Similar Concentrations Research Articles

Thermal and rheological behaviour of stearate-based phase change nanofluids

A comprehensive study has been performed on the thermal and rheological behaviour of two sets of isooctyl stearate (PureTemp 8, PT8) based nanofluids with different concentrations of spherical MgO nanoparticles (up to 15 wt%) and graphene nanoplatelets (up to 2 wt%). The results show that the presence of the nanomaterials does not significantly alter the phase change temperatures of the base fluids, although the latent heat decreases by 27% and 7.6% for 15 wt% MgO and 1.0 wt% GnP-based nanofluids, respectively. Both nanomaterials are found to increase the thermal diffusivity of the nanofluids. GnP-based suspensions have a higher thermal diffusivity than the MgO ones at similar nanomaterial concentrations. Rheological analyses show that MgO-PT8 nanofluids behave as a viscoplastic material (solid at zero shear rate); whereas the GnP-PT8 samples are viscoelastic (liquid at zero shear rate). MgO nanoparticles promote the formation of large fractal agglomerates, leading to a strong gel network of particles within PT8, while platelet-shaped GnP gives a fluid-like behaviour.

An integrated Monte Carlo track-structure simulation framework for modeling inter and intra-track effects on homogenous chemistry

Objective. The TOPAS-nBio Monte Carlo track structure simulation code, a wrapper of Geant4-DNA, was extended for its use in pulsed and longtime homogeneous chemistry simulations using the Gillespie algorithm. Approach. Three different tests were used to assess the reliability of the implementation and its ability to accurately reproduce published experimental results: (1) a simple model with a known analytical solution, (2) the temporal evolution of chemical yields during the homogeneous chemistry stage, and (3) radiolysis simulations conducted in pure water with dissolved oxygen at concentrations ranging from 10 μM to 1 mM with [H2O2] yields calculated for 100 MeV protons at conventional and FLASH dose rates of 0.286 Gy s−1 and 500 Gy s−1, respectively. Simulated chemical yield results were compared closely with data calculated using the Kinetiscope software which also employs the Gillespie algorithm. Main results. Validation results in the third test agreed with experimental data of similar dose rates and oxygen concentrations within one standard deviation, with a maximum of 1% difference for both conventional and FLASH dose rates. In conclusion, the new implementation of TOPAS-nBio for the homogeneous long time chemistry simulation was capable of recreating the chemical evolution of the reactive intermediates that follow water radiolysis. Significance. Thus, TOPAS-nBio provides a reliable all-in-one chemistry simulation of the physical, physico-chemical, non-homogeneous, and homogeneous chemistry and could be of use for the study of FLASH dose rate effects on radiation chemistry.

Application of Positive Matrix Factorization for Source Apportionment of Polycyclic Aromatic Hydrocarbons (PAH) in the Adriatic Sea, and the Evaluation of PAH-Related Carcinogenic Risks

Concentrations of polycyclic aromatic hydrocarbons (PAH) were studied in 36 sediment samples collected from 29 sites in the central Adriatic Sea. The total concentration of PAH showed high variability, ranging from 42.85 µg kg−1 in open sea sediments to 28,662 µg kg−1 in the sediments of Šibenik Bay. Unsubstituted, parent PAH were dominant PAH compounds in the entire area of Šibenik Bay and most of the stations in the coastal area. In Kaštela Bay, methyl PAH concentrations were higher than the concentrations of unsubstituted PAH, whereas in the sediments along the mid-Adriatic transect, similar concentrations of both PAH fractions were determined. PAH sources were investigated by applying the Positive Matrix Factorization software developed by the U.S. Environmental Protection Agency (USEPA). The results indicate the presence of four sources, two of which can be considered petrogenic and two pyrogenic. The contribution of the sources to the total concentration PAH at each station indicates the dominance of pyrogenic sources in Šibenik Bay and at most stations in the coastal area. In the sediments along the mid-Adriatic transversal, as well as in Kaštela Bay, PAHs originate mainly from petrogenic sources. The obtained results show that PMF can be a suitable tool for control of PAH pollution and thus, for the management of various activities in the Adriatic region. Seasonal differences between the contributions of sources in the Kaštela and Šibenik bays indicate that the contribution of traffic to the total concentration of PAH was higher during the tourist season. The carcinogenic risk of PAH determined by toxicity equivalent (TEQ) calculations showed an increased carcinogenic risk in the whole area of Šibenik Bay, regardless of the number of PAH compounds considered for the calculations. A low PAH-related carcinogenic risk was found for the rest of the study area.

Geochemical characterization evidence for the climate variability of the Mid-Pliocene warm period in the Nihewan Basin, North China

The mid-Pliocene warm period (mPWP) is regarded as an important geological analogue for predicting future climate characteristics and trends, due to its similar atmospheric CO2 concentration to that of the modern period. Within a chronologic framework provided by magnetostratigraphy, we analyzed the carbonate δ18O and geochemical element contents of 243 sediment samples from the NHA drill core in the Nihewan Basin, and combined them with grain size and magnetic susceptibility records. Our results revealed the paleoclimatic characteristics in the Nihewan Basin during 3.66–2.89 Ma for the first time. The interval of 3.58–3.31 Ma had the warmest and most stable climate during this interval, with low-amplitude fluctuations in all proxies, and with the following general characteristics: δ18O < −8‰, CIA > 40%, Rb/Sr > 0.3, ∑REE > 180 μg/g, and TiO2 > 0.7%). The climate remained warm overall during 3.31–3.10 Ma, but there were three pronounced cold events (at ∼3.30 Ma, ∼3.23 Ma, and ∼ 3.14 Ma) with the following general characteristics: δ18O > −7‰, CIA < 35%, Rb/Sr < 0.2, ∑REE < 160 μg/g, TiO2 < 0.6%). These events are correlative with increases in global ice volume, corresponding respectively to Marine Isotope Stage (MIS) M2, KM6, and KM2. The climate cooled substantially after 3.10 Ma, and most of the proxy index values were close to those during the three previous cold events. We ascribe this to increases in global ice volume and the strengthening of the East Asian winter monsoon.

Coagulation and proteolysis of high-protein milks in the gastric environment

Gastric digestion of 2 commercial ultrafiltered milks and milk enriched with skim milk powder (to simulate concentration by reverse osmosis) was investigated and compared with the digestion of nonconcentrated milk. Curd formation and proteolysis of high-protein milks in simulated gastric conditions were studied using oscillatory rheology, extrusion testing, and gel electrophoresis. The presence of pepsin in the gastric fluid triggered coagulation at pH >6 and the elastic modulus of gels from high-protein milks was ~5 times larger than the gel from reference milk. Despite similar protein concentrations, the coagulum from milk enriched with skim milk powder showed higher resistance to shear deformation than the coagula from ultrafiltered milks. The gel structure was also more heterogeneous. During digestion, the degradation of coagula from high-protein milks was slowed down compared with the coagulum from reference milk, and intact milk proteins were still detected after 120 min. Differences in the digestion patterns of coagula from high-protein milks were observed and were associated with the proportion of minerals bound to caseins and the denaturation rate of whey proteins.

Investigation on the interactions of resinous and asphaltenic synthetic oils and silicon oxide nanoparticles stabilized by different ionic liquid-based surfactants: interfacial tension and wettability alteration studies

The effects of the main components of crude oil, especially resin and asphaltene fractions, are essential concerns for efficient enhanced oil recovery (EOR) processes, especially during chemical injection processes. This importance comes from the nature of these two fractions which can act as surface active agents with undeniable effects on the used chemical for interfacial tension (IFT) reduction and wettability alteration. In this way, the effect of silicon oxide nanoparticles (SiO2-NPs) concomitant with two ionic liquids (ILs), namely 1-dodecyl-3-methyl imidazolium chloride ([C12mim][Cl]) and 1-octadecyl-3-methyl imidazolium chloride ([C18mim][Cl]), is investigated on the wettability alteration and IFT reduction using synthetic oils prepared by dissolving the extracted resin and asphaltene fractions with a concentration of 1–5 wt%. The measurements reveal that the effect of resin fraction is less than the asphaltene fraction for IFT reduction and wettability alteration. The sole presence of resin fraction reduces the IFT from 35.3 to 28.3 mN/m as the concentration is increased from 1 to 5 wt%, while a similar increase in the asphaltene fraction concentration reduces the IFT from 35.5 to 19.1 mN/m. Besides, the results reveal that the presence of [C12mim][Cl] in the range of 0–1000 ppm leads to a reduction in IFT from its maximum value of 35.3 to 0.81 mN/m, while in the case of [C18mim][Cl] with similar concentration variation, IFT is reduced from 35.3 to 0.7 which means the better effect of IL with longer chain length on the IFT reduction. Further analysis revealed that the effect of asphaltene fraction on the IFT is higher than resin fraction since the minimum IFT value was observed for [C18mim][Cl] with the value of 0.58 mN/m, while the contact angle (CA) values revealed revers effect for asphaltene fraction compared with the resin fraction. In general, regardless of the used IL, it seems that ILs leading to better wettability conditions which are crucial for EOR purposes and even better IFT values that can mobilize the trapped oil toward production points. Besides, further measurements revealed a positive effect of SiO2-NPs concomitant with the ILs to move the wettability toward the strongly water-wet condition with CA values of 29.2° and 28.3° for SiO2-NPs concentration of 1000 ppm and 1000 ppm of concentration for [C12mim][Cl] and [C18mim][Cl], respectively, for resinous synthetic oil (RSO) (5 wt%) while no meaningful effect regarding the SiO2-NPs presence at the different concentrations (100–2000 ppm) is found on the IFT reduction. A similar trend is observed for asphaltenic synthetic oil (5 wt%)/aqueous solution (SiO2-NPs with a concentration of 1000 ppm + ILs with a concentration of 1000 ppm) which reduces the CA to 26.3° and 37.8° for [C12mim][Cl] and [C18mim][Cl]), respectively.

Desilicated ZSM-5 zeolites for optimized xenon adsorption at very low pressure

Selective Xe adsorption on regenerable porous materials such as activated carbons, MOFs and zeolites has been found to be promising and economically attractive. The beneficial effect of silver doping of zeolites on Xe adsorption and Xe/Kr separation has been studied for numerous zeolites such as Ag-ZSM-5, Ag-mordenite and Ag-chabazite. Among them, we had shown that Ag-exchanged ZSM-5 is the most effective material for atmospheric Xe capture and selective separation at very low pressure (ppm level). A linear tendency was observed with a ratio of 2 mol of Ag for 1 mol of strong adsorption sites. Based on this observed tendency, we hypothesize that increasing the number of exchangeable sites by lowering the Si/Al ratio could be an approach to improve silver loading and selective xenon adsorption.The aim of this study is to evaluate the impact of desilication of ZSM-5 zeolites on decreasing their Si/Al ratio and increasing the concentration of sodium-exchanged sites and, possibly, strong silver-based adsorption sites. We have shown here that light desilication of this parent ZSM-5 makes it possible to significantly increase xenon uptake at very low pressure. The desilication creates a larger concentration of Al in the zeolite and thus enables a larger concentration of silver to be loaded. Yet we found that for severe desilication, decreased xenon uptake is observed, likely due to the facilitated formation of silver particles in which the core atoms are not accessible for xenon uptake. It appears that a concentration of 0.5 mmol g−1 of strong adsorption sites is a maximum achievable value for the Ag-ZSM-5 system. Surprisingly, we found that the parent ZSM-5 zeolite prepared by organic templating yields Ag-ZSM-5 with a similar concentration of strong adsorption sites but at higher silver loading. We could hypothesize that silanol defects present in commercial zeolites may be responsible for the stabilization of silver clusters.

Multilayer amorphous-crystalline high-entropy metal films

High-entropy alloys (HEA) are multi-element materials and contain at least five elements of similar concentration. HEA are, as a rule, single- phase thermodynamically stable substitutional solid solutions, mainly based on a body-centered cubic and face-centered cubic crystal lattice. Solid solution stabilization during the crystallization of a high-entropy alloy is provided by the interaction of a number of factors, namely, a high mixing entropy and low diffusion rate of components, and a low growth rate of crystallites from the melt. The purpose of this work was to obtain new knowledge about the structure and properties of high-entropy films synthesized on a metal substrate during deposition of a multi-element metal plasma in argon atmosphere. The plasma was formed as a result of independent plasma-assisted electric arc cathodes of the following metals: Ti, Al, Cu, Nb, Zr sputtering. As a result of the performed studies, the deposition mode was revealed, which allows the formation of films of various thicknesses of close to equiatomic composition. Transmission electron microscopy methods have established that the films are multilayer formations and have nanoscale amorphous-crystalline structure. Microhardness of the films significantly depends on the ratio of number of the forming elements and varies from 12 to 14 GPa, Young’s modulus – from 230 to 310 GPa. Crystallization of the films was carried out by irradiation with a pulsed electron beam. As a result of processing, a two-phase state is formed. The main phase is α-NbZrTiAl with a volume-centered cubic crystal lattice with a parameter of 0.32344 nm; the second phase of CuZr composition has a simple cubic lattice.

CAD Modeling method of the electrospun membrane under multifractal dimension optimization control.

Based on an analysis of large sample data, this paper improves the calculation method of the fractal dimension in an electrospun membrane and proposes a method to generate a computer-aided design (CAD) model of an electrospun membrane under the control of fractal dimension. Fifteen electrospun membrane samples of PMMA and PMMA/poly(vinylidene fluoride) (PVDF) materials were prepared under similar concentrations and voltage parameters, and 525 SEM images of the surface morphology with a resolution of 2560 × 1920 were taken as a dataset. The feature parameters, such as fiber diameter and direction, are extracted from the image. Second, based on the minimum value of the power law behavior, the pore perimeter data were preprocessed to calculate the fractal dimensions. A 2D model was reconstructed randomly based on the inverse transformation of the characteristic parameters. The genetic optimization algorithm adjusts the fiber arrangement to realize the control of characteristic parameters, such as the fractal dimension. Based on the 2D model, a long fiber network layer with a thickness consistent with the depth of the SEM shooting is generated in ABAQUS software. Finally, a solid CAD model of the electrospun membrane with realistic thickness was constructed by combining multiple fiber layers. The result shows that the improved fractal dimension exhibits multifractal characteristics and distinct sample differences, which are more similar to the experimental results. The proposed 2D modeling method of the long fiber network can allow the control of various characteristic parameters, including the fractal dimension, and can generate the required model quickly.

Early death (ED) in elderly acute promyelocytic leukemia (APL) patients treated with lower induction doses of all-trans retinoic acid (ATRA).

e19012 Background: With the introduction of the differentiating agent ATRA, APL has progressed from being one of the most life-threatening diseases to becoming the most curable subtype of adult AML. However, despite this advancement, death within the first 30 days of treatment amongst elderly patients remains a critical issue with ED rates reportedly as high as 20-50%. There is limited data looking at the elderly population due to often being excluded from clinical trials given age associated with being prominent negative risk factor. Pharmacokinetic studies comparing 25 mg/m2/day and 45 mg/m2/day doses in adult patients have shown similar peak concentrations and mean area under the curve. Notably, low dose ATRA has been offered in pediatric patients in order to reduce incidence of differentiation syndrome. Differentiation syndrome is a key contributor to ED in elderly APL patients causing treatment failure. We propose that lower doses of ATRA in the elderly reduces the impact differentiation syndrome has on induction mortality amongst elderly APL patients and leads to a lower rate of ED. Methods: Fifteen APL patients &gt; 60 years of age were treated. Thirteen received low doses of ATRA (equal to or less than 25mg/m2/day) and two received standard doses of ATRA (45mg/m2/day). Arsenic trioxide was also used in addition to cytoreductive agents, such as cytarabine, hydroxyurea, and idarubicin as needed during induction. Dose reductions and regimens were based on age, comorbidities, and overall clinical judgement. During the course of treatment, further dose reductions and pauses in therapy were made based on clinical course. Results: A total of 15 elderly APL patients were treated between May 2017 and November 2020 at cancer centers within Georgia and South Carolina. The age range was 65-88 years old with a median age of 71 years old. 9/15 (60%) were female and 2/15 (13%) were classified as high risk. 13/15 were Caucasian and the remaining 2 were African American. Amongst the 13 APL patients who received lower doses of ATRA, one ED was noted. This occurred in 81-year-old Caucasian male with low risk APL who had multiple significant comorbidities and elected to halt treatment and pursue hospice. Amongst the 2 low risk APL patients who received standard doses of ATRA, one ED was noted due to differentiation syndrome. This patient also had many significant comorbidities. Conclusions: The ED rate in elderly APL patients treated with low doses of ATRA during induction was noted to be 1/13 (7.7%) which is significantly lower than what has been reported in literature. [Table: see text]

Quantifying neuronal biomarkers in aqueous humor in individuals undergoing routine cataract surgery and correlating with age and cognition

AbstractBackgroundPlasma and cerebrospinal fluid (CSF) levels of neuronal biomarkers have been associated with Alzheimer’s disease (AD). The aqueous humor, which can be collected during routine cataract surgery, may have similar concentrations of neuronal biomarkers to CSF.MethodThis proof‐of‐concept study prospectively enrolled adults without a diagnosis of cognitive impairment undergoing cataract surgery at a tertiary academic medical center. Participants underwent Montreal Cognitive Assessment (MoCA blind version 7.1, “abnormal” &lt; 18) at the time of study enrollment. Aqueous samples were collected during cataract surgery through a surgical paracentesis. Samples were analyzed using an ultrasensitive single‐molecule array (SiMoA). Assessed biomarkers included phosphorylated tau (pTau)‐181, amyloid‐beta (Aß)‐42, Aß‐40, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP). Correlations were assessed using Spearman’s rank correlation (rho).ResultSixteen eyes of 16 patients (average MoCA 19.2) underwent aqueous sampling to assess pTau‐181 and 7 eyes of 7 separate patients (average MoCA 20.0) underwent aqueous and plasma sampling to assess Aß‐42, Aß‐40, NfL, and GFAP. Aqueous pTau‐181 increased with increasing age (rho = 0.67, p = 0.0046). No aqueous or plasma biomarkers were significantly correlated with MoCA scores (all p &gt; 0.05). Aqueous and plasma levels of biomarkers were not significantly correlated.ConclusionNeuronal biomarkers are measurable in aqueous humor using SiMoA analysis; however, these biomarkers did not significantly correlate with MoCA scores in a cognitively normal population. Further study in individuals with a known diagnosis of Alzheimer’s disease or mild cognitive impairment is indicated.

SARS-CoV-2 IgG Spike antibody levels and avidity in natural infection or following vaccination with mRNA-1273 or BNT162b2 vaccines

ABSTRACT Certain aspects of the immunogenicity and effectiveness of the messenger ribonucleic acid (mRNA) vaccines (mRNA-1273 and BNT162b2) developed in response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic are still uncharacterized. Serum or plasma samples from healthy donor recipients of either vaccine (BNT162b2 n = 53, mRNA-1273 n = 49; age 23–67), and individuals naturally infected with SARS-CoV-2 (n = 106; age 18–82) were collected 0–2 months post-infection or 1- and 4 months after second dose of vaccination. Anti-Spike antibody levels and avidity were measured via an enzyme-linked immunosorbent assay (ELISA). Overall, vaccination induced higher circulating anti-Spike protein immunoglobulin G (IgG) antibody levels and avidity compared to infection at similar time intervals. Both vaccines produced similar anti-Spike IgG concentrations at 1 month, while mRNA-1273 demonstrated significantly higher circulating antibody concentrations after 4 months. mRNA-1273 induced significantly higher avidity at month 1 compared to BNT162b2 across all age groups. However, the 23–34 age group was the only group to maintain statistical significance by 4 months. Male BNT162b2 recipients were approaching statistically significant lower anti-Spike IgG avidity compared to females by month 4. These findings demonstrate enhanced anti-Spike IgG levels and avidity following vaccination compared to natural infection. In addition, the mRNA-1273 vaccine induced higher antibody levels by 4 months compared to BNT162b2.

A compendium of bacterial and archaeal single-cell amplified genomes from oxygen deficient marine waters

Oxygen-deficient marine waters referred to as oxygen minimum zones (OMZs) or anoxic marine zones (AMZs) are common oceanographic features. They host both cosmopolitan and endemic microorganisms adapted to low oxygen conditions. Microbial metabolic interactions within OMZs and AMZs drive coupled biogeochemical cycles resulting in nitrogen loss and climate active trace gas production and consumption. Global warming is causing oxygen-deficient waters to expand and intensify. Therefore, studies focused on microbial communities inhabiting oxygen-deficient regions are necessary to both monitor and model the impacts of climate change on marine ecosystem functions and services. Here we present a compendium of 5,129 single-cell amplified genomes (SAGs) from marine environments encompassing representative OMZ and AMZ geochemical profiles. Of these, 3,570 SAGs have been sequenced to different levels of completion, providing a strain-resolved perspective on the genomic content and potential metabolic interactions within OMZ and AMZ microbiomes. Hierarchical clustering confirmed that samples from similar oxygen concentrations and geographic regions also had analogous taxonomic compositions, providing a coherent framework for comparative community analysis.

Covalent immobilization of tyrosinase on magnetic multi-walled carbon nanotubes for inhibitor screening.

The inhibition of tyrosinase is considered to be a common therapeutic strategy for some hyperpigmentation disorders. Screening of tyrosinase inhibitors is of great significance to the treatment of pigmentation diseases. In this study, tyrosinase was covalently immobilized on magnetic multi-walled carbon nanotubes for the first time, and the immobilized tyrosinase was applied for ligand fishing of tyrosinase inhibitors from complex medicinal plants. The immobilized tyrosinase was characterized by transmission electron microscopy, atomic force microscopy, Fourier-transform infrared spectroscopy, vibratingsamplemagnetometry, and thermo-gravimetric analyzer, which indicated that tyrosinase was immobilized onto magnetic multi-walled carbon nanotubes. The immobilized tyrosinase showed better thermal stability and reusability than the free one. The ligand was fished out from Radix Paeoniae Alba and identified as 1,2,3,4,6-pentagalloylglucose by ultra-performance liquid chromatography-quadrupole time-of-flight high-resolution mass spectrometry. 1,2,3,4,6-pentagalloylglucose was found to be a tyrosinase inhibitor with similar half maximal inhibitory concentration values of 57.13±0.91μM compared to kojic acid (41.96±0.78μM). This work not only established a new method for screening tyrosinase inhibitors but also holds considerable potential for exploring the new medicinal value of medicinal plants.

Comparison of lithium borate fusion and four-acid digestions for the determination of whole-rock chemistry – implications for lithogeochemistry and mineral exploration

Mining and exploration companies routinely use four-acid digestion (4AD), inductively coupled plasma, atomic emission spectra/mass spectrometry methods from commercial assay laboratories for analysing drill and rock samples for lithogeochemical assessment and resource reporting. This method is also known to exhibit lower recovery of elements hosted by resistate minerals. To assess the impact of lower recoveries on lithogeochemical interpretation, a suite of commonly used elements for lithogeochemical analysis (high-field-strength elements Zr, Hf, Nb, Ta, Ti and Eu and transition elements V and Sc) was analysed by 4AD and alkali fusion/acid digestion (AFAD). Lower recoveries in the 4AD relative to the AFAD were recorded for Zr, Hf, Nb, Ta, Ti and Eu; Sc and V reported similar concentrations for both decomposition methods. Despite the lower recoveries for Nb, Ta and Ti, element ratios were largely preserved with the 4AD method due to the recoveries covarying at a 1:1 ratio. A plot of Ti/Nb against V/Sc was found to be largely unaffected by decomposition method, producing similar compositional classifications between the two digestion methods. Use of the Eu anomaly (Eu/Eu*) to determine plagioclase fractionation was also found to be unaffected by decomposition method. In contrast, a standard Zr/Ti v. Nb/Y discrimination plot produced incorrect classifications with 4AD producing more mafic and alkaline classifications relative to the AFAD method. Magmatic fertility interpretations utilizing Zr/Hf were also found to be affected in the 4AD results due to the lower recovery of Zr relative to Hf. This resulted in a bias in the 4AD results and produced false-positive anomalism in fertility assessments. Multiple decomposition methods including combinations of acid and fusion methods are recommended for lithogeochemical analysis utilizing large regions of the periodic table. However, if only 4AD data are available, plots such as Ti/Nb v. V/Sc and Nb/Ta, which preserve their ratios, can be used for lithogeochemical classification. Supplementary material: Wholerock geochemical data and detailed methods are available at https://doi.org/10.6084/m9.figshare.c.6444444

Med Check: Zuranolone for Depression, Uzedy for Schizophrenia, and More

Back to table of contents Previous article Next article Med CheckFull AccessMed Check: Zuranolone for Depression, Uzedy for Schizophrenia, and MoreTerri D’ArrigoTerri D’ArrigoSearch for more papers by this authorPublished Online:25 May 2023https://doi.org/10.1176/appi.pn.2023.06.6.1Zuranolone Found to Quickly Reduce Major Depression SymptomsAdults with major depressive disorder may experience mood improvements within days of taking zuranolone (50 mg/day), a study published in May in The American Journal of Psychiatry (AJP) suggests. Zuranolone is an oral, once-daily neuroactive steroid that acts on GABA-A receptors.The phase 3 trial included patients who were between the ages of 18 and 64 years, had received a diagnosis of major depressive disorder, had been experiencing symptoms of depression for a least four weeks, and had a Hamilton Depression Rating Scale (HAM-D) score of at least 24 at screening and before they started taking the assigned study medication.The researchers randomized 534 participants to take either 14 days of treatment with zuranolone 50 mg/day or placebo in the evening. The researchers evaluated the participants 10 times over the course of the 42-day trial using such assessments as the HAM-D, the Columbia–Suicide Severity Rating Scale, the Clinical Global Impressions severity score, and more.Compared with patients who took placebo, those who took zuranolone demonstrated a statistically significant improvement in depressive symptoms at day 15. “Numerically greater improvements in depressive symptoms for zuranolone versus placebo were observed by day 3 (least squares mean change from baseline HAM-D score, −9.8 vs. −6.8), which were sustained at all visits throughout the treatment and follow-up periods of the study,” the researchers wrote.FDA Approves Uzedy for Treating SchizophreniaIn April the U.S. Food and Drug Administration (FDA) approved Uzedy (risperidone extended-release injectable suspension) for the treatment of schizophrenia in adults, Teva and MedinCell announced. Uzedy is a long-acting subcutaneous antipsychotic that may be given in one- or two-month dosing intervals.In the phase 3 RISE trial, 544 patients aged 13 to 65 years with schizophrenia were randomized to receive a subcutaneous injection of Uzedy (either once per month or once every two months) or placebo. Those who received Uzedy once per month or once every two months had a reduction of 80.0% and 62.5% in the risk to relapse compared with those who received placebo, respectively. Results were similar in the phase 3 SHINE trial, which examined the long-term safety of the drug for up to 56 weeks in 336 patients aged 13 to 65 years with schizophrenia.A companion survey of participants in the SHINE trial found that 89% of patients and 92% of health professionals rated administration of Uzedy as easy when asked how easy or difficult it was to receive or administer the medication in its current form. Further, 70% of patients reported that Uzedy provided a better injection experience than their previous long-acting injectables (LAIs).Abilify Asimtufii Approved for Schizophrenia, Bipolar I TreatmentAbilify Asimtufii (aripiprazole extended release injectable suspension) has been approved by the FDA for the treatment of schizophrenia in adults and as a monotherapy treatment of bipolar I disorder in adults, Otsuka and Lundbeck announced in April. Abilify Asimtufii is a long-acting subcutaneous atypical antipsychotic that may be given every two months.The approval was based on safety and efficacy data from trials of Abilify Maintena, which is for once monthly dosing, and on the results of a phase 1-2 study. In the phase 1-2 study, 266 adults with schizophrenia or bipolar I disorder were randomly assigned to receive either Abilify Asimtufii 960 mg every 56 days, for a total of four injections or Abilify Maintena 400 mg administered every 28 days for a total of eight injections. Treatment with Abilify Asimtufii resulted in similar aripiprazole plasma concentrations and efficacy to Abilify Maintena. ■ ISSUES NewArchived

Impact of dry sourdough based on a fermented chickpea starter on quality characteristics and shelf life of gluten-free bread

The impact of drying of rice-chickpea flour sourdough (SD) made by a fermented chickpea extract (FCE) starter on rice flour-corn starch gluten-free (GF) batter and bread physicochemical properties were explored; FCE was prepared by submerged fermentation (37 °C × 15 h) of ground chickpeas. A liquid (freshly made) and two dried FCE-sourdoughs, dehydrated (air heating at 30 °C) or lyophilized, as well as a control formulation (without FCE-SD) were prepared at 80, 90, 100 and 110% (flour mixture basis) added water levels. Firmness, consistency, cohesiveness, and viscosity index of the batters, as evaluated by back extrusion testing, decreased by increasing the added water level in the formulation and increased by inclusion of the dehydrated sourdough preparation (p < 0.05). The lyophilized and liquid sourdough-containing breads exhibited the lowest pH and the highest specific volume, while dehydrated sourdough bread exhibited higher pH than the rest of the SD-containing breads and similar specific volume to that of control. Nevertheless, both dry FCE-SD preparations increased the crust redness and all FCE-SD breads had similar concentrations of butyric/isobutyric acids indicating a butyric fermentation during FCE preparation. Texture profile analysis revealed that both liquid and lyophilized sourdough improved crumb texture and retarded the bread staling process compared to control and dehydrated sourdough formulations (p < 0.05). The former products thus gained higher preference by a non-trained sensory evaluation panel. Overall, the lyophilized FCE-SD showed analogous potential with the liquid sourdough to improve quality attributes and shelf life of gluten-free breads, whereas the dehydrated FCE-SD (mild heating) did not fully retain its functionality.

Bromine and Chlorine Disinfection of Cryptosporidium parvum Oocysts, Bacillus atrophaeus Spores, and MS2 Coliphage in Water.

Conventional water treatment practices utilizing chemical disinfection, especially chlorination, are considered generally effective in producing microbiologically safe drinking water. However, protozoan pathogens such as oocysts of Cryptosporidium parvum are very resistant to chlorine, which has led to consideration of alternative disinfectants for their control. Free bromine, HOBr, has not been evaluated extensively as an alternative halogen disinfectant for inactivation of Cryptosporidium parvum in drinking water or reclaimed water for non-potable uses. Bromine is a versatile disinfectant consisting of different chemical forms with persistent microbicidal efficacy under varied water quality conditions and is effective against a range of waterborne microbes of health concern. The objectives of this study are to (1) compare the efficacy of free bromine to free chlorine at similar concentrations (as milligrams per liter) for disinfection of Cryptosporidium parvum oocysts, Bacillus atrophaeus spores, and MS2 coliphage in a model buffered water and (2) evaluate the kinetics of inactivation of these microorganisms using appropriate disinfection models. Overall, at a target concentration of ∼5 mg/L, bromine averaged 0.6 log (73.8%) reductions of C. parvum oocyst infectivity after 300 min (CT: 1166 min·mg/L) and produced up to a 0.8 log reduction disinfectant activity. An ∼5.0 mg/L chlorine dose increased oocyst infectivity by only 0.4 log (64%) after 300 min (CT: 895 min·mg/L). Bacillus atrophaeus spores and MS2 coliphage treated with bromine and chlorine were reduced by 4 log10 (99.99%) for both disinfectants over the duration of the experiments.

Application of a novel PhysioCell apparatus for biopredictive dissolution tests of oral immediate release formulations – A case study workflow for in vitro-in vivo predictions

Biorelevant dissolution tests of oral solid dosage forms open the gate to valid in vitro-in vivo predictions (IVIVP). A recently developed apparatus, PhysioCell, allows mimicking the fluid flow and pressure waves occurring in the human fasted stomach. In this work, we used the PhysioCell to perform IVIVP for vortioxetine immediate-release (IR) tablets: the originator (Brintellix) and generic product candidates (VORTIO). The dissolved drug was monitored in the gastric (StressCell) and intestinal (Collection Vessel) compartments that contained biorelevant media. Simulated intermittent gastric stress at 15 min and “housekeeping wave” at 30 min increased the dissolution of Brintellix formulations only. A mechanistic model that best described the observations involved the first-order tablet disintegration with a stress-induced enhancement for Brintellix, dissolution of solid particles in the StressCell, and drug transfer to the Collection Vessel. Then, a semi-mechanistic pharmacokinetic model with dissolution parameters as inputs simulated vortioxetine plasma concentrations in healthy volunteers after single and multiple dosing of Brintellix. Despite different dissolution characteristics, VORTIO provided similar concentration profiles to the originator. In conclusion, PhysioCell dissolution tests, combined with semi-mechanistic IVIVP, can be successfully used to develop IR dosage forms exhibiting gastric stress-related effects.

Occurrence and tissue distribution of 33 legacy and novel per- and polyfluoroalkyl substances (PFASs) in Baikal seals (Phoca sibirica)

Per- and polyfluoroalkyl substances (PFASs) are bioaccumulative and associated with adverse effects in both wildlife and humans. The occurrence of 33 PFASs was assessed in the plasma, liver, blubber, and brain of 18 Baikal seals (Phoca sibirica) (16 pups and 2 adult females) from Lake Baikal, Russia (in 2011). Of the 33 congeners analysed for: perfluorooctanosulfonic acid (PFOS), 7 long chain perfluoroalkyl carboxylic acids (C8–C14 PFCAs) and 1 branched PFCA (perfluoro-3,7-dimethyloctanoic acid; P37DMOA) were most frequently detected. The PFASs in plasma and liver with the highest median concentrations were legacy congeners: perfluoroundecanoic acid (PFUnA; plasma: 11.2 ng/g w.w.; liver: 7.36 ng/g w.w.), PFOS (plasma: 8.67 ng/g w.w.; liver: 9.86 ng/g w.w.), perfluorodecanoic acid (PFDA; plasma: 5.13 ng/g w.w.; liver: 6.69 ng/g w.w.), perfluorononanoic acid (PFNA; plasma: 4.65 ng/g w.w.; liver: 5.83 ng/g w.w.) and perfluorotridecanoic acid (PFTriDA; plasma: 4.29 ng/g w.w.; liver: 2.55 ng/g w.w.). PFASs were detected in the brain of Baikal seals, indicating that PFASs cross through the blood–brain barrier. In blubber, the majority of PFASs were detected in low abundance and concentrations. In contrast to legacy PFASs, novel congeners (e.g., Gen X) were either detected infrequently or not found in Baikal seals. The worldwide occurrence of PFASs in pinnipeds was compared and lower median concentrations of PFOS were observed in Baikal seals relative to other pinnipeds. Conversely, similar concentrations of long chain PFCAs were found in Baikal seals compared to other pinnipeds. Furthermore, human exposure was assessed by estimating weekly intakes (EWI) of PFASs through Baikal seal consumption. Although PFASs concentrations were comparatively low relative to other pinnipeds, consumption of Baikal seal could exceed current regulatory guidelines.