Physicochemical and Mechanical Properties of Non-Isocyanate Polyhydroxyurethanes (NIPHUs) from Epoxidized Soybean Oil: Candidates for Wound Dressing Applications.

Only 0.1% of polyurethanes available on the market are from renewable sources. With increasing concern about climate change, the substitution of monomers derived from petrochemical sources and the application of eco-friendly synthesis processes is crucial for the development of biomaterials. Therefore, polyhydroxyurethanes have been utilized, as their synthesis route allows for the carbonation of vegetable oils with carbon dioxide and the substitution of isocyanates known for their high toxicity, carcinogenicity, and petrochemical origin. In this study, polyhydroxyurethanes were obtained from carbonated soybean oil in combination with two diamines, one that is aliphatic (1,4-butadiamine (putrescine)) and another that is cycloaliphatic (1,3-cyclohexanobis(methylamine)). Four polyhydroxyurethanes were obtained, showing stability in hydrolytic and oxidative media, thermal stability above 200 °C, tensile strength between 0.9 and 1.1 MPa, an elongation at break between 81 and 222%, a water absorption rate up 102%, and contact angles between 63.70 and 101.39. New formulations of bio-based NIPHUs can be developed with the inclusion of a cycloaliphatic diamine (CHM) for the improvement of mechanical properties, which represents a more sustainable process for obtaining NIPHUs with the physicochemical, mechanical, and thermal properties required for the preparation of wound dressings.

Inter-Reader Consistency and Exclusionary Findings During Radiographic Screening for Phase 3 Trials of Tanezumab in Patients With Osteoarthritis.

Objective: Describe the radiograph-based screening program and frequencies of ineligibility in 3 large, international, randomized, double-blind, phase 3 studies of subcutaneous tanezumab in patients with osteoarthritis (OA). Design: Standardized bilateral shoulder, hip, and knee screening radiographs were obtained by trained imaging technologists and centrally read by 1 of 5 musculoskeletal radiology experts trained using a program-specific imaging atlas. Inter-reader consistency was tracked with test cases blindly inserted into the reader queue. Readers attended quarterly calibration meetings. Protocol-specified radiographic exclusion criteria included rapidly progressive OA (RPOA) or risk factors for RPOA (including severe malalignment of the knee, subchondral insufficiency fracture, atrophic OA, and osteonecrosis). Patients reporting disproportionate pain to radiographic evidence of OA in the hip or knee (without other pathology) were ineligible under a nonradiographic exclusion criterion. Results: At >480 international sites, 23,079 patients entered screening and 13,797 were radiographically assessed. Across 6 sets of quarterly testing, pairwise central reader agreement on radiographic eligibility was 72-87% (kappa: 0.41-0.71) and on radiographic OA grading 77-84% (kappa: 0.68-0.75). Among the 5,773/13,797 (41.8%) patients who met exclusionary criteria, 27% had disproportionate pain to radiographic findings (~10% of knee/hip radiographs). RPOA or risk factors for RPOA were each identified in <5% of patients (usually 1 joint) and <3% of knee/hip/shoulders. Conclusions: The phase 3 tanezumab screening program demonstrated the utility of radiographs to screen patients entering NGF inhibitor trials. A high degree of reader concordance was achieved. RPOA and risk factors for RPOA were not commonly observed. NCT02697773, NCT02709486, NCT02528188.

LA ACTIVACIÓN DE LA VÍA DE SEÑALIZACIÓN PI3K/AKT POR EL FACTOR DE CRECIMIENTO SIMILAR A LA INSULINA TIPO II ESTIMULA LA EXPRESIÓN DEL mARN DE LA METALOPROTEINASA 9 EN CÉLULAS DE CORIOCARCINOMA / ACTIVATION OF THE PI3K/AKT SIGNALLING PATHWAY BY INSULIN-LIKE GROWTH FACTOR TYPE II STIMULATES METALLOPROTEINASE 9mRNA EXPRESSION IN CHORIOCARCINOMA CELLS / PERCURSO SINALIZAÇÃO PI3K/AKT ACTIVADO POR INSULINA-COMO FACTOR DE CRESCIMENTO TIPO II ESTIMULA METALOPROTEINASE 9 mARN EXPRESION CORIOCARCINOMA EM CÉLULAS

Las metaloproteinasas 2 y 9 (MMP-2 y MMP-9) y el inhibidor-1 de MMP (TIMP-1) podrían contribuir a la regulación del comportamiento invasivo de las células trofoblásticas, efecto que podría ser mediado por el factor de crecimiento similar a la insulina tipo II (IGF-II), el cual regula el desarrollo y la función del trofoblasto en la interfase materno-fetal. El objetivo de este estudio fue investigar el rol de la vía de señalización PI3K/AKT activada por IGF-II en la expresión de MMP-2 y MMP-9 involucradas en el proceso de invasión en la línea celular JEG-3, de coriocarcinoma humano. La expresión del mARN de MMP-2, MMP-9 y TIMP-1 fue evaluada, en dichas células, por la técnica de RT-PCR empleando diferentes dosis de IGF-II y diferentes condiciones, mientras que la vía de señalización fue evaluada usando la técnica de Western blot. Se encontró que el IGF-II no contribuye a la proliferación de las células trofoblásticas; sin embargo, este promueve la expresión del mARN de MMP-9 y TIMP-1 pero no de MMP-2, de forma dependiente de la dosis. El efecto en la expresión de MMP-9 es mediado a través de IGF-II por la activación de la vía de señalización PI3K/ AKT después de la fosforilación del receptor de IGF-I (IGF-IR). De acuerdo con los resultados, se propone un modelo en el cual la interacción de IGF-II con IGF-IR conduce a la activación de PI3K/AKT y la subsecuente expresión y activación de MMP-9. Esta activación es un requisito esencial para el proceso invasivo.

Metalloproteinases 2 and 9 (MMP-2 and MMP-9) and TissueInhibitor-1 ofMMPs (TIMP-1) could contribute to regulate the invasive behaviour of trophoblastic cells, effect which could be mediated by Insulin-like growth factor type II (IGF-II), which regulates the development and function of trophoblast at the foetal-maternal interface. The aim of this study was to investigate the role of the PI3K/AKT signalling pathway activated by IGF-II in the expression of MMP-2 and MMP-9 involved in the invasion process in the human choriocarcinoma cell line JEG-3. MMP-2, MMP-9 and TIMP-1 mARN expression in those cells were evaluated by RT-PCR using different IGF-II doses and conditions while signalling pathway was evaluated using Western blot. It was found that IGF-II does not contribute to trophoblastic cells proliferation, however, it promotes mARN expression of MMP-9 and TIMP-1, but not of MMP-2, in a dose-dependent way. The effect on MMP-9 expression is mediated through IGF-II activation of PI3K/AKT signalling pathway after phosphorylation of the IGF-I receptor (IGF-IR). According with the results a model is proposed in which the interaction of IGF-II with IGF-IR leads to PI3K/AKT activation and subsequent expression and activation of MMP-9. This activation is an essential requirement for the invasive process.

As metaloproteinasas 2 y 9 (MMP-2 y MMP-9) e o inibidor-1 de MMPs (TIMP-1) poderiam contribuir à regulação do comportamento invasivo das células trofoblásticas, efeito que poderia ser mediado pelo Factor de Crescimento Similar à Insulina tipo II (IGF-II), o qual regula o desenvolvimento e função do trofoblasto na interface materno-fetal. O objectivo deste estudo foi investigar o papel da via de sinalização PI3K/AKT activada por IGF-II na expressão de MMP-2 e MMP-9 envolvidos no processo de invasão na linha celular JEG-3, de coriocarcinoma humano. A expressão do mARN de MMP-2, MMP-9 y TIMP-1, foi avaliada, em ditas células, pela técnica de RT-PCR utilizando diferentes doses de IGF-II e diferentes condições, enquanto que a via de sinalização foi avaliada usando a técnica de Western-blot. Foi encontrado que o IGF-II não contribui à proliferação das células trofoblásticas, no entanto, este promoveu a expressão do mARN de MMP-9 e TIMP-1 mas não de MMP-2, de forma dependente da dose. O efeito na expressão de MMP-9 é mediado através de IGF-II pela activação da via de sinalização PI3K/AKT depois da fosforilação do receptor de IGF-I (IGF-IR). De acordo aos resultados é proposto um modelo, no qual a interacção de IGF-II com IGF-IR conduz à activação de PI3K/AKT e à subsequente expressão e activação de MMP-9. Esta activação é um requisito essencial para o processo invasivo.

Sindromes de preexcitación ventricular en la región de Azuero / Ventricular pre-excitation syndromes in the Azuero region

Se revisaron 10,000 electrocardiogramas de la región de Azuero econtrándose 0,8% de preexcitaciones. La frecuencia de Wolff-Parkinson-White fue de 0,15% mientras que la Lown-Ganong-Levine fue de 0,65%. En los casos de Wolff-Parkinson-White hubo predominio de varones y mayor número de casos del tipo B sin que la diferencia fuera estadísticamente significativa. En los casos de Lown-Ganong-Levine hubo predominio estadísticamente significativo del sexo femenino