State of the Art in the Current Management and Future Directions of Targeted Therapy for Differentiated Thyroid Cancer

Two-thirds of differentiated thyroid cancer (DTC) patients with distant metastases would be classified as radioactive iodine-refractory (RAIR-DTC), evolving into a poor outcome. Recent advances underlying DTC molecular mechanisms have shifted the therapy focus from the standard approach to targeting specific genetic dysregulations. Lenvatinib and sorafenib are first-line, multitargeted tyrosine kinase inhibitors (TKIs) approved to treat advanced, progressive RAIR-DTC. However, other anti-angiogenic drugs, including single targeted TKIs, are currently being evaluated as alternative or salvage therapy after the failure of first-line TKIs. Combinatorial therapy of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signalling cascade inhibitors has become a highly advocated strategy to improve the low efficiency of the single agent treatment. Recent studies pointed out targetable alternative pathways to overcome the resistance to MAPK and PI3K pathways’ inhibitors. Because radioiodine resistance originates in DTC loss of differentiation, redifferentiation therapies are currently being explored for efficacy. The present review will summarize the conventional management of DTC, the first-line and alternative TKIs in RAIR-DTC, and the approaches that seek to overcome the resistance to MAPK and PI3K pathways’ inhibitors. We also aim to emphasize the latest achievements in the research of redifferentiation therapy, immunotherapy, and agents targeting gene rearrangements in advanced DTC.     

Comparative Proteomic Profiling of Secreted Extracellular Vesicles from Breast Fibroadenoma and Malignant Lesions: A Pilot Study

Extracellular vesicles (EVs) shuttle proteins, RNA, DNA, and lipids crucial for cell-to-cell communication. Recent findings have highlighted that EVs, by virtue of their cargo, may also contribute to breast cancer (BC) growth and metastatic dissemination. Indeed, EVs are gaining great interest as non-invasive cancer biomarkers. However, little is known about the biological and physical properties of EVs from malignant BC lesions, and even less is understood about EVs from non-malignant lesions, such as breast fibroadenoma (FAD), which are clinically managed using conservative approaches. Thus, for this pilot study, we attempted to purify and explore the proteomic profiles of EVs from benign breast lesions, HER2+ BCs, triple–negative BCs (TNBCs), and continuous BC cell lines (i.e., BT-549, MCF–10A, and MDA-MB-231), combining experimental and semi-quantitative approaches. Of note, proteome-wide analyses showed 49 common proteins across EVs harvested from FAD, HER2+ BCs, TNBCs, and model BC lines. This is the first feasibility study evaluating the physicochemical composition and proteome of EVs from benign breast cells and primary and immortalized BC cells. Our preliminary results hold promise for possible implications in precision medicine for BC.     

Treatment of Fenton‐refractory olive oil mill wastes by electrochemical oxidation with boron‐doped diamond anodes

In this work, the electrochemical oxidation of an actual industrial waste with conductive diamond anodes has been studied. The wastewater is the effluent of a wastewater treatment plant consisting of a Fenton reactor followed by a settler and a sand filter, in which the wastes generated in an olive oil mill are treated. These wastes contain a residual chemical oxygen demand of nearly 700 mg dm^?3 which cannot be further oxidized with the Fenton process. The electrolyses were carried out under galvanostatic conditions, using a bench‐scale plant equipped with a single‐compartment electrochemical flow cell. Boron‐doped diamond (BDD) and stainless steel (AISI 304) were use as anode and cathode of the cell, respectively. The complete mineralization of the waste was obtained with high current efficiencies limited only by mass transport processes. This confirms that besides the hydroxyl radical‐mediated oxidation that occurs in the Fenton process, the electrochemical oxidation with conductive diamond electrodes combines other important oxidation processes such as direct electro‐oxidation on the BDD surface and oxidation mediated by other electrochemically formed compounds generated in this electrode. Copyright © 2006 Society of Chemical Industry     

Chemical durability and microstructural analysis of glasses soaked in water and in biological fluids

A new glass, obtained from Bioglass^® BG45S5 original composition by substituting CaO with MgO, was produced and its chemical durability and microstructural characteristics were compared with that of Bioglass^®.The two glasses (labelled as BG45 and MG45) were soaked up to 4 weeks at physiological temperature in different solutions, i.e. bi-distilled water, Hank's Buffered Salt Solution 61200 (labelled as HBSS+), Hank's Buffered Salt Solution 14170 (labelled as HBSS−), and Kokubo's SBF. Moreover, the influence of either flat or flake surfaces was analysed for both glasses. Results showed that the chemical durability of a glass in saline at 37 °C, evaluated through pH and ICP-AES chemical analysis of the leached components, depended mainly on the chemical composition of the soaking solution. Moreover, the MG45 glass never exhibited hydroxyapatite crystal formation on its surface also after soaking in calcium-containing solutions. The apatite crystallisation and deposition mechanism, typical of a bioactive glass, was induced only if the glass itself contained calcium. The contemporaneous presence of calcium in the glass and in the soaking solution improved the reactivity of the glass, as apatite crystals nucleated in a shorter time and grew more quickly. As regards the morphology of the glass surface, rougher surfaces favoured the formation of hydroxyapatite crystals on glasses containing calcium.     

Guava seed storage protein: Fractionation and characterization

In the present work, guava seed storage proteins have been fractionated and characterized. Glutelins (86-90 g/100 g) and globulins (≈10 g/100 g) are the main components of the protein extract. Albumins and prolamins are minor components (≈2 g/100 g). Guava seed glutelin extracts, like rice and amaranth glutelins, are legumine-like proteins that, due to their solubility properties, have to be extracted using extreme pH (borate buffer, pH 10, Gt-Bo; NaOH pH 12 Gt-Na), denaturing (borate buffer plus sodium dodecyl sulfate, Gt-BoSDS) or reducing conditions (borate buffer plus 2-mercaptoethanol, Gt-BoME; borate buffer plus sodium dodecyl sulfate and 2-mercaptoethanol, Gt-BoSDSME). The highest yield was obtained with SDS extraction, suggesting that proteins in the seeds form aggregates stabilized mainly by non-covalent interactions. Glutelins are mainly composed of 65 and 67 kD subunits, with a lower proportion of 55 kD subunits. These subunits are formed by disulfide bond-linked polypeptides with molecular masses 40-45 kD, 22-27 kD and 23-25 kD, respectively. The guava seeds protein isolate (GSI) exhibited a polypeptide profile very similar to that of the glutelin fraction.The guava seed could be an alternative source of protein for human and animal consume, additional to this to solve at least in part the pollution problem that fruit processing industry has for discarding this material.     

Electromagnetic interference from digital signal transmission onpower line carrier channels

A procedure is presented to evaluate the electromagnetic field generated by a digital transmission system on multiconductor power-line carrier channels. The vertical component of the electric field and the horizontal component of the magnetic field are defined by approximate formulaes of varying accuracy, depending on the frequency and the distance from phase conductors. Field sources are the currents traveling along the line, which are evaluated by means of an accurate simulation model of the transmission system and a rigorous wave propagation algorithm. Frequency spectra and lateral profiles of the field components are computed for single-phase and two-phase couplings on a horizontal power line. Digital channel capacity is shown to increase as the pulse repetition interval T decreases. However, if T increases, the harmonic content of the input signal code increases and, consequently, electromagnetic pollution rises for a given carrier channel. It is concluded that the EMI (electromagnetic interference) level is an important constraint which must be taken into account when choosing T and, more generally, in the design of the digital transmission system     

Determination of citrus jams genuineness by flavonoid analysis

An easy technique that enables the analysis of flavonoids from citrus jams is described. The flavonoids from commercial sour orange, sweet orange, mandarin, lemon, bitter lemon, grapefruit and lime jams were analysed by HPLC. Each citrus jam has a characteristic flavonoid pattern that can be used in genuineness determinations. Commercial jams produced with mixtures of orange, lemon and grapefruit can easily be characterized by HPLC. No differences between the flavonoid profiles of natural fruits and those of the corresponding jams were observed, showing that the manufacturing process does not affect the flavonoid profile and, therefore, that this profile can be used in genuineness studies.     

Interaction of proteins with the mRNA for ribosomal protein L1 in Xenopus: structural characterization of in vivo complexes and identification of proteins that bind in vitro to its 5'UTR

Xenopus r-protein mRNAs are known to be coordinately regulated at the translational level. To find out if RNA/protein interactions are involved in this control mechanism, we have characterized the particles containing the translationally repressed rp-mRNA and we have investigated the proteins that specifically bind to this type of mRNA. By sedimentation analysis and isopycnic centrifugation we have found that the repressed rp-mRNAs are assembled in slow sedimenting complexes where the RNA is prevalent over the protein mass (2.3 to 1). This composition is maintained also after in vitro reconstitution of the particle. We carried out also a detailed analysis of in vitro RNA/protein complex formation by focusing our attention on the 5'UTR, very similar in different rp-mRNAs and important in the translational regulation. We describe specific interactions of L1 mRNA with four proteins. The binding site of two of them, 57 kD and 47 kD, is in the typical pyrimidine sequence at the 5' end and is position dependent. Proteins of the same size interact also with the analogous region of r-protein S1 and L14 mRNA, not with unrelated RNAs. Binding of two other proteins, 31 kD and 24 kD, in the downstream region of the 5'UTR was also observed. The most evident 57 kD protein has been partially purified. Although the binding of these proteins to the r-protein mRNA 5'UTR is specific, their involvement in the translation regulation remains to be proved.     

Hierarchical linear models in psychiatry: A bibliometric study

Development of research methods requires a systematic review of their status. This study focuses on the use of Hierarchical Linear Modeling methods in psychiatric research. Evaluation includes 207 documents published until 2007, included and indexed in the ISI Web of Knowledge databases; analyses focuses on the 194 articles in the sample. Bibliometric methods are used to describe the publications patterns. Results indicate a growing interest in applying the models and an establishment of methods after 2000. Both Lotka’s and Bradford’s distributions are adjusted to the data.     

Effect of selected ions from lyotropic series on lipid oxidation rate

Organic or inorganic salts, commonly present in foods as natural components or ingredients, can affect the hydrophobic/hydrophilic interactions among food components. In particular, modifying the physicochemical equilibrium in the media, the ionic species forming salts could affect the kinetics of chemical reactions occurring in foods. The aim of the present research was to study the influence of different ionic species from lyotropic series on the kinetics of lipid oxidation. For this purpose, salts containing antichaotropic (carbonate and acetate), neutral (Na⁺, K⁺) and chaotropic ions (Cl⁻) were added to soybean oil. Results indicate that potassium carbonate and potassium acetate present a strong antioxidant capacity, whereas no effect was detected for NaCl and KCl. The salt antioxidant activity was prevalently attributed to the antichaotropic anionic species present in the media, which could interact with hydroperoxides by virtue of their ability to form hydrogen bonds. These results appear to be of considerable interest for controlling the development of rancidity in foods.