Tuning chelation by the surfactant-like peptide A6H using predetermined pH values

We examine the self-assembly of a peptide A6H comprising a hexa-alanine sequence A6 with a histidine (H) “head group”, which chelates Zn2+ cations. We study the self assembly of A6H and binding of Zn2+ ions in ZnCl2 solutions, under acidic and neutral conditions. A6H self-assembles into nanotapes held together by a β-sheet structure in acidic aqueous solutions. By dissolving A6H in acidic ZnCl2 solutions, the carbonyl oxygen atoms in A6H chelate the Zn2+ ions and allow for β-sheet formation at lower concentrations, consequently reducing the onset concentration for nanotape formation. A6H mixed with water or ZnCl2 solutions under neutral conditions produces short sheets or pseudocrystalline tapes, respectively. The imidazole ring of A6H chelates Zn2+ ions in neutral solutions. The internal structure of nanosheets and pseudocrystalline sheets in neutral solutions is similar to the internal structure of A6H nanotapes in acidic solutions. Our results show that it is possible to induce dramatic changes in the self-assembly and chelation sites of A6H by changing the pH of the solution. However, it is likely that the amphiphilic nature of A6H determines the internal structure of the self-assembled aggregates independent from changes in chelation

Trends and outcome of neoadjuvant treatment for rectal cancer: A retrospective analysis and critical assessment of a 10-year prospective national registry on behalf of the Spanish Rectal Cancer Project

Introduction: Preoperative treatment and adequate surgery increase local control in rectal cancer. However, modalities and indications for neoadjuvant treatment may be controversial. Aim of this study was to assess the trends of preoperative treatment and outcomes in patients with rectal cancer included in the Rectal Cancer Registry of the Spanish Associations of Surgeons. Method: This is a STROBE-compliant retrospective analysis of a prospective database. All patients operated on with curative intention included in the Rectal Cancer Registry were included. Analyses were performed to compare the use of neoadjuvant/adjuvant treatment in three timeframes: I)2006–2009; II)2010–2013; III)2014–2017. Survival analyses were run for 3-year survival in timeframes I-II. Results: Out of 14, 391 patients, 8871 (61.6%) received neoadjuvant treatment. Long-course chemo/radiotherapy was the most used approach (79.9%), followed by short-course radiotherapy ± chemotherapy (7.6%). The use of neoadjuvant treatment for cancer of the upper third (15-11 cm) increased over time (31.5%vs 34.5%vs 38.6%, p = 0.0018). The complete regression rate slightly increased over time (15.6% vs 16% vs 18.5%; p = 0.0093); the proportion of patients with involved circumferential resection margins (CRM) went down from 8.2% to 7.3%and 5.5% (p = 0.0004). Neoadjuvant treatment significantly decreased positive CRM in lower third tumors (OR 0.71, 0.59–0.87, Cochrane-Mantel-Haenszel P = 0.0008). Most ypN0 patients also received adjuvant therapy. In MR-defined stage III patients, preoperative treatment was associated with significantly longer local-recurrence-free survival (p < 0.0001), and cancer-specific survival (p < 0.0001). The survival benefit was smaller in upper third cancers. Conclusion: There was an increasing trend and a potential overuse of neoadjuvant treatment in cancer of the upper rectum. Most ypN0 patients received postoperative treatment. Involvement of CRM in lower third tumors was reduced after neoadjuvant treatment. Stage III and MRcN + benefited the most

Regional heterogeneity and firms’ innovation: the role of regional factors in industrial R&D in India

This study makes an early attempt to estimate the magnitude and intensity of manufacturing firms’ R&D by Indian states during the period 1991‒2008 and analyses the role of regional factors on firm-level R&D activities. As there is little research on state-wise R&D performance of firms in India, this study serves an important contribution to the academic and policy realm. It has brought out the fact the total manufacturing R&D investment in India is unevenly distributed regionally with a few states accounting for disproportionate share of it. Regional heterogeneity or inter-state disparities in R&D has increased between the 1990s and the first decade of the twenty-first century. In view of this persistent regional heterogeneity in R&D, the study has developed and estimated an empirical model for a sample of 4545 Indian manufacturing firms with R&D facilities located in single state and that explicitly includes regional factors as probable factors affecting R&D. The three-step Censored Quantitle Regression results confirm that regional factors play an important role in shaping the R&D intensity of the sample of firms. This led us to some useful policy suggestions for regional governments to promote local firms’ R&D activities

Encuesta de opinión sobre los Algoritmos erapéuticos de la Consellería de Sanitat de la Generalitat Valenciana

Objetivos: Los algoritmos terapéuticos desarrollados por la Conselleria de Sanitat de la Comunitat Valenciana han sido cuestionados en diversos ámbitos. Para conocer la opinión de los reumatólogos de esta Comunitat a este respecto se ha elaborado una encuesta online dirigida a los socios de la Sociedad Valenciana de Reumatología (SVR). Material y métodos: Encuesta presentada a los 143 socios de la SVR (89 de ellos socios numerarios) mediante un sistema online (Monkey Sur- vey) abierto durante 3 semanas en el mes de Julio de 2014. Resultados: Se han obtenido 36 respuestas válidas. Un 97% de los res- pondedores utiliza la receta electrónica de forma habitual. El 92% encuentra los algoritmos terapéuticos inapropiados. Mas del 97% encuentran que los algoritmos les dificulta realizar la prescripción en algunos o muchos de sus pacientes. Casi el 64% de los respondedores eliminaría totalmente el uso de algoritmos, en tanto que el 55% los modi- ficaría a nivel informático y un 28% consideran que son conceptualmen- te inapropiados. El 86% esta totalmente de acuerdo con el Posiciona- miento de la SVR respecto a los algoritmos, y el 14% parcialmente. El 100% de los respondedores recomiendan que dicho documento se envíe a la Conselleria con el fin de que se revisen los algoritmos informatizados. Conclusión: La gran mayoría de los reumatólogos que han respondido la presente encuesta están disconformes con el procedimiento informático insertado en la receta electrónica, y muchos también con el aspecto conceptual de los algoritmos actuales. Es necesario un mayor consenso sobre los algoritmos y una revisión de su implementación informática

Tuning Chelation by the Surfactant-Like Peptide A₆H Using Predetermined pH Values

We examine the self-assembly of a peptide A₆H comprising a hexa-alanine sequence A₆ with a histidine (H) “head group”, which chelates Zn²⁺ cations. We study the self-assembly of A₆H and binding of Zn²⁺ ions in ZnCl₂ solutions, under acidic and neutral conditions. A₆H self-assembles into nanotapes held together by a β-sheet structure in acidic aqueous solutions. By dissolving A₆H in acidic ZnCl₂ solutions, the carbonyl oxygen atoms in A₆H chelate the Zn²⁺ ions and allow for β-sheet formation at lower concentrations, consequently reducing the onset concentration for nanotape formation. A₆H mixed with water or ZnCl₂ solutions under neutral conditions produces short sheets or pseudocrystalline tapes, respectively. The imidazole ring of A₆H chelates Zn²⁺ ions in neutral solutions. The internal structure of nanosheets and pseudocrystalline sheets in neutral solutions is similar to the internal structure of A₆H nanotapes in acidic solutions. Our results show that it is possible to induce dramatic changes in the self-assembly and chelation sites of A₆H by changing the pH of the solution. However, it is likely that the amphiphilic nature of A₆H determines the internal structure of the self-assembled aggregates independent from changes in chelation