FUNCTIONALIZED HALLOYSITE NANOTUBES FOR ENHANCED REMOVAL OF Hg2+ IONS FROM AQUEOUS SOLUTIONS

Water is essential for humans, animals, and plants; pollutants, usually derived from anthropogenic activities, can have a serious effect on its quality. Heavy metals are significant pollutants and are often highly toxic to living organisms, even at very low concentrations. Among the numerous removal techniques proposed, adsorption onto suitable adsorbent materials is considered to be one of the most promising. The objective of the current study was to determine the effectiveness of halloysite nanotubes (HNT) functionalized with organic amino or thiol groups as adsorbent materials to decontaminate polluted waters, using the removal of Hg2+ ions, one of the most dangerous heavy metals, as the test case. The effects of pH, ionic strength (I), and temperature of the metal ion solution on the adsorption ability and affinity of both materials were evaluated. To this end, adsorption experiments were carried out with no ionic medium and in NaNO3 and NaCl at I = 0.1 mol L−1, in the pH range 3–5 and in the temperature range 283.15–313.15 K. Kinetic and thermodynamic aspects of adsorption were considered by measuring the metal ion concentrations in aqueous solution. Various equations were used to fit experimental data, and the results obtained were explained on the basis of both the adsorbent’s characterization and the Hg2+ speciation under the given experimental conditions. Thiol and amino groups enhanced the adsorption capability of halloysite for Hg2+ ions in the pH range 3–5. The pH, the ionic medium, and the ionic strength of aqueous solution all play an important role in the adsorption process. A physical adsorption mechanism enhanced by ion exchange is proposed for both functionalized materials

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+ > Cu2+ > Cd2+

Modulating membrane shape and mechanics of minimal cells by light: area increase, softening and interleaflet coupling of membrane models doped with azobenzene-lipid photoswitches

Light can effectively interrogate biological systems providing control over complex cellular processes. Particularly advantageous features of photo-induced processes are reversibility, physiological compatibility, and spatiotemporal precision. Understanding the underlying biophysics of light-triggered changes in bio-systems is crucial for cell viability and optimizing clinical applications of photo-induced processes in biotechnology, optogenetics and photopharmacology. Employing membranes doped with the photolipid azobenzene-phosphatidylcholine (azo-PC), we provide a holistic picture of light-triggered changes in membrane morphology, mechanics and dynamics. We combine microscopy of giant vesicles as minimal cell models, Langmuir monolayers, and molecular dynamics simulations. We employ giant vesicle elelctrodeformation as a facile and accurate approach to quantify the magnitude, reversibility and kinetics of light-induced area expansion/shrinkage as a result of azo-PC photoisomerization and content. Area increase as high as ~25% and a 10-fold decrease in the membrane bending rigidity is observed upon trans-to-cis azo-PC isomerization. These results are in excellent agreement with simulations data and monolayers. Simulations also show that trans-to-cis isomerization of azo-PC decreases the membrane leaflet coupling. We demonstrate that light can be used to finely manipulate the shape and mechanics of photolipid-doped minimal cell models and liposomal drug carriers, thus, presenting a promising therapeutic alternative for the repair of cellular disorders.Competing Interest StatementThe authors have declared no competing interest

<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

Perception of Time-Discrete Haptic Feedback on the Waist is Invariant with Gait Events

The effectiveness of haptic feedback devices highly depends on the perception of tactile stimuli, which differs across body parts and can be affected by movement. In this study, a novel wearable sensory feedback apparatus made of a pair of pressure-sensitive insoles and a belt equipped with vibrotactile units is presented; the device provides time-discrete vibrations around the waist, synchronized with biomechanically-relevant gait events during walking. Experiments with fifteen healthy volunteers were carried out to investigate users' tactile perception on the waist. Stimuli of different intensities were provided at twelve locations, each time synchronously with one pre-defined gait event (i.e. heel strike, flat foot or toe off), following a pseudo-random stimulation sequence. Reaction time, detection rate and localization accuracy were analyzed as functions of the stimulation level and site and the effect of gait events on perception was investigated. Results revealed that above-threshold stimuli (i.e. vibrations characterized by acceleration amplitudes of 1.92g and 2.13g and frequencies of 100 Hz and 150 Hz, respectively) can be effectively perceived in all the sites and successfully localized when the intertactor spacing is set to 10 cm. Moreover, it was found that perception of time-discrete vibrations was not affected by phase-related gating mechanisms, suggesting that the waist could be considered as a preferred body region for delivering haptic feedback during walking

Randomised trials and meta-analyses of double vs triple antithrombotic therapy for atrial fibrillation-ACS/PCI: A critical appraisal

•The optimal antithrombotic regimen to be used in patients with AF and PCI or ACS is still debated.•Each of the six randomised controlled trials comparing double to triple therapy has limitations.•None was powered to assess differences between treatment arms in ischaemic event rates.•The contrasting results regarding ischaemic events within published meta-analyses can be explained by heterogeneity, incompleteness and varying definitions of stent thrombosis.•The overall reduced bleeding rates, but increased early definite and probable stent thrombosis rates with double versus triple antithrombotic therapy encourage consideration of triple therapy during the first weeks from PCI followed by double therapy

Repurposing of plasminogen: An orphan medicinal product suitable for SARS-CoV-2 inhalable therapeutics

The SARS-CoV-2 infection is associated with pulmonary coagulopathy, which determines the deposition of fibrin in the air spaces and lung parenchyma. The resulting lung lesions compromise patient pulmonary function and increase mortality, or end in permanent lung damage for those who have recovered from the COVID-19 disease. Therefore, local pulmonary fibrinolysis can be efficacious in degrading pre-existing fibrin clots and reducing the conversion of lung lesions into lasting scars. Plasminogen is considered a key player in fibrinolysis processes, and in view of a bench-to-bedside translation, we focused on the aerosolization of an orphan medicinal product (OMP) for ligneous conjunctivitis: human plasminogen (PLG-OMP) eye drops. As such, the sterile and preservative-free solution guarantees the pharmaceutical quality of GMP production and meets the Ph. Eur. requirements of liquid preparations for nebulization. PLG-OMP aerosolization was evaluated both from technological and stability viewpoints, after being submitted to either jet or ultrasonic nebulization. Jet nebulization resulted in a more efficient delivery of an aerosol suitable for pulmonary deposition. The biochemical investigation highlighted substantial protein integrity maintenance with the percentage of native plasminogen band &gt; 90%, in accordance with the quality specifications of PLG-OMP. In a coherent way, the specific activity of plasminogen is maintained within the range 4.8–5.6 IU/mg (PLG-OMP pre-nebulization: 5.0 IU/mg). This is the first study that focuses on the technological and biochemical aspects of aerosolized plasminogen, which could affect both treatment efficacy and clinical dosage delivery. Increasing evidence for the need of local fibrinolytic therapy could merge with the availability of PLG-OMP as an easy handling solution, readily aerosolizable for a fast translation into an extended clinical efficacy assessment in COVID-19 patients

Microvascular Dysfunction in Heart Failure With Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) is an increasingly studied entity accounting for 50% of all diagnosed heart failure and that has claimed its own dignity being markedly different from heart failure with reduced EF in terms of etiology and natural history (Graziani et al., 2018). Recently, a growing body of evidence points the finger toward microvascular dysfunction as the major determinant of the pathological cascade that justifies clinical manifestations (Crea et al., 2017). The high burden of comorbidities such as metabolic syndrome, hypertension, atrial fibrillation, chronic kidney disease, obstructive sleep apnea, and similar, could lead to a systemic inflammatory state that impacts the physiology of the endothelium and the perivascular environment, engaging complex molecular pathways that ultimately converge to myocardial fibrosis, stiffening, and dysfunction (Paulus and Tschope, 2013). These changes could even self-perpetrate with a positive feedback where hypoxia and locally released inflammatory cytokines trigger interstitial fibrosis and hypertrophy (Ohanyan et al., 2018). Identifying microvascular dysfunction both as the cause and the maintenance mechanism of this condition has opened the field to explore specific pharmacological targets like nitric oxide (NO) pathway, sarcomeric titin, transforming growth factor beta (TGF-β) pathway, immunomodulators or adenosine receptors, trying to tackle the endothelial impairment that lies in the background of this syndrome (Graziani et al., 2018;Lam et al., 2018). Yet, many questions remain, and the new data collected still lack a translation to improved treatment strategies. To further elaborate on this tangled and exponentially growing topic, we will review the evidence favoring a microvasculature-driven etiology of this condition, its clinical correlations, the proposed diagnostic workup, and the available/hypothesized therapeutic options to address microvascular dysfunction in the failing heart

Exoskeletons for workers: A case series study in an enclosures production line

This case-series study aims to investigate the effects of a passive shoulder support exoskeleton on experienced workers during their regular work shifts in an enclosures production site. Experimental activities included three sessions, two of which were conducted in-field (namely, at two workstations of the painting line, where panels were mounted and dismounted from the line; each session involved three participants), and one session was carried out in a realistic simulated environment (namely, the workstations were recreated in a laboratory; this session involved four participants). The effect of the exoskeleton was evaluated through electromyographic activity and perceived effort. After in-field sessions, device usability and user acceptance were also assessed. Data were reported individually for each participant. Results showed that the use of the exoskeleton reduced the total shoulder muscular activity compared to normal working conditions, in all subjects and experimental sessions. Similarly, the use of the exoskeleton resulted in reductions of the perceived effort in the shoulder, arm, and lower back. Overall, participants indicated high usability and acceptance of the device. This case series invites larger validation studies, also in diverse operational contexts