Low Activity Research Articles

Effect of a virtual walking and exercise-based intervention on muscle strength and activation in people with incomplete spinal cord injury

This study aims to assess the effect of combining virtual walking (VW) therapy with a physical exercise (PE) program compared to PE alone on lower limb strength and muscle activation in people with incomplete spinal cord injury (iSCI). 38 participants performed 3 sessions/week during 6 weeks of Experimental Intervention (EI): VW and PE; or Control intervention (CI): Placebo-VW and PE. Strength and muscle activation of main lower limb muscles were assessed. EI group exhibited a general strength increase after intervention (T2), (16.31–34.72 N), and maintained this improvement up to 1-month-follow-up (T3) for hip abduction and extension movements. The CI group only showed improvements in hip abduction and extension movements (18.34 (7.13) N and 19.98 (9.60) N, respectively). EI group also exhibited an increase of activation in all agonistic muscles in T2 (36.02–20.24 µV), except gastrocnemius. Gastrocnemius and rectus femoris activation as antagonistic decreased during dorsal flexion (− 14.28 (5.61) µV) and hip extension (− 14.78 [6.11] µV), respectively. CI group only showed an activation increase of agonistic muscles of hip abduction and extension (22.16 (9.80) µV and 28.82 (9.14) µV, respectively), without changes in antagonistic activation. VW could enhance the PE effects regarding muscle strength and activation in people with iSCI.Registration number: NCT04809987.

Epidemiological status, development trends, and risk factors of disability-adjusted life years due to diabetic kidney disease: A systematic analysis of Global Burden of Disease Study 2021.

Approximately 40% of individuals with diabetes worldwide are at risk of developing diabetic kidney disease (DKD), which is not only the leading cause of kidney failure, but also significantly increases the risk of cardiovascular disease, causing significant societal health and financial burdens. This study aimed to describe the burden of DKD and explore its cross-country epidemiological status, predict development trends, and assess its risk factors and sociodemographic transitions. Based on the Global Burden of Diseases (GBD) Study 2021, data on DKD due to type 1diabetes (DKD-T1DM) and type 2diabetes (DKD-T2DM) were analyzed by sex, age, year, and location. Numbers and age-standardized rates were used to compare the disease burden between DKD-T1DM and DKD-T2DM among locations. Decomposition analysis was used to assess the potential drivers. Locally weighted scatter plot smoothing and Frontier analysis were used to estimate sociodemographic transitions of DKD disability-adjusted life years (DALYs). The DALYs due to DKD increased markedly from 1990 to 2021, with a 74.0% (from 2,228,000 to 3,876,000) and 173.6% (from 4,123,000 to 11,279,000) increase for DKD-T1DM and DKD-T2DM, respectively. In 2030, the estimated DALYs for DKD-T1DM surpassed 4.4million, with that of DKD-T2DM exceeding 14.6million. Notably, middle-sociodemographic index (SDI) quintile was responsible for the most significant DALYs. Decomposition analysis revealed that population growth and aging were major drivers for the increased DKD DALYs in most GBD regions. Interestingly, the most pronounced effect of positive DALYs change from 1990 to 2021 was presented in high-SDI quintile, while in low-SDI quintile, DALYs for DKD-T1DM and DKD-T2DM presented a decreasing trend over the past years. Frontiers analysis revealed that there was a negative association between SDI quintiles and age-standardized DALY rates (ASDRs) in DKD-T1DM and DKD-T2DM. Countries with middle-SDI shouldered disproportionately high DKD burden. Kidney dysfunction (nearly 100% for DKD-T1DM and DKD-T2DM), high fasting plasma glucose (70.8% for DKD-T1DM and 87.4% for DKD-T2DM), and non-optimal temperatures (low and high, 5.0% for DKD-T1DM and 5.1% for DKD-T2DM) were common risk factors for age-standardized DALYs in T1DM-DKD and T2DM-DKD. There were other specific risk factors for DKD-T2DM such as high body mass index (38.2%), high systolic blood pressure (10.2%), dietary risks (17.8%), low physical activity (6.2%), lead exposure (1.2%), and other environmental risks. DKD markedly increased and varied significantly across regions, contributing to a substantial disease burden, especially in middle-SDI countries. The rise in DKD is primarily driven by population growth, aging, and key risk factors such as high fasting plasma glucose and kidney dysfunction, with projections suggesting continued escalation of the burden by 2030.

Discriminating neural ensemble patterns through dendritic computations in randomly connected feedforward networks.

Co-active or temporally ordered neural ensembles are a signature of salient sensory, motor, and cognitive events. Local convergence of such patterned activity as synaptic clusters on dendrites could help single neurons harness the potential of dendritic nonlinearities to decode neural activity patterns. We combined theory and simulations to assess the likelihood of whether projections from neural ensembles could converge onto synaptic clusters even in networks with random connectivity. Using rat hippocampal and cortical network statistics, we show that clustered convergence of axons from three to four different co-active ensembles is likely even in randomly connected networks, leading to representation of arbitrary input combinations in at least 10 target neurons in a 100,000 population. In the presence of larger ensembles, spatiotemporally ordered convergence of three to five axons from temporally ordered ensembles is also likely. These active clusters result in higher neuronal activation in the presence of strong dendritic nonlinearities and low background activity. We mathematically and computationally demonstrate a tight interplay between network connectivity, spatiotemporal scales of subcellular electrical and chemical mechanisms, dendritic nonlinearities, and uncorrelated background activity. We suggest that dendritic clustered and sequence computation is pervasive, but its expression as somatic selectivity requires confluence of physiology, background activity, and connectomics.

Abscisic acid receptors functionally converge across 500 million years of land plant evolution.

Abscisic acid (ABA) functions as a central regulator of dehydration responses in land plants. As such, ABA signaling was pivotal in facilitating the colonization of terrestrial habitats. The conserved ABA signal transduction module consists of 2C-type protein phosphatases (PP2Cs) and their ABA-triggered inhibitors, PYRABACTIN RESISTANCE 1-like proteins (PYLs). Recent evidence indicates that ABA perception emerged from a latent signaling pathway involving a constitutively PP2C-inhibiting PYL homolog. Consequently, ancestral ABA receptors exerted high background signaling, limiting the dynamic range of ABA-dependent signaling. In angiosperms, ABA receptor families are characteristically large and diverse and include a clade-specific subgroup whose members form homodimers, thereby assuming strict ABA dependency. Here, we show that ABA receptors in mosses originate from an independent expansion, giving rise to three subfamilies. Yeast two-hybrid and invitro PP2C-inhibition assays indicate that moss PYLs feature low basal activities. However, size-exclusion chromatography and additional lines of evidence suggest that moss PYLs are predominantly monomeric. A combination of mutational analysis with biochemical and physiological assays reveals that the reduced basal activities of moss PYLs are achieved through unique sets of amino acid variations. Finally, introducing causal variations to dimeric receptors dramatically compromises their ABA responsiveness, suggesting that the two evolutionary trajectories are mutually exclusive. Hence, mosses appear to have evolved a parallel mechanism to mitigate the ancestrally high background signal of the core ABA perception apparatus. This convergence highlights the shared imperative of expanding the amplitude of a central, highly adaptive signaling pathway.

Discriminating neural ensemble patterns through dendritic computations in randomly connected feedforward networks

Co-active or temporally ordered neural ensembles are a signature of salient sensory, motor, and cognitive events. Local convergence of such patterned activity as synaptic clusters on dendrites could help single neurons harness the potential of dendritic nonlinearities to decode neural activity patterns. We combined theory and simulations to assess the likelihood of whether projections from neural ensembles could converge onto synaptic clusters even in networks with random connectivity. Using rat hippocampal and cortical network statistics, we show that clustered convergence of axons from three to four different co-active ensembles is likely even in randomly connected networks, leading to representation of arbitrary input combinations in at least 10 target neurons in a 100,000 population. In the presence of larger ensembles, spatiotemporally ordered convergence of three to five axons from temporally ordered ensembles is also likely. These active clusters result in higher neuronal activation in the presence of strong dendritic nonlinearities and low background activity. We mathematically and computationally demonstrate a tight interplay between network connectivity, spatiotemporal scales of subcellular electrical and chemical mechanisms, dendritic nonlinearities, and uncorrelated background activity. We suggest that dendritic clustered and sequence computation is pervasive, but its expression as somatic selectivity requires confluence of physiology, background activity, and connectomics.

Burden and attributable risk factors of non-communicable diseases and subtypes in 204 countries and territories, 1990-2021: a systematic analysis for the global burden of disease study 2021.

Understanding based on up-to-date data on the burden of non-communicable diseases (NCDs) is limited, especially regarding how subtypes contribute to the overall NCD burden and the attributable risk factors across locations and subtypes. We aimed to report the global, regional, and national burden of NCDs, subtypes, and attributable risk factors in 2021, and trends from 1990 to 2021 by age, sex, and socio-demographic index (SDI). We used data from the Global Burden of Disease Study 2021 to estimate the prevalence, deaths, and disability-adjusted life years (DALYs) for NCDs and subtypes, along with attributable risk factors. Estimates were presented with 95% uncertainty intervals (UI). Relationships between NCD DALYs and SDI across regions and countries were estimated using smoothing splines models. In 2021, NCDs accounted for 7.3 trillion global cases, 43.8 million deaths, and 1.73 billion DALYs. Global age-standardized rates showed NCD prevalence at 91034.0, deaths at 529.7, and DALYs at 20783.0 per 100000 population, with changes of -0.1%,-27.9%, and -19.4% from 1990, respectively. Subtypes with the highest age-standardized DALYs were cardiovascular disease (5056), neoplasms (2954), and other NCDs (1913 per 100000 population), with diabetes and kidney diseases increasing by 25.6% since 1990. Regionally, Oceania had the highest age-standardized DALYs (28782.0) in 2021, while Southern Sub-Saharan Africa saw the largest increase (+8.0%) since 1990. Nationally, Nauru reported the highest age-standardized DALYs (42754.3), with Lesotho experiencing the largest increase since 1990 (+38.4%). Cardiovascular diseases had the highest age-standardized DALYs among subtypes across 16 of 21 regions and 159 of 204 countries. Key risk factors globally were high systolic blood pressure (contributing to 12.8% of age-standardized DALYs), dietary risks (10.0%), and tobacco usage (9.9%), with the most significant increase in high body-mass index (+57.8%). High systolic blood pressure was the biggest attributable risk factor for NCDs in 9 regions and 101 countries. Age-standardized data reveal higher NCD prevalence in women and greater mortality and DALYs in men, with DALYs spiking post-45 for both sexes. Men have higher DALYs attributed to most risk factors, excluding those from unsafe sex, intimate partner violence, low physical activity, and high body-mass index. Age-standardized DALYs of NCDs generally decline with the SDI spectrum. Dominant NCD risk factors follow gender-age and SDI-based trajectories. Despite declining age-standardized prevalence, death rates, and DALYs for NCDs, they remain a major health issue. Emphasis on managing cardiovascular diseases, cancers, diabetes, kidney diseases, and mental disorders is essential. The burden of NCDs is more severe in low-SDI countries and among males. Prevention efforts should prioritize blood pressure control, dietary improvements, and tobacco reduction, tailoring interventions according to gender-age-based and SDI-development-based trajectories of dominant risk factors.

Light chain Split Luciferase assay implicates pathological NOTCH3 thiol reactivity in inherited cerebral small vessel disease.

Stereotyped mutations in NOTCH3 drive CADASIL, the leading inherited cause of stroke and vascular dementia. The vast majority of these mutations result in alterations in the number of cysteines in the gene product. However, non-cysteine altering pathogenic mutations have also been identified, making it challenging to discriminate pathogenic from benign NOTCH3 sequence variants. Here, we present a method for quantitative assessment of NOTCH3 mutants, the light chain split luciferase (LSL) assay. In LSL, NOTCH3 mutant fragments, cloned between a split luciferase open reading frame, are transfected into cells, producing secreted luciferase activity that is dependent on the normal structure of NOTCH3. Insertion of point mutants that cause CADASIL results in significantly lower activity. Using a panel of 47 sequences, we determined the sensitivity and specificity of LSL for pathogenic NOTCH3 mutation discrimination to be 100% and 93%. LSL was also modestly successful in differentiated pathogenic proteins responsible for Marfan's disease and Stiff Skin Syndrome. Two additional parameters from the LSL analysis (TCEP rescue of activity and secretion index), were also shown to be useful in characterizing NOTCH3 mutants. We show that the spacing and primary sequence of the light chain module is an important component of the LSL assay, as a single light chain cysteine is critical for pathogenic sequence discrimination. Furthermore, we show that activity of CADASIL mutant reporters is amplified by application of cysteine-reactive iodoacetamide, suggesting that LSL may be deployed to screen for novel compounds that suppress pathogenic conformations of NOTCH3.

Associations between physical activity and heart disease among middle-aged and older Chinese adults

ObjectiveTo quantify the risk of heart diseases (HD) and determine the relationship between physical activity (PA) dimensions and HD among Chinese middle-aged and older individuals.MethodsUsing data from the China Health and Retirement Longitudinal Study (CHARLS, 2018), 16,927 participants were included in this study. Multivariate logistic regression was performed to determine the association between HD risk and PA dimensions, including volume, intensity, frequency, and duration. Restricted cubic spline analysis was conducted to assess the dose-response relationship between PA and HD risk.ResultsCompared to the least active participants, a low risk of HD was significantly associated with a higher PA volume. With regards to frequency, a lower HD risk was associated with performing vigorous PA except for 3–5 days/week. The frequency and duration of light as well as moderate PA had no significant associations with HD risk after adjusted by using covariates. A non-linear association was also noted, with increased PA being associated with decreased HD risk, with steeper reductions in HD risk at low activity levels than at high activity levels. There was a non-linear association between PA and HD risk in participants in male and aged older than 65 years.ConclusionsAn inverse non-linear dose-response association was detected between the total volume of PA and HD risk. As PA increased to 4,000 METs-min/week, HD risk in the overall population decreased by approximately 26%, while further increases in PA did not produce any further marked reduction in the risk. A vigorous intensity of PA was associated with a reduced risk of HD and is strongly recommended.

Fasting plasma methylglyoxal concentrations are associated with higher numbers of circulating intermediate and non-classical monocytes but with lower activation of intermediate monocytes: the Maastricht Study.

Elevated methylglyoxal (MGO) levels and altered immune cell responses are observed in diabetes. MGO is thought to modulate immune cell activation. The current study investigated whether fasting or post-glucose-load plasma MGO concentrations are associated with circulating immune cell counts and activation in a large cohort study. 696 participants of The Maastricht Study (age 60.3 ± 8.4 years, 51.9% women) underwent an oral glucose tolerance test (OGTT). Fasting and post-OGTT plasma MGO concentrations were measured using mass spectrometry. Numbers and activation of circulating immune cells at fasting state were quantified using flow cytometry. Activation scores were calculated by averaging individual marker z-scores for neutrophils (CD11b, CD11c, CD16) and classical, intermediate, and non-classical monocytes (CD11b, CD11c, CX3XR1, HLA-DR). Associations were analysed using multiple linear regression adjusted for potential confounders. Stratified analyses were performed for glucose metabolism status for associations between plasma MGO levels and immune cell counts. Higher fasting plasma MGO concentrations were significantly associated with higher numbers of intermediate (β = 0.09 [95%CI 0.02; 0.17]) and non-classical monocytes (0.08 [0.002; 0.15]), but with lower activation scores for the intermediate monocytes (-0.14 [-0.22; -0.06]). Stratified analyses showed that positive associations between fasting plasma MGO levels and numbers of intermediate and non-classical monocytes appear only in participants with type 2 diabetes. Post-OGTT plasma MGO concentrations were not consistently associated with immune cells counts or activation. Higher fasting plasma MGO concentrations are associated with higher intermediate and non-classical monocyte counts but with lower activation of intermediate monocytes.

Electrochemical insights into the direct dissolution of impure sphalerites and their partial oxidation in an acidic environment

This study examined the electrodissolution mechanism of five impure sphalerite samples, which differ significantly in purity levels, along with their partially oxidized counterparts in a 0.5 M H2SO4. Partially oxidized samples were prepared through an incomplete leaching of sphalerite using H2SO4 with Fe2(SO4)3.H2O as an oxidizing agent. The original sphalerite samples and the partially oxidized samples were referred to as SP and POS samples, respectively. Analyses using XRD, SEM, Raman spectroscopy, and electrochemical techniques suggested presence of elemental sulfur and a metal-deficient layer on the surface of the POS samples. Cyclic voltammetry revealed that the sample with the highest iron content exhibited the highest electrochemical response, while the sphalerite with the highest lead concentration had the lowest activity. Electrochemical impedance spectroscopy (EIS) studies showed that impedance values were higher in the POS samples compared to the PS samples, indicating a correlation within the passivation phenomenon. In conclusion, these findings suggested that the sphalerite dissolution process is primarily controlled by charge transfer and kinetic polarization. This understanding can lead to the development of more selective and sustainable extraction methods and improving the overall economic viability of zinc hydrometallurgical operations.

Selective Activation of the Infraspinatus During External Rotation Exercises in Participants with Rounded Shoulder Posture: Comparison of Three Common Exercises and Muscle Architecture-Based Exercise

Background and Objectives: The infraspinatus muscle is critical for shoulder stability and external rotation, yet achieving selective activation during exercises remains challenging. This study explores the effectiveness of a novel muscle architecture-based position (MABER) compared to traditional exercises in individuals with rounded shoulder posture. Materials and Methods: This prospective, cross-sectional study evaluated the selective activation of the infraspinatus during external rotation exercises in participants with rounded shoulder posture. Thirty-two participants (17 males and 15 females) were recruited. Electromyographic (EMG) activity of the middle trapezius, posterior deltoid, and infraspinatus muscles in the dominant limb was recorded during four exercise positions: standing external rotation (SER), side-lying external rotation (SDER), scapular plane external rotation (SPER), and MABER. Results: MABER produced the highest infraspinatus activity (p < 0.001), while the lowest activity was observed during SPER (p < 0.001). The SER position generated higher posterior deltoid activity compared to other positions (p < 0.001). The SDER position demonstrated the highest infraspinatus/posterior deltoid activity ratio (p < 0.001). Conclusions: The MABER position can be used as an effective exercise to strengthen the infraspinatus muscle. This study contributes to the literature by comparing MABER with traditional exercises and highlights its potential benefits for individuals with rounded shoulder posture.

The Effect of Strength Training Targeting Medial Thigh Muscles on Neuromuscular and Biomechanical Risk Factors for Anterior Cruciate Ligament Injury: A Randomized Controlled Trial

BackgroundKnee valgus loading is thought to be an important contributor to noncontact anterior cruciate ligament (ACL) injuries, but the effects of training programs focusing on decreasing knee valgus loading on lower extremity biomechanics with respect to ACL injury risk remain unclear. Thus, this study aimed to examine the effect of strength training designed to strengthen the medial thigh muscles on lower extremity joint kinematics, kinetics and muscle activity during single-leg landing.MethodsA total of 35 healthy participants randomly conducted either exercises targeting medial thigh muscles (intervention group) or exercises that did not target specific lower extremity muscles (control group). Three-dimensional hip, knee, and ankle kinematic/kinetic data and muscle activity for lower extremity muscles were obtained during single-leg landing. Two-way analyses of variance were conducted for each dependent variable to determine the effect of 8-week of strength training targeting medial thigh muscles.ResultsThe intervention group showed decreased knee varus-valgus excursion (P = 0.009), peak valgus moment (P = 0.032), and peak hip internal rotation moment (P = 0.009) but increased gluteus medius activity in the precontact phase (P = 0.012) and vastus medialis-to-vastus lateralis (VM: VL) coactivation ratio in the postcontact phase (P = 0.043). The change in coronal plane knee excursion was negatively correlated with both the change in gluteus medius activity (R2 = 0.321, P = 0.014) and the change in VM: VL coactivation ratio (R2 = 0.276, P = 0.025).ConclusionsStrength training targeting medial thigh muscles can modify the biomechanics associated with ACL injuries; thus, this intervention might be considered when designing ACL injury prevention programs to reduce dynamic knee valgus during sports-related tasks.

A case of high tibial osteotomy in a patient with psoriatic arthritis.

Traditionally, patients with rheumatic diseases, such as rheumatoid arthritis (RA), were considered off-limits for joint-sparing surgery. In the present study, we report bilateral knee joints of psoriatic arthritis coexisting with osteoarthritis, with good, albeit short-term, results. 62-year-old woman was treated for psoriatic arthritis with a biologic (adalimumab). The Disease Activity in Psoriatic Arthritis index was 7.24, indicating low disease activity. She had been suffering from bilateral knee pain for some time and was treated conservatively by her local doctor, but the pain persisted, and she came to visit us. At the initial visit, tenderness in the medial joint line of both knees and hydrarthrosis in the right knee were observed. Radiographs at the time of the initial examination showed medial type osteoarthritis (Kellgren-Lawrence classification IV) in both knees. First, interlocking closed wedge high tibial osteotomy (CWHTO) was performed on the right knee. This was followed 1 year later by right knee implant removal and interlocking CWHTO on the left knee, and implant removal on the left knee 1 year after that. The joint range of motion improved in both knees preoperatively and postoperatively, and the change in the Knee Injury and Osteoarthritis Outcome Score total from preoperative to 1 year postoperatively was from 26.0 to 59.4 points for the right knee and from 48.6 points to 70.5 points for the left knee, with improvement in both knees. Considering the patient's background, we considered high tibial osteotomy if the disease activity was controlled. However, if the disease worsens in the future, joint destruction may occur, so careful follow-up is necessary.

Survival in patients with CKD 3–5 after 12 months of exercise training – a post-hoc analysis of the RENEXC trial

BackgroundPhysical performance is low and physical activity declines in people with chronic kidney disease (CKD). Both factors are associated with decreased survival. Our hypothesis was that improved physical performance after 12 months of exercise training would result in better survival in patients with CKD stages 3 to 5 not on kidney replacement therapy (KRT). Our aims in this study were to investigate the survival effects of (1) baseline physical performance and (2) physical performance after 12 months of exercise training.MethodsThis is a post-hoc analysis of the RENEXC trial, a randomized controlled study comparing 12 months of strength- and balance training both in combination with aerobic training. Both groups improved physical performance with no between group differences. Patients were categorized into five groups: improved ≥ 5%, unchanged, deteriorated ≥ 5%, non-completers, missing data. Univariate and multivariate Cox regression analyses were used and adjusted for age, sex, comorbidity, time on dialysis and time with a kidney transplant.Results151 patients participated, mean age 66 ± 14 years, 65% men, eGFR 22.5 ± 8.2 ml/min/1.73m2, average follow-up 60 months.Multivariate analysesThe baseline 6-minute walk test (6MWT) (HR 0.996; 95% CI [0.993–0.998]) and 30-second sit-to-stand (30s-STS) (HR 0.94 CI [0.89–1.0]) were positively associated with survival. After 12 months of exercise improved handgrip strength (HGS) right (HR 2.66; 95% CI [1.07–6.59]) was associated with better survival compared with deterioration. Improvement compared with noncompletion was associated with better survival (6MWT (HR 2.88; 95% CI [1.4–5.88]), HGS right (HR 4.44; 95% CI [1.79–10.98]), functional reach (HR 3.69; 95% CI [1.82–7.48]), isometric quadriceps strength right (HR 2.86; 95% CI [1.43–5.72]), 30s-STS (HR 3.44; 95% CI [1.66–7.11]).ConclusionBaseline walking distance, muscular strength and endurance in the legs were independently associated with survival in people with CKD stages 3–5 without KRT. After completing 12 months of exercise training improved walking distance, muscular strength and endurance, and balance were positively associated with survival, compared with noncompleters. Better physical performance at baseline and the ability to complete 12 months of exercise training conferred survival benefits. There are probably several factors affecting better survival. These factors require elucidation in future studies.Trial registrationClinicalTrials.gov NCT02041156. Registration date 20,240,107.

Selective alkaline leaching of vanadium, chromium and aluminium from fly ash residue

ABSTRACT Vanadium, chromium and aluminium have many applications in several fields. For instance, vanadium alloys are considered a promising candidate for low activation structural material for fusion reactors and aerospace applications while aluminium is used in the reactor tanks of research reactors, core grids, neutron beam tubes, etc. Recently, nuclear fuel vendors have been researching and testing fuel with the outside of the zirconium alloy cladding coated with a thin layer of chromium. Fly ash resulting from power plants contains appreciable amounts of those metals. To minimise the environmental impact due to land disposal of fly ash, the removal of vanadium, chromium and aluminium was investigated using an alkaline leaching process, followed by a second step of metal recovery from leachates involving extraction, stripping and precipitation. Sodium hydroxide was chosen as a selective leaching agent for the metals under study. The best conditions for recovery were optimised based on the results obtained involving the study of different factors affecting the process. At room temperature and solid/liquid ratio of 1/10, the respective leaching percentages of V, Al and Cr reached maximum values of 70%, 48% and 36% after 2 h of continuous leaching. Combining extraction, stripping and precipitation methods enabled the recovery percents of V, Cr and Al to be 96.2%, 90.5% and 84.0%, respectively.

Influence of Alumina and Silica Supports on the Performance of Nickel Catalysts for Methane Partial Oxidation

Rising greenhouse gas concentrations are causing climatic change that threatens ecosystem sustainability. This study investigated the impact of silica incorporation into alumina-supported nickel catalysts for the partial oxidation of methane (POM), a crucial process for syngas production. The investigation also focuses on the impact of using different calcination temperatures. The catalysts were synthesized using the impregnation method and structurally characterized with BET, TPR, FTIR, UV, XRD, TGA, Raman, and TEM analysis techniques. These characterization techniques revealed that increasing the silica content reduced the surface area and weakened the interaction between nickel and the support. The calcination temperature significantly influenced catalyst properties, affecting pore structure, nickel reducibility, and the formation of nickel aluminates and silicates. Activity tests of synthesized catalysts were performed in a packed-bed reactor at 600 °C with a 24 mL/min gas flow rate. The catalyst composition of 5Ni/10Si + 90Al demonstrated the highest activity, achieving optimal performance at lower calcination temperatures. This catalyst generates a greater concentration of active sites, primarily due to nickel oxide (NiO), which creates these sites through both mild and strong interactions. The degree of graphitization is notably lowest for the 5Ni/10Si + 90Al composition. This catalyst achieved an impressive hydrogen yield of approximately 54%, with an H2/CO ratio of 3.4 over a streaming period of up to 240 min. When the silica loading exceeds 10 wt.%, the interaction between the metal and the support weakens, resulting in a significant decrease in surface area and, subsequently, lower catalytic activity. The 5Ni/10Si + 90Al catalyst, which was prepared with calcination temperatures above 500 °C, has very few active sites during the Partial Oxidation of Methane (POM) reaction at a reaction temperature of 600 °C. This catalyst also exhibits a high degree of crystallinity, which leads to reduced exposure of the active sites. As a result, incorporating higher weight percentages of silica into the 5Ni/xSi + (100 − x) Al catalysts results in decreased activity. When the silica loading exceeds 10 wt.%, the interaction between the metal and the support weakens, resulting in a significant decrease in surface area and, subsequently, lower catalytic activity. The 5Ni/10Si + 90Al catalyst, which was prepared with calcination temperatures above 500 °C, has very few active sites during the POM reaction at a reaction temperature of 600 °C. This catalyst also exhibits a high degree of crystallinity, which leads to reduced exposure of the active sites. As a result, incorporating higher wt.% of silica into the 5Ni/xSi + (100 − x) Al catalysts results in decreased activity. These findings highlight the complex interplay between silica content, calcination temperature, and catalyst properties, significantly influencing catalytic performance in POM.

P0694 Clinical response trajectories identify distinct subpopulations of ulcerative colitis patients and are linked to disease outcome across different therapy classes. Patient level analysis of 2378 participants from 6 randomized controlled trials in moderate-severe UC representing 8 different mechanisms of action.

Abstract Background In randomized placebo-controlled trials (RCTs) for ulcerative colitis (UC), remission rates below 40% (wk52). Landmark analyses using independent endpoints provide approvable estimands for overall efficacy but overlook individual variability.Notably, a subset of patients achieves deeper remission levels. Post hoc analysis of the SELECTION trial (filgotinib) demonstrated that treating daily PRO2 scores (stool frequency, rectal bleeding) as time-series data reveals discrete subpopulations.Patients with in the faster response trajectory groups achieve wk52 endpoints at higher rates including disease control. Methods In a cross-industry/academic collaboration, data from 2,378 UC responders from RCTs of adalimumab, brepocitinib, etrasimod, etrolizumab, ozanimod, ritlecitinib, ustekinumab, and vedolizumab in UC were analyzed for PRO2-based treatment response trajectories using Group-based trajectory modeling (GBTM). Using random-effects logistic regression, trajectory groups were linked to wk 12 and 52 outcomes, including comprehensive disease control (CDC), defined as achieving remission in endoscopy, symptoms, lab markers, and histology. Meta-analyses of baseline demographics/disease characteristics examined predictors of trajectory group affiliation and CDC at wk 52. Results GBTM identified 3–5 distinct response trajectories for each mechanism of action (MOA), ranging from super-fast responses to slow and incomplete responses or relapse, based on PRO2 dynamics. Meta-analysis revealed baseline factors associated with faster response, including prior biologic failure, lower endoscopic activity (Mayo-ES 2 vs. 3), lower Robarts Histology Index, lower baseline disease activity and male sex (0.78 [0.66, 0.93]) (Fig1). Across therapies, remission, mucosal healing, and comprehensive disease control (CDC) were most frequently achieved in fast and super-fast responders (15–37%), compared to slow or non-responders (2.6–8.1%). Random-effects logistic regression confirmed better clinical outcomes for faster responders (Tab1). Conclusion Distinct subgroups (response trajectories) with specific PRO2-based response dynamics were consistently identified. In all trials, patients with (super)fast responses had significantly higher odds of achieving mucosal healing, deep remission, and comprehensive disease control (CDC) at wk52. While some baseline characteristics were linked to faster responses, they only partially account for the observed separation of patient groups. Response trajectories likely reflect underlying heterogeneity in disease biology in the interaction with the different MOA (i.e. endotypes). RNASeq analysis of transcriptome regulation in these patients aims to further explore this hypothesis. References Schreiber S et al. UEG Journal, doi:10.1002/ueg2.12686

P0946 Switching from intravenous to subcutaneous Infliximab in patients with immune mediated diseases in clinical remission

Abstract Background We aimed to report on the efficacy and safety of elective switching from intravenously (IV) to subcutaneously (SC) administered Infliximab (IFX) in patients with immune mediated diseases. Methods This was a multicenter retrospective study in which we analyzed data collected from consecutive patients with immune mediated diseases treated in a hospital setting. Each hospital department was considered a study center and overall, 8 gastroenterology departments, 6 rheumatology departments and 1 dermatology department from 13 Greek hospitals, that are all referral centers, recruited patients for the study. Patients with Crohn’s disease (CD), Ulcerative Colitis (UC), Spondyloarthritis (SpA), Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) and chronic plaque Psoriasis (PsO) who were receiving IFX-IV for maintenance of remission and were switched to IFX-SC based on their physician’s choice were included. All patients with gastrointestinal and skin diseases were in clinical remission, while those with musculoskeletal disease had inactive disease or low disease activity. The primary endpoint was disease deterioration during the follow up period, according to disease specific composite measures. Results Between April 2023 and April 2024, a total of 344 patients (CD=136, UC=62, SpA=52, PsA=38, RA=7, PsO=44, co-existence of more than one disease=5) were switched from IFX-IV to IFX-SC. The mean duration of treatment with IFX before switching was a mean (SD) 53.7 (36.2) months. Eleven patients (3.2%) were receiving combination treatment with an immunomodulator and 2 patients (0.6%) were using oral or iv steroids at the time of switch. After a mean (SD) follow up period of 8 (4) months, 12 patients (3.5%) discontinued treatment with IFX-SC. Five of them (1.5%) because of disease worsening and the remaining 7 (2.0%) because of the occurrence of side effects. All other 332 patients (96.5%) showed favorable response, none of them requested an unscheduled visit, or developed an adverse event (clinical or laboratory) or needed escalation of treatment. Conclusion Elective switching from IFX-IV to IFX-SC seems to be an effective and safe approach in real-world every day clinical practice to maintain long-term clinical remission, inactive disease or low disease activity in patients with immune-mediated diseases.

Adrenalectomy improves MSG-induced obesity in rats by increasing UCP-1 levels in interscapular brown adipose tissue

The administration of monosodium glutamate (MSG) to neonates has been shown to result in hypothalamic damage and development of metabolic syndrome. The objective of this study was to investigate whether bilateral adrenalectomy (ADX) could alter sympathetic activity in adult MSG rats, with the potential to contribute to the improvement of metabolic syndrome by interfering with intermediary metabolism. Following a period of 99 days, the rats that received the control treatment and MSG were subjected to bilateral adrenalectomy (ADX). The following experimental groups were established, and designated as follows: CTL-SHAM, CTL-ADX, MSG-SHAM, and MSG-ADX. The subjects were 109 and 110 days-old at the time of the experiment. The assessment included murinometric and biochemical parameters, an intravenous glucose tolerance test (IVGTT), sympathetic nerve activity in interscapular brown adipose tissue (iBAT), and protein content of β3-adrenergic receptor (β3-ADR) and uncoupling protein 1 (UCP-1). The MSG rats presented metabolic syndrome, which was associated with lower sympathetic activity and a decreased content of the β3-adrenergic receptor when compared to the controls in iBAT. We can conclude that the lower β3-adrenergic receptor contributed to the maintenance of obesity in the MSG rats model. Although it has an adverse effect on the glucose tolerance of CTL-ADX animals, the typical features of metabolic syndrome in adult MSG rats were mitigated by ADX. These effects included an enhancement of UCP-1 in iBAT, a reduction in fat accumulation, and an improvement in glycemia, thereby contributing to an improvement in metabolic syndrome.

P0528 Leukocyte Adhesive Function as Potential Predictive Marker for Treatment Response to Vedolizumab Among Bio-naive Patients with Crohn’s Disease

Abstract Background Vedolizumab (VDZ) is approved for the treatment of Crohn’s diseases (CD), but around 60% of patients fail to respond. Predicting response to VDZ, especially prior to treatment, is desirable but remains challenging. In this study, we investigated if α4β7 and α4β1 integrin activity may be used to predict response to VDZ. Methods Both α4β7 and α4β1 integrin activity were assessed using Leukocyte adhesive function assay (LAFA). LAFA uses microfluidic techniques to mimic blood circulation in vitro. Blood samples were fluorescently labelled and then pulled into microfluidic channels precoated with either MAdCAM-1 or VCAM-1 as substrates. Interactions between leukocytes and substrates was recorded and analysed by cell tracking software. Cell kinetic parameters were calculated and used for the assessment of α4β7 and α4β1 integrin activity. Mn2+ was applied as activator to assess the full potential of integrin activity. Bio-naive CD patients were recruited and all received VDZ as treatment. Treatment response was assessed at week 14 by endoscopy. Patients were classified as primary loss of response to VDZ if the simplified endoscopic score for CD at week 14 failed to decrease by 25% compared to baseline. Blood samples were collected at weeks 0 (prior to VDZ infusion), 2, 6 and 14 and then applied for LAFA. The differences in α4β7 and α4β1 integrin activity between VDZ responders and non-responders were prospectively assessed and a prediction model was subsequently established. Results A total of 27 patients were recruited and received VDZ. Twenty patients were classified as responders and seven as non-responders. No difference was found in α4β7 integrin activity on CD4 and CD8 cells between responders and non-responders, either before or after VDZ treatment. However, a lower α4β1 integrin activity was found on CD4 and CD8 cells among VDZ non-responders at week 0 compared with responders in the presence of Mn2+. Using the best LAFA-derived markers, a model to predict VDZ non-responders at week 0 was developed, in which a sensitivity of 0.90 and a specificity of 0.73 were achieved, a substantially better performance than the existing prediction tool CDST. In addition, α4β1 integrin activity on CD4 and CD8 cells among non-responders was gradually enhanced following subsequent VDZ treatment, which was not detected in responders (figure), implying a possible mechanism underlining primary loss of response to VDZ. Conclusion Patients with a low α4β1 integrin activity at week 0 which can be enhanced after VDZ, is likely to be primary non-responders to VDZ. Integrin activity measured by LAFA prior to treatment may be used as new diagnostic tool for the prediction VDZ response in bio-naïve CD patients. References Dulai PS, Boland BS, Singh S, et al. Development and Validation of a Scoring System to Predict Outcomes of Vedolizumab Treatment in Patients With Crohn’s Disease. Gastroenterology. 2018;155(3):687-695.e10. doi:10.1053/j.gastro.2018.05.039