Mesoporous thin films on graphene FETs: nanofiltered, amplified and extended field-effect sensing.

The ionic screening and the response of non-specific molecules are great challenges of biosensors based on field-effect transistors (FETs). In this work, we report the construction of graphene based transistors modified with mesoporous silica thin films (MTF-GFETs) and the unique (bio)sensing properties that arise from their synergy. The developed method allows the preparation of mesoporous thin films free of fissures, with an easily tunable thickness, and prepared on graphene-surfaces, preserving their electronic properties. The MTF-GFETs show good sensing capacity to small probes that diffuse inside the mesopores and reach the graphene semiconductor channel such as H+, OH-, dopamine and H2O2. Interestingly, MTF-GFETs display a greater electrostatic gating response in terms of amplitude and sensing range compared to bare-GFETs for charged macromolecules that infiltrate the pores. For example, for polyelectrolytes and proteins of low MW, the amplitude increases almost 100% and the sensing range extends more than one order of magnitude. Moreover, these devices show a size-excluded electrostatic gating response given by the pore size. These features are even displayed at physiological ionic strength. Finally, a developed thermodynamic model evidences that the amplification and extended field-effect properties arise from the decrease of free ions inside the MTFs due to the entropy loss of confining ions in the mesopores. Our results demonstrate that the synergistic coupling of mesoporous films with FETs leads to nanofiltered, amplified and extended field-effect sensing (NAExFES).

Thermodynamics of cell penetrating peptides on lipid membranes: sequence and membrane acidity regulate surface binding.

Cell-penetrating peptides (CPPs) are molecules that traverse cell membranes and facilitate the cellular uptake of nano-sized cargoes. In this work we characterize the adsorption of amphipathic and purely cationic CPPs on membranes containing acidic lipids. We describe how the peptide primary sequence, the location of amino-acids within the sequence, the membrane composition, and the pH of the environment, determine both the surface concentration of the peptides and the molecular organization of the interface. Our results are obtained by applying a molecular theory that takes into account the size, shape, protonation state, charge distribution and conformational flexibility of the peptides, as well as the acid-base chemistry of the lipids. We find that peptide adsorption and binding free energy result from a balance between electrostatic and van der Waals interactions, and between chemical and entropic effective forces. We observe that, within a range of physiologically relevant parameters, acidic lipids respond to pH in ways that fully promote or deplete the surface accumulation of CPPs. Membrane acidity emerges thus as a crucial parameter to consider when designing CPP-based cargo-delivery vehicles.

Adsorption and insertion of polyarginine peptides into membrane pores: The trade-off between electrostatics, acid-base chemistry and pore formation energy.

The mechanism that arginine-rich cell penetrating peptides (ARCPPs) use to translocate lipid membranes is not entirely understood. In the present work, we develop a molecular theory that allows to investigate the adsorption and insertion of ARCPPs on membranes bearing hydrophilic pores. This method accounts for size, shape, conformation, protonation state and charge distribution of the peptides; it also describes the state of protonation of acidic membrane lipids. We present a systematic investigation of the effect of pore size, peptide concentration and sequence length on the extent of peptide adsorption and insertion into the pores. We show that adsorption on the intact (non-porated) lipid membrane plays a key role on peptide translocation. For peptides shorter than nona-arginine, adsorption on the intact membrane increases significantly with chain length, but it saturates for longer peptides. However, this adsorption behavior only occurs at relatively low peptide concentrations; increasing peptide concentration favors adsorption of the shorter molecules. Adsorption of longer peptides increases the intact membrane negative charge as a result of further deprotonation of acidic lipids. Peptide insertion into the pores depends non-monotonically on pore radius, which reflects the short range nature of the effective membrane-peptide interactions. The size of the pore that promotes maximum adsorption depends on the peptide chain length. Peptide translocation is a thermally activated process, so we complement our thermodynamic approach with a simple kinetic model that allows to rationalize the ARCPPs translocation rate in terms of the free energy gain of adsorption, and the energy cost of creating a transmembrane pore with peptides in it. Our results indicate that strategies to improve translocation efficiency should focus on enhancing peptide adsorption.

Aprendizaje en iirugía mediante laparatomía exporatoria por trauma penetrante.. experiencia en el hospital general de ciudad juárez / Learning in laparotomy-based abdominal surgery for managinf penetrating trauma: experience in the Ciudad Juárez General Hospital

Antecedentes. No se cuenta con un estudio previo que permita evaluar la formación del residente de cirugía general en un hospital enfocado al trauma. Objetivo. Evaluar el papel que desempeña el trauma abdominal penetrante en la formación del residente de cirugía general. Material y métodos. Pacientes con trauma abdominal penetrante durante un año. Las variables analizadas fueron: causa de la lesión, tipo de laparotomía, rol desempeñado por el residente ayudante/cirujano, órganos lesionados, tratamiento establecido, complicaciones y mortalidad. Estudio descriptivo, transversal. Análisis con porcentajes como medidas de resumen y Chi cuadrado de Pearson para obtener la diferencia significativa. Resultados. 203 pacientes sometidos a laparotomía, 109 heridas por arma de fuego y 105 por arma blanca. Se realizaron 139 laparotomías terapéuticas, 49 no terapéuticas y 15 cirugías de control de daño. 24 fueron por residente de primer año, 85 por los de segundo año y en 94 actuaron los de tercer año. De 272 lesiones, 184 lo fueron en víscera hueca, 78 en órgano sólido y 10 lesiones vasculares; se tuvieron 28 complicaciones postquirúrgicas, siendo las más comunes sepsis (8 pacientes) y cinco infecciones del sitio quirúrgico. Conclusiones. Durante la formación del cirujano es importante el desarrollo de las habilidades técnicas en la sala de operaciones y el manejo integral del paciente con trauma abdominal desde su ingreso a la sala de urgencias. No se han establecidos parámetros claros en cuanto al número de pacientes que deben ser evaluados ni el número de procedimientos quirúrgicos que se deben realizar durante la formación un residente.

Background. Prior studies could not be found for evaluating general surgery residency training in a hospital focusing on trauma. Objective. Evaluating the role of penetrating abdominal trauma in general surgery residency training. Materials and methods. Patients suffering from penetrating abdominal trauma over the course of a year. The variables analysed were cause of the lesion, type of laparotomy, the role played by the resident assistant / surgeon, damaged organs, established treatment, complications and mortality. This was a cross-sectional descriptive study. Analysis was done with percentages as means of summary and Pearson’s chi-square test for obtaining significant differences. Results. 203 patients underwent laparotomy, 109 were wounded by firearms and 105 had knife wounds. 139 therapeutic laparotomies were performed, 49 nontherapeutic ones and 15 damage-control surgeries. 24 were attended by first-year residents, 85 by second-year ones and 94 by residents in their third year. 184 of the 272 wounds were in hollow viscera, 78 in solid organs and 10 were vascular wounds; 28 post-surgical complications occurred, the most common ones being sepsis (8 patients) and surgical site infection (5 cases). Conclusions. An important part of a surgeon’s training concerns acquiring technical abilities in the operating room and the integral management of patients suffering abdominal trauma from the time of their being admitted to the emergency room. Clear parameters have not been established regarding the number of patients who should be evaluated or the number of surgical procedures which must be performed during a resident’s formation.