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We developed a monolateral external fixation system for bone elongation easier to assemble than commercial systems since the clamps can be laterally assembled to the rail in contrast to the commercial systems where the clamps can only be assembled from the ends. The system is formed by clamps, screws, and a rail. The rail is composed of two carbon fiber circular rods of ½” diameter and 42-cm length. The clamps can slide with respect to the rail to allow bone distraction or may be fixed to the rail by using a wedge and a screw. The prototype was mechanically evaluated under the ASTM F1541 standard. The stiffness in axial, Medio Lateral bending (ML), Antero Posterior bending (AP), and flexo-torsional load were 117 N/mm, 46 N/mm, 8.7 N/mm, and 5.8 N-mm/°, respectively, which are on the range of stiffness of commercial systems. 

We developed a monolateral external fixation system for bone elongation easier to assemble than commercial systems since the clamps can be laterally assembled to the rail in contrast to the commercial systems where the clamps can only be assembled from the ends. The system is formed by clamps, screws, and a rail. The rail is composed of two carbon fiber circular rods of ½” diameter and 42-cm length. The clamps can slide with respect to the rail to allow bone distraction or may be fixed to the rail by using a wedge and a screw. The prototype was mechanically evaluated under the ASTM F1541 standard. The stiffness in axial, Medio Lateral bending (ML), Antero Posterior bending (AP), and flexo-torsional load were 117 N/mm, 46 N/mm, 8.7 N/mm, and 5.8 N-mm/°, respectively, which are on the range of stiffness of commercial systems.

This paper describes designing and constructing a test machine having an 1,800 N capacity and maximum 3 Hz frequency which will be used in static and dynamic testing of biological tissues and orthopedic devices such as external fixers. It consists of an octagonal base with 500 mm distance between faces and a crosshead which slides between two columns (useful 350 mm opening) thus allowing changing the height (maximum 600 mm) according to the size of the specimen to be tested. A ball screw actuator is mounted over the crosshead which transforms a servomotor’s rotating movement into a lineal movement (maximum 150 mm stroke). First validations indicated that the machine performed within the design parameters. This project shows that the technology required for supporting research is possible in developing countries thereby avoiding dependence on foreign companies for supporting, maintaining and updating equipment. Some conditions were also produced for the evolution of mechanical engineering in Colombia.

El sistema de fijación externa ATLAS para el tratamiento de fracturas fue desarrollado por el Grupo de Biomecánica de la Universidad del Valle para que pudiera ser utilizado en amplios sectores de la población a un precio razonable. Se presenta la caracterización experimental y analítica de dos configuraciones no convencionales del sistema, las cuales fueron sometidas a pruebas estáticas y cíclicas. Adicionalmente, se desarrolló un modelo matemático mediante elementos finitos, el cual fue calibrado con los resultados experimentales. Este estudio demostró un adecuado desempeño del sistema, caracterizado por su buena estabilidad y una rigidez comparable a la obtenida con un fijador comercial de la compañía suiza AO® en configuraciones similares. Por otra parte, con las pruebas de carga variable se verificó la estabilidad de tres configuraciones en rutinas simuladas de marcha. Queda así plenamente validada la utilización del sistema ATLAS el cual ya había demostrado su buen comportamiento en pruebas previas.

Se describe el diseño y la construcción de una prensa con una capacidad de 1.800 N y una frecuencia máxima de 3 Hz que será utilizada para realizar pruebas estáticas y dinámicas de tejidos biológicos y elementos ortopédicos como fijadores externos. Consta de una base octagonal con una distancia entre caras de 500 mm y un travesaño que desliza sobre dos columnas (distancia útil de 350 mm), permitiendo así modificar la altura de trabajo (máxima de 600 mm) de acuerdo con el tamaño del elemento a probar. Sobre el travesaño está montado un actuador de tornillo con tuerca de bolas recirculantes, el cual transforma la rotación de un servomotor en un desplazamiento lineal (máximo de 150 mm). Las primeras validaciones indicaron un comportamiento de la prensa dentro de los parámetros de diseño estipulados. Este proyecto tiende a demostrar que en países en desarrollo es posible generar la tecnología necesaria para apoyar la investigación, lo que evita crear una dependencia de las compañías extranjeras para la modernización, el soporte y el mantenimiento del equipo. Adicionalmente, se generan condiciones para la evolución de la ingeniería mecánica en Colombia.

Background Solitary fibrous tumour (SFT) is a rare mesenchymal malignancy that lacks robust prognostic and predictive biomarkers. Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like modifier, associated with tumour progression, and with poor survival of SFT patients, as previous published by our group. Here, we describe the role of ISG15 in the biology of this rare tumour. Methods ISG15 expression was assessed by immunohistochemistry in tissue microarrays from SFT patients and tested for correlation with progression-free survival and overall survival (OS). The effects of ISG15 knockdown or induction were investigated for cancer stem cell (CSC) characteristics and for drug sensitivity in unique in vitro models of SFT. Results The prognostic value of ISG15 for OS was validated at protein level in malignant SFT patients, prospectively treated with pazopanib and enrolled in GEIS-32 trial. In SFT in vitro models, ISG15 knockdown lead to a decrease in the expression of CSC-related genes, including SOX2, NANOG, ALDH1A1, ABCB1 and ABCC1 . Likewise, ISG15 downregulation decreased the clonogenic/ tumoursphere-forming ability of SFT cells, while enhancing apoptotic cell death after doxorubicin, pazopanib or trabectedin treatment in 3D cell cultures. The regulation of CSC-related genes by ISG15 was confirmed after inducing its expression with interferon-β1; ISG15 induction upregulated 1.28- to 451-fold the expression of CSC-associated genes. Conclusions ISG15 is a prognostic factor in malignant SFT, regulating the expression of CSC-related genes and CSCs maintenance. Our results suggest that ISG15 could be a novel therapeutic target in SFT, which could improve the efficacy of the currently available treatments.

HMGA1 is a structural epigenetic chromatin factor that has been associated with tumor progression and drug resistance. Here, we reported the prognostic/predictive value of HMGA1 for trabectedin in advanced soft-tissue sarcoma (STS) and the effect of inhibiting HMGA1 or the mTOR downstream pathway in trabectedin activity. The prognostic/predictive value of HMGA1 expression was assessed in a cohort of 301 STS patients at mRNA (n = 133) and protein level (n = 272), by HTG EdgeSeq transcriptomics and immunohistochemistry, respectively. The effect of HMGA1 silencing on trabectedin activity and gene expression profiling was measured in leiomyosarcoma cells. The effect of combining mTOR inhibitors with trabectedin was assessed on cell viability in vitro studies, whereas in vivo studies tested the activity of this combination. HMGA1 mRNA and protein expression were significantly associated with worse progression-free survival of trabectedin and worse overall survival in STS. HMGA1 silencing sensitized leiomyosarcoma cells for trabectedin treatment, reducing the spheroid area and increasing cell death. The downregulation of HGMA1 significantly decreased the enrichment of some specific gene sets, including the PI3K/AKT/mTOR pathway. The inhibition of mTOR, sensitized leiomyosarcoma cultures for trabectedin treatment, increasing cell death. In in vivo studies, the combination of rapamycin with trabectedin downregulated HMGA1 expression and stabilized tumor growth of 3-methylcholantrene-induced sarcoma-like models. HMGA1 is an adverse prognostic factor for trabectedin treatment in advanced STS. HMGA1 silencing increases trabectedin efficacy, in part by modulating the mTOR signaling pathway. Trabectedin plus mTOR inhibitors are active in preclinical models of sarcoma, downregulating HMGA1 expression levels and stabilizing tumor growth.

Non-invasive ventilation (NIV) is an effective form of treatment in patients with obesity hypoventilation syndrome (OHS) who have concomitant severe obstructive sleep apnoea (OSA). However, there is a paucity of evidence on the efficacy of NIV in patients with OHS without severe OSA. We performed a multicentre randomised clinical trial to determine the comparative efficacy of NIV versus lifestyle modification (control group) using daytime arterial carbon dioxide tension (PaCO2) as the main outcome measure. Between May 2009 and December 2014 we sequentially screened patients with OHS without severe OSA. Participants were randomised to NIV versus lifestyle modification and were followed for 2 months. Arterial blood gas parameters, clinical symptoms, health-related quality of life assessments, polysomnography, spirometry, 6-min walk distance test, blood pressure measurements and healthcare resource utilisation were evaluated. Statistical analysis was performed using intention-to-treat analysis. A total of 365 patients were screened of whom 58 were excluded. Severe OSA was present in 221 and the remaining 86 patients without severe OSA were randomised. NIV led to a significantly larger improvement in PaCO2 of -6 (95% CI -7.7 to -4.2) mm Hg versus -2.8 (95% CI -4.3 to -1.3) mm Hg, (p<0.001) and serum bicarbonate of -3.4 (95% CI -4.5 to -2.3) versus -1 (95% CI -1.7 to -0.2 95% CI)  mmol/L (p<0.001). PaCO2 change adjusted for NIV compliance did not further improve the inter-group statistical significance. Sleepiness, some health-related quality of life assessments and polysomnographic parameters improved significantly more with NIV than with lifestyle modification. Additionally, there was a tendency towards lower healthcare resource utilisation in the NIV group. NIV is more effective than lifestyle modification in improving daytime PaCO2, sleepiness and polysomnographic parameters. Long-term prospective studies are necessary to determine whether NIV reduces healthcare resource utilisation, cardiovascular events and mortality. NCT01405976; results.

Background: Although smell and taste disorders are highly prevalent symptoms of COVID-19 infection, the predictive factors leading to long-lasting chemosensory dysfunction are still poorly understood. Methods: 102 out of 421 (24.2%) mildly symptomatic COVID-19 patients completed a second questionnaire about the evolution of their symptoms one year after the infection using visual analog scales (VAS). A subgroup of 69 patients also underwent psychophysical evaluation of olfactory function through UPSIT. Results: The prevalence of chemosensory dysfunction decreased from 82.4% to 45.1% after 12 months, with 46.1% of patients reporting a complete recovery. Patients older than 40 years (OR = 0.20; 95% CI: [0.07, 0.56]) and with a duration of loss of smell longer than four weeks saw a lower odds ratio for recovery (OR = 0.27; 95% CI: [0.10, 0.76]). In addition, 28 patients (35.9%) reported suffering from parosmia, which was associated with moderate to severe taste dysfunction at the baseline (OR = 7.80; 95% CI: [1.70, 35.8]). Among the 69 subjects who underwent the UPSIT, 57 (82.6%) presented some degree of smell dysfunction, showing a moderate correlation with self-reported VAS (r = −0.36, p = 0.0027). Conclusion: A clinically relevant number of subjects reported persistent chemosensory dysfunction and parosmia one year after COVID-19 infection, with a moderate correlation with psychophysical olfactory tests.