Near-Wall Aggregation of Amyloidogenic Aβ 1-40 Peptide: Direct Observation by the FRET

The formation of amyloid fibrils is one of the variants of the self-organization of polypeptide chains. For the amyloid aggregation, the solution must be oversaturated with proteins. The interface of the liquid (solution) and solid (vessel walls) phases can trigger the adsorption of protein molecules, and the resulting oversaturation can initiate conformational transitions in them. In any laboratory experiment, we cannot exclude the presence of surfaces such as the walls of vessels, cuvettes, etc. However, in many works devoted to the study of amyloid formation, this feature is not considered. In our work, we investigated the behavior of the Aβ 1-40 peptide at the water–glass, water–quartz, and water–plastic interface. We carried out a series of simple experiments and showed that the Aβ 1-40 peptide is actively adsorbed on these surfaces, which leads to a significant interaction and aggregation of peptides. This means that the interface can be the place where the first amyloid nucleus appears. We suggest that this effect may also be one of the reasons for the difficulty of reproducing kinetic data when studying the aggregation of the amyloid of the Aβ 1-40 peptide and other amyloidogenic proteins

A combined hydro-pyrometallurgical process for zinc oxide and iron oxide extraction from electric arc furnace dust waste

Electric arc furnace (EAF) dust waste is generated during EAF steelmaking process. Zinc and iron which comprise the highest composition in EAF dust are secondary resources for making steel products. They mainly present in the form of stable zinc ferrite (ZnFe2O4), leading to the extraction process difficult. In this study, a combined hydro-pyrometallurgical process was developed to extract both zinc oxide and iron oxide from EAF dust. Initially, hydrometallurgical leaching was used to leach zinc and iron from EAF dust. Results show that 10 M of hydrochloric acid (HCl) at 25°C can achieve zinc and iron leaching of 92% and 91%, respectively. The liquid solution post leaching was subjected to pyrometallurgical process to form Fe2O3 mixture at 250°C while retaining zinc chloride (ZnCl2) as solid residue. Then, the obtained ZnCl2 was treated with sodium hydroxide (NaOH) and nitric acid (HNO3) to form ZnO. The Fe2O3 and ZnO extraction were 2.5 g and 1.5 g, respectively out of 10 g of EAF dust with their respective purity of 87% and 98%. The developed process can provide new insight into recovering zinc oxide and iron oxide simultaneously from EAF dust, thereby paving the way to circular economy development and sustainable steel dust waste management for steel industries.

Ionic Liquids and Water: Hydrophobicity vs. Hydrophilicity

Many chemical processes rely extensively on organic solvents posing safety and environmental concerns. For a successful transfer of some of those chemical processes and reactions to aqueous media, agents acting as solubilizers, or phase-modifiers, are of central importance. In the present work, the structure of aqueous solutions of several ionic liquid systems capable of forming multiple solubilizing environments were modeled by molecular dynamics simulations. The effect of small aliphatic chains on solutions of hydrophobic 1-alkyl-3-methylimidazolium bis(trifluoromethyl)sulfonylimide ionic liquids (with alkyl = propyl [C3C1im][NTf2], butyl [C4C1im][NTf2] and isobutyl [iC4C1im][NTf2]) are covered first. Next, we focus on the interactions of sulphonate- and carboxylate-based anions with different hydrogenated and perfluorinated alkyl side chains in solutions of [C2C1im][CnF2n+1SO3], [C2C1im][CnH2n+1SO3], [C2C1im][CF3CO2] and [C2C1im][CH3CO2] (n = 1, 4, 8). The last system considered is an ionic liquid completely miscible with water that combines the cation N-methyl-N,N,N-tris(2-hydroxyethyl)ammonium [N1 2OH 2OH 2OH]+, with high hydrogen-bonding capability, and the hydrophobic anion [NTf2]–. The interplay between short- and long-range interactions, clustering of alkyl and perfluoroalkyl tails, and hydrogen bonding enables a wealth of possibilities in tailoring an ionic liquid solution according to the needs.

Precision Medicine in Autoimmune Thyroiditis and Hypothyroidism

Autoimmune thyroid diseases (AITD) are T-cell-mediated organ specific autoimmune disorders, deriving from an altered response of the immune system that leads to the immune attack to the thyroid. Hashimoto’s thyroiditis (HT) and Graves’ disease (GD) are the two principal AITD clinical presentations. Hypothyroidism and thyrotoxicosis are, respectively, the clinical hallmarks of HT and GD. Patients with autoimmune thyroiditis are treated daily with synthetic L-thyroxine (L-T4) at the dose of 1.5–1.7 μg/kg. Various L-T4 formulations are commercially available (tablet, liquid solution, or soft gel capsule). L-T4 in tablets is generally prescribed to treat hypothyroidism, whereas the liquid formulation, or soft gel capsules, can be administered in hypothyroid patients in case of malabsorption or in patients in therapy with drugs interfering with L-T4 absorption. Furthermore, myoinositol has a crucial role in thyroid autoimmunity and function. Clinical studies reported a significant decline in TSH and antithyroid autoantibodies levels after treatment with myoinositol + selenium in patients with subclinical hypothyroidism and autoimmune thyroiditis. Moreover, thyroidectomy can be rarely recommended in patients with autoimmune thyroiditis, with cosmetic reasons for a goiter, or with important signs or symptoms of local compression, or nodular disease with a “suspicious” cytology for malignancy. Furthermore, a recent randomized trial suggested that total thyroidectomy can improve quality of life and fatigue, while medical therapy did not. In this review, we overview currently available evidence in personalized medicine in patients with autoimmune thyroiditis and hypothyroidism. Further research is needed in larger population to investigate the effect of these new treatments on quality of life.

Low-Cost Polyethylene Terephthalate Fluidic Sensor for Ultrahigh Accuracy Measurement of Liquid Concentration Variation

A low-cost polyethylene terephthalate fluidic sensor (PET-FS) is demonstrated for the concentration variation measurement on fluidic solutions. The PET-FS consisted of a triangular fluidic container attached with a birefringent PET thin layer. The PET-FS was injected with the test liquid solution that was placed in a common path polarization interferometer by utilizing a heterodyne scheme. The measured phase variation of probe light was used to obtain the information regarding the concentration change in the fluidic liquids. The sensor was experimentally tested using different concentrations of sodium chloride solution showing a sensitivity of 3.52 ×104 deg./refractive index unit (RIU) and a detection resolution of 6.25 × 10−6 RIU. The estimated sensitivity and detection resolutions were 5.62 × 104 (deg./RIU) and 6.94 × 10−6 RIU, respectively, for the hydrochloric acid. The relationship between the measured phase and the concentration is linear with an R-squared value reaching above 0.995.

A Prospective Observational Multicenter Study on Deferiprone & Deferasirox in Clinical Practice of Pediatric Patients with Transfusion-Dependent B-Thalassemia

Background: Iron overload is inevitable but a manageable complication of frequent blood transfusion, the effectiveness and safety of two iron chelation therapy in young children with transfusion-dependent B thalassemia (TDB-T) using either deferiprone (DFP) or deferasirox (DFX) were well studied in clinical trials. The primary objectives were; reporting efficacy and frequency of all adverse events (AEs) as compared with published data. Secondary objective was reporting deviation from guidelines, The analysis of clinical data is the first step to design new strategies Methodology: An investigator initiated 2-year multicenter prospective study enrolling over 6 months period; 302 children with TDB-T from 11 centers; keeping pre-transfusion Hb >8gm/dl. When serum ferritin (SF) reached around 1000 ng/ml; they had received according to availability; either DFP liquid solution in a dose; 75 mg/kg/day (n=62) or DFX (n=240); (dispersed tablet; 25% or film-coated tablet 75% in a dose; 20-25 mg/kg/d or its equivalent). CBC was done biweekly in DFP and pre-transfusion in DFX group. Liver transaminases, serum creatinine and (SF) were done /3 months. Changes in growth velocity over time were documented. Results: 66% were males, age at enrolment was; (11-19 and 14-26 months) in DFP and DFX respectively; they had received (6-8) and (7-11) transfusions prior to chelation in both groups respectively in addition to (16-21) during the study. 20% of patients did not achieve the target pre-transfusion Hb level. At initiation of DFP; SF median; 960 (IQR; 122 ng/ml) while those on DFX had SF; median 1070 (IQR 138 ng/ml) both groups had comparable transfusion iron input during the study. At 24 months of regular transfusion-chelation; SF < 1000 ng/ml was noticed in 65% and 60% of the patients respectively with good growth velocity in children using either chelator. Unnecessary over-dosing of DFX > 40 mg/kg was observed in 5%, meanwhile 3.2% had received DFP in a dose >75-100 mg/kg while SF was <1500 ng/ml. Under-reporting of adverse events in both groups was observed; 5% GIT upset, neither arthralgia nor agranulocytosis, neutropenia (3.2%) in DFP group and CBC was not checked biweekly; but only prior to transfusion. 4-5 % had elevated transaminases in both chelators, while patients on DFX reported; GIT upset in 4.2% and rash in 1.6%. Elevated serum creatinine > 33% from baseline on 2 successive visits was observed in 5% in DFX without reducing the dose or re-check. No unexpected, serious severe adverse events were reported in both groups. Poorly controlled patients with SF > 1500 ng /ml at 12 or 24 months were 12, 8% in DFP group; in contrast to 15%, 10% in DFX group respectively; with no statistical difference; (compliance was comparable). The total DFP and DFX discontinuation ratio was 5% in each group. Conclusion: infants and young children with TDB-T naïve to chelation were put on mono-therapy at younger age than reported before. Both chelators were effective, well tolerated and with no severe safety concerns; however deviation from guidelines was observed as; unnecessary over-dosing of DFX and under-reporting of AEs in both groups in real life practice. Disclosures Hamdy: ApoPharma: Honoraria; Amgen: Honoraria; Bayer: Honoraria; Novartis: Honoraria; NovoNordisk: Honoraria; Roche: Honoraria; Takeda: Honoraria.

Characteristics of wood pellets from over-dry sawdust waste

Wood pellets are renewable fuels from biomass which can be an alternative substitute for petroleum fuels. One of the raw materials for making wood pellets is sawdust from the sawmill industry or other wood craftsmen. Sawdust waste that dumped for a long time will reduce its moisture content (over-dry) and will be difficult to form into pellets. In this paper, we studied the effect of adding liquid solution ie. water, tapioca starch solution, pure molasses solution and dilute molasses solution on over-dry sawdust to the characteristic properties of wood pellet torrefaction. The sawdust material was collected from the wood sawmill in the Bogor District. There were five treatments i.e sawdust (control), sawdust + 10% water, sawdust + 10% tapioca starch solution, sawdust + 10% pure molasses solution, sawdust + 10% diluted molasses solution. The wood pellet torrefaction properties were investigated using a manual hot press at the temperature of 210°C. The results showed that the addition of pure molasses solution produced better pellets than other treatments, with properties i.e water content of 2.65%, the ash content of 1.45%, volatile matter 76.72%, fixed carbon 19.18%, the calorific value of 19.56 MJkg−1, density 0.84 gcm−3, and compressive strength 52.22 kgcm−2.

Non-inferiority of liquid thyroxine in comparison to tablets formulation in the treatment of children with congenital hypothyroidism

Objectives The aim of the current prospective randomized control study was to assess efficacy, safety, and non-inferiority of a new liquid L-thyroxine formulation dissolved in glycerol and water (T4® drops, produced by a Greek pharmaceutical Company, Uni-Pharma, Athens, Greece) in comparison to the standard Tablets form (T4® tablets, Uni-Pharma, Athens, Greece) in the substitutive treatment of children with congenital hypothyroidism (CH). Methods Thirty-nine children with CH, aged 3–12 years old, were enrolled in the study, after parental Informed Consent has been obtained, while three patients were lost from follow-up. At baseline, all participants had normal thyroid-stimulating hormone (TSH) and Free T4 values. Patients were randomly subdivided according to the assigned treatment in Group A (n=17)-Tablet Form and Group B (n=19)-Liquid Form. TSH and Free T4 levels were evaluated at 0, 2, 4, and 6 months. Results TSH values showed a statistically significant difference (p=0.017) between groups only at six months (Group A having higher TSH levels than Group B, albeit within the normal range), while Free T4 levels had no statistical difference throughout the six month study period and were always within the normal range. Moreover, dose adjustments were more frequent in Group A (p=0.038) during the six months. Liquid L-thyroxine substitutive treatment exhibited no statistically significant adverse effects in comparison to the widely used tablets. Conclusions Levothyroxine (LT4) as liquid solution formulation is safe and noninferior to the widely used L-thyroxine Tablets, with less need for dose adjustment, and can therefore be safely used in the treatment of children with CH.

Sorting of Poly-disperse Particle by Entrapment using Liquid Carrier System

A thin viscous layer is found over a substrate when it is immersed in a polymer solution. The layer thickness depends on the polymer and solvent type, their volume fraction, and the substrate. If the liquid solution contains particles, they are entrapped on the viscous polymer layer, acting as the binder. The trade-off between the viscous force and the centrifugal force on the particle determines the entrapment. Furthermore, the size of entrained particles are dictated by the binder concentration of the solution., A particle filtration technique is presented using the entrapment phenomenon from a poly-disperse mixture. A dimensionless number called the entrapment factor is introduced to correlate the particle entrapment with various parameters. By changing the entrapment factor, three distinct entrapment regimes are achieved and explained from a poly-disperse mixture. The experimental result shows that entrapped particles become larger as the factor increases, which can be controlled with multiple parameters of the dipping process. The proposed technique can lead to a filtration process of the wide-range poly-disperse particle mixture over the capillary filtration processes.