Nanostructure ITO and Get More of It. Better Performance at Lower Cost.

In this paper, we investigated how different growth conditions (i.e., temperature, growth time, and composition) allows for trading off cost (i.e., In content) and performance of nanostructured indium tin oxide (ITO) for biosensing applications. Next, we compared the behavior of these functionalized nanostructured surfaces obtained in different growth conditions between each other and with a standard thin film as a reference, observing improvements in effective detection area up to two orders of magnitude. This enhanced the biosensor's sensitivity, with higher detection level, better accuracy and higher reproducibility. Results show that below 150 °C, the growth of ITO over the substrate forms a homogenous layer without any kind of nanostructuration. In contrast, at temperatures higher than 150 °C, a two-phase temperature-dependent growth was observed. We concluded that (i) nanowire length grows exponentially with temperature (activation energy 356 meV) and leads to optimal conditions in terms of both electroactive surface area and sensitivity at around 300 °C, (ii) longer times of growth than 30 min lead to larger active areas and (iii) the In content in a nanostructured film can be reduced by 10%, obtaining performances equivalent to those found in commercial flat-film ITO electrodes. In summary, this work shows how to produce appropriate materials with optimized cost and performances for different applications in biosensing.

Merging Ligand-Based and Structure-Based Methods in Drug Discovery: An Overview of Combined Virtual Screening Approaches.

Virtual screening (VS) is an outstanding cornerstone in the drug discovery pipeline. A variety of computational approaches, which are generally classified as ligand-based (LB) and structure-based (SB) techniques, exploit key structural and physicochemical properties of ligands and targets to enable the screening of virtual libraries in the search of active compounds. Though LB and SB methods have found widespread application in the discovery of novel drug-like candidates, their complementary natures have stimulated continued efforts toward the development of hybrid strategies that combine LB and SB techniques, integrating them in a holistic computational framework that exploits the available information of both ligand and target to enhance the success of drug discovery projects. In this review, we analyze the main strategies and concepts that have emerged in the last years for defining hybrid LB + SB computational schemes in VS studies. Particularly, attention is focused on the combination of molecular similarity and docking, illustrating them with selected applications taken from the literature.

Tuning the deposition parameters for optimizing the faradaic and non-faradaic electrochemical performance of nanowire array-shaped ITO electrodes prepared by electron beam evaporation.

Nanostructured indium tin oxide (ITO) surfaces present an interesting yet unusual combination of properties (high electrical conductivity and optical transparency) at a high surface-to-volume ratio. Thus, previous studies presented nanostructured ITO electrodes as potentially suitable platforms for electrochemical biosensors, but still there is a lack of research on the optimization of preparation methods for such electrodes. We present a systematic study on the properties of nanostructured ITO electrodes prepared by physical deposition, where the substrate temperature was tuned for achieving the best combination of structural properties (namely electrical conductivity and optical transparency) and electrochemical performance. Analysis of faradaic cyclic voltammetry (CV) was performed to determine the electroactive surface area of the samples, and these results were benchmarked against those obtained by non-faradaic CV and Mott-Schottky (MS) analysis. The latter was useful to determine the dependence of some intrinsic features of the semiconductor on the substrate temperature during deposition. The results show that, out of a wide temperature range covering from 200 °C to 500 °C, there is a two-phase temperature-dependent growth, explained by the Stranski-Krastanov and self-catalytic vapor-liquid-solid (VLS) methods, and, on the other hand, that there is an optimal growth temperature at 300 °C that maximizes the electroactive surface area and sensitivity. This means that cost-effective electrodes can be prepared at low temperatures outperforming in terms of electroactive surface area, surface capacitance and sensitivity. As a proof-of-concept, nanostructured ITO electrodes were electrochemically derivatized with aryl diazonium salts (as a first step towards biochemical functionalization), and the performance of the optimized electrodes was tested in a real scenario.

A low-cost and miniaturized potentiostat for sensing of biomolecular species such as TNF-α by electrochemical impedance spectroscopy.

Miniaturizing potentiostats, keeping their cost low and yet preserving full measurement characteristics (e.g. bandwidth, determination of capacitive/inductive contribution to sensor's impedance and parallel screening) is still an unresolved challenge in bioelectronics. In this work, the combination of simple analogue circuitry together with powerful microcontrollers and a digital filter implementation is presented as an alternative to complex and incomplete architectures reported in the literature. A low-cost acquisition electronic system fully integrated with a biosensors platform containing eight gold working microelectrodes and integrated reference and counter electrodes was developed and validated. The manufacturing cost of the prototype was kept below 300 USD. The performance of the proposed device was benchmarked against a commercial impedance analyzer through the electrochemical analysis of a highly sensitive biosensor for the detection of tumor necrosis factor α (TNF-α) within the randomly chosen range of 266pg/mL to 666ng/mL in physiological medium (PBS). A strong correlation between the outputs of both devices was found in a critical range of frequencies (1-10Hz), and several TNF-α cytokine concentrations were properly discriminated. These results are very promising for the development of low-cost, portable and miniaturized electrochemical systems for point-of-care and environmental diagnosis.

Irradiación de áreas ganglionares en pacientes sin linfadenectomía axilar / Axillary radiation in patients without axillary lymphadenectomy

La biopsia selectiva del ganglio centinela (BSGC) es actualmente una propuesta estándar para la estadificación de la axila en pacientes con cáncer de mama con una clara tendencia a minimizar la cirugía axilar incluso en presencia de ganglio centinela (GC) positivo. En caso de GC negativo la BSGC ha reemplazado a la linfadenectomía axilar (LA) demostrando equivalente supervivencia, mientras que los más sólidos consensos (American Society of Clinical Oncology) y, hasta fechas recientes, las guías de la National Comprehensive Cancer Network recomendaban completar la LA cuando se identifican metástasis en el GC. Esto da como resultado un excelente control locorregional y proporciona información que permite tomar decisiones sobre tratamientos adyuvantes tanto al oncólogo médico como al oncólogo radioterápico. No obstante, en los últimos tiempos múltiples estudios han debatido el valor terapéutico de la linfadenectomía quirúrgica, cobrando especial relevancia a raíz de la publicación del ensayo del American College of Surgeons Oncology Group (ACOSOG) Z0011, en el que se cuestiona el valor de esta actitud terapéutica y se propone únicamente una BSGC, omitiéndose la LA, en pacientes seleccionadas con uno o 2 GC positivos. La evidencia científica nos dice que la radioterapia puede jugar un papel fundamental en el control de la enfermedad axilar y, a fecha de hoy, no sabemos si la baja tasa de recidiva a este nivel, en los estudios mencionados, puede estar influida por la irradiación de la mama y axila inferior. Serían necesarios estudios con un diseño apropiado para contestar esta pregunta. En ausencia de más datos, nuestra propuesta es la irradiación axilar valorando individualmente los factores de riesgo de recidiva locorregional(AU)

Sentinel lymph node biopsy (SLNB) is currently a standard approach for staging of the axilla in patients with breast cancer, with a clear tendency to minimize surgery even in the presence of a positive axillary sentinel lymph node (SLN). The strongest consensus (American Society of Clinical Oncology) and, until recently, the National Comprehensive Cancer Network guidelines used to recommend complete axillary lymphadenectomy when metastases were identified in the SLN. However, SLNB has replaced axillary lymphadenectomy in SLN-negative patients and has demonstrated equivalent survival. This approach results in excellent locoregional control and provides information that allows both the medical oncologist and the radiation oncologist to take decisions about adjuvant treatments. Many recent studies, however, have debated the therapeutic value of surgical lymphadenectomy. This debate has become particularly important after the publication of the trial of the American College of Surgeons Oncology Group (ACOSOG) Z0011, which questions the value of this therapeutic approach and proposes SLNB alone, without lymphadenectomy, in selected patients with one or 2 positive SLN. The scientific evidence indicates that radiotherapy may play a major role in the control of axillary disease and, to date, it is not known whether the low recurrence rate in the axilla reported in the above-mentioned studies may have been influenced by radiation of the breast and lower axilla. To answer this question, new and appropriately designed trials are needed. In the absence of more data, we propose the use of axillary radiation, but with assessment of the risk factors for locoregional recurrence in each patient(AU)

Discovery of a novel class of zwitterionic, potent, selective and orally active S1P1 direct agonists.

Amido-1,3,4-thiadiazoles have been identified as a novel structural class of potent and selective sphingosine-1-phosphate receptor subtype 1 agonists. Starting from a micromolar HTS hit with the help of an in-house homology model, robust structural-activity relationships were developed to yield compounds with good selectivity and excellent in vivo efficacy in rat models.

Highly potent aminopyridines as Syk kinase inhibitors.

A novel class of potent Syk inhibitors has been developed from rational design. Highly potent aminopyridine derivatives bearing a 4-trifluoromethyl-2-pyridyl motif and represented by compound 13b IC(50): 0.6 nM were identified. Substitution by a 2-pyrazinyl motif and SAR expansion in position 4 of the central core provided diverse potent non-cytotoxic Syk inhibitors showing nanomolar activity inhibiting human mast cell line LAD2 degranulation.

Pyrazine-based Syk kinase inhibitors.

A series of aminopyrazines as inhibitors of Syk kinase activity and showing inhibition of LAD2 cells degranulation is described. Optimization of the carboxamide motif with aminomethylpiperidines provided high potency inhibiting Syk but low cellular activity. Amides of cis and trans adamantanol showed good inhibitory activity against Syk as well as remarkable activity in LAD2 cells degranulation assay.