EPA Consensus Project Paper: Shifting from the "Analogic Virtual Patient" to the "Digital Virtual Patient" in Prosthodontics. A Scoping Review.

AIMS: To determine whether the use of single or combined mechanical and virtual articulators, as well as facebows, jaw motion trackers, face scanners, and related devices, actually improve the efficacy of the prosthesis obtained in terms of lifespan and patient-related outcomes. To coin the terms Analogic and Digital Virtual Patients (AVP and DVP) as an attempt to analyze, clarify and synthesize terminology and workflows related to previously so-called devices. MATERIALS AND METHODS: A scoping review was accomplished involving different databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-ScR) checklist and JBI guidance were followed to extract data regarding the Population, Context and Concept established. RESULTS: Available literature on the efficacy of using devices and techniques related to both AVP and DVP workflows showed arguable study designs, great heterogeneity, and questionable quality. CONCLUSIONS: The terms AVP and DVP have been coined as a first step to clarify and simplify concepts and workflows related to the use of both mechanical and virtual articulators, as well as facebows, or facial and intraoral scanners, among others. This scoping review cannot claim that an AVP approach leads to more effective and efficient prosthetic restorations.

Impact of the coronavirus pandemic on maxillofacial trauma: A retrospective study in southern Spain.

BACKGROUND: The coronavirus pandemic has impacted health systems worldwide, with Spain being one of the most affected countries. However, little is known about the extent to which the effects of staying home, social distancing, and quarantine measures have influenced the epidemiology of patients with maxillofacial trauma. The aim of this study was to analyze the impact of the coronavirus pandemic on the incidence, demographic patterns, and characteristics of maxillofacial fractures in the largest hospital in southern Spain. MATERIAL AND METHODS: Data from patients who underwent surgery for maxillofacial fractures during the first year of the pandemic between 16 March 2020 and 14 March 2021 (pandemic group) were retrospectively compared with a control group during the equivalent period of the previous year (pre-pandemic group). The incidence was compared by weeks and by lockdown periods of the population. Demographic information, aetioloy, fracture characteristics, treatment performed, and days of preoperative stay were evaluated. Descriptive and bivariate statistics were calculated (p<0.05). RESULTS: During the first year of the pandemic, there was a 35.2% reduction in maxillofacial fractures (n=59) compared to the pre-pandemic year (n=91, p=0.040). A significant drop was detected during the total home lockdown period of the population (p=0.028). In the pandemic group, there was a reduction in fractures due to interpersonal aggressions, an increase in panfacial fractures, a significant increase in other non-facial injuries associated with polytrauma (p=0.037), a higher number of open reduction procedures with internal fixation, and a significantly longer mean preoperative stay (p=0.016). CONCLUSIONS: The first pandemic year was associated with a decline in the frequency of maxillofacial trauma and a change in the pattern and characteristics of fractures. Inter-annual epidemiological knowledge of maxillofacial fractures may be useful for more efficient planning of resource allocation and surgical practice strategy during future coronavirus outbreaks and population lockdowns.

Tratamiento Conservador del Fibroma Desmoplásico Maxilar en Paciente Pediátrico. Seguimiento a Dos Años: Reporte de Caso y Revisión de la Literatura

RESUMEN: El fibroma desmoplasico (FD) es una neoplasia intraósea benigna, localmente agresiva, de muy baja frecuencia - especialmente en niños pequeños - y es considerada la contraparte ósea de la fibromatosis tipo desmoide. Se han descrito tratamientos que van desde la enucleación y legrado hasta la resección del segmento óseo afectado, debido a su alta tasa de recidiva. Sin embargo, se ha establecido un consenso para evitar dichas recidivas, que consiste en realizar una resección segmentaria con márgenes de seguridad. En este reporte de caso se decidió realizar un tratamiento conservador debido a la edad de la paciente, siendo el caso más joven reportado en la literatura con un FD maxilar y, de esta manera, evitar mutilaciones y necesidad de reconstrucción ósea a tan corta edad, considerando también su estado de crecimiento, generación de potenciales asimetrías o desarrollo facial anormal que podría generar secuelas estéticas y funcionales, alterando su calidad de vida.

ABSTRACT: Desmoplastic fibroma (DF) is a benign, locally aggressive, intraosseous neoplasm of very low frequency - especially in young children - and is considered the bony counterpart of desmoid-type fibromatosis. Treatments ranging from enucleation and curettage to resection of the affected bone segment have been described, due to its high recurrence rate. However, a consensus has been established to avoid such recurrences, which consists in performing a segmental resection with safety margins. In this case report, it was decided to carry out a conservative treatment due to the age of the patient, being the youngest case reported in the literature with a maxillary DF and, in this way, avoiding mutilations and the need for bone reconstruction at such a young age. Also considering their growth status, generation of potential asymmetries or abnormal facial development that could generate aesthetic and functional sequelae, altering their quality of life.

What should I do if I Want to Start and Academic Research Career?

ABSTRACT: The incorporation of young researchers to universities today poses challenges and reflections. Several concepts that should be kept in mind when starting an academic career are analyzed, with an emphasis on research. Adequate postgraduate training, the type of higher education institution, contractual forms, insertion and interaction with groups, time dedicated to research, equipment available for research and research funds are concepts that are analyzed to guide young researchers in the beginning of an academic career at a university.

RESUMEN: La incorporación de jóvenes investigadores a las universidades hoy en día plantea desafíos y reflexiones. Se analizan varios conceptos que se deberían tener presentes al momento de comenzar una carrera académica, con énfasis en la investigación. La adecuada formación de posgrado, el tipo de institución de educación superior, formas contractuales, inserción e interacción con los grupos, tiempo dedicado a la investigación, equipamiento disponible para las investigaciones y fondos de investigación son conceptos que se analizan para orientar a jóvenes investigadores en el inicio de una carrera académica en una universidad.

Electromiografía de Superficie y Articulografía Electromangética para Análisis de Dimensión Vertical. Reporte de Protocolo / Surface Electromyography and Electromagnetic Articulography to Analyze VerticalDimension. Protocol Report

INTRODUCCIÓN: La correcta determinación de la Dimensión Vertical (DV) es esencial al momento de rehabilitar a un paciente. En la literatura existen escasas investigaciones que relacionen en conjunto la DV con otras variables como actividad electromiográfica.El objetivo de este estudio es describir una técnica para el análisis de la DVa través del Espacio Libre de Inoclusión (ELI), mediante la utilización de articulografíaelectromagnética y electromiografía de superficie. MATERIAL Y MÉTODOS: Se registró la DV mediante el uso de un articulógrafo electromagnético AG501 simultáneamente con la actividad electromiográfica de músculos masetero y temporal mediante la utilización de electromiógrafo de superficie EMG VIII, según protocolo de DVO y DVP.El estudio se realizó en el Laboratorio de Fisiología Oral del Centro de Investigación en Ciencias Odontológicas (CICO) con la Aprobación del Comité Ético Científico de la Universidad de La Frontera. RESULTADOS: Se obtuvo un protocolo para el uso de electromiografía y articulografía electromagnética 3D en el análisis de dimensión vertical, el cual permite caracterizar la dimensión vertical mediante una medición de distanciavertical, medición de distancia 3D, ángulo de apertura y la actividad eléctrica de los músculos elevadores de la mandíbula a distintos grados de apertura

INTRODUCTION: The correct determination of the Vertical Dimension (VD) is essential when rehabilitating a patient. There is little research in the literature that collectively relates the VD to other variables such as electromyographic activity. The objective of this study is to describe a technique for the analysis of the VD through the Interocclusal Distance, using electromagnetic articulography and surface electromyography. MATERIAL AND METHODS: The VD was recorded by using an AG501 electromagnetic articulgraph simultaneously with the electromyographic activity of masseter and temporal muscles using EMG VIII surface electromyograph, according to DVO and DVP protocol. The study was carried out in the Oral Physiology Laboratory of the Center for Research in Dental Sciences (CICO) with the approval of the Scientific Ethical Committee of the University of La Frontera. RESULTS: A protocol was obtained for the use of electromyography and 3D electromagnetic articulography in the vertical dimension analysis, which allows the vertical dimension to be characterized by a vertical distance measurement, 3D distance measurement, opening angle and the electrical activity of the lifting muscles of the jaw to different degrees of opening

Machine learning at the interface of structural health monitoring and non-destructive evaluation.

While both non-destructive evaluation (NDE) and structural health monitoring (SHM) share the objective of damage detection and identification in structures, they are distinct in many respects. This paper will discuss the differences and commonalities and consider ultrasonic/guided-wave inspection as a technology at the interface of the two methodologies. It will discuss how data-based/machine learning analysis provides a powerful approach to ultrasonic NDE/SHM in terms of the available algorithms, and more generally, how different techniques can accommodate the very substantial quantities of data that are provided by modern monitoring campaigns. Several machine learning methods will be illustrated using case studies of composite structure monitoring and will consider the challenges of high-dimensional feature data available from sensing technologies like autonomous robotic ultrasonic inspection. This article is part of the theme issue 'Advanced electromagnetic non-destructive evaluation and smart monitoring'.

Morphological variations of the mandibular canal in digital panoramic radiographs: a retrospective study in a Chilean population.

BACKGROUND: Morphological variations of the mandibular canal (MC) have been described in literature, so the clinician must be able to recognise them and adapt their treatment accordingly. The aim of this study was to determine the prevalence of morphological variations of the MC using digital panoramic radiographs (DPR) of Chilean patients. MATERIALS AND METHODS: A retrospective study in which 1400 DPR were analysed to identify cases of bifid, trifid and retromolar MC. The radiographs were analysed independently by two examiners who had previously been trained by a specialist in oral and maxillofacial radiology. Inclusion and exclusion criteria were applied to reach a final sample. RESULTS: Nine hundred and twenty-five radiographs were included (599 female, 326 male; mean age 36.1 ± 15.54 years). The prevalence of bifid MC was 11% (n = 102), with no significant differences by sex (p = 0.069). Proportion of bifid MC was higher among younger patients (p = 0.038). Prevalence of morphologi- cal variations of type 1 bifid MC was 7.4% (n = 69), type 2 was 2.3% (n = 23), type 3 was 0% (n = 0) and type 4 was 1.1% (n = 10). Prevalence of retromolar canal was 0.9% (n = 8), with no significant differences by sex (p = 0.893) or age (p = 0.371); of these, 2 (0.2%) cases were forward type and 6 (0.6%) cases were retromolar type. No cases of trifid MC were found. CONCLUSIONS: Digital panoramic radiographs are useful for detecting morphological variations of the MC; we were able to identify three types of bifid MC as well as retromolar canals. Proper identification of these variations by an easily accessible examination is important for avoiding possible complications in clinical-surgical practice.

Delay in starting radiotherapy due to neoadjuvant therapy does not worsen survival in unresected glioblastoma patients

Purpose: We retrospectively examined the potential effect on overall survival (OS) of delaying radiotherapy to administer neoadjuvant therapy in unresected glioblastoma patients. Patients and methods: We compared OS in 119 patients receiving neoadjuvant therapy followed by standard treatment (NA group) and 96 patients receiving standard treatment without neoadjuvant therapy (NoNA group). The MaxStat package of R identified the optimal cut-off point for waiting time to radiotherapy. Results: OS was similar in the NA and NoNA groups. Median waiting time to radiotherapy after surgery was 13 weeks for the NA group and 4.2 weeks for the NoNA group. The longest OS was attained by patients who started radiotherapy after 12 weeks and the shortest by patients who started radiotherapy within 4 weeks (12.3 vs 6.6 months) (P = 0.05). OS was 6.6 months for patients who started radiotherapy before the optimal cutoff of 6.43 weeks and 19.1 months for those who started after this time (P = 0.005). Patients who completed radiotherapy had longer OS than those who did not, in all 215 patients and in the NA and NoNA groups (P = 0.000). In several multivariate analyses, completing radiotherapy was a universally favorable prognostic factor, while neoadjuvant therapy was never identified as a negative prognostic factor. Conclusion: In our series of unresected patients receiving neoadjuvant treatment, in spite of the delay in starting radiotherapy, OS was not inferior to that of a similar group of patients with no delay in starting radiotherapy

No disponible

Delay in starting radiotherapy due to neoadjuvant therapy does not worsen survival in unresected glioblastoma patients.

PURPOSE: We retrospectively examined the potential effect on overall survival (OS) of delaying radiotherapy to administer neoadjuvant therapy in unresected glioblastoma patients. PATIENTS AND METHODS: We compared OS in 119 patients receiving neoadjuvant therapy followed by standard treatment (NA group) and 96 patients receiving standard treatment without neoadjuvant therapy (NoNA group). The MaxStat package of R identified the optimal cut-off point for waiting time to radiotherapy. RESULTS: OS was similar in the NA and NoNA groups. Median waiting time to radiotherapy after surgery was 13 weeks for the NA group and 4.2 weeks for the NoNA group. The longest OS was attained by patients who started radiotherapy after 12 weeks and the shortest by patients who started radiotherapy within 4 weeks (12.3 vs 6.6 months) (P = 0.05). OS was 6.6 months for patients who started radiotherapy before the optimal cutoff of 6.43 weeks and 19.1 months for those who started after this time (P = 0.005). Patients who completed radiotherapy had longer OS than those who did not, in all 215 patients and in the NA and NoNA groups (P = 0.000). In several multivariate analyses, completing radiotherapy was a universally favorable prognostic factor, while neoadjuvant therapy was never identified as a negative prognostic factor. CONCLUSION: In our series of unresected patients receiving neoadjuvant treatment, in spite of the delay in starting radiotherapy, OS was not inferior to that of a similar group of patients with no delay in starting radiotherapy.

Bilateral bifid mandibular canal: a case report using cone beam computed tomography.

The mandibular canal (MC) originates in the mandibular foramen and runs bilaterally through the mandibular ramus and body, ending in the mental foramen. One of the most common anatomical variations is bifid MC, the configurations of which have been classified into four categories and sub-categories. The prevalence of these variations depends on the imaging method used. Studies carried out in panoramic X-rays and cone beam computed tomography (CBCT) show prevalences varying between 1% and 20%. In this case report we present the finding of a bilateral bifid MC by CBCT examination; we describe its location and morphological characteristics. The variation found was a type 1 bilateral bifid MC, which consists in an accessory canal originating from a single mandibular foramen and extending to the third molar or its immediate surroundings. In this report we discuss the importance of detecting these anatomical variations, as well as their implications in clinical practice.

Distal root curvatures in mandibular molars: analysis using digital panoramic X-rays.

BACKGROUND: The aim of this study was to describe the degree of curvature in distal roots in the first and second permanent mandibular molars in a Chilean patient sample. A cross-sectional descriptive study was conducted in which digital panoramic X-rays were analysed. MATERIALS AND METHODS: Examinations of patients under 18 years, with signs of distortion or alteration in the contrast or the presence of pathologies that affected visualisation of the roots and pulp-chamber floor of the teeth to be analysed were excluded. Using the AutoCad software, an angle was drawn to represent the curve of the root in its different thirds, drawing lines inside the root canal from the pulp-chamber floor to the dental apex. Using the classic definition of dilaceration (root curvature > 90°), its prevalence was established. 412 teeth and roots were analysed, finding a dilaceration prevalence of 0.73% (n = 3). 84.72% of the roots presented some type of curvature. RESULTS: The middle third had the highest percentage of curvatures and the greatest average of angular curvature, whereas the cervical third was the straightest. No significant differences were found between the degree of curvature and the gender of the subjects, except for the apical third of tooth 3.6. The analysis of curvature by root third offers to the clinician a better perspective of the directional change of the roots and does not limit it to just the presence of curves in the apical third. CONCLUSIONS: The report of the angular degree of the curvatures, in addition to the prevalence of dilacerations, informs to the clinicians about the likelihood of finding difficulties when treating root canals. (Folia Morphol 2018; 77, 1: 131-137).

Prevalence and morphometric analysis of idiopathic osteosclerosis in a Chilean population.

BACKGROUND: The aim of this study was to analyse the prevalence and morpho-metric parameters of idiopathic osteosclerosis (IO) in a Chilean population. IO is an intraosseous growth of compact, benign, unilocular, non-expandable bone that is referred to as an anatomical variation. MATERIALS AND METHODS: A cross-sectional study was performed using 1000 digital panoramic radiographs of adults in which data on the location (maxillary/ mandibular, right/left hemiarcades), shape, position to the dental apex, and the prevalence of IOs were observed in relation to gender and age. The morphometric parameters evaluated were area, height, width, and the linear distances of the IO up to the midline and at the base of the mandible. RESULTS: The overall prevalence was 2.8% (27 individuals), with the majority of cases in women (66.7%) in the second, third, and fifth decades of life, but without significant differences. All cases were present in the mandible (100%), usually in the left hemiarcade (59.3%), molar (48.2%) and premolar (44.4%) regions; at the height of the dental apices (65.5%), with an irregular shape (40.7%) and round (37%). The area of the IOs was 33.9 ± 20.1 mm2, with a height of 7.7 ± ± 3.1 mm, width of 6.6 ± 3.1 mm, and the distance from the IO to the mandible median line was 26.6 ± 10.7 mm and 9.7 ± 3.7 mm to the mandibular base. CONCLUSIONS: All the data observed corroborate with previous studies; the IO does not present a large difference in the Chilean population evaluated compared to pre-vious studies carried out in other populations. (Folia Morphol 2018; 77, 2: 272-278).

Injection in temporomandibular joint of rats. Description of technical protocol.

The development of animal models for research has been very diffused. Osteoarthritis is a joint degenerative pathology that induces cartilage erosion, chondrocyte proliferation and osteophyte formation. The aim of this paper is to present a technical procedure to perform the injection of monosodium iodine acetate in the temporomandibular joints of rats to generate osteoarthritis and to contribute to future research analysis related to pathology progression and proper treatment performance. The use of rat models may be a complex process because of their size, but they can be compared to the human temporomandibular joint due to the similar characteristics and the possibility of performing diagnosis and treatment protocols in order to detect this pathology.

Shadow prices of emerging pollutants in wastewater treatment plants: Quantification of environmental externalities.

Conventional wastewater treatment plants (WWTPs) are designed to remove mainly the organic matter, nitrogen and phosphorus compounds and suspended solids from wastewater but are not capable of removing chemicals of human origin, such as pharmaceutical and personal care products (PPCPs). The presence of PPCPs in wastewater has environmental effects on the water bodies receiving the WWTP effluents and renders the effluent as unsuitable as a nonconventional water source. Considering PPCPs as non-desirable outputs, the shadow prices methodology has been implemented using the output distance function to measure the environmental benefits of removing five PPCPs (acetaminophen, ibuprofen, naproxen, carbamazepine and trimethoprim) from WWTP effluents discharged to three different ecosystems (wetland, river and sea). Acetaminophen and ibuprofen show the highest shadow prices of the sample for wetland areas. Their values are 128.2 and 11.0 €/mg respectively. These results represent a proxy in monetary terms of the environmental benefit achieved from avoiding the discharge of these PPCPs in wetlands. These results suggest which PPCPs are urgent to remove from wastewater and which ecosystems are most vulnerable to their presence. The findings of this study will be useful for the plant managers in order to make decisions about prioritization in the removal of different pollutants.

Low power RF amplifier circuit for ion trap applications.

A low power RF amplifier circuit for ion trap applications is presented and described. The amplifier is based on a class-D half-bridge amplifier with a voltage mirror driver. The RF amplifier is composed of an RF class-D amplifier, an envelope modulator to ramp up the RF voltage during the ion analysis stage, a detector or amplitude demodulation circuit for sensing the output signal amplitude, and a feedback amplifier that linearizes the steady state output of the amplifier. The RF frequency is set by a crystal oscillator and the series resonant circuit is tuned to the oscillator frequency. The resonant circuit components have been chosen, in this case, to operate at 1 MHz. In testings, the class-D stage operated at a maximum of 78 mW at 1.1356 MHz producing 225 V peak.

Relación entre fuerza masticatoria máxima funcional e índices antropométricos en adultos jóvenes chilenos / Relationship between the maximum bite force and anthropometric indexes in Chilean young adults

La morfología del esqueleto craneofacial está influida por la función masticatoria, siendo el factor más influyente en la determinación del biotipo facial. Así, el objetivo de esta investigación fue obtener la fuerza masticatoria máxima funcional (FMMF) de dientes molar e incisivo, y relacionarlos con cuatro índices antropométricos según el sexo y la relación oclusal. Este estudio incluyó una muestra de 101 jóvenes, entre 18 y 25 años de edad, con un perfil esqueletal tipos I, II y III, molar e incisal. Se utilizó un dispositivo de medición de fuerza portátil. Los individuos fueron sentados en posición ortostática e instruidos a morder lo más fuerte posible en posición de oclusión máxima habitual. Para las mediciones se ocupó una regla milimetrada calibrada y un compás de punta roma. Hubo diferencias significativas, entre ambos sexos, solo en la región molar (p= 0,004). Los valores de las medias de todos los índices en los individuos de clase II fueron mayores. Al relacionar las FMMF con los índices antropométricos, solo hubo diferencias significativas a nivel incisal con el índice de la rama (IR) y con el índice cigomandibular (ICM) (p= 0,000, respectivamente). Además, no hubo diferencias significativas (p= 0,486; 0,097; 0,154; 0,601; 0,196; 0,269, respectivamente) al relacionar las FMMF de los dientes molares, incisivos y los índices antropométricos, según la relación oclusal. Se puede concluir que según el sexo, hubo diferencias significativas solo en la región molar. Los sujetos con una relación oclusal clase II presentaron mayores valores de FMMF y mayores valores de índices antropométricos. Se observaron diferencias significativas al relacionar las FMMF de la región incisal con el IR y el ICM y no se identificaron diferencias significativas al relacionar las FMMF de los dientes molar e incisal, junto a los índices estudiados, según la relación oclusal (AU)

The morphology of the craniofacial skeleton is influenced by the bite force, which is the most influencing factor in the determination of the facial biotype. Thus, the objective of this research was to obtain the maximum bite force (MBF) of molar and incisor teeth, and to connect them to four anthropometric indexes according to sex, and occlusal relationship. This study included a sample of 101 young people, between the ages of 18 and 25, with type I, II and III molar and incisor skeletal profiles. A portable force measuring device was used. The individuals were seated in orthostatic position and instructed to bite as hard as possible in normal maximum occlusion position. A caliper ruler and compass were used to measure. There were significant differences between both sexes, only in the molar region (p= 0,004). The values of the averages of all the class II sienindividuals were higher. When connecting the MBF with the anthropometric indexes, there were only differences at the incisor tooth level with the mandibular ramus (IR) and the ziggo mandibular indexes (ICM) (p= 0,000, respectively). Furthermore, there were no significant differences (p= 0,486; 0,097; 0,154; 0,601; 0,196; 0,269, respectively) when connecting the MBF of the molar and incisor teeth and the anthropometric indexes, according to the occlusal relationship. We can conclude that according to sex, there were significant differences in the molar region. The subjects with a class II occlusal relationship presented higher values of MBF and higher values of anthropometric indexes. Significant differences were observed when connecting the MBF of the anterior tooth region with the IR and the ICM and there were no significant differences identified when connecting the MBF of the molar and incisor teeth, with the indexes studied according to the occlusal relationship (AU)

OC-04 - Tissue factor positive microvesicles activate platelets in vitro and in vivo and enhance thrombosis in mice.

INTRODUCTION: Cancer patients have a 4- to 7- fold increased risk of venous thromboembolism (VTE) compared with general population. Most tumor cells express tissue factor (TF) and constitutively release small membrane microvesicles called tumor microvesicles (TMVs). Clinical studies have shown that circulating MP-TF activity is associated with VTE in pancreatic cancer but not in other types of cancer. Thrombin is a potent platelet agonist and activates platelets via protease activated receptors (PARs). AIM: To determine the contribution of the TF+ TMV-thrombin-platelet pathway to cancer-associated thrombosis. MATERIALS AND METHODS: A human pancreatic adenocarcinoma cell line expressing high levels of TF (BxPc-3) was selected to study the effect of TF+ TMVs on platelet activation and thrombosis. RESULTS: TF+ TMVs induced platelet activation in vitro in a thrombin-dependent manner. The presence of orthotopically grown BxPc-3 tumors in mice was associated with increased levels of thrombin-antithrombin III complexes (TATc) and larger thrombi in an inferior vena cava stenosis model compared with control mice. Furthermore, injection of BxPc-3 TF+ TMVs into mice triggered platelet activation and enhanced venous thrombosis in a TF-dependent manner. Importantly, BxPc-3 TF+ TMV-enhanced thrombosis was reduced in Par4-deficient mice and wild-type mice treated with the platelet inhibitor clopidogrel, suggesting that platelet activation was required for the enhanced thrombosis. CONCLUSIONS: These studies suggest that platelet inhibitors may reduce thrombosis in cancer patients with elevated levels of TF+ TMVs.

Ultrasound-assisted extraction of hemicelluloses from grape pomace using response surface methodology.

An ultrasound-assisted procedure was applied to the extraction of hemicelluloses from grape pomace at a mild temperature (20°C). A Central composite design (CCD) was employed to optimize the ultrasound-assisted extraction (UAE) of hemicelluloses from grape pomace with the aim to maximize their extraction yield, and, also, the obtention of the main polymers forming this fraction: Xyloglucans (XLG), Mannans (MAN) and Xylans (XN). Extraction time (X1), solid:liquid ratio (X2) and KOH concentration (X3) were the variables used to optimize the process. The conditions that maximize (1) the extraction yield of hemicelluloses and the contents of (2) XLG, (3) MAN and (4) XN, were: (1) X1=2.6h; X2=1:48 (w/v); X3=0.4M, (2) X1=2.9h; X2=1:57 (w/v); X3=2.25M, (3) X1=2.7h; X2=1:58(w/v);X3=2.2M, and (4) X1=3h; X2=1:60 (w/v); X3=2.3M, respectively. Under these conditions, the maximum extraction yield of hemicelluloses, XLG, MAN and XN contents were: ∼7.9±0.2%, ∼3.6±0.02%, ∼1.1±0.04% and ∼1.2±0.02%, respectively. Close agreement between experimental and predicted values was found. The results suggest that the ultrasound-assisted extraction could be a good option for the extraction of hemicellulosic polysaccharides from grape pomace at industrial level.

Antiphospholipid antibody-mediated effects in an arterial model of thrombosis are dependent on Toll-like receptor 4.

Patients with antiphospholipid syndrome (APS) produce antiphospholipid antibodies (aPL) and develop vascular thrombosis that may occur in large or small vessels in the arterial or venous beds. On the other hand, many individuals produce aPL and yet never develop thrombotic events. Toll-like receptor 4 (TLR4) appears to be necessary for aPL-mediated prothrombotic effects in venous and microvascular models of thrombosis, but its role in arterial thrombosis has not been studied. Here, we propose that aPL alone are insufficient to cause thrombotic events in an arterial model of APS, and that a concomitant trigger of innate immunity (e.g. TLR4 activation) is required. We show specifically that anti-ß2-glycoprotein I (anti-ß2GPI) antibodies, a subset of aPL, accelerated thrombus formation in C57BL/6 wild-type, but not TLR4-deficient, mice in a ferric chloride-induced carotid artery injury model. These aPL bound to arterial and venous endothelial cells, particularly in the presence of ß2GPI, and to human TLR4 by enzyme-linked immunoassay. Arterial endothelium from aPL-treated mice had enhanced leukocyte adhesion, compared to control IgG-treated mice. In addition, aPL treatment of mice enhanced expression of tissue factor (TF) in leukocytes induced by the TLR4 ligand lipopolysaccharide (LPS). aPL also enhanced LPS-induced TF expression in human leukocytes in vitro. Our findings support a mechanism in which aPL enhance TF expression by leukocytes, as well as augment adhesion of leukocytes to the arterial endothelium. The activation of TLR4 in aPL-positive individuals may be required to trigger thrombotic events.

Tissue factor-positive tumor microvesicles activate platelets and enhance thrombosis in mice.

UNLABELLED: ESSENTIALS: Cancer patients have a high rate of venous thrombosis (VT) but the underlying mechanisms are unknown. Tumor-derived, tissue factor-positive microvesicles in platelet activation in vitro and in vivo were studied. Tumor-derived, tissue factor-positive microvesicles enhanced VT in mice. Platelets may contribute to VT in some cancer patients, and this could be prevented with antiplatelet drugs. BACKGROUND: Cancer patients have an approximately 4-fold increased risk of venous thromboembolism (VTE) compared with the general population, and cancer patients with VTE have reduced survival. Tumor cells constitutively release small membrane vesicles called microvesicles (MVs) that may contribute to thrombosis in cancer patients. Clinical studies have shown that levels of circulating tumor-derived, tissue factor-positive (TF(+) ) MVs in pancreatic cancer patients are associated with VTE. Objectives We tested the hypothesis that TF(+) tumor-derived MVs (TMVs) activate platelets in vitro and in mice. MATERIALS AND METHODS: We selected two human pancreatic adenocarcinoma cell lines expressing high (BxPc-3) and low (L3.6pl) levels of TF as models to study the effect of TF(+) TMVs on platelets and thrombosis. RESULTS AND CONCLUSIONS: We found that both types of TF(+) TMVs activated human platelets and induced aggregation in vitro in a TF and thrombin-dependent manner. Further, injection of BxPc-3 TF(+) TMVs triggered platelet activation in vivo and enhanced thrombosis in two mouse models of venous thrombosis in a TF-dependent manner. Importantly, BxPc-3 TF(+) TMV-enhanced thrombosis was reduced in Par4-deficient mice and in wild-type mice treated with clopidogrel, suggesting that platelet activation was required for enhanced thrombosis. These studies suggest that TF(+) TMV-induced platelet activation contributes to thrombosis in cancer patients.