Changes In Parameters Research Articles

Анализ эффективности и безопасности применения CFTR-модулятора лумакафтор/ивакафтор у пациентов с муковисцидозом в разных возрастных группах

Russia’s first registered CFTR-modulator lumacaftor/ivacaftor was developed for patients with cystic fibrosis (CF) with the F508del/F508del genotype. The purpose of this research was to study the efficacy and safety of lumacaftor/ivacaftor therapy in different age groups. Materials and methods used: the data of homozygotes for F508del aged 2 to 18 y/o in the Russian CF Patient Registry who had been treated with lumacaftor/ivacaftor were analyzed. The effectiveness of therapy was evaluated in 3 age groups based on examination data, nutritional status, spirometry, sweat test at the start of therapy and after 12 months. In order to assess the safety, examination data, assessment of adverse events (AE), blood biochemical parameters, blood pressure and lens condition were taken into account in 334 pediatric patients in the first month of therapy and in 180 after 12 months. Results: decrease in sweat conductivity was noted in three age groups (p<0.001), only in the 2 to 6 y/o age group were negative values obtained in 6.8%. An increase in BMI was observed in the 6 to 12 y/o and 12 to 18 y/o age groups (р<0.001) whilst an improvement in FVC was observed only in the 12 to 18 y/o age group (p=0.015). Changes in biochemical parameters were statistically significant, both downward and upward, only in the age groups of 6 to 12 y/o and 12 to 18 y/o, changing not significantly. Withdrawal of the drug was required in only a single patient with a persistent increase in transaminase level. Fluctuations in blood pressure occurred within the normal age limits. Frequency of AE was comparable with the results of other studies, it was noted at the start in all groups and after 12 months more often in the age group of 12 to 18 y/o. The best tolerance was noted in the age group of 2 to 6 y/o. Conclusion: for the first time, the efficacy and tolerability of lumacaftor/ivacaftor in patients with CF in Russia was studied against the age aspect according to the 2022-2024 Registry. In the 2 to 6 y/o age group, the achievement of normal sweat test values and the lowest number of adverse reactions were noted, while in the 12 to 18 y/o age group, the positive dynamics were noted for a greater number of indicators, incl. an increase in FVC.

Safety of a Medicinal Product Based on Human Glial Progenitor Cells: A Pilot Study of Retrobulbar Administration in C57BL/6J Mice

INTRODUCTION. Stem cell therapy is a promising treatment method for various diseases and injuries, but its safety has yet to be determined. Therefore, studying the safety of administering a xenogeneic cell-based medicinal product (CBMP) into the retro-orbital venous sinus is essential for developing protocols for further studies of potential medicinal products for neurological conditions.AIM. The aim of the study was to determine the optimal dose of a CBMP derived from glial progenitor cells (GPCs) and to evaluate its safety during retrobulbar administration in C57BL/6J mice.MATERIALS AND METHODS. GPCs were derived from human induced pluripotent stem cells by stepwise differentiation and cultured in DMEM/F12 supplemented with epidermal growth factor and ciliary neurotrophic factor. Matrigel was used as a substrate. GPCs were injected into the retro-orbital venous sinus of male C57BL/6J mice under isoflurane anaesthesia once a week for two months. The study analysed changes in biochemical blood parameters and behaviour. The quantities of activated astrocytes and glial cells were determined by postmortem immunohistochemical staining.RESULTS. The administration of GPCs at a dose of 500×103 cells/mouse, which was selected using literature data, induced an increase in the plasma levels of ala nine aminotransferase and aspartate aminotransferase. This could indicate cell damage and the development of inflammatory reactions. At doses reduced to one-third the initial GPC concentration or lower, the biochemical blood parameters of the treatment groups did not differ significantly from those of the control group. There were no significant differences in neuroinflammatory markers between the groups receiving GPCs at different doses, except for an increase in astrocyte activation at a dose of 150×103 cells/mouse, which could potentially indicate inflammatory processes in the brain. The study detected no pathological changes in the brain or cell damage markers in the blood of mice after retrobulbar GPC injections of 15×103 or 50×103 cells/mouse.CONCLUSIONS. The study results indicate that long-term therapy with GPCs is potentially safe for mice if the dose is optimal. The authors suggest using the optimal doses and the administration route established in this study for further research into the safety of intravenous administration of CBMPs for neurological conditions.

The association of early passive mobilization with intracranial pressure in the adult intensive care unit: A prospective, cohort study.

Early mobilization are key components of the ABCDEF Care Bundle and critical treatments to reduce acquired muscle weakness, delirium and prolonged intensive care unit (ICU) stay. This study aimed to determine whether routine early mobilization related to intracranial pressure in intensive care patients on mechanical ventilation, using optic nerve sheath diameter measurement (ONSD). This study was planned as a prospective, cohort study in the third-step adult ICU of a faculty hospital. The study included only patients who were intubated and followed up on a mechanical ventilator and were clinically stable. Passive range of motion (PROM) exercises were performed daily by the physiotherapists as part of routine care from the day of hospitalization. ONSD was assessed before, during and 10 min after PROM exercises. The study included 20 eligible patients out of the 142 who were evaluated upon admission to the ICU. The median age of the patients was 65 years, and nine (45%) of them were female. The analyses showed that there was no statistically significant change in ONSD during and at the end of the PROM (ONSD right eye p:.621, Partial η2: 0.025, ONSD left eye p:.935, Partial η2: 0.004). Similarly, there was no statistically significant change in haemodynamic parameters in during and at the end of the PROM (Heart beat p:.849, Partial η2: 0.009, Systolic Pressure p:.435, Partial η2: 0.043, Diastolic Pressure p:.128, Partial η2:0.103, Saturation p:.103, Partial η2: 0.113 and Respiratory rate p:.071, Partial η2:0.130). This study suggests that daily extremity physiotherapy exercises can be safely applied without causing increased intracranial pressure or haemodynamic instability in intensive care patients followed up on mechanical ventilation, including patients with vasopressor therapy. Early mobilization, including PROM, is considered safe in terms of intracranial pressure for intubated patients in the ICU.

Accommodating version of a schematic eye for emmetropia and myopia.

To develop an accommodating, wide-angle, schematic eye for emmetropia and myopia in which spectacle refraction and accommodation level are input parameters. The schematic eye is based on an earlier unaccommodated refraction-dependent eye for myopia developed by Atchison in 2006. This has a parabolic gradient index lens and parameters derived from biometric and optical measurements on young adults. Several parameters are linearly dependent upon spectacle refraction (anterior radius of curvature of the cornea, axial length and vertex radii of curvature and conic asphericities of a biconic retina). The new accommodated schematic eye incorporates accommodation-dependent changes in several lens-related parameters. These changes are based on literature values for anterior chamber depth, lens thickness, vitreous chamber depth, lens surface radii of curvature and lens front surface asphericity. A parabolic variation of refractive index with relative distance from the lens centre is retained, with the same edge and centre refractive indices as the earlier model, but the distribution has been manipulated to maintain focus near the retina for the emmetropic case at 0 and 4 D accommodation. The asphericity of the lens back surface is changed so that spherical aberration and peripheral refraction approximately match typical literature trends. The model is used to compare spherical aberration and peripheral refraction in eyes with up to 4 D of myopia and 4 D of accommodation. The levels of spherical aberration in the unaccommodated schematic eyes are similar to literature values for young adults, but the changes in spherical aberration with accommodation are approximately two-thirds of that found in an experimental study. As intended, peripheral refractions in the accommodated schematic eyes are similar to those of their unaccommodated counterparts. The wide-angle model extends the range of schematic eyes to include both refraction and accommodation as variable input parameters. It may be useful in predicting aspects of retinal image quality.

Hip geometry and strength remain stable the first year after kidney transplantation – an ibandronate/placebo post hoc analysis

Abstract The sensitivity of bone mineral density (BMD) to identify patients with high fracture risk after kidney transplantation is low, wherefore alternative tools are needed. Hip Structure Analysis (HSA) provides an estimation of hip structural geometry and strength based on conventional DXA scans for hip analyses. We aimed to investigate the effect of antiresorptive therapy on hip geometrical and strength parameters by HSA. In a post hoc analysis of a 12-month randomized, double-blind, placebo-controlled trial evaluating the effect of ibandronate in addition to active vitamin D and calcium in kidney transplant recipients (KTR), we re-analyzed dual total hip and femoral neck DXA scans to measure cortical bone thickness (CBT) in the femoral neck (CBTNECK), calcar (CBTCALCAR), and shaft (CBTSHAFT), along with femur neck width, hip axis length, and to estimate Buckling Ratio and Strength Index. DXA measurements were performed within 5 weeks after transplantation and repeated at 10 weeks and 1-year post-transplant. The study included a total of 127 de novo KTR with eGFR >30 mL/min at baseline. The five geometrical and the strength and stability hip parameters remained stable over the first post-transplant year irrespective of antiresorptive therapy. We detected no statistically significant between-group differences in any of the HSA measures. Change in geometrical hip parameters and Buckling Ratio over the study duration was not correlated with change in plasma parathyroid hormone or change in dual total hip BMD. In this study, the so far largest of HSA in KTR, antiresorptive therapy with ibandronate for 12 months did not affect measures of hip geometry or strength. Clinical Trial Registration: www.clinicaltrials.gov as NCT00423384, EudraCT number 2006-003884-30.

Individual Differences in Stride Length During Powered Exoskeleton Walking Due to Changes in Quasi-Stiffness Control Parameter

Active exoskeletons are driven by controllers that execute commands that respond to a user’s intent. It is unclear how precise these systems need to be to assist humans efficiently and reduce the risk of injury. This study evaluated participants’ stride length during powered ankle exoskeleton walking while controlling the quasi-stiffness coefficient, the relationship between exoskeleton ankle torque and ankle angle. Compared with the reference quasi-stiffness value, 31% of participants showed a statistically significant increase in normalized stride length (NSL) at high and low quasi-stiffness coefficients. In comparison, 50% showed a statistically significant decrease in NSL. Only 19% showed a statistically significant increase at either low or high quasi-stiffness coefficients. The results suggest that it is essential to consider individual responses, as different stride lengths emerged from changes in quasi-stiffness across participants. This knowledge is important for improving user experience and performance and ensuring the system is used efficiently.

Effect of radiofrequency ablation on improving cardiac structure and function in patients with atrial fibrillation and functional mitral regurgitation

Objective: Exploring the effect of radiofrequency ablation treatment to restore sinus rhythm on the improvement of functional mitral regurgitation (FMR) and cardiac structure in patients with atrial fibrillation combined with moderate or severe FMR, compared with drug therapy alone. Methods: This retrospective cohort study consecutively enrolled patients diagnosed with persistent atrial fibrillation and moderate or severe FMR who were admitted to the Third Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2021. Forty-eight patients who were treated with radiofrequency ablation and maintained sinus rhythm were enrolled in the ablation group, and 63 patients who were treated with medication alone during the same period were in the medicine group. Patients in the ablation group and medicine group were matched in a 1∶1 ratio using a propensity score, and 41 patients were finally included in each of the 2 groups. All patients reexamined echocardiography after 3-month of treatment. The proportion of patients with FMR improvement and the differences in changes of cardiac structural and functional parameters were compared between groups. Results: After propensity score matching, the ablation group was aged (69.3±7.1) years with 21 males (51.2%) and the medicine group was aged (71.3±9.4) years with 21 males (51.2%). The echocardiography after 3-month of treatment showed the rate of FMR improvement was significantly higher in the ablation group than in the medicine group (19 (46.3%) vs. 33 (80.5%), P<0.001), and patients in the ablation group showed a significant decrease in FMR extent (Δmitral regurgitation area: (-1.30±2.64) cm2 vs. (-3.55±2.50) cm2, P<0.001), left atrial size (Δleft atrial diameter: (-0.17±3.78) mm vs. (-2.46±4.01) mm, P=0.009) and E/e' (ΔE/e':-2.54±7.34 vs.-6.34±7.08, P=0.021) compared with the medicine group. There was also a significant decrease in left ventricular size (Δleft ventricular end diastolic diameter: (-3.12±6.62) mm vs. (-0.73±3.62) mm, P=0.046) and significant increase in left ventricular ejection fraction (Δleft ventricular ejection fraction: (2.73±9.69) % vs. (-0.93±5.41) %, P=0.038) in ablation group. Conclusion: Performing radiofrequency ablation to restore sinus rhythm can effectively reduce the severity of mitral regurgitation and improve left atrial and left ventricular remodeling and cardiac function in patients with atrial fibrillation and FMR.

Investigation of heat generation and radiation effects on boundary layer flow of Prandtl liquid with Cattaneo–Christov double diffusion models

In this analysis, a bidirectional stretched sheet is used to produce a 3D\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\mathcal{D}$$\\end{document} flow of Prandtl liquid with improve mass diffusion and heat conduction models. This study advances knowledge of magnetohydrodynamics, radiation impacts, and heat production in fluid dynamics and transport processes. The Prandtl fluid model is critical for modeling non-Newtonian fluids, capturing its viscoelastic features, and allowing for precise simulation in industrial applications. It gives a mathematical foundation for analyzing complex fluid behaviors, which is necessary for optimizing operations utilizing such fluids. It uses the boundary layer method to simplify the fundamental equations and Cattaneo–Christov double diffusion models. The optimal homotopy analysis method is used to solve nonlinear ODEs caused by non-dimensional similarity variables. This investigation undertakes the calculation of drag coefficient for surfaces mass transfer rates and heat transfer rates proximate to the solid boundary. Furthermore, it conducts a comprehensive analysis of the influences exerted by various parameters on concentration and temperature profiles employing graphical representations for a rigorous examination. The Prandtl fluid model describes the viscoelastic characteristics of non-Newtonian fluids through constitutive equations, dimensional evaluation, and numerical simulations, which are frequently validated by experiments. The results show that changes in thermal and concentration relaxation parameters are accompanied by a decline in temperature. Temperature field rises as the thermal radiation parameter and heat generation increases. The work's novelty consists in its advanced modeling of Prandtl non-Newtonian fluids via Cattaneo–Christov double diffusion models, which incorporate magnetohydrodynamics and radiation effects and use optimal homotopy analysis for accurate parametric analyses of heat and mass transfer.

Diffusion capacity and static hyperinflation as markers of disease progression predict 3-year mortality in COPD: Results from COSYCONET.

Chronic obstructive pulmonary disease (COPD) exhibits diverse patterns of disease progression, due to underlying disease activity. We hypothesized that changes in static hyperinflation or KCO % predicted would reveal subgroups with disease progression unidentified by preestablished markers (FEV1, SGRQ, exacerbation history) and associated with unique baseline biomarker profiles. We explored 18-month measures of disease progression associated with 18-54-month mortality, including changes in hyperinflation parameters and transfer factor, in a large German COPD cohort. Analysing data of 1364 patients from the German observational COSYCONET-cohort, disease progression and improvement patterns were assessed for their impact on mortality via Cox hazard regression models. Association of biomarkers and COPD Assessment test items with phenotypes of disease progression or improvement were evaluated using logistic regression and random forest models. Increased risk of 18-54-month mortality was linked to decrease in KCO % predicted (7.5% increments) and FEV1 (20 mL increments), increase in RV/TLC (2% increments) and SGRQ (≥6 points), and an exacerbation grade of 2 at 18 months. Decrease in KCO % predicted ≥7.5% and an increase of RV/TLC ≥2% were the most frequent measures of 18-month disease progression occurring in ~52% and ~46% of patients, respectively. IL-6 and CRP thresholds exhibited significant associations with medium- and long-term disease measures. In a multicentric cohort of COPD, new markers of current disease activity predicted mid-term mortality and could not be anticipated by baseline biomarkers.

The influence of storage conditions on the dynamics of physicochemical markers of champignon (Agaricus bisporus) quality

Agaricus bisporus are the most common cultivated mushrooms. Champignons are a source of chitin, glycogen and minerals, and also have attractive organoleptic properties. Physicochemical and organoleptic characteristics of fresh Agaricus bisporus undergo significant changes during storage due to moisture transpiration, respiration and oxidative processes. The purpose of this work was to study the influence of storage conditions of cultivated champignons with unstained cap epithelium on the dynamics of their physicochemical parameters, as well as its relationship with changes in organoleptic parameters. The mushrooms were stored in refrigerated chambers at a constant temperature of +2 °C and +6 °C in polypropylene trays placed in bags made of biaxially oriented polypropylene (BOPP) perforated film and polyethylene (PE) film without perforation. Under all storage conditions studied, the nature of the dynamics of physicochemical parameters was close to linear (with the exception of the humidity of fruiting bodies when stored in PE film) — the calculated values of the Pearson correlation coefficient ranged from 0.67 to 0.97. Using two-factor analysis of variance, the influence of both packaging material and storage temperature on the dynamics of soluble solids content and mushroom tissue density was confirmed. When stored in PE film without perforation, a more intense negative dynamics of these criteria was observed compared to storage in perforated BOPP film. The identified difference is explained by the fact that in packaging made of PE film without perforation, conditions for anaerobic respiration were formed by the end of storage — the oxygen content decreased from 20.5% to 1.5–2.5%, which also contributed to the activation of decay processes. With increasing storage temperature, a more intense change in physicochemical parameters was observed, which was associated with an increase in metabolic rate. The relationship between the dynamics of all studied physicochemical quality markers and the dynamics of sensory assessments (with the exception of the marker "content of soluble solids" when stored in a perforated BOPP film at a temperature of 2 °C) has been statistically confirmed. Based on the results of the studies, the applicability of the criteria “humidity of fruiting bodies”, “content of soluble dry substances” and “density of fungal tissue” as markers for assessing the quality of cultivated Agaricus bisporus was confirmed.

Impact of the frequency error of direct digital synthesizers on the evaluation of two-photon light shift in atom gravimeters

One major systematic error for free-fall atom gravimeters is the effect of two-photon light shift (LS2). In the process of evaluating LS2, the results can be affected by the residual frequency error of direct digital synthesizers due to necessary experimental parameter changes. In this paper, the impact of the coupling effect between the frequency error and LS2 has been investigated and analyzed, along with the related physical mechanisms. The parameters of the frequency error sequence, such as the time step of δt and the time delay of Δt, significantly affect the bias and uncertainty of LS2. Notably, when these parameters are significantly altered or misaligned, the impact can reach several tens of µGal. Conversely, when they remain within the optimal ranges, the impact can be minimal. Specifically, when δt is less than or equal to 10 µs, the impact on the LS2 bias is less than 0.3 µGal, with the contribution to the total uncertainty of the gravity value being approximately 0.1 µGal. Furthermore, after correcting the phase shift introduced by the frequency error, the evaluation results have a similar improvement effect on the whole. Compared to the LS2 theoretical value, the residual is generally on the order of µGal. Through the comprehensive analysis and optimization, as well as related experiments, this cross-effect is managed and decoupled, leading to accurate LS2 evaluation results. This improvement ensures a better accuracy in the obtained absolute gravity values. The analysis methods discussed can provide an effective strategy for enhancing the performance of atom gravimeters.

The effect of the composition of hepatoprotective action on biochemical and morphostructural changes in the body of laying hens under thermal stress

To reduce the negative effects of hyperthermia on the body of farm animals and poultry, various drugs and feed additives are currently used. Which do not have sufficiently adaptogenic and antitoxic properties. We studied the effect of a hepatoprotective composition consisting of dried live yeast, amorphous silicon dioxide, propylene glycol, calcium propionate, ascorbic acid, manganese, copper and zinc chelates, methionine and choline chloride on the variability of biochemical and morphological parameters of the body of laying hens under temperature stress. It was simulated by increasing the air temperature in a building where laying hens were kept from 18.0 ± 1.0 °C to 28.0 ± 1.0 °C for 48 hours. Due to hyperthermia, changes in biochemical and morphofunctional parameters were observed in the tissues and organs of birds. The obtained values of the biochemical parameters of blood serum in the birds of the control group indicated the intensity of the adaptive capabilities of their body. A complex of morphological changes confirmed a violation of protein metabolism and the regenerative-compensatory process. Pathological changes in the structure of the duodenum, characteristic of catarrhal-necrotic duodenitis, were identified. The stress reaction was also reflected in the condition of the heart muscle, in which an inflammatory process developed against the background of granular dystrophy of cardiomyocytes. The results of biochemical studies of blood serum in birds of the experimental group indicated an increase in the anti-stress response to a temperature stimulus under the influence of the studied composition (tendency to increase glucose and calcium, increase alkaline phosphatase activity by 47.4 %). The introduction of a hepatoprotective composition into the diet of laying hens during periods of temperature stress did not lead to disruption of the structure of tissues and organs, preserving cellular metabolic mechanisms. The

The Correlation between Serum Cortisol Concentration in Mammals and the Level of Global Seismic Activity.

A positive correlation was found between the level of global seismic activity and dynamics of cortisol concentration in blood serum of male rabbits (r=0.33, p=0.01) and Campbell's dwarf hamsters (r=0.38, p=0.04). For a small group of healthy volunteers (n=5), we also found a positive correlation between cortisol levels and the number of major earthquakes, excluding aftershocks (r=0.36, p=0.009) and a negative correlation with IL-18 levels (r=-0.28, p=0.04). The body response to earthquakes is not delayed, and the numerous aftershocks do not seem to affect the biological indicators under study. These facts showed that the earthquakes themselves do not affect the cortisol level via the changes of the environmental parameters. In contrast, the underlying biotropic factor is an unknown trigger responsible for an increase in the number of potent earthquakes. Evidently, it is important to take into account the level of global seismicity as a marker of this trigger provoking the rise of glucocorticoid hormones.

Design of Exterior Orientation Parameters Variation Real-Time Monitoring System in Remote Sensing Cameras

The positional accuracy of satellite imagery is essential for remote sensing cameras. However, vibrations and temperature changes during launch and operation can alter the exterior orientation parameters of remote sensing cameras, significantly reducing image positional accuracy. To address this issue, this article proposes an exterior orientation parameter variation real-time monitoring system (EOPV-RTMS). This system employs lasers to establish a full-link active optical monitoring path, which is free from time and space constraints. By simultaneously receiving star and laser signals with the star tracker, the system monitors changes in the exterior orientation parameters of the remote sensing camera in real time. Based on the in-orbit calibration geometric model, a new theoretical model and process for the calibration of exterior orientation parameters are proposed, and the accuracy and effectiveness of the system design are verified by ground experiments. The results indicate that, under the condition of a centroid extraction error of 0.1 pixel for the star tracker, the EOPV-RTMS achieves a measurement accuracy of up to 0.6″(3σ) for a single image. Displacement variation experiments validate that the measurement error of the system deviates by at most 0.05″ from the theoretical calculation results. The proposed EOPV-RTMS provides a new design solution for improving in-orbit calibration technology and image positional accuracy.

Age-related changes in gait, balance, and strength parameters: A cross-sectional study.

Longevity is increasing worldwide due to improvements in healthcare and living standards. Aging is often associated with disability and multiple health concerns. To address these challenges, effective interventions are essential. This study investigated potential age-related declines in gait, balance, and strength. We also sought to assess any relationships between these three parameters and explore potential differences between women and men. Healthy individuals over 50 years of age were recruited for this cross-sectional study. Upper extremity (grip) strength and lower extremity (knee) strength of the dominant side were measured. Static balance was performed on the force plate in different situations each for 30 seconds: bilateral stance with eyes open, bilateral stance with eyes closed, as well as dominant leg and non-dominant leg unilateral stance with eyes open. Gait was measured during level walking using an optical motion capture system. Additionally, the dynamic stability margin (DSM) was calculated for the level walking trials. The study results indicated that gait parameters were not significantly affected by age (p≥0.12), while knee and grip strength, along with several balance parameters, showed a significant decline with age. All individuals were able to maintain their bipedal balance, but their center of pressure movement increased significantly by age (p≤0.028). Z-scores were calculated to compare significant age parameters. Unipedal stance time was found to be the most affected by age compared to other contributing factors (p≤0.001). The duration of unipedal balance showed the most significant change per decade (non-dominant: -0.62 SDs; dominant: -0.53 SDs), while strength measures exhibited the lowest amount of change per decade (grip strength: -0.34 SDs; knee strength: -0.26 SDs). Sex differences were observed exclusively in strength parameters, with no discernible impact on the decline in balance parameters. These findings suggest that the duration of unipedal stance can serve as a reliable and gender-independent measure of neuromuscular aging for both elderly male and female subjects.

63 Utilization of vasopressin and norepinephrine in neonates with cardiorespiratory compromise: A multicenter retrospective cohort study in Canada

Abstract Background Data regarding neonatal clinical experience with Vasopressin (VA) and Norepinephrine (NE) are limited to small studies. The lack of large-scale studies with safety and efficacy data is preventing the widespread adoption of these agents. Objectives To describe epidemiological data on utilization of NE and VA in neonates including their indications, effectiveness and overall outcomes across 3 tertiary Neonatal Intensive Care Units (NICU) in Canada. Design/Methods This retrospective cohort study involved neonates who received NE or VA between January 1, 2015-December 31, 2020 at 3 tertiary NICUs. Data regarding demographic information, indications of use, dosing details, and clinical outcomes were described using mean, standard deviations (SD), frequencies and percentages. When appropriate, a comparative analysis was performed using Mann-Whitney U tests or the chi-square test as appropriate. Post-initiation changes in physiological variables and laboratory parameters over time were analyzed using repeated measure ANOVA. Results 133 neonates (VA:70, NE:63) were included in this study. Baseline demographic features, clinical characteristics at initiation, indication of use, dosing details and clinical response in neonates exposed to both agents are summarized in Table 1. VA was commonly used for oxygenation failure due to persistent pulmonary hypertension of the newborn (PPHN), while NE was commonly used for hypotension due to septic shock. NE was frequently used as a 1st line inotropic agent, whereas VA was used more as an additive agent [30 (47.6%) vs 12 (18.6%); p=&amp;lt;0.001]. During treatment, lower sodium levels were recorded in the VA group vs the NE group [126.5 (8.6) vs 132 (7); p=.035], but other safety parameters were similar. The time to reach predefined stability parameters were similar in both groups. Significant improvement in physiological parameters were seen over time with both agents (Figure 1). Mortality within 7 days of use was high in the cohort, but comparable between VA and NE groups [18 (25.7%) vs 22 (34.9%), p=0.206]. Other neonatal morbidities were comparable between groups (Table 1). Conclusion This multicenter study provides pragmatic insights into the current use of NE and VA in neonates. Our study reports the effective use of each agent in distinct patient subgroups. This cohort represented neonates with high illness severity; however, exposure to either agent did not independently increase the risk of mortality or adverse outcomes. Further prospective studies exploring its optimal use and cardiopulmonary effects would be interesting.

Electric Field Influence on CO Clathrate Hydrates.

We consider carbon monoxide (CO) confined in the hydrogen-bonded building blocks of sI and sII clathrate hydrates, viz., (512, 51262, 51264) cages, within the density functional theory-based calculations. We study their response to the applied electric fields in terms of changes in the geometrical parameters, dipole moment, HOMO-LUMO gap, and vibrational frequency shift. We examine the stability of CO clathrate hydrate building block cages and identify a possible indication of the field-induced release of CO.

Bioequivalence and Pharmacokinetic Evaluation of Regorafenib Tablets in Healthy Chinese Volunteers.

This was a single-center, randomized, open-label, 2-formulation, and 2-cycle crossover trial conducted in 48 healthy Chinese volunteers, under fasting and fed conditions. The participants received oral doses of the test formulation (regorafenib) and reference formulation (40mg) during each study period. Blood samples were collected before and up to 144hours after the formulations were administered to determine changes in the pharmacokinetic parameters and adverse reactions, which were then used to evaluate bioequivalence and safety. The geometric mean ratios of maximum blood concentration, area under the plasma concentration-time curve from time 0 to the last quantifiable concentration, and area under the plasma concentration-time curve from time 0 to infinity for regorafenib were as follows: 94.7%, 91.4%, and 91.7%, respectively, under fasting conditions; and 94.6%, 97.7%, and 98.8%, respectively, under fed conditions. The 90% confidence intervals for the geometric mean ratios were within the 80%-125% equivalence interval for both the fasting and fed tests. Ingesting high-fat and high-calorie foods increases exposure to regorafenib, leading to slower rates of absorption. The safety profiles of the 2 preparations were similar.

Cross-border supply chain coordination of low-carbon agricultural products under the risk of supply uncertainty.

The purpose of this paper is to discuss how cross-border e-commerce enterprises can promote the sustainable development of the supply chain by optimizing the risk of supply disruption and product quality control mechanism of the cross-border supply chain of low-carbon agricultural products in the face of the problem of uneven quality and inventory shortage that prevails in the supply chain of low-carbon agricultural products under the framework of low-carbon economy. Methods: A two-level supply chain model consisting of a risk-averse cross-border e-commerce enterprise and two risk-neutral overseas suppliers is constructed to compare the optimal strategies and their coordination effects under the centralized and decentralized decision-making modes, and to deeply analyze the supply chain's operation mechanism. Further, the quality cost factor is introduced and an option contract model is designed to quantitatively analyze the impact of different decision-making scenarios and parameter changes on the overall supply chain performance. The results of the study show that under the coordination of option contract, the profit of cross-border e-commerce companies tends to decrease as the risk of supply disruption increases, while the profit of suppliers rises accordingly. Meanwhile, improving the quality of agricultural products can significantly improve the overall profitability of the supply chain. The cost-sharing mechanism is positively related to the profit of cross-border e-commerce companies, but negatively affects the profit of suppliers. In addition, the adjustment of the option price is directly associated with the increase of the specific supplier's profit and the decrease of the cross-border e-commerce enterprise's profit. Conclusion: By constructing and analyzing the option contract model considering the risk of supply disruption, this study effectively reveals the key influencing factors and their interactions in the cross-border supply chain of low-carbon agricultural products, and provides cross-border e-commerce enterprises with specific strategies to achieve coordination of the supply chain contract, improve product quality, and mitigate the risk of supply disruption, and then promote the sustainable development of the supply chain of low-carbon agricultural products.

Improvements in Cardiopulmonary Exercise Test Results in Atrial Fibrillation Patients After Radiofrequency Ablation in Kazakhstan

This prospective study evaluates the impact of radiofrequency ablation (RFA) on cardiorespiratory indicators in patients with long-standing persistent atrial fibrillation admitted to the Heart Center UMC between January 2022 and April 2024 in Astana, Kazakhstan. The study aims to assess the functional cardiac benefits of RFA. Out of 717 registered atrial fibrillation patients, 104 were examined before and 3 months after ablation, focusing on cardiorespiratory parameters. A before-and-after analysis using linear mixed models was applied to evaluate changes in cardiorespiratory parameters post-RFA. Significant improvements were noted across various measures. VO2 max increased from 11.5 ± 4.4 mL/kg/min to 18.0 ± 4.5 mL/kg/min (p &lt; 0.001). Oxygen uptake improved from 7.2 ± 2.6 mL/beat to 11.0 ± 3.4 mL/beat (p &lt; 0.001). The 6-min walking test distance rose from 306 ± 82 m to 400 ± 48 m (p &lt; 0.001). METs increased from 4.4 ± 1.6 to 8.0 ± 1.3 (p &lt; 0.001). Heart rate at peak exercise decreased from 175.5 ± 18.6 to 147.2 ± 12.3 beats per minute (p &lt; 0.001). NT-proBNP levels decreased from 1357 ± 1182 to 415 ± 339 pg/mL (p &lt; 0.001). Patients with persistent atrial fibrillation undergoing RFA showed functional improvements in CPET indicators such as VO2 max, METs, O2 pulse, heart rate, and the 6-min walking test. Improvements were also seen in Nt-proBNP analysis. These results emphasize the need for longitudinal follow-up to optimize outcomes and minimize medical risks.