Microfluidic platform for electrophysiological studies on Xenopus laevis oocytes under varying gravity levels

Voltage clamp measurements reveal important insights into the activity of membrane ion channels. While conventional voltage clamp systems are available for laboratory studies, these instruments are generally unsuitable for more rugged operating environments. In this study, we present a non-invasive microfluidic voltage clamp system developed for the use under varying gravity levels. The core component is a multilayer microfluidic device that provides an immobilisation site for Xenopus laevis oocytes on an intermediate layer, and fluid and electrical connections from either side of the cell. The configuration that we term the asymmetrical transoocyte voltage clamp (ATOVC) also permits electrical access to the cytosol of the oocyte without physical introduction of electrodes by permeabilisation of a large region of the oocyte membrane so that a defined membrane patch can be voltage clamped. The constant low level air pressure applied to the oocyte ensures stable immobilisation, which is essential for keeping the leak resistance constant even under varying gravitational forces. The ease of oocyte mounting and immobilisation combined with the robustness and complete enclosure of the fluidics system allow the use of the ATOVC under extreme environmental conditions, without the need for intervention by a human operator. Results for oocytes over-expressing the epithelial sodium channel (ENaC) obtained under laboratory conditions as well as under conditions of micro- and hypergravity demonstrate the high reproducibility and stability of the ATOVC system under distinct mechanical scenarios

Large Cell Neuroendocrine Carcinoma of the Lung: Current Understanding and Challenges

Large cell neuroendocrine carcinoma of the lung (LCNEC) is a rare and highly aggres-sive type of lung cancer, with a complex biology that shares similarities with both small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). The prognosis of LCNEC is poor, with a median overall survival of 8–12 months. The diagnosis of LCNEC requires the identification of neuroendocrine morphology and the expression of at least one of the neuroendocrine markers (chromogranin A, synaptophysin or CD56). In the last few years, the introduction of next-generation sequencing allowed the identification of molecular subtypes of LCNEC, with prognostic and potential therapeutic implications: one subtype is similar to SCLC (SCLC-like), while the other is similar to NSCLC (NSCLC-like). Because of LCNEC rarity, most evidence comes from small retrospective studies and treatment strategies that are extrapolated from those adopted in patients with SCLC and NSCLC. Nevertheless, limited but promising data about targeted therapies and immune checkpoint inhibitors in patients with LCNEC are emerging. LCNEC clinical management is still controversial and standardized treatment strategies are currently lacking. The aim of this manuscript is to review clinical and molecular data about LCNEC to better understand the optimal management and the potential prognostic and therapeutic implications of molecular subtypes

Lymph node ratio predicts efficacy of postoperative radiation therapy in nonmetastatic Merkel cell carcinoma: A population-based analysis

Background: After radical resection of a nonmetastatic Merkel cell carcinoma (M0 MCC), postoperative radiation therapy (RT) is recommended as it improves survival. However, the role of RT in specific subgroups of M0 MCC is unclear. We sought to identify whether there is a differential survival benefit from RT in specific M0 MCC patient subgroups. Methods: M0 MCC patients from the Surveillance, Epidemiology, and End Results (SEER) database registry were collected. The best prognostic age, tumor size, and lymph node ratio (LNR, ratio between positive lymph nodes and resected lymph nodes) cutoffs were calculated. The primary endpoint was overall survival (OS). Results: A total of 5644 M0 MCC patients (median age 77 years, 62% male) were included: 4022 (71%) node-negative (N0) and 1551 (28%) node-positive (N+). Overall, 2682 patients (48%) received RT. Age > 76.5 years, tumor size >13.5 mm, and LNR >0.215 were associated with worse OS. RT was associated with longer OS in the M0 MCC, N0, and N+ group and independently associated with a 25%, 27%, and 26% reduction in the risk for death, respectively. RT benefit on survival was increased in tumor size >13.5 mm in the N0 group and LNR >0.215 in the N+ group. No OS benefit from RT was observed in T4 tumors (N0 and N+ groups). Conclusions: RT was associated with improved survival in M0 MCC, irrespective of the nodal status. LNR >0.215 is a useful prognostic factor for clinical decision-making and for stratification and interpretation of clinical trials

Estimación de la edad en el período fetal y perinatal por estadios de desarrollo de la dentición

En este trabajo se propone una metodología para la estimación de la edad a partir del desarrollo de la dentición temporaria en el período fetal y perinatal. Los datos de referencia para la estimación de edad por estadios de desarrollo de la dentición se focalizan en la dentición permanente y en edades posteriores al nacimiento. Por otro lado, respecto de la dentición temporaria y en el período prenatal, no se han sistematizado las edades para cada estadio de desarrollo sino que se ha descrito el proceso de maduración dentaria.Facultad de Ciencias Médica

Estimación de la edad en el período fetal y perinatal por estadios de desarrollo de la dentición

En este trabajo se propone una metodología para la estimación de la edad a partir del desarrollo de la dentición temporaria en el período fetal y perinatal. Los datos de referencia para la estimación de edad por estadios de desarrollo de la dentición se focalizan en la dentición permanente y en edades posteriores al nacimiento. Por otro lado, respecto de la dentición temporaria y en el período prenatal, no se han sistematizado las edades para cada estadio de desarrollo sino que se ha descrito el proceso de maduración dentaria.Facultad de Ciencias Médica

Efficient fabrication of high-density ensembles of color centers via ion implantation on a hot diamond substrate

Nitrogen-Vacancy (NV) centers in diamond are promising systems for quantum technologies, including quantum metrology and sensing. A promising strategy for the achievement of high sensitivity to external fields relies on the exploitation of large ensembles of NV centers, whose fabrication by ion implantation is upper limited by the amount of radiation damage introduced in the diamond lattice. In this works we demonstrate an approach to increase the density of NV centers upon the high-fluence implantation of MeV N2+ ions on a hot target substrate (>550 {\deg}C). Our results show that, with respect to room-temperature implantation, the high-temperature process increases the vacancy density threshold required for the irreversible conversion of diamond to a graphitic phase, thus enabling to achieve higher density ensembles. Furthermore, the formation efficiency of color centers was investigated on diamond substrates implanted at varying temperatures with MeV N2+ and Mg+ ions revealing that the formation efficiency of both NV centers and magnesium-vacancy (MgV) centers increases with the implantation temperature.Comment: 12 pages, 5 figure

Efecto de células madre mesenquimales en la proliferación tumoral

En los últimos años el estudio de las células madre mesenquimales (CMM) ha generado muchas especulaciones acerca de su utilización clínica ya que al ser un importante componente del microambiente tumoral, se han convertido en foco de atención para nuevas terapias anti-cancerígenas. En trabajos previos, algunos autores han demostrado que éstas inhiben la proliferación del tumor mientras que otros afirman que lo promueven. En el presente estudio se analiza el efecto de las CMM derivadas de cordón umbilical (CMM-CU) sobre la curva de crecimiento y la síntesis de ADN (ADNs) de un carcinoma mamario murino denominado TN60.Facultad de Ciencias Médica