Time-dependent Changes Research Articles

Investigation into the Time-Dependent Characteristics of Stress and Deformation of Weak Surrounding Rock and Lining Structure in Operational Tunnels: Model Test

During the long-term operation of tunnels, surrounding rock undergoes creep effects under environmental loads, resulting in changes in the aging evolution model of stress and deformation in surrounding rock and lining, which affects the long-term operational safety of the tunnel. Therefore, using the model test device for time-dependent characteristics of stress and deformation of weak surrounding rock and lining structure in operational tunnels, taking into account the influence of tunnel burial depth and lateral pressure coefficient of surrounding rock, a model test on time-dependent characteristics of stress and deformation in weak surrounding rock and lining structure was conducted, and the stress and deformation time-varying curves at key locations of surrounding rock and lining were obtained. The time characteristics of surrounding rock stress, the contact force between surrounding rock and lining, internal force, and displacement of lining structure were analyzed. Research findings indicate that the stress of surrounding rock, the internal force and displacement of lining structure, and the contact force between surrounding rock and lining all increase and tend to be stable over time under constant load. This implies that the stress and deformation of the surrounding rock and lining structure exhibit time-dependent changes. With changes in burial depth and lateral pressure coefficient, significant variations are observed in the various indicators of stress and deformation in the surrounding rock and lining structure, indicating both time-dependent and long-term characteristics in terms of stress and deformation. The research results provide basic data support for the study of the time-dependent characteristics of stress and deformation between weak surrounding rock and lining structures in operational tunnels and can provide theoretical and technical guidance for the long-term service status discrimination and disaster prevention and control of operational tunnels.

Metabolomics Analysis of Rabbit Plasma after Ocular Exposure to Vapors of Sulfur Mustard.

Sulfur mustard (SM) is a highly potent alkylating vesicant agent and remains a relevant threat to both civilians and military personnel. The eyes are the most sensitive organ after airborne SM exposure, causing ocular injuries with no antidote or specific therapeutics available. In order to identify relevant biomarkers and to obtain a deeper understanding of the underlying biochemical events, we performed an untargeted metabolomics analysis using liquid chromatography coupled to high-resolution mass spectrometry of plasma samples from New Zealand white rabbits ocularly exposed to vapors of SM. Metabolic profiles (332 unique metabolites) from SM-exposed (n = 16) and unexposed rabbits (n = 8) were compared at different time intervals from 1 to 28 days. The observed time-dependent changes in metabolic profiles highlighted the profound dysregulation of the sulfur amino acids, the phenylalanine, the tyrosine and tryptophan pathway, and the polyamine and purine biosynthesis, which could reflect antioxidant and anti-inflammatory activities. Taurine and 3,4-dihydroxy-phenylalanine (Dopa) seem to be specifically related to SM exposure and correspond well with the different phases of ocular damage, while the dysregulation of adenosine, polyamines, and acylcarnitines might be related to ocular neovascularization. Additionally, neither cysteine, N-acetylcysteine, or guanine SM adducts were detected in the plasma of exposed rabbits at any time point. Overall, our study provides an unprecedented view of the plasma metabolic changes post-SM ocular exposure, which may open up the development of potential new treatment strategies.

Evolution of an Extended Pathogenicity Motif in VP2 of Infectious Pancreatic Necrosis Virus Isolates from Farmed Rainbow Trout in Turkey.

Infectious pancreatic necrosis virus (IPNV) causes economic losses with a highly variable mortality rate worldwide, especially in rainbow trout. The virus has a double-stranded bi-partite RNA genome designated segment A and B. New complete genome sequences of nine rainbow trout isolates from Turkey were determined and subjected to phylogenetic analysis, identifying all as genotype 5 (serotype Sp). A time-dependent change in the extended pathogenicity motif of VP2 from P217T221A247 (PTA) to PTE P217T221E247 over a period of 10 years was identified. A wider analysis of 99 IPNV sequences from Turkey and Iran revealed the emergence of the motif PTE from 2007 to 2017, inducing significant morbidity in fry by 2013. In fact, displacement of the PTA motif, by the PTE motif in IPNV isolates appeared to be connected to a production peak of rainbow trout in 2013. An additional CAI analysis provided more evidence, indicating that rainbow trout culture in Turkey has an influence on the evolution of IPNV.

Ibogaine Induces Cardiotoxic Necrosis in Rats-The Role of Redox Processes.

Ibogaine is an organic indole alkaloid that is used in alternative medicine to combat addiction. Numerous cases of life-threatening complications and sudden deaths associated with ibogaine use have been reported, and it has been hypothesized that the adverse effects are related to ibogaine's tendency to induce cardiac arrhythmias. Considering that the bioavailability of ibogaine and its primary metabolite noribogaine is two to three times higher in female rats than in male rats, we here investigated the effect of a single oral dose (1 or 20 mg/kg) of ibogaine on cardiac histopathology and oxidative/antioxidant balance. Our results show that ibogaine induced dose-dependent cardiotoxic necrosis 6 and 24 h after treatment and that this necrosis was not a consequence of inflammation. In addition, no consistent dose- and time-dependent changes in antioxidant defense or indicators of oxidative damage were observed. The results of this study may contribute to a better understanding of ibogaine-induced cardiotoxicity, which is one of the main side effects of ibogaine use in humans and is often fatal. Nevertheless, based on this experiment, it is not possible to draw a definitive conclusion regarding the role of redox processes or oxidative stress in the occurrence of cardiotoxic necrosis after ibogaine administration.

Eicosapentaenoic acid and Arachidonic acid Protection Against Left Ventricle Pathology: the Multi-Ethnic Study of Atherosclerosis.

We have shown that ω3 polyunsaturated fatty acids (PUFAs) reduce risk for heart failure, regardless of ejection fraction status. Ventricular remodeling and reduced ventricular performance precede overt hear failure, however there is little insight into how PUFAs contribute to maladaptive signaling over time. PUFAs are agonists for regulatory activity at g-protein coupled receptors such as Ffar4, and downstream as substrates for monooxygenases (e.g lipoxygenase, cytochrome p450, or cyclooxygenase (COX)) which mediate intracellular adaptive signaling. Plasma phospholipid PUFA abundance at Exam 1 as mass percent EPA, DHA, and arachidonic acid (AA) from the Multi-Ethnic Study of Atherosclerosis (MESA) were evaluated using pathway modeling to determine the association with time-dependent changes in left ventricular (LV) mass (LVM), end-diastolic LV volume (EDV), and end-systolic volume (ESV) measured by cardiac MRI at Exams 1 and 5. Ejection fraction (EF) and mass:volume (MV) were calculated posteriorly from the first three. 2,877 subjects had available MRI data. Participants with low AA and EPA had accelerated age-dependent declines in LVM. Males with low AA and EPA also had accelerated declines in EDV, but among females there was no PUFA association with EDV declines and exam 5 EDV status was positively associated with AA. Both sexes had nearly the same positive association of AA with changes in ESV. Plasma phospholipid AA and EPA are prospectively associated with indices of heart remodeling, including ventricular remodeling and performance. Combined AA and EPA scarcity was associated with the most accelerated age-related changes and exam 5 status, while the greatest benefits were found among participants with both PUFAs. This suggests that both PUFAs are required for optimal slowing of age-related declines in ventricular function.

Modulation of Lipid Dynamics in the β-Amyloid Aggregates Induced Membrane Fragmentation.

Nonspecific membrane disruption is considered a plausible mechanism for the cytotoxicity induced by β-amyloid (Aβ) aggregates. In scenarios of high local Aβ concentrations, a two-step membrane fragmentation model has been proposed. Initially, membrane-embedded Aβ oligomeric aggregates form, followed by membrane fragmentation. However, the key molecular-level interactions between Aβ oligomeric aggregates and lipids that drive the second-stage membrane fragmentation remain unclear. This study monitors the time-dependent changes in lipid dynamics and water accessibility of model liposomes during Aβ-induced membrane fragmentation. Our results indicate that lipid dynamics on the nanosecond to microsecond time scale undergo rapid acceleration upon initial incubation with membrane-incorporated Aβ oligomeric aggregates, followed by a slow deceleration process. Concurrently, lipid headgroups become less accessible to water. Both observations suggest a carpet-like mechanism of membrane disruption for the Aβ-induced membrane fragmentation process.

Use of Syzygium aromaticum L. Fermented Plant Extract to Enhance Antioxidant Potential: Fermentation Kinetics

The concept of our research is related to the use of stems from S. aromaticum L. in the fermentation process in order to obtain new cosmetic raw materials with high antioxidant potential that are safe for human fibroblasts (HDFs) and keratinocytes (HaCaTs). This evaluation involves treating cell lines with different concentrations of fermented extracts to establish a noncytotoxic dose range. The focus was on evaluating antioxidant activity (AA), total polyphenol content (TPC), and lactic acid efficiency (LAe). For this purpose, the most favourable technological parameters of the fermentation process of stems were determined, including the type of microorganisms, initial sugar content, plant raw material content, and fermentation time. In the present study, lactic acid was obtained with maximum efficiency by stem fermentation in the presence of lactic acid bacteria (LAB) and molasses as a source of six-carbon sugars. In addition, fermentation kinetics was investigated, the essence of which was to identify the technological parameters that allow the highest values of the main functions describing the process (AA, TPC LAe). Two kinetic models were used to determine the kinetics of process function changes during fermentation. The most favourable fermentation conditions for maximum antioxidant activity (26.88 mmol Tx/L ± 0.19), total polyphenol content (5.96 mmol GA/L ± 0.19), and lactic acid efficiency (88% ± 1) were: type of microorganism L. rhamnosus MI-0272, initial sugar content 3.20%, plant raw material content 6.40%, and a fermentation time of 9 days. The values of chelating activity (ChA), AA, and TPC in the fermented stems increased more than two-fold compared to the non-fermented extracts. Reducing activity (RA) and LAe increased to 46.22 mmol Fe3+/L ± 0.29 and 88% ± 1, respectively. Of the kinetic models adopted, follow-up reaction equations and first-order equations best described the time-dependent changes taking place. This study shows that the process function values of AA and LAe are dependent on the LAB strain and the content of the plant material, and the rate of change of TPC may largely depend on the forms of phenolic compounds formed during fermentation.

Oligomeric amyloid-β targeted contrast agent for MRI evaluation of Alzheimer's disease mouse models.

Oligomeric amyloid beta (oAβ) is a toxic factor that acts in the early stage of Alzheimer's disease (AD) and may initiate the pathologic cascade. Therefore, detecting oAβ has a crucial role in the early diagnosis, monitoring, and treatment of AD. The purpose of this study was to evaluate MRI signal changes in different mouse models and the time-dependent signal changes using our novel gadolinium (Gd)-dodecane tetraacetic acid (DOTA)- ob5 aptamer contrast agent. We developed an MRI contrast agent by conjugating Gd-DOTA-DNA aptamer called ob5 to evaluate its ability to detect oAβ deposits in the brain using MRI. A total of 10 control mice, 9 3xTg AD mice, and 11 APP/PS/Tau AD mice were included in this study, with the age of each model being 16 or 36 weeks. A T1-weighted image was acquired at the time points before (0min) and after injection of the contrast agent at 5, 10, 15, 20, and 25min. The analyses were performed to compare MRI signal differences among the three groups and the time-dependent signal differences in different mouse models. Both 3xTg AD and APP/PS/Tau AD mouse models had higher signal enhancement than control mice at all scan-time points after injection of our contrast media, especially in bilateral hippocampal areas. In particular, all Tg AD mouse models aged 16 weeks showed a higher contrast enhancement than those aged 36 weeks. For 3xTg AD and APP/PS/Tau AD groups, the signal enhancement was significantly different among the five time points (0min, 5min, 10min, 15min, 20min, and 25min) in multiple ROI areas, typically in the bilateral hippocampus, left thalamus, and left amygdala. The findings of this study suggest that the expression of the contrast agent in different AD models demonstrates its translational flexibility across different species. The signal enhancement peaked around 15-20min after injection of the contrast agent. Therefore, our novel contrast agent targeting oAβ has the potential ability to diagnose early AD and monitor the progression of AD.

The Factors Affecting the Stability of IOP Homeostasis.

Shear-induced nitric oxide (NO) production by Schlemm's canal (SC) endothelial cells provides a fast, IOP-sensitive feedback signal that normally contributes to IOP homeostasis. Our goal was to analyze the response of this homeostatic system under constant flow perfusion (as occurs in vivo) vs. constant pressure perfusion (as typical for laboratory perfusions). A mathematical model of aqueous humor dynamics, including shear-mediated NO signaling, was formulated and analyzed for stability. The model includes Goldmann's equation, accounting for proximal and distal outflow resistance, and describes how elevated IOP causes narrowing of SC lumen that increases the shear stress on SC cells. Elevated shear stress stimulates NO production, which acts to reduce outflow resistance and relax trabecular meshwork cells to decrease trabecular meshwork stiffness, affecting the SC luminal caliber. During constant flow perfusion, the outflow system is typically stable, returning to baseline IOP after a perturbation. In contrast, during constant pressure perfusion, the outflow system can become unstable and exhibit a time-dependent change in outflow resistance that diverges from baseline. The stability of shear mediated IOP homeostasis is predicted to differ critically between constant flow vs. constant pressure perfusion. Because outflow facility is typically measured at a constant pressure in the laboratory, this instability may contribute to the characteristic time-dependent increase in outflow facility, known as washout, observed in many nonhuman species. Studies of IOP homeostasis should consider how the outflow system may respond differently under constant pressure vs. constant flow perfusion.

Effect of oral tryptamines on the gut microbiome of rats—a preliminary study

Background Psilocybin and related tryptamines have come into the spotlight in recent years as potential therapeutics for depression. Research on the mechanisms of these effects has historically focused on the direct effects of these drugs on neural processes. However, in addition to such neural effects, alterations in peripheral physiology may also contribute to their therapeutic effects. In particular, substantial support exists for a gut microbiome-mediated pathway for the antidepressant efficacy of other drug classes, but no prior studies have determined the effects of tryptamines on microbiota. Methods To address this gap, in this preliminary study, male Long Evans rats were treated with varying dosages of oral psilocybin (0.2 or 2 mg/kg), norbaeocystin (0.25 or 2.52 mg/kg), or vehicle and their fecal samples were collected 1 week and 3 weeks after exposure for microbiome analysis using integrated 16S ribosomal DNA sequencing to determine gut microbiome composition. Results We found that although treatment with neither psilocybin nor norbaeocystin significantly affected overall microbiome diversity, it did cause significant dose- and time-dependent changes in bacterial abundance at the phylum level, including increases in Verrucomicrobia and Actinobacteria, and decreases in Proteobacteria. Conclusion and Implications These preliminary findings support the idea that psilocybin and other tryptamines may act on the gut microbiome in a dose- and time-dependent manner, potentially identifying a novel peripheral mechanism for their antidepressant activity. The results from this preliminary study also suggest that norbaeocystin may warrant further investigation as a potential antidepressant, given the similarity of its effects to psilocybin.

Water sorption modeling and monolayer of biological and food materials

Despite water molecules are strongly hydrogen bonding to hydrophilic solids, the Brunauer-Emmet-Teller (BET) and Guggenheim-Anderson-de Boer (GAB) surface adsorption models have been widely accepted to describe water sorption properties of biological and food materials. These mathematically quite similar models use parameters which include a theoretical ‘monolayer’ value and one or two other parameters which describe ‘surface affinity’ in thermodynamic terms as heat of sorption. A high surface affinity indicates a strong surface binding of water molecules and preferential monolayer adsorption prior to multilayer sorption. Conversely, biological materials are water plasticized and suffer physicochemical changes at various stages of water sorption. Dynamic water sorption measurements often show regions where time-dependent changes in material characteristics, such as viscous flow and crystallization, may occur as a result of the glass transition. The two or three parameters of the BET and GAB models, respectively, are useful in the analysis of water sorption characteristics of individual substances, although the existence of a monolayer particularly in multicomponent materials may not be justified. Fitting the models to experimental data may occur rather for empirical than theoretical reasons.

Characterization of contact evolution on sand grain surfaces and their time-dependent contact properties based on Greenwood and Williamson model

This paper focuses on the microscopic roughness of silica sand grain, and its morphological evolution (contact maturing) under a constant load. The surface topology with rich texture is obtained by Atomic Force Microscopy and various roughness parameters are investigated by statistical approaches. The surface profiles in the same contact region before and after being subjected to sustained loading are both measured to identify time-dependent morphological changes on the contact surface. The two congruent surface topologies, initial and mature surfaces, not only show the delayed fracturing of contact asperities, but also present quantitative differences in the spatial roughness parameters over time. These differences are intensified with consideration of upper profiles only, indicating that asperities with higher elevations are susceptible to the contact maturing process. With the geometric information obtained from the same region at two different measurement times, the Greenwood and Williamson asperity model of rough surface is used to estimate contact proximity, real area of the load-bearing contacts, and the number of contact spots. The model results of the post-loaded surface incorporated with true surface profiles show an increased number of contact points as well as the true contact area under constant loading. It is expected that subcritical fracturing of contact asperities leads to closer proximity of contact entities when loaded by prolonged loading, resulting in firmer and stiffer intergranular contact. This may very well be the reason for time effects in sand assemblies.

Cholecystokinin receptor type A are involved in the circadian rhythm of the mouse retina

The retina is the only organ projecting external light to the suprachiasmatic nucleus. Cholecystokinin receptor type A (Cckar/Cckar) is one of the essential factors for light reception in retinal cells. As there was a lack of literature on the matter, we aimed to elucidate the cause of the time-dependent phase change in clock gene expression. We found that Cckar mRNA expression in retinal cells exhibited diurnal variations. The rhythm of expression of the clock gene Per1/Per2 in retinal cells was altered in Cckar−/− mice. The light sensitivity of retinal cells was evaluated in wild-type mice, which showed c-Fos was activated in the ganglion cell layer more than in the inner granular layer. This increase in the number of c-Fos-positive cells was suppressed by lorglumide, a Cckar antagonist. Treatment of rat retina primary cells with lorglumide suppressed Per2 transcription, which was altered in a time-dependent manner relative to the Per2 expression. Light irradiation studies in Cckar−/− mice did not exhibit an increase in Period expression in the suprachiasmatic nucleus. These results indicate that Cckar is among the factors that regulate the cycle of clock genes on the retina. Cckar knockout attenuates the light responsiveness of suprachiasmatic nucleus and reduces the expression amplitude of Period genes in the retina. Thus, Cckar may contribute to entrainment of the light environment and maintenance of the expression cycle of Period gene, which is one of the core clock genes.

Time dependent changes in the compression behavior of single wheat kernels upon tempering

Time dependent changes in the compression behavior of single wheat kernels upon tempering

Effect of Holder Pasteurization, Mode of Delivery, and Infant's Gender on Fatty Acid Composition of Donor Breast Milk.

Breast milk (BM) plays a crucial role in providing essential fatty acids (FA) and energy for the growing infant. When the mother's own BM is not available, nutritional recommendations suggest donor milk (DM) in clinical and home practices. BM was collected from a variety of donor mothers in different lactation stages. Holder pasteurization (HoP) eliminates potential contaminants to ensure safety. FA content of BM samples from the Breast Milk Collection Center of Pécs, Hungary, were analyzed before and after HoP. HoP decreases the level of C6:0, C8:0, C14:1n-5c, C18:1n-9c, C18:3n-6c, C18:3n-3c, and C20:4n-6c in BM, while C14:0, C16:0, C18:1n-9t, C22:0, C22:1n-9c, C24:0, C24:1n-9c, and C22:6n-3c were found in elevated concentration after HoP. We did not detect time-dependent concentration changes in FAs in the first year of lactation. BM produced for girl infants contains higher C20:2n-6c levels. In the BM of mothers who delivered via cesarean section, C12:0, C15:0, C16:0, C17:0, C18:0, C18:1n-9t, C22:1n-9c levels were higher, while C18:2n-6c, C22:0, C24:0, and C22:6n-3c concentrations were lower compared to mothers who gave birth spontaneously. FAs in BM are constant during the first year of lactation. Although HoP modifies the concentration of different FAs, pasteurized DM provides essential FAs to the developing infant. Current data providing information about the FA profile of BM gives origination to supplementation guidelines.

Longitudinal changes in the volume of residual lung lobes after lobectomy for lung cancer: a retrospective cohort study.

It is unclear how the residual lobe volume changes over time after lobectomy. This study aims to clarify the temporal patterns of volume changes in each remaining lung lobe post-lobectomy. A retrospective review was conducted on patients who underwent lobectomy for lung cancer at Yueyang Central Hospital from January to December 2021. Lung CT images were reconstructed in three dimensions to calculate the volumes of each lung lobe preoperatively and at 1, 6, and 12months postoperatively. A total of 182 patients were included. Postoperatively, the median total lung volume change rates relative to preoperative values were -20.1%, -9.3%, and -5.9% at 1, 6, and 12months, respectively. Except for the right middle lobe in patients who underwent right upper lobectomy, the volumes of individual lung lobes exceeded preoperative values. The volume growth of the lung on the side of the resection was significantly more than that of the lung on the opposite side. For left lobectomy patients, the right lower lobe's volume change rate exceeded that of the right upper and middle lobes. Among right lobectomy patients, the left lower lobe and the relatively inferior lobe of right lung had higher volume change rates than the superior one. Right middle lobe change rate was more in patients with right lower lobectomy than right upper lobectomy. Six months postoperatively, FEV1% and right middle lobectomy were positively correlated with the overall volume change rate. One year postoperatively, only age was negatively correlated with the overall volume change rate. 75 patients had pulmonary function tests. Postoperative FEV1 change linearly correlated with 1-year lung volume change rate, but not with theoretical total lung volume change rate or segmental method calculated FEV1 change. Time-dependent compensatory volume changes occur in remaining lung lobe post-lobectomy, with stronger compensation observed in the relatively inferior lobe compared to the superior one(s). Preoperative lung function and age may affect compensation level.

Time-dependent activation and repolarization changes following left bundle branch area pacing versus conventional biventricular pacing in patients with dyssynchronous heart failure

Abstract Background Cardiac Resynchronization Therapy (CRT) is the standard treatment for patients with dyssynchronous heart failure. Despite the effectiveness of conventional biventricular pacing (BiVP), 6-16% of patients develop ventricular tachyarrhythmias (VTAs) within a year of implantation. The relationship between BiVP and the development of VTAs is still under debate. During BiVP, the left-sided epicardium-to-endocardium activation creates a non-physiological activation and hence a non-physiological repolarization, which might trigger VTAs. A novel alternative treatment option to BiVP that on the contrary induces a left ventricular endocardium-to-epicardium activation, is left bundle branch area pacing (LBBAP). We hypothesized that LBBAP leads to a more homogenous repolarization than conventional BiVP. Purpose To compare time-dependent activation and repolarization changes in patients with dyssynchronous heart failure receiving LBBAP versus BiVP. Methods Patients eligible for CRT who underwent LBBAP (n=21) or BiVP (n=94) were retrospectively included. Standard 12-lead electrocardiograms obtained prior to implantation [baseline], shortly following implantation (0-2 days, [acute phase]), and after prolonged pacing during follow-up (31-180 days, [chronic phase]) were analyzed. QRS duration and QRS area were calculated through reconstruction of the vectorcardiogram and further analyzed together with corrected QT (QTc) and corrected Tpeak-Tend (Tp-e,c) intervals using a semi-automatic approach in MATLAB. Differences between LBBAP and BiVP patients were determined using the Mann-Whitney U-test. Time-dependent changes within groups were determined using the Wilcoxon signed-rank tests. Significance was defined as a p-value ≤0.05. Results (see figure): Compared to baseline, QRS duration and QRS area decreased significantly during the acute phase (both p < 0.01) and stabilized during chronic pacing for both BiVP and LBBAP patients. Differences in QRS duration or QRS area between LBBAP and BiVP were not significant at any of the time points. In the acute phase, BiVP resulted in a temporary and significant prolongation of both QTc and Tp-e,c compared to baseline (both p < 0.01). However, there was a subsequent shortening observed between the acute and chronic phases for both QTc and Tp-e,c (both p < 0.01). Compared to baseline, LBBAP acutely shortened Tp-e,c (p = 0.02) and tended to shorten QTc. During chronic pacing, LBBAP shortened QTc and Tp-e,c compared to baseline (p = 0.01 and p < 0.01). The decreases in QTc and Tp-e,c were larger in LBBAP than in BiVP patients in the acute and chronic pacing phase (all p <0.01). Conclusion CRT induces activation changes in both BiVP and LBBAP patients to a comparable extent. While BiVP leads to an acute increase in repolarization dispersions, LBBAP reduces markers of repolarization dispersion compared to baseline. The diminished dispersion of repolarization might contribute to an antiarrhythmic effect with LBBAP.

#340 Time dependent changes in the treatment of relapsing Minimal Change Disease – a multicenter cohort study

Abstract Background and Aims Prednisolone monotherapy is the most used initial immunosuppressive treatment for nephrotic syndrome in adults with Minimal Change Disease (MCD) but choice of treatment in relapsing MCD is not as well described. With the introduction of new drugs and increased concern relating to the adverse events of prednisolone, treatment might have changed over time. The aim of this study is to describe changes in daily clinical practice of relapsing MCD within the last 35 years. Method A multicenter, retrospective analysis of adult patients with biopsy proven MCD from 13 hospitals from 1987-2022 in Denmark and the Netherlands. Patients were identified from the pathology registers. Information on treatment and clinical outcomes was retrieved from health records. Relapse is defined when the nephrologist found indication to restart an immunosuppressive treatment or increase the ongoing immunosuppression in patients in partial or complete remission. Results We included 167 Dutch and 72 Danish patients (n = 239) with MCD. Most patients (n = 205, 86%) were initially treated with prednisolone monotherapy. Overall, 93% (n = 220) gained remission and 56% (n = 123) of those who went into remission had one or more relapse with 68% of these occurring in the first year after remission. At the time of relapse, 89% were in complete remission and 11% were in partial remission. At first relapse, prednisolone monotherapy was the most prescribed treatment both before and after 2010 (69% and 45%, respectively), while the use of CNI tripled after 2010 (p = 0.002) (10% to 32%). At second relapse, prescription of CNI after 2010 showed a five-fold increase compared with before 2010 (49% vs 10%, respectively) while the use of prednisolone monotherapy was halved (50% to 24%). The use of cyclophosphamide decreased by two-thirds (32% to 10%) after 2010. Before 2010, 54% of patients received prednisolone monotherapy for their third to 14th relapse, but after 2010 this decreased to 26%. The use of rituximab and CNI both increased and after 2010 these were both prescribed to about one third of patients at third to 14th relapse. The use of cyclophosphamide decreased from 30% to 2% comparing before and after 2010. Rituximab was only used after 2010, and more frequently with the number of relapses (6% at first relapse and 36% at third to 14th relapse). Regardless of the choice of treatment the rates of remission were high. Conclusion The treatment of relapses has changed over time with a reduced use of prednisolone monotherapy and cyclophosphamide and increased use of CNI and rituximab.

Materials Characterization of Stereolithography 3D Printed Polymer to Develop a Self-Driven Microfluidic Device for Bioanalytical Applications.

Stereolithography (SLA) 3D printing is a rapid prototyping technique and reproducible manufacturing platform, which makes it a useful tool to develop advanced microfluidic devices for bioanalytical applications. However, limited information exists regarding the physical, chemical, and biological properties of the photocured polymers printed with SLA. This study demonstrates the characterization of a commercially available SLA 3D printed polymer to evaluate the potential presence of any time-dependent changes in material properties that may affect its ability to produce functional, capillary-action microfluidic devices. The printed polymer was analyzed with Fourier transform infrared-attenuated total reflectance, contact angle measurements, tensile test, impact test, scanning electron microscopy, and fluid flow analysis. Polymer biocompatibility was assessed with propidium iodide flow cytometry and an MTT assay for cell viability. The material characterization and biocompatibility results were then implemented to design and fabricate a self-driven capillary action microfluidic device for future use as a bioanalytical assay. This study demonstrates temporally stable mechanical properties and biocompatibility of the SLA polymer. However, surface characterization through contact angle measurements shows the polymer's wettability changes over time which indicates there is a limited postprinting period when the polymer can be used for capillary-based fluid flow. Overall, this study demonstrates the feasibility of implementing SLA as a high-throughput manufacturing method for capillary action microfluidic devices.

Effective electro-removal of glyphosate and glufosinate from aqueous solutions via capacitive deionization

Both glyphosate (Gly) and glufosinate (Glu) are commonly used as herbicides, which has caused rising concerns about their impact on the environment and human health. Capacitive deionization (CDI) is a newly developed energy-efficient water treatment technique that effectively removes inorganic and small organic molecules under the electric field. In this work, a carbon electrode-based CDI device was used in the electro-removal of Gly and Glu in an aqueous solution with an excellent removal rate of up to 95 % under various conditions. Furthermore, maximum electro-removal rates of 1.99 μmol∙cm−2∙min−1 for Gly and 1.33 μmol∙cm−2∙min−1 for Glu were also achieved, except with super-high removal rates of 100 % (Gly) and 97.6 % (Glu) in actual Gly and Glu-containing lake water, demonstrating the feasibility of the CDI device in real aqueous systems. In-situ electro-oxidation that occurred during the electrosorption process was confirmed by analyzing the three-electrode system-based electrochemical behaviors and tracing the time-dependent changes of the suspicious degradation products. Transition state (TS) search and molecular dynamics (MD) simulations were employed to study the microscopic processes theoretically, revealing the degradation pathways and thermodynamic characteristics of Gly and Glu. This research presents a novel avenue for the decomposition and removal of herbicides from water, leveraging the inherent side reactions of CDI systems as an advantage to decontaminate organic pollutants.