-Free DNA-Based Liquid Biopsy Markers for the Non-Invasive Prognosis and Monitoring of Metastatic Pancreatic Cancer

Liquid biopsy may assist in the management of cancer patients, which can be particularly applicable in pancreatic ductal adenocarcinoma (PDAC). In this study, we investigated the utility of circulating cell-free DNA (cfDNA)-based markers as prognostic tools in metastatic PDAC. Plasma was obtained from 61 metastatic PDAC patients, and cfDNA levels and fragmentation were determined. BEAMing technique was used for quantitative determination of RAS mutation allele fraction (MAF) in cfDNA. We found that the prognosis was more accurately predicted by RAS mutation detection in plasma than in tissue. RAS mutation status in plasma was a strong independent prognostic factor for both overall survival (OS) and progression-free survival (PFS). Moreover, RAS MAF in cfDNA was also an independent risk factor for poor OS, and was strongly associated with primary tumours in the body/tail of the pancreas and liver metastases. Higher cfDNA levels and fragmentation were also associated with poorer OS and shorter PFS, body/tail tumors, and hepatic metastases, whereas cfDNA fragmentation positively correlated with RAS MAF. Remarkably, the combination of CA19-9 with MAF, cfDNA levels and fragmentation improved the prognostic stratification of patients. Furthermore, dynamics of RAS MAF better correlated with patients’ outcome than standard CA19-9 marker. In conclusion, our study supports the use of cfDNA-based liquid biopsy markers as clinical tools for the non-invasive prognosis and monitoring of metastatic PDAC patients

The Combination of Neutrophil–Lymphocyte Ratio and Platelet–Lymphocyte Ratio with Liquid Biopsy Biomarkers Improves Prognosis Prediction in Metastatic Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a highly inflammatory microenvironment and liquid biopsy has emerged as a promising tool for the noninvasive analysis of this tumor. In this study, plasma was obtained from 58 metastatic PDAC patients, and neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), circulating cell-free DNA (cfDNA) concentration, and circulating RAS mutation were determined. We found that NLR was significantly associated with both overall survival (OS) and progression-free survival. Remarkably, NLR was an independent risk factor for poor OS. Moreover, NLR and PLR positively correlated, and combination of both inflammatory markers significantly improved the prognostic stratification of metastatic PDAC patients. NLR also showed a positive correlation with cfDNA levels and RAS mutant allelic fraction (MAF). Besides, we found that neutrophil activation contributed to cfDNA content in the plasma of metastatic PDAC patients. Finally, a multi-parameter prognosis model was designed by combining NLR, PLR, cfDNA levels, RAS mutation, RAS MAF, and CA19-9, which performs as a promising tool to predict the prognosis of metastatic PDAC patients. In conclusion, our study supports the idea that the use of systemic inflammatory markers along with circulating tumor-specific markers may constitute a valuable tool for the clinical management of metastatic PDAC patients

Comparación entre dos tipos de gastrostomías quirúrgicas, abierta y laparoscópica, en nutrición enteral domiciliaria

Objetivo: Exponer las complicaciones de las gastrostomías quirúrgicas utilizadas como vía de soporte nutricional enteral domiciliario (SNED) y detectar si existen diferencias entre las dos técnicas usadas en nuestro medio: Cirugía abierta vs laparoscópica. Material y métodos: Estudio observacional descriptivo de carácter retrospectivo de las gastrostomías quirúrgicas realizadas entre los años 1994 y 2009 seguidas por nuestra unidad. Se han analizado las complicaciones detectadas en consulta durante el seguimiento de pacientes con SNED a través de gastrostomía quirúrgica realizada con técnica laparotómica abierta vs laparoscópica, valorando: fuga del contenido gástrico al exterior, irritación de la pared abdominal, presencia de exudado, presencia de exudado con cultivo positivo que requirió tratamiento antibiótico, quemadura o pérdida de sustancia de la zona periostomía, rotura de balón, úlcera de decúbito por la sonda y formación de granuloma. Resultados: Durante los años 1994-2009 se realizaron 57 gastrostomías quirúrgicas: 47 por técnica laparótomica (abierta) convencional y 10 por vía laparoscópica. La edad media de los pacientes fue de 57,51 ± 17,29 años. La causa más frecuente que motivó la realización de la gastrostomía quirúrgica fue el cáncer de esófago (38,6%) seguido de alteraciones neurológicas (26,3%) y tumores de cabeza y cuello (26,3%). El 97,9% de los pacientes a los que se realizó una gastrostomía quirúrgica abierta presentaron al menos una complicación, es decir que solo el 2,1% estuvieron libres de complicaciones; mientras que el 50% de los que se sometieron a una gastrostomía laparoscópica no tuvo ninguna. Las complicaciones más frecuentes fueron la presencia de fuga del contenido gástrico y la irritación de la pared abdominal que se presentaron en el 89,4% y 83% respectivamente de las gastrostomías laparotómicas frente a la aparición de solo el 30% de ambas complicaciones en las gastrostomías laparoscópicas siendo la diferencia estadísticamente significativa (p Aim: Exposing the complications of surgical gastrostomies used as way of home enteral nutritional support (HEN) and detecting the differences between the two techniques used in our environment: Open Surgery vs Laparoscopic Surgery. Material and methods: Retrospective descriptive observational study of the surgical gastrostomies performed between 1994 and 2009 followed up by our unit. Have been analyzed the complications detected in our practice during the follow-up of patients with HEN performed via open laparotomy vs. laparoscopic tecniques, assessing: leaks of gastric fluid to the exterior, abdominal wall irritation, presence of exudate, presence of exudate with positive culture that required antibiotical treatment, burning or loss of substance of the periostomic zone, breach of balloon, decubitus ulcer caused by the tube and formation of granuloma. Results: Between 1994 and 2009, 57 surgical gastrostomies were performed: 47 using the conventional laparotomic (open) tecnique and 10 laparoscopies. The average age of the patients was 57.51 ± 17.29 years old. The most common cause for the performance of surgical gastrostomy was esophageal cancer (38.6%) followed by neurologic alterations (26.3%) and head and neck tumors (26.3%). 97.9% of the patients who underwent to surgical gastrostomy presented at least one complication, meaning that only 2.1% were free of complications; meanwhile, 50% of the patients were laparoscopic gastrostomy was performed had none of these complications. The most common complications were the presence of leaks of gastric fluid and abdominal wall irritation that appeared on 89.4% and 83% respectively of the laparotomic gastrostomies versus the presence of only 30% of both complications in laparoscopic gastrostomies being the difference statistically significant (p < 0.01). Conclusions: After the introduction of the laparoscopic technique in the performance of surgical gastrostomies has been observed a decrease of the complications occured during the home enteral nutritional support related to surgical gastrostomies