<b><i>Topoisomerase 1</i></b> Promoter Variants and Benefit from Irinotecan in Metastatic Colorectal Cancer Patients

Objective: Topoisomerase 1 (topo-1) is an important target for the treatment of metastatic colorectal cancer (CRC). The aim of the present study was to evaluate the correlation between topo-1 single-nucleotide polymorphisms (SNPs) and clinical outcome in metastatic CRC (mCRC) patients. Methods: With the use of specific software (PROMO 3.0), we performed an in silico analysis of topo-1 promoter SNPs; the rs6072249 and rs34282819 SNPs were included in the study. DNA was extracted from 105 mCRC patients treated with FOLFIRI ± bevacizumab in the first line. SNP genotyping was performed by real-time PCR. Genotypes were correlated with clinical parameters (objective response rate, progression-free survival, and overall survival). Results: No single genotype was significantly associated with clinical variables. The G allelic variant of rs6072249 topo-1 SNP is responsible for GC factor and X-box-binding protein transcription factor binding. The same allelic variant showed a nonsignificant trend toward a shorter progression-free survival (GG, 7.5 months; other genotypes, 9.3 months; HR 1.823, 95% CI 0.8904-3.734; p = 0.1). Conclusion: Further analyses are needed to confirm that the topo-1 SNP rs6072249 and transcription factor interaction could be a part of tools to predict clinical outcome in mCRC patients treated with irinotecan-based regimens

Chelating Agents for the Sequestration of Mercury(II) and Monomethyl Mercury(II)

Both mercury(II) and monomethyl mercury(II) poisonings are of great concern for several reasons. As it happens for other metals, chelation therapy is the most indicated treatment for poisoned patients. The efficacy of the therapy and the reduction of side-effects can be sensibly enhanced by an accurate knowledge of all the physiological mechanisms involved in metal uptake, transport within and between various tissues, and (possibly) clearance. All these aspects, however, are strictly dependent on the chemical speciation (i.e., the distribution of the chemical species of a component in a given system) of both the metal and the chelating agent in the systems where they are present. In this light, this review analyzes the state of the art of research performed in this field for mercury(II) and methylmercury(II). After a brief summary of their main sources, the physiological patterns for the treatment of mercury poisoning have also been considered. The binding ability of various chelating agents toward mercury has been then analyzed by modeling the behavior of the main classes of ligands present in biological fluids and/or frequently used in chelation therapy. Their sequestering ability has been successively evaluated by means of a semiempirical parameter already proposed for its objective quantification, and the main characteristics of an efficient chelating agent have been evaluated on this basis

The effect of metal cations on the aqueous behavior of dopamine. Thermodynamic investigation of the binary and ternary interactions with cd2+, cu2+ and uo22+ in nacl at different ionic strengths and temperatures

The interactions of dopamine [2-(3,4-Dihydroxyphenyl)ethylamine, (Dop−)] with cadmium(II), copper(II) and uranyl(VI) were studied in NaCl(aq) at different ionic strengths (0 ≤ I/mol dm−3 ≤ 1.0) and temperatures (288.15 ≤ T/K ≤ 318.15). From the elaboration of the experimental data, it was found that the speciation models are featured by species of different stoichiometry and stability. In particular for cadmium, the formation of only MLH, ML and ML2 (M = Cd2+; L = dopamine) species was obtained. For uranyl(VI) (UO22+), the speciation scheme is influenced by the use of UO2(acetate)2 salt as a chemical; in this case, the formation of ML2, MLOH and the ternary MLAc (Ac = acetate) species in a wide pH range was observed. The most complex speciation model was obtained for the interaction of Cu2+ with dopamine; in this case we observed the formation of the following species: ML2, M2L, M2L2, M2L2(OH)2, M2LOH and ML2OH. These speciation models were determined at each ionic strength and temperature investigated. As a further contribution to this kind of investigation, the ternary interactions of dopamine with UO22+/Cd2+ and UO22+/Cu2+ were investigated at I = 0.15 mol dm−3 and T = 298.15K. These systems have different speciation models, with the MM’L and M2M’L2OH [M = UO22+; M’ = Cd2+ or Cu2+, L = dopamine] common species; the species of the mixed Cd2+ containing system have a higher stability with respect the Cu2+ containing one. The dependence on the ionic strength of complex formation constants was modelled by using both an extended Debye–Hückel equation that included the Van’t Hoff term for the calculation of the formation enthalpy change values and the Specific Ion Interaction Theory (SIT). The results highlighted that, in general, the entropy is the driving force of the process. The quantification of the effective sequestering ability of dopamine towards the studied cations was evaluated by using a Boltzmann-type equation and the calculation of pL0.5 parameter. The sequestering ability was quantified at different ionic strengths, temperatures and pHs, and this resulted, in general, that the pL0.5 trend was always: UO22+ &gt; Cu2+ &gt; Cd2+

Assessment of intuitiveness and comfort of wearable haptic feedback strategies for assisting level and stair walking

Nowadays, lower-limb prostheses are reaching real-world usability especially on ground-level walking. However, some key tasks such as stair walking are still quite demanding. Providing haptic feedback about the foot placement on the steps might reduce the cognitive load of the task, compensating for increased dependency on vision and lessen the risk of falling. Experiments on intact subjects can be useful to define the feedback strategies prior to clinical trials, but effective methods to assess the efficacy of the strategies are few and usually rely on the emulation of the disability condition. The present study reports on the design and testing of a wearable haptic feedback system in a protocol involving intact subjects to assess candidate strategies to be adopted in clinical trials. The system integrated a sensorized insole wirelessly connected to a textile waist belt equipped with three vibrating motors. Three stimulation strategies for mapping the insole pressure data to vibrotactile feedback were implemented and compared in terms of intuitiveness and comfort perceived during level and stair walking. The strategies were ranked using a relative rating approach, which highlighted the differences between them and suggested guidelines for their improvement. The feedback evaluation procedure proposed could facilitate the selection and improvement of haptic feedback strategies prior to clinical testing

8-hydroxyquinoline-2-carboxylic acid as possible molybdophore: A multi-technique approach to define its chemical speciation, coordination and sequestering ability in aqueous solution

8-hydroxyquinoline-2-carboxylic acid (8-HQA) has been found in high concentrations (0.5–5.0 mmol·dm−3) in the gut of Noctuid larvae (and in a few other lepidopterans), in which it is proposed to act as a siderophore. Since it is known that many natural siderophores are also involved in the uptake and metabolism of other essential elements than iron, this study reports some results on the investigation of 8-HQA interactions with molybdate (MoO42−, i.e., the main molybdenum form in aqueous environments), in order to understand the possible role of this ligand as molybdophore. A multi-technique approach has been adopted, in order to derive a comprehensive set of information necessary to assess the chemical speciation of the 8-HQA/MoO42− system, as well as the coordination behavior and the sequestering ability of 8-HQA towards molybdate. Chemical speciation studies have been performed in KCl(aq) at I = 0.2 mol·dm−3 and T = 298.15 K by ISE-H+ (glass electrode) potentiometric and UV/Vis spectrophotometric titrations. CV (Cyclic Voltammetry), DP-ASV (Differential Pulse-Anodic Stripping Voltammetry), ESI-MS experiments and quantum mechanical calculations have been also performed to derive information about the nature and possible structure of species formed. These results are also compared with those reported for the 8-HQA/Fe3+ system in terms of chemical speciation and sequestering ability of 8HQA

Diagnostic, therapeutic and health-care management protocol in thyroid surgery: a position statement of the Italian Association of Endocrine Surgery Units (U.E.C. CLUB)

PURPOSE: The diagnostic, therapeutic and health-care management protocol (Protocollo Gestionale Diagnostico-Terapeutico-Assistenziale, PDTA) by the Association of the Italian Endocrine Surgery Units (U.E.C. CLUB) aims to help treat the patient in a topical, rational way that can be shared by health-care professionals. METHODS: This fourth consensus conference involved: a selected group of experts in the preliminary phase; all members, via e-mail, in the elaboration phase; all the participants of the XI National Congress of the U.E.C. CLUB held in Naples in the final phase. The following were examined: diagnostic pathway and clinical evaluation; mode of admission and waiting time; therapeutic pathway (patient preparation for surgery, surgical treatment, postoperative management, management of major complications); hospital discharge and patient information; outpatient care and follow-up. RESULTS: A clear and concise style was adopted to illustrate the reasons and scientific rationales behind behaviors and to provide health-care professionals with a guide as complete as possible on who, when, how and why to act. The protocol is meant to help the surgeon to treat the patient in a topical, rational way that can be shared by health-care professionals, but without influencing in any way the physician-patient relationship, which is based on trust and clinical judgment in each individual case. CONCLUSIONS: The PDTA in thyroid surgery approved by the fourth consensus conference (June 2015) is the official PDTA of U.E.C. CLUB

Prognostic relevance of a T-type calcium channels gene signature in solid tumours: A correlation ready for clinical validation

BackgroundT-type calcium channels (TTCCs) mediate calcium influx across the cell membrane. TTCCs regulate numerous physiological processes including cardiac pacemaking and neuronal activity. In addition, they have been implicated in the proliferation, migration and differentiation of tumour tissues. Although the signalling events downstream of TTCC-mediated calcium influx are not fully elucidated, it is clear that variations in the expression of TTCCs promote tumour formation and hinder response to treatment.MethodsWe examined the expression of TTCC genes (all three subtypes; CACNA-1G, CACNA-1H and CACNA-1I) and their prognostic value in three major solid tumours (i.e. gastric, lung and ovarian cancers) via a publicly accessible database.ResultsIn gastric cancer, expression of all the CACNA genes was associated with overall survival (OS) among stage I-IV patients (all pConclusionsAlterations in CACNA gene expression are linked to tumour prognosis. Gastric cancer represents the most promising setting for further evaluation

Detecting early signals of COVID-19 outbreaks in 2020 in small areas by monitoring healthcare utilisation databases: first lessons learned from the Italian Alert_CoV project

During the COVID-19 pandemic, large-scale diagnostic testing and contact tracing have proven insufficient to promptly monitor the spread of infections.AimTo develop and retrospectively evaluate a system identifying aberrations in the use of selected healthcare services to timely detect COVID-19 outbreaks in small areas. Methods: Data were retrieved from the healthcare utilisation (HCU) databases of the Lombardy Region, Italy. We identified eight services suggesting a respiratory infection (syndromic proxies). Count time series reporting the weekly occurrence of each proxy from 2015 to 2020 were generated considering small administrative areas (i.e. census units of Cremona and Mantua provinces). The ability to uncover aberrations during 2020 was tested for two algorithms: the improved Farrington algorithm and the generalised likelihood ratio-based procedure for negative binomial counts. To evaluate these algorithms' performance in detecting outbreaks earlier than the standard surveillance, confirmed outbreaks, defined according to the weekly number of confirmed COVID-19 cases, were used as reference. Performances were assessed separately for the first and second semester of the year. Proxies positively impacting performance were identified. Results: We estimated that 70% of outbreaks could be detected early using the proposed approach, with a corresponding false positive rate of ca 20%. Performance did not substantially differ either between algorithms or semesters. The best proxies included emergency calls for respiratory or infectious disease causes and emergency room visits. Conclusion: Implementing HCU-based monitoring systems in small areas deserves further investigations as it could facilitate the containment of COVID-19 and other unknown infectious diseases in the future

Stability of core/shell quantum dots-role of pH and small organic ligands

The improvement of knowledge about the toxicity and even processability, and stability of quantum dots (QD) requires the understanding of the relationship between the QD binding head group, surface structure, and interligand interaction. The scanned stripping chronopotentiometry and absence of gradients and Nernstian equilibrium stripping techniques were used to determine the concentration of Cd dissolved from a polyacrylate-stabilized CdTe/CdS QD. The effects of various concentrations of small organic ligands such as citric acid, glycine, and histidine and the roles of pH (4.5–8.5) and exposure time (0–48 h) were evaluated. The highest QD dissolution was obtained at the more acidic pH in absence of the ligands (52 %) a result of the CdS shell solubility. At pH 8.5 the largest PAA ability to complex the dissolved Cd leads to a further QD solubility until the equilibrium is reached (24 % of dissolved Cd vs.4 % at pH 6.0). The citric acid presence resulted in greater QD dissolution, whereas glycine, an amino acid, acts against QD dissolution. Surprisingly, the presence of histidine, an amino acid with an imidazole functional group, leads to the formation of much strong Cd complexes over time, which may be non-labile, inducing variations in the local environment of the QD surface

The Improvement of Durability of Reinforced Concretes for Sustainable Structures: A Review on Different Approaches

The topic of sustainability of reinforced concrete structures is strictly related with their durability in aggressive environments. In particular, at equal environmental impact, the higher the durability of construction materials, the higher the sustainability. The present review deals with the possible strategies aimed at producing sustainable and durable reinforced concrete structures in different environments. It focuses on the design methodologies as well as the use of unconventional corrosion-resistant reinforcements, alternative binders to Portland cement, and innovative or traditional solutions for reinforced concrete protection and prevention against rebars corrosion such as corrosion inhibitors, coatings, self-healing techniques, and waterproofing aggregates. Analysis of the scientific literature highlights that there is no preferential way for the production of “green” concrete but that the sustainability of the building materials can only be achieved by implementing simulta-neous multiple strategies aimed at reducing environmental impact and improving both durability and performances