Finding the perfect match between nanoparticles and microfluidics to respond to cancer challenges

The clinical translation of new cancer theranostic has been delayed by inherent cancerâ s heterogeneity. Additionally, this delay has been enhanced by the lack of an appropriate in vitro model, capable to produce accurate data. Nanoparticles and microfluidic devices have been used to obtain new and more efficient strategies to tackle cancer challenges. On one hand, nanoparticles-based therapeutics can be modified to target specific cells, and/or molecules, and/or modified with drugs, releasing them over time. On the other hand, microfluidic devices allow the exhibition of physiologically complex systems, incorporation of controlled flow, and control of the chemical environment. Herein, we review the use of nanoparticles and microfluidic devices to address different cancer challenges, such as detection of CTCs and biomarkers, point-of-care devices for early diagnosis and improvement of therapies. The future perspectives of cancer challenges are also addressed herein.F.R. Maia acknowledges Portuguese Foundation for Scienceand Technology (FCT) for her work contract under theTransitional Rule DL 57/2016 (CTTI-57/18-I3BS5). J. M.Oliveira thanks FCT for his distinction attributed under theFCT Investigator program (IF/01285/2015)

A model updating technique based on FRFs for damped structures

Model updating methods often neglect that in fact all physical structures are damped. Such simplification relies on the structural modelling approach, although it compromises the accuracy of the predictions of the structural dynamic behaviour. In the present work, the authors address the problem of finite element (FE) model updating based on measured frequency response functions (FRFs), considering damping. The proposed procedure is based upon the complex experimental data, which contains information related to the damped FE model parameters and presents the advantage of requiring no prior knowledge about the damping matrix structure or its content, only demanding the definition of the damping type. Numerical simulations are performed in order to establish the applicability of the proposed damped FE model updating technique and its results are discussed in terms of the correlation between the simulated experimental complex FRFs and the ones obtained from the updated FE model

The continuous manufacturing of terpin

The continuous or semi-continuous production of terpin from a-pinene by hydration, using 40S sulfuric acid as a catalyst, was studied in a batch laboratory reactor as well as at pilot scale. It was concluded that the mixing intensity affects the distribution of products and that the greatest yields are obtained in a semi-continuous or continuous process

Production de vins mousseux a partir de "Vinhos Verdes" blancs monovarietaux

On a fait l'étude comparative de vins mousseux élaborés à partir de vins de base issus de cinq cépages recommandés pour la Région: Loureiro, Trajadura, Avesso, Pedernã et Azal blanc, en ce qui concerne les propriétés organoleptiques. Les vins de base ont été produits selon le processus utilisé dans la Région -égrappage, pressurage, débourbage et fermentation alcoolique-, ayant été soumis aussi à une fermentation malolactique. La prise de mousse a été effectuée en bouteille, avec des levures immobilisées en billes d'alginate, pendant cinq mois à 14 °C. Les propriétés sensorielles des vins ont été évaluées en utilisant des fiches classificatrices et descriptives, par une chambre de neuf dégustateurs expérimentés. Le traitement statistique des résultats, effectué par le logiciel SPSS, a été fait en recourrant à l'analyse de variance. On a trouvé quelques différences parmi les cinq vins mousseux surtout en ce qui concerne l'aspect du cordon et l'arôme. Cependant, tous ces vins ont obtenu des classifications globales au-dessus de l'acceptable, atteignant parfois l'excellent. Ces résultats préliminaires ainsi obtenus, basés sur les caractéristiques organoleptiques, suggèrent la possibilité d'obtenir des vins mousseux de qualité à partir des cépages de "Vinho Verde"

Evaluation Of Osteoporosis Using Ultrasound

We have developed an equipment using ultrasound transducers to help in the diagnosis of osteoporosis. The equipment consists of an X-Y axes displacement system controlled by a microcomputer and uses two ultrasound transducers in opposite sides to inspect the calcaneus region of the patient. We have used two pairs of transducers with 500 kHz and 1 MHz central frequencies. Each pair of transducers was fixed in the X-Y displacement system submerged in a small water tank with a support for the foot of the patient. The transmitter was excited with pulses of 400-600 kHz or 800-1200 kHz and the ultrasound waves propagating through the bone in the calcaneus region are received by the opposite transducer, amplified and acquired in a digital oscilloscope. The data are transferred to the microcomputer and the ultrasound attenuation and the ultrasound transmission velocity are determined. The system was tested in patients, selected from a group that had already been diagnosed using a DEXA equipment. The results showed that there is a decrease in the ultrasound transmission velocity and the ultrasound attenuation in osteoporotic patients when compared to healthy patients of the same sex and age group. The conclusion is that ultrasound attenuation and the transmission velocity in the calcaneus region may be used as parameters in the evaluation of osteoporosis using our new system.398227828

Ultrasonic Doppler Blood Flowmeter For Extracorporeal Circulation

In cardiac surgeries it is frequently necessary to carry out interventions in internal heart structures, and where the blood circulation and oxygenation are made by artificial ways, out of the patient's body, in a procedure known as extracorporeal circulation (EC). During this procedure, one of the most important parameters, and that demands constant monitoring, is the blood flow. In this work, an ultrasonic pulsed Doppler blood flowmeter, to be used in an extracorporeal circulation system, was developed. It was used a 2 MHz ultrasonic transducer, measuring flows from 0 to 5 liters/min, coupled externally to the EC arterial line destined to adults perfusion (diameter of 9.53 mm). The experimental results using the developed flowmeter indicated a maximum deviation of 3.5% of full scale, whilst the blood flow estimator based in the rotation speed of the peristaltic pump presented deviations greater than 20% of full scale. This ultrasonic flowmeter supplies the results in a continuous and trustworthy way, and it does not present the limitations found in those flowmeters based in other transduction methods. Moreover, due to the fact of not being in contact with the blood, it is not disposable and it does not need sterilization, reducing operational costs and facilitating its use.397844845

In vivo assessment of the impedance ratio method used in electronic foramen locators

<p>Abstract</p> <p>Background</p> <p>The results of an <it>in vivo </it>study on the "ratio method" used in electronic foramen locators (EFL) are presented. EFLs are becoming widely used in the determination of the working length (WL) during the root canal treatment. The WL is the distance from a coronal reference point to the point at which canal preparation and filling should terminate. The "ratio method" was assessed by many clinicians with the aim of determining its ability to locate the apical foramen (AF). Nevertheless, <it>in vivo </it>studies to assess the method itself and to explain why the "ratio method" is able to locate the apical foramen and is unable to determine intermediate distances were not published so far.</p> <p>Methods</p> <p>A developed apparatus applies an electrical current signal with constant amplitude of 10 μA_RMSthrough the endodontic file within the root canal. The applied current signal is composed by summing six sine waves, from 250 Hz to 8 kHz. Data were acquired with the endodontic file tip at 7 different positions within root canals. In the frequency domain the quotients between the amplitude of a reference frequency and the amplitudes of the other frequencies components were calculated. Twenty one root canals were analyzed in vivo, during the endodontic treatment of twelve teeth of different patients, with age between 20 to 55 years.</p> <p>Results</p> <p>For the range of frequencies used in the commercial EFLs and for distances ranging from -3 mm to -1 mm of the AF, the impedance of the root canal is mainly resistive. However, when the file tip gets closer to AF, the root canal electrical impedance starts to change from a mainly resistive to a complex impedance. This change in the measured root canal impedance starts when the file tip is near -1.0 mm from the AF, getting stronger as the file tip gets closer to the AF. This change in the impedance behavior affects the ratio (quotient) of the impedance measured at different frequencies. Through graphic analysis it is demonstrated why EFLs based on the ratio method are unable to accurately measure any distances between - 3.0 and -0.5 mm from the apical foramen. The only reliable measurement is the 0 mm distance, which is when the file tip is at the AF.</p> <p>Conclusions</p> <p>The electrical impedance values of 21 root canals were <it>in vivo </it>studied. The results confirm the ability of EFLs that are based on the ratio method to accurately locate the AF position and explain why they are unable to determine the file tip position along the root canal.</p

Glial Cell Line-Derived Neurotrophic Factor-Loaded CMCht/PAMAM Dendrimer Nanoparticles for Peripheral Nerve Repair

(1) Background: Peripheral nerve injuries represent a major clinical challenge. If nerve ends retract, there is no spontaneous regeneration and grafts are required to proximate the nerve ends and give continuity to the nerve. (2) Methods: GDNF-loaded NPs were characterized physicochemically. For that, NPs stability at different pH’s was assessed, and GDNF release was studied through ELISA. In vitro studies are performed with Schwann cells, and the NPs are labeled with fluorescein-5(6)-isothiocyanate for uptake experiments with SH-SY5Y neural cells. (3) Results: GDNF-loaded NPs are stable in physiological conditions, releasing GDNF in a two-step profile, which is beneficial for nerve repair. Cell viability is improved after 1 day of culture, and the uptake is near 99.97% after 3 days of incubation. (4) Conclusions: The present work shows the efficiency of using CMCht/PAMAM NPs as a GDNF-release system to act on peripheral nerve regeneration.This work was supported by the Portuguese Foundation for Science and Technology for the funds provided under the distinction attributed to JMO (IF/01285/2015) and the project NanOptoNerv (ref. PTDC/NAN-MAT/29936/2017). The work was also supported by the European Commission and FEDER program, the JUSTHera project (NORTE-01-0145-FEDER-000055), and the 0624_2IQBIONEURO_6_E project (Inter-regional cooperation program VA Spain-Portugal POCTEP 2014-2020)

Peptide-modified dendrimer nanoparticles for targeted therapy of colorectal cancer

Peptides have recently emerged as a promising class of targeting ligands forspecific drug delivery in cancer treatment, which avoid undesirable side effectsof the systemic administration of chemotherapeutics. Their conjugation withnanoparticles has been demonstrated to improve the functionality of peptidesresulting in a versatile platform for biomedical applications. In this work, thedevelopment of carboxymethylchitosan/poly(amidoamine) (CMCht/PAMAM)dendrimer nanoparticles functionalized with YIGSR laminin receptor bindingpeptide for the active targeting and specific delivery of therapeutic agents intocolorectal cancer cells is described. The successful functionalization isconfirmed by several physico-chemical characterization techniques. Theselectivity of the YIGSR-CMCht/PAMAM dendrimer nanoparticles is firstvalidated in vitro using a micropatterned array of 67 kDa laminin receptor.Next, the specificity of YIGSR-CMCht/PAMAM dendrimers nanoparticlestoward laminin receptor is further confirmed both in 2D and 3D settings usingHCT-116 colorectal cancer cells and L929 fibroblasts in co-culture. Finally,gemcitabine-loaded YIGSR-CMCht/PAMAM dendrimer nanoparticles inducea targeted mortality on HCT-116 cancer cells in a co-culture scenario. Overall,the study shows solid evidence that YIGSR laminin receptor binding peptidecoupled to CMCht/PAMAM dendrimer nanoparticles may be employed as ananticancerous target for the specific and intracellular delivery ofchemotherapeutic agents.This work was financially supported through the project FROnTHERA (NORTE-01-0145-FEDER-000023), Norte Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); M.R.C. for her Ph.D. scholarship NORTE-08-5369-FSE-000044, funded by Programa Operacional Regional do Norte, Fundo Social Europeu, Norte 2020 TERM&SC and EMBO Short-Term Fellowship 7232. J.M.O. for his distinction attributed under the FCT Investigator program (IF/00423/2012 and IF/01285/2015; F.R.M. acknowledges FCT for her work contract under the Transitional Rule DL 57/2016 (CTTI-57/18-I3BS(5)). D.C. acknowledges the financial support from the Portuguese Foundation for Science and Technology (FCT) under the program CEEC Individual 2017 (CEECIND/00352/2017). D.C. and S.C.K. for the Portuguese Foundation for Science and Technology (FCT) under the scope of the project 2MATCH (PTDC/BTMORG/28070/2017) funded by the Programa Operacional Regional do Norte supported by European Regional Development Funds (ERDF). This work is also partially supported by the IET Harvey Engineering Research Award 2018 (ENG ThE CANCER) and the European Union Framework Program for Research and Innovation Horizon 2020 on FoReCaST project under Grant Agreement No. 668983

Development of conjugated kefiran-chondroitin sulphate cryogels with enhanced properties for biomedical applications

Hydrogels based on natural polysaccharides can have unique properties and be tailored for several applications, which may be mainly limited by the fragile structure and weak mechanical properties of this type of system. We successfully prepared cryogels made of newly synthesized kefiran exopolysaccharide-chondroitin sulfate (CS) conjugate via carbodiimide-mediated coupling to overcome these drawbacks. The freeze-thawing procedure of cryogel preparation followed by lyophilization is a promising route to fabricate polymer-based scaffolds with countless and valuable biomedical applications. The novel graft macromolecular compound (kefiran-CS conjugate) was characterized through 1H-NMR and FTIR spectroscopy—which confirmed the structure of the conjugate, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)—which mirrored good thermal stability (degradation temperature of about 215 °C) and, finally, gel permeation chromatography–size exclusion chromatography (GPC-SEC)—which proved an increased molecular weight due to chemical coupling of kefiran with CS. At the same time, the corresponding cryogels physically crosslinked after the freeze-thawing procedure were investigated by scanning electron microscopy (SEM), Micro-CT, and dynamic rheology. The results revealed a prevalent contribution of elastic/storage component to the viscoelastic behavior of cryogels in swollen state, a micromorphology with micrometer-sized open pores fully interconnected, and high porosity (ca. 90%) observed for freeze-dried cryogels. Furthermore, the metabolic activity and proliferation of human adipose stem cells (hASCs), when cultured onto the developed kefiran-CS cryogel, was maintained at a satisfactory level over 72 h. Based on the results obtained, it can be inferred that the newly freeze-dried kefiran-CS cryogels possess a host of unique properties that render them highly suitable for use in tissue engineering, regenerative medicine, drug delivery, and other biomedical applications where robust mechanical properties and biocompatibility are crucial.This research was funded by the Foundation for Science and Technology (FCT) from Portugal, with references CEECIND/00111/2017 and SFRH/BPD/94277/2013, respectively.H.R. and C.G. were supported by the Foundation for Science and Technology (FCT) from Portugal, with references CEECIND/00111/2017 and SFRH/BPD/94277/2013, respectively. The authors would like to express their sincere gratitude to Emanuel Fernandes for his invaluable contribution to this research by performing the STA experiment. The authors thank the financial support provided under the project “HEALTH-UNORTE: Setting-up biobanks and regenerative medicine strategies to boost research in cardiovascular, musculoskeletal, neurological, oncological, immunological and infectious diseases”, reference NORTE-01-0145-FEDER-000039, funded by the Norte Portugal Regional Coordination and Development Commission (CCDR-N), under the NORTE2020 Program