Predicting type of delivery by identification of obstetric risk factors through data mining

In Maternity Care, a quick decision has to be made about the most suitable delivery type for the current patient. Guidelines are followed by physicians to support that decision; however, those practice recommendations are limited and underused. In the last years, caesarean delivery has been pursued in over 28% of pregnancies, and other operative techniques regarding specific problems have also been excessively employed. This study identifies obstetric and pregnancy factors that can be used to predict the most appropriate delivery technique, through the induction of data mining models using real data gathered in the perinatal and maternal care unit of Centro Hospitalar of Oporto (CHP). Predicting the type of birth envisions high-quality services, increased safety and effectiveness of specific practices to help guide maternity care decisions and facilitate optimal outcomes in mother and child. In this work was possible to acquire good results, achieving sensitivity and specificity values of 90.11% and 80.05%, respectively, providing the CHP with a model capable of correctly identify caesarean sections and vaginal deliveries.

Cationic Liposomes as antigenic delivery systems: development of an immunoprotective strategy against Candida albicans

Tese de Doutoramento Biologia Molecular e Ambiental - Especialidade em Biologia Celular e Saúde

Assessment of liposome disruption to quantify drug delivery in vitro

Efficient liposome disruption inside the cells is a key for success with any type of drug delivery system. The efficacy of drug delivery is currently evaluated by direct visualization of labeled liposomes internalized by cells, not addressing objectively the release and distribution of the drug. Here, we propose a novel method to easily assess liposome disruption and drug release into the cytoplasm. We propose the encapsulation of the cationic dye Hoechst 34,580 to detect an increase in blue fluorescence due to its specific binding to negatively charged DNA. For that, the dye needs to be released inside the cell and translocated to the nucleus. The present approach correlates the intensity of detected fluorescent dye with liposome disruption and consequently assesses drug delivery within the cells.

Poly(2-hydroxyethyl methacrylate): A new star polymer

Multiarm star polymers are attractive materials due to their unusual bulk and solution properties. They are considered analogues of dendrimers with a wide range of applications, such as drug delivery, membranes, coatings and lithography.1 The advent of controlled polymerization made possible the existence of this unique class of organic nanoparticles (ONPs).2 Two major synthetic strategies are usually employed in the preparation of star polymers, the core-first and arm-first approaches. The core-first approach involves a controlled living polymerization using a multiarm initiator core while the arm-first methodology is based in the quenching of living polymers with multifunctional coupling agent or bifunctional vinyl compounds. Herein, we present the synthesis and characterization of a new star polymer, the multiarm star poly(2-hydroxyethyl methacrylate). The tetra-armed star polymer was prepared by reversible addition fragmentation chain-transfer (RAFT) polymerization using the core-first approach. The RAFT chain-transfer agent (RAFT CTA) pentaerythritol tetrakis[2-(dodecylthiocarbonothioylthio)-2-methylpropionate] was used as multiarm initiator core were 2-hydroxyethyl methacrylate (HEMA) was polymerized using AIBN as radical initiator. Structural characterization was performed by 1H NMR and FTIR. The new polymer is able to uptake large quantities of organic solvents, forming gels. The rheological behavior of these gels was also investigated.

Effect of short chain fructooligosaccharides (scFOS) on immunological status and gut microbiota of gilthead sea bream (Sparus aurata) reared at two temperatures

The effects of dietary short chain fructooligosaccharides (scFOS) incorporation on hematology, fish immune status, gut microbiota composition, digestive enzymes activities, and gut morphology, was evaluated in gilthead sea bream (Sparus aurata) juveniles reared at 18 °C and 25 °C. For that purpose, fish with 32 g were fed diets including 0, 0.1, 0.25 and 0.5% scFOS during 8 weeks. Overall, scFOS had only minor effects on gilthead sea bream immune status. Lymphocytes decreased in fish fed the 0.1% scFOS diet. Fish fed the 0.5% scFOS diet presented increased nitric oxide (NO) production, while total immunoglobulins (Ig) dropped in those fish, but only in the ones reared at 25 °C. Red blood cells, hemoglobin, bactericidal activity and NO were higher at 25 °C, whereas total white blood cells, circulating thrombocytes, monocytes and neutrophils were higher at 18 °C. In fish fed scFOS, lymphocytes were higher at 18 °C. Total Ig were also higher at 18 °C but only in fish fed 0.1% and 0.5% scFOS diets. No differences in gut bacterial profiles were detected by PCR-DGGE (polymerase chain reaction denaturing gradient gel electrophoresis) between dietary treatments. However, group's similarity was higher at 25 °C. Digestive enzymes activities were higher at 25 °C but were unaffected by prebiotics incorporation. Gut morphology was also unaffected by dietary prebiotic incorporation. Overall, gut microbiota composition, digestive enzymes activities and immunity parameters were affected by rearing temperature whereas dietary scFOS incorporation had only minor effects on these parameters. In conclusion, at the tested levels scFOS does not seem worthy of including it in gilthead sea bream juveniles diets.

“Learning-by-producing” in the fashion value chain

Proceedings da AUTEX 2015, Bucareste, Roménia.

Estudo da logística do armazenamento e distribuição interna de consumíveis clínicos de uma unidade hospitalar

Dissertação de mestrado em Engenharia Industrial

Effect of the alkyl chain length of the ionic liquid anion on polymer electrolytes properties

New polymer electrolytes (PEs) based on chitosan and three ionic liquid (IL) families ([C2mim][CnSO3], [C2mim][CnSO4] and [C2mim][diCnPO4]) were synthesized by the solvent casting method. The effect of the length of the alkyl chain of the IL anion on the thermal, morphological and electrochemical properties of the PEs was studied. The solid polymer electrolytes (SPE) membranes were analyzed by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray (EDX), polarized optical microscopy (POM), atomic force microscopy (AFM), complex impedance spectroscopy (ionic conductivity) and cyclic voltammetry (CV). The obtained results evidenced an influence of the alkyl chain length of the IL anion on the temperature of degradation, birefringence, surface roughness and ionic conductivity of the membranes. The DSC, XRD and CV results showed independency from the length of the IL-anion-alkyl chain. The PEs displayed an predominantly amorphous morphology, a minimum temperature of degradation of 135 °C, a room temperature (T = 25 °C) ionic conductivity of 7.78 × 10−4 S cm−1 and a wide electrochemical window of ∼ 4.0 V.

Singularities of the dynamical structure factors of the spin-1/2 XXX chain at finite magnetic field

We study the longitudinal and transverse spin dynamical structure factors of the spin-1/2 XXX chain at finite magnetic field h, focusing in particular on the singularities at excitation energies in the vicinity of the lower thresholds. While the static properties of the model can be studied within a Fermi-liquid like description in terms of pseudoparticles, our derivation of the dynamical properties relies on the introduction of a form of the ‘pseudofermion dynamical theory’ (PDT) of the 1D Hubbard model suitably modified for the spin-only XXX chain and other models with two pseudoparticle Fermi points. Specifically, we derive the exact momentum and spin-density dependences of the exponents ζτ(k) controlling the singularities for both the longitudinal  and transverse (τ = t) dynamical structure factors for the whole momentum range  , in the thermodynamic limit. This requires the numerical solution of the integral equations that define the phase shifts in these exponents expressions. We discuss the relation to neutron scattering and suggest new experiments on spin-chain compounds using a carefully oriented crystal to test our predictions.

Vanishing spin stiffness in the spin-1/2 Heisenberg chain for any nonzero temperature

Whether at the zero spin density m = 0 and finite temperatures T > 0 the spin stiffness of the spin-1/2 XXX chain is finite or vanishes remains an unsolved and controversial issue, as different approaches yield contradictory results. Here we explicitly compute the stiffness at m = 0 and find strong evidence that it vanishes. In particular, we derive an upper bound on the stiffness within a canonical ensemble at any fixed value of spin density m that is proportional to m2L in the thermodynamic limit of chain length L → ∞, for any finite, nonzero temperature, which implies the absence of ballistic transport for T > 0 for m = 0. Although our method relies in part on the thermodynamic Bethe ansatz (TBA), it does not evaluate the stiffness through the second derivative of the TBA energy eigenvalues relative to a uniform vector potential. Moreover, we provide strong evidence that in the thermodynamic limit the upper bounds on the spin current and stiffness used in our derivation remain valid under string deviations. Our results also provide strong evidence that in the thermodynamic limit the TBA method used by X. Zotos [Phys. Rev. Lett. 82, 1764 (1999)] leads to the exact stiffness values at finite temperature T > 0 for models whose stiffness is finite at T = 0, similar to the spin stiffness of the spin-1/2 Heisenberg chain but unlike the charge stiffness of the half-filled 1D Hubbard model.

Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity

Clinical effectiveness of imatinib mesylate in cancer treatment is compromised by its off-target cardiotoxicity. In the present study, we have developed physically stable imatinib mesylate-loaded poly(lactide-co-glycolide) nanoparticles (INPs) that could sustainably release the drug, and studied its efficacy by in vitro anticancer and in vivo cardiotoxicity assays. MTT (methylthiazolyldiphenyl-tetrazolium bromide) assay revealed that INPs are more cytotoxic to MCF-7 breast cancer cells compared to the equivalent concentration of free imatinib mesylate. Wistar rats orally administered with 50 mg/kg INPs for 28 days showed no significant cardiotoxicity or associated changes. Whereas, increased alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels, and reduced white blood cell, red blood cell, and hemoglobin content were observed in the animals administered with free drug. While the histological sections from hearts of animals that received INPs did not show any significant cardiotoxic symptoms, loss of normal architecture and increased cytoplasmic vacuolization were observed in the heart sections of animals administered with free imatinib mesylate. Based on these results, we conclude that nano-encapsulation of imatinib mesylate increases its efficacy against cancer cells, with almost no cardiotoxicity.

In vitro and in vivo studies of temozolomide loading in zeolite structures as drug delivery systems for glioblastoma

Zeolites Y (faujasite) and MOR (mordonite) were used as hosts for temozolomide (TMZ), a current good-standard chemotherapeutic agent used in the treatment of glioblastoma brain tumors. TMZ was loaded into zeolites by liquid-phase adsorption at controlled pH. FTIR, 1H NMR, MS, SEM, UV/vis and chemical analysis demonstrated the successful loading of TMZ into zeolite hosts. The hydrolysis of TMZ in MTIC (TMZ metabolite) after the preparation of drug delivery systems (DDS) was observed in simulated body fluid. The effect of zeolites and DDS were evaluated on the viability of glioblastoma cell lines. Unloaded Y zeolite presented toxicity to cancer cells in contrast to MOR. In accordance, the best results in potentiation of the TMZ effect was obtained with MOR. We found that mordonite loaded with 0.026 mmol of TMZ was able to decrease the half maximal inhibitory concentrations (IC50) at least 3-fold in comparison to free temozolomide both in vitro and in vivo.

Micro- and mesoporous structures as drug delivery carriers for salicylic acid

The potential of salicylic acid (SA) encapsulated in porous materials as drug delivery carriers for cancer treatment was studied. Different porous structures, the microporous zeolite NaY, and the mesoporous SBA-15 and MCM-41 were used as hosts for the anti-inflammatory drug. Characterization with different techniques (FTIR, UV/vis, TGA, 1H NMR, and 13C CPMAS NMR) demonstrated the successful loading of SA into the porous hosts. The mesoporous structures showed to be very efficient to encapsulate the SA molecule. The obtained drug delivery systems (DDS) accommodated 0.74 mmol (341 mg/gZEO) in NaY and 1.07 mmol (493 mg/gZEO) to 1.23 mmol (566 mg/gZEO) for SBA-15 and MCM-41, respectively. Interactions between SA molecules and pore structures were identified. A fast and unrestricted liberation of SA at 10 min of the dissolution assay was achieved with 29.3, 46.6, and 50.1 µg/mL of SA from NaY, SBA-15, and MCM-41, respectively, in the in vitro drug release studies (PBS buffer pH 7.4, 37 °C). Kinetic modeling was used to determine the release patterns of the DDS. The porous structures and DDS were evaluated on Hs578T and MDA-MB-468 breast cancer cell lines viability. The porous structures are nontoxic to cancer cells. Cell viability reduction was only observed after the release of SA from MCM- 41 followed by SBA-15 in both breast cancer cell lines.

Presence of starch enhances in vitro biodegradation and biocompatibility of a gentamicin delivery formulation

The effect of α-amylase degradation on the release of gentamicin from starch-conjugated chitosan microparticles was investigated up to 60 days. Scanning electron microscopic observations showed an increase in the porosity and surface roughness of the microparticles as well as reduced diameters. This was confirmed by 67% weight loss of the microparticles in the presence of α-amylase. Over time, a highly porous matrix was obtained leading to increased permeability and increased water uptake with possible diffusion of gentamicin. Indeed, a faster release of gentamicin was observed with α-amylase. Starch-conjugated chitosan particles are non-toxic and highly biocompatible for an osteoblast (SaOs-2) and fibroblast (L929) cell line as well as adipose-derived stem cells. When differently produced starch-conjugated chitosan particles were tested, their cytotoxic effect on SaOs-2 cells was found to be dependent on the crosslinking agent and on the amount of starch used.

Marine origin polysaccharides in drug delivery systems

Oceans are a vast source of natural substances. In them, we find various compounds with wide biotechnological and biomedical applicabilities. The exploitation of the sea as a renewable source of biocompounds can have a positive impact on the development of new systems and devices for biomedical applications. Marine polysaccharides are among the most abundant materials in the seas, which contributes to a decrease of the extraction costs, besides their solubility behavior in aqueous solvents and extraction media, and their interaction with other biocompounds. Polysaccharides such as alginate, carrageenan and fucoidan can be extracted from algae, whereas chitosan and hyaluronan can be obtained from animal sources. Most marine polysaccharides have important biological properties such as biocompatibility, biodegradability, and anti-inflammatory activity, as well as adhesive and antimicrobial actions. Moreover, they can be modified in order to allow processing them into various shapes and sizes and may exhibit response dependence to external stimuli, such as pH and temperature. Due to these properties, these biomaterials have been studied as raw material for the construction of carrier devices for drugs, including particles, capsules and hydrogels. The devices are designed to achieve a controlled release of therapeutic agents in an attempt to fight against serious diseases, and to be used in advanced therapies, such as gene delivery or regenerative medicine.