Additional Beneficial Effects Research Articles

(Invited) Solvation Control in Deep Eutectic Solvent Electrolytes for Stable Plating/Stripping of Zn in Battery Applications

Within the field of battery applications, deep eutectic solvents (DESs) have emerged as innovative electrolytes for rechargeable Zinc-ion batteries (ZIBs) . ZIBs traditionally employ neutral or weakly acidic aqueous electrolytes, which are susceptible to the standard anode drawback such as dendrite formation and passivation. DES-based electrolytes can facilitate the reversible plating and stripping of Zn, mitigating also dendrite growth . One notable benefit of DES solvents over their aqueous counterparts is that the concentration of electroactive species controls the shape evolution of electrodes during electroplating. For this reason, the coordination chemistry and metal complex formed between the Lewis acid of the metal and the Lewis base of the DES play a central role. Moreover, water can be added to the eutectic mixtures to increase the diffusion coefficient of the electroactive species and lower the electrolyte viscosity without destroying the eutectic nature if the concentration is kept under 40%.Regarding metal plating/stripping processes, DESs offer a notable advantage due to their high capacity to dissolve metal salts, oxides, and hydroxides, inhibiting the formation of insoluble oxides and hydroxides . Moreover, the unique coordination properties of Zn2+ in DESs lead to an atypical voltammetric behavior, characterized by a cathodic peak in the cathodic branch of the anodic-going scan. The mechanistic studies of Zn electrodeposition onto glassy carbon (GC) from DESs have concluded that the metal is formed by the reduction of an intermediate Zn-containing species. Finally, the reactivity of choline chloride and ethylene glycol can impact coordination in that these species can be dehydrogenated at negative potential forming RO¯, which can replace one or more chloride ligands in [ZnCl4]2− . The correlation between the chemistry of Zn2+ solutions and DESs is elucidated, and the peculiarities of Zn electrochemistry can be rationalized in terms of the DES–electrode interface structure. Although few studies on hydrated DESs have been conducted, the literature remains scant.Shi et al. conducted a study on DES composed of ZnCl2 and acetamide with different concentration of water. The authors employed various spectroscopic techniques, including FT-IR, Raman, and 17O NMR, to investigate the effect of water on the coordination geometry of Zn2+ and its consequent impact on Zn plating. Interestingly, the authors observed that the addition of small amounts of water, below the threshold for direct water-water interaction, resulted in significant alterations of the Zn2+ coordination geometry. In fact, based on the accepted view that Zn electrodeposition is a process that involves desolvation and charge-transfer steps, [ZnCl(acetamide)2(H2O)]+ was shown to undergo successive deamidation and dehydration, yielding [ZnCl(acetamide)]+ from which the metal center is finally reduced. Although [ZnCl(acetamide)3]+ is the most stable species, the energy barrier for dehydration is significantly lower than that for deamidation. Therefore, [ZnCl(acetamide)2(H2O)]+ with lower dissociation energy is the actual electroactive species . The solvation of Zn also affects the nucleation overpotential, as Zn2+ in hydrated DES exhibits faster desolvation kinetics, resulting in a lower nucleation overpotential. In addition, Zhao et al. investigated the properties of a “water-in-DES” electrolyte (~30 mol.% H2O) based on the urea/LiTFSI/Zn(TFSI)2 mixture and discovered that the preferential interaction between water and metal cations promotes interfacial charge transfer. Notwithstanding the important contribution of these papers, the mechanism of Zn electrodeposition in DES has not been conclusively assessed. To address this knowledge gap, our research aims to investigate Zn electrodeposition from two distinct, hydrated DESs: ChU and ChEG with approximately 30% H2O content. To gain control of the impact of the cathode material, we carried out our electrochemical tests by employing GC, Zn, Pt and Au electrodes. Furthermore, to evaluate the performance of these electrolytes under realistic device conditions, electrochemical cycling tests were conducted on symmetric CR2023 coin cells.In this study, we have demonstrated the beneficial effect of water addition on reducing the electrolyte viscosity, which consequently resulted in lower anodic and cathodic overpotentials and improved charge/discharge cyclability. Specifically, the electrolytes ChEG and ChU failed due to passivation and short circuits, respectively. The ChU electrolyte showed regular chronopotentiometric transients until cell failure, and this was supported by multiple cyclic voltammetry (CV) measurements, which showed reversible Zn plating/stripping in this system. Notably, our cell cycling tests were performed at higher current densities and exhibited longer lifetimes compared to previous literature reports. The unusual CV patterns observed with gold and glassy carbon (GC) electrodes, featuring cathodic peaks on both forward and backward scans, were elucidated using complementary electrochemical and in situ Raman spectroscopy measurements. Figure 1

Combined Exercise Training and Nutritional Interventions or Pharmacological Treatments to Improve Exercise Capacity and Body Composition in Chronic Obstructive Pulmonary Disease: A Narrative Review.

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease that is associated with significant morbidity, mortality, and healthcare costs. The burden of respiratory symptoms and airflow limitation can translate to reduced physical activity, in turn contributing to poor exercise capacity, muscle dysfunction, and body composition abnormalities. These extrapulmonary features of the disease are targeted during pulmonary rehabilitation, which provides patients with tailored therapies to improve the physical and emotional status. Patients with COPD can be divided into metabolic phenotypes, including cachectic, sarcopenic, normal weight, obese, and sarcopenic with hidden obesity. To date, there have been many studies performed investigating the individual effects of exercise training programs as well as nutritional and pharmacological treatments to improve exercise capacity and body composition in patients with COPD. However, little research is available investigating the combined effect of exercise training with nutritional or pharmacological treatments on these outcomes. Therefore, this review focuses on exploring the potential additional beneficial effects of combinations of exercise training and nutritional or pharmacological treatments to target exercise capacity and body composition in patients with COPD with different metabolic phenotypes.

Effects of empagliflozin on right ventricular adaptation to pressure overload.

Right ventricular (RV) failure is the prime cause of death in patients with pulmonary arterial hypertension. Novel treatment strategies that protect the RV are needed. Empagliflozin, a sodium-glucose co-transporter-2 inhibitor, shows cardioprotective effects on the left ventricle in clinical and preclinical studies, but its direct effects on RV remain elusive. We investigated the effects of empagliflozin on RV dysfunction induced by pulmonary trunk banding (PTB). Male Wistar rats (116 ± 10 g) were randomized to PTB or sham surgery. One week after surgery, PTB animals received empagliflozin mixed into the chow (300 mg empagliflozin/kg chow; PTB-empa, n = 10) or standard chow (PTB-control, n = 10). Sham rats (Sham, n = 6) received standard chow. After five weeks, RV function was evaluated by echocardiography, cardiac MRI, and invasive pressure-volume measurements. PTB caused RV failure evident by decreased cardiac output compared with sham. PTB-empa rats had a 49% increase in water intake compared with PTB-control yet no differences in hematocrit or blood glucose. Treatment with empagliflozin decreased RV end-systolic pressures without any changes in RV cardiac output or ventricular-arterial coupling (Ees/Ea). The decrease in RV end-systolic pressure was complemented by a slight reduction in RV cross sectional area as a sign of reduced hypertrophy. Load-independent measures of RV systolic and diastolic function were not affected in PTB-empa rats compared with PTB-control. Empagliflozin treatment reduced RV end-systolic pressure in RV failure induced by pressure overload. Further studies are needed to elucidate whether this simply relates to a diuretic effect and/or additional independent beneficial RV effects.

Improved mechanical and frictional properties of hypereutectic Al-Si alloy by modifying Si phase with La addition

Hypereutectic Al-Si alloys play an important role in the automotive industry and wear-resistance field. In this study, B390 hypereutectic Al-Si alloys with different La additions (0, 0.2, 0.4, 0.6 wt%) are solidified under permanent magnet stirring. The beneficial effects of La addition on the B390 alloy are investigated by XRD, DSC, SEM, EPMA, hardness tester, tensile tester and wear tester. Experimental results indicate that as the La addition increases from 0 to 0.4 wt%, the Si phase evolves from coarse needle-like to fine coral-like particles, and the mean size decreases from 18.6 µm to 4.7 µm. Moreover, the introduction of La to B390 alloy would result in an enhancement in tensile strength from 115.7 MPa to 162.1 MPa, and an increase in the Rockwell hardness from 58.5HRB to 66.4HRB. In addition, the average friction coefficient of the alloy decreases from 0.55 to 0.48 with the increasing La addition from 0 to 0.4 wt%, indicating an obvious improvement in frictional properties. It is noted that adding 0.6 wt%La cannot further improve the Si phase or enhance its properties of the B390 alloy in comparison to the addition of 0.4 wt%La. These results confirm that a suitable La addition is feasible and economical to improve materials performance of hypereutectic Al-Si alloy.

Combination Therapy with Luspatercept and the Ferroportin Inhibitor Vamifeport Is Superior to Either Drug Alone in Improving Anemia and Reducing Myeloid Skewing in MDS

Background: Patients with myelodysplastic syndromes (MDS) are prone to develop iron overload as a consequence of ineffective erythropoiesis and chronic transfusion therapy. Although iron overload is a common feature in MDS, it has remained unclear whether and how iron excess is detrimental for MDS pathophysiology. Recently, we have shown that iron restriction by the oral ferroportin (FPN) inhibitor vamifeport improves anemia and reduces myeloid skewing, being of benefit for MDS as single treatment. Luspatercept is a recombinant fusion protein acting as TGF-β superfamily ligands trap which has recently gained FDA approval for the treatment of anemia in transfusion-dependent low-risk MDS patients. Luspatercept promotes erythropoietin (EPO)-independent maturation of late-stage erythroid cells, resulting in increased hemoglobin and red blood cells (RBCs) count. However, this drug - due to a lack of improvement in myeloid skewing and AML evolution - is considered a non-disease-modifying therapy. Aims: In this study we investigated the effect of a combined therapy using luspatercept and the FPN inhibitor vamifeport in a preclinical MDS mouse model, with the hypothesis that both drugs could have additive effects with further benefit for the disease. Methods: To this end, we administered the FPN inhibitor vamifeport in NUP98-HOXD13 MDS mice for 3 months (0.5 mg/ml into drinking water), combined with luspatercept for the last 2 months (5 mg/kg twice a week, subcutaneous injection), starting at 3 months of age. Mice receiving the combined treatment were compared to those untreated or receiving single treatments. Results: At steady-state MDS mice develop anemia, neutropenia and lymphopenia, together with an iron overload phenotype, hallmarked by inappropriately low hepcidin levels, elevated serum iron and transferrin saturation, non-transferrin-bound iron (NTBI) formation and tissue iron deposition. Vamifeport administration in MDS mice reduced serum iron and NTBI formation and prevented tissue iron loading, either as a single or combined treatment with luspatercept. Luspatercept and vamifeport, as single-agent treatment, ameliorated anemia and the maturation of bone marrow and splenic RBCs in MDS mice. The combined therapy further improved anemia compared to the treatments with either drugs alone, as suggested by the higher hemoglobin levels, hematocrit and RBC count, and the decreased number of early erythroid precursors, sign of more effective erythropoiesis. Importantly, vamifeport, but not luspatercept, significantly altered myeloid skewing in MDS, revealing a major role of the iron status in myeloid expansion. Myeloid bias, monitored as percentage of CD11b + Gr1 + myeloid cells in the bone marrow was attenuated by iron restriction in vamifeport-treated MDS mice compared to control and luspatercept-treated MDS animals. The combined treatment merkedly reduced myeloid skewing in MDS mice, similarly to the single vamifeport treatment. Furthermore, the number of immature cKit + myeloid blasts in the peripheral blood of MDS animals were decreased by vamifeport alone and in combination with luspatercept, but not by luspatercept alone. Finally, splenomegaly was reduced in MDS mice treated with vamifeport alone or in combination with luspatercept, confirming that iron restriction improves ineffective erythropoiesis and limits myeloid skewing. Overall, the combination therapy with vamifeport and luspatercept showed superior effects in improving anemia and myeloid bias as compared to single treatments. Conclusion: In conclusion, our results show that iron restriction by vamifeport enhances the erythroid maturation action of luspatercept, likely by improving iron utilization in erythroid cells and ameliorating their survival. Furthermore, vamifeport improves the myeloid skewing in the MDS model, suggesting disease-modifying activity as single agent as well as combined therapy with luspatercept. Together, these data prove that combo therapies aimed at restricting iron and boosting erythroid maturation may offer additive beneficial effects in MDS and provide pre-clinical evidence for combining iron restriction and TFG-β superfamily ligand-trap approaches as more effective therapeutic strategies for the treatment of MDS.

Obesity and Acute Kidney Injury in Patients with ST-Elevation Myocardial Infarction

Background: Data on the association between obesity and acute kidney injury (AKI) in patients with ST-elevation myocardial infarction (STEMI) are sparse and inconclusive. We aimed to evaluate the association between obesity and AKI and the outcome in these patients. Methods: A retrospective observational study of 3979 STEMI patients undergoing percutaneous coronary intervention (PCI) was performed at a single center. Patients with and without AKI were compared. Patients were also divided into three categories according to BMI, and these were compared. All-cause mortality was determined at 30 days and over a median period of 7.0 years. Results: The incidence of AKI was similar in all BMI categories. There was no association between BMI categories and AKI (p = 0.089). The Spearman correlation coefficient between BMI categories and AKI showed no correlation (r = −0.005; p = 0.75). More AKI patients died within 30 days and in the long term [137 (18.5%) and 283 (38.1%) patients in the AKI group died compared to 118 (3.6%) and 767 (23.1%) in the non-AKI group; p < 0.0001]. AKI was harmful in all BMI categories (p < 0.0001) and was associated with more than a 2.5-fold and a 1.5-fold multivariable-adjusted 30-day and long-term mortality risk, respectively (aOR 2.59; 95% CI 1.84–3.64; p < 0.0001, aHR 1.54; 95% CI 1.32–1.80; p < 0.0001). BMI categories were not associated with 30-day mortality (p = 0.26) but were associated with long-term mortality (p < 0.0001). Overweight and obese patients had an approximately 25% lower long-term multivariable-adjusted risk of death than normal-weight patients. In patients with AKI, BMI was only associated with long-term risk (p = 0.022). Obesity had an additional beneficial effect in these patients, and only patients with obesity, but not overweight patients, had a lower multivariable adjusted long-term mortality risk than normal-weight patients (aHR 062; 95% CI 0.446–0.88 p = 0.007). Conclusions: In patients who experienced AKI, obesity had an additional positive modifying effect. Our data suggest that the incidence of AKI in STEMI patients is not BMI-dependent.

Vitamin D – a scoping review for Nordic nutrition recommendations 2023

Vitamin D is an essential nutrient. Its role in calcium and phosphorous metabolism, and in the development and maintenance of a healthy skeleton is well documented. In addition, there is some evidence for vitamin D decreasing total mortality and cancer mortality modestly, but not cancer incidence. Vitamin D is unique, as both diet and sun induced production in skin are sources to this vitamin. Individual vitamin D status is thus a sum of both sun exposure and dietary intakes. The discovery of vitamin D receptors and the activation of biological active vitamin D in numerous tissues and organs in the body has given support to hypothesis on vitamin D having extra-skeletal functions. The scientific literature on vitamin D and several health outcomes is high in numbers and has been increasing exponentially the last two decades. However, despite this large body of scientific publications and improvement in study quality, vitamin D supplementation has not shown to give additional health benefits when status is in sufficient range (i.e. circulating 25 hydroxyvitamin D >50 nmol/L). Well-designed studies on insufficient or deficient individuals are lacking.
 The totality of evidence does not support that increased intake of vitamin D beyond current recommendation will have additional beneficial health effects.

Study of apparent effective ionization coefficient in CO2 and Ar gas mixtures

Ar:CO2 gas mixtures have recently received research interest due to the possibly beneficial effects of Ar addition to CO2 for CO2 conversion using electrical discharges. For any gas discharge, knowledge of fundamental parameters, such as the effective ionization coefficient, is necessary to optimize the efficiency of the discharge for a particular application. The reduced apparent effective ionization coefficient αea/N is a measure of total ionization. αea/N is influenced by electron impact ionization, electron attachment and also by charge transfer reaction, Penning ionization, and photoionization. This study determined the αea/N of Ar:CO2 gas mixtures in the pressure range of 10–800 Torr and reduced electric field strength E/N range of 40–1200 Td utilizing a steady-state non-self-sustaining Townsend discharge. Experimental results were compared with calculations of Boltzmann equation solver BOLSIG+. Differences between measurements and calculations increased with decreasing CO2 content in the mixture down to 20%, and the differences were highest at low E/N values (below 150 Td). As the simple modification of the model, contribution of ionization of CO2 by Penning transfer from Ar* 3p53d excited states (13.86 eV) was added to the BOLSIG+ calculations, which resulted in good fit of the experimental measurements. Comparison of CO2 addition to Ar with the addition of O2 or N2 revealed that ionization of CO2 or O2 from Ar* 3p53d excited states influences ionization in Ar:CO2 and Ar:O2 mixtures but not in Ar:N2 mixtures, due to the different ionization energies of CO2, O2, and N2.

Effect of Wheat Residue-Derived Biochar on Naphthalene Adsorption in Loess Soil in Northwest China

Research on the environmental behavior of polycyclic aromatic hydrocarbons (PAHs) in soil is limited, particularly regarding the influence of biochar on naphthalene (NAP) adsorption on the loess soil of Northwest China. In this study, a batch equilibrium experiment was used to analyze the sorption kinetics, sorption isotherms, and influencing factors of NAP adsorption by biochar derived from wheat residue at various pyrolysis temperatures on loess soil. The results indicated that NAP adsorption onto biochar-modified soil was rapid, within 6 h, and reached equilibrium after 20 h. The sorption kinetics was accurately described by a pseudo-second-order model. Additionally, the sorption isotherms were best described by the Freundlich model, indicating a multilayer adsorption mechanism. The average value of KF decreased as follows: BC-600 (2.03) > BC-400 (1.52) > BC-200 (1.25) > soil (0.91), indicating that biochar addition was beneficial for the adsorption of NAP on loess soil. The Gibbs free energy (ΔGθ) of NAP was less than zero, and the enthalpy (ΔHθ) and entropy (ΔSθ) values were greater than zero, suggesting that the adsorption occurred spontaneously through an endothermic reaction. Furthermore, the initial concentration of NAP influenced its adsorption amount. Pyrolysis temperatures of 400 °C and 600 °C resulted in higher NAP adsorption capacities, highlighting the beneficial effect of biochar addition on enhancing NAP adsorption in loess soil. However, at a pyrolysis temperature of 200 °C, the process of carbonization became incomplete, resulting in a reduction in the adsorption amount.

CD22L Conjugation to Insulin Attenuates Insulin-Specific B Cell Activation.

Pancreatic islet-reactive B lymphocytes promote Type 1 diabetes (T1D) by presenting an antigen to islet-destructive T cells. Teplizumab, an anti-CD3 monoclonal, delays T1D onset in patients at risk, but additional therapies are needed to prevent the disease entirely. Therefore, bifunctional molecules were designed to selectively inhibit T1D-promoting anti-insulin B cells by conjugating a ligand for the B cell inhibitory receptor CD22 (i.e., CD22L) to insulin, which permit these molecules to concomitantly bind to anti-insulin B cell receptors (BCRs) and CD22. Two prototypes were synthesized: 2:2 insulin-CD22L conjugate on a 4-arm PEG backbone, and 1:1 insulin-CD22L direct conjugate. Transgenic mice (125TgSD) expressing anti-insulin BCRs provided cells for in vitro testing. Cells were cultured with constructs for 3 days, then assessed by flow cytometry. Duplicate wells with anti-CD40 simulated T cell help. A 2-insulin 4-arm PEG control caused robust proliferation and activation-induced CD86 upregulation. Anti-CD40 further boosted these effects. This may indicate that BCR-cross-linking occurs when antigens are tethered by the PEG backbone as soluble insulin alone has no effect. Addition of CD22L via the 2:2 insulin-CD22L conjugate restored B cell properties to that of controls without an additional beneficial effect. In contrast, the 1:1 insulin-CD22L direct conjugate significantly reduced anti-insulin B cell proliferation in the presence of anti-CD40. CD22L alone had no effect, and the constructs did not affect the WT B cells. Thus, multivalent antigen constructs tend to activate anti-insulin B cells, while monomeric antigen-CD22L conjugates reduce B cell activation in response to simulated T cell help and reduce pathogenic B cell numbers without harming normal cells. Therefore, monomeric antigen-CD22L conjugates warrant futher study and may be promising candidates for preclinical trials to prevent T1D without inducing immunodeficiency.

The beneficial effect of barley straw extract addition on the growth of two aquatic invasive alien species (Elodea nuttallii and Cabomba caroliniana) under laboratory conditions

AbstractBarley straw has been used around the world for decades as a simple, cost-effective and harmless phytoplankton growth inhibition method. Although the effect of this method on algal blooms is quite well depicted, it has not yet been tested what effect it has on submerged vascular plants and if it could be used to control the spread of alien macrophytes. In this study two highly invasive plant species: Cabomba caroliniana and Elodea nuttallii were exposed to different concentration of the barley straw extract (BSE) in laboratory conditions for a duration of four weeks. In the course of the investigations, responses of 8 traits associated with growth, biomass and chlorophyll concentration of specimens to three dosages (Low, Medium, High) of BSE corresponding to concentrations: 0.03, 0.30 and 1.50 ml l−1 were analysed. The result showed that although dry mass and total length of the plants did not differ significantly between the test groups, increase in tillering and internodes number was observed for certain concentrations of the extract. This shows that if BSE has any effect on submerged macrophytes it is a positive one and thus the method is not suitable for invasive submerged aquatic plant control. Furthermore, it is recommended that before using barley straw for algae bloom control one should make sure that there are no alien aquatic submerged plants in the area that could benefit from such a treatment.

The beneficial effect of Fe addition in PbTe-Ni diffusion bonded thermoelectric contact interfaces – A comprehensive phase evolution study

The development of reliable interconnects in thermoelectric (TE) modules is essential for the durability and serviceability of these solid-state devices. PbTe-based devices are used in mid-temperature range applications, with Ni being the most preferred interconnect. Ni reacts with PbTe to form a binary intermetallic, Ni3Te2 (β2). The sustained growth of this phase at higher service temperatures is adversarial to the long-term reliability of interconnects. This paper reports and discusses the beneficiary role of minor Fe-addition in the Ni contact alloy to arrest such unwarranted chemical interaction while ensuring proper bonding. PbTe and Ni-Fe (Fe = 1 at.%, 5 at.%) discs are diffusion bonded at 700 °C for various holding times. The current investigation leads to three noteworthy observations: 1) the formation of Fe-enriched Ni-Fe phase islands at the interface at microscale (1 - 10 µm), (2) Fe-segregation at the local interfaces (∼ 10 nm), and (3) the growth of a Ni-rich metastable Ni3-xTe phase, not present in Ni-Te binary phase diagram. Detailed examinations of these phenomena and crystallographic relations (β2 and Ni3-xTe) are conducted through advanced analytical TEM/STEM techniques. Furthermore, the PbTe-Ni reaction formulation is modified to accommodate such a Fe-enrichment phenomenon and is validated through free energy calculations.

Comparison of subthalamic unilateral and bilateral theta burst deep brain stimulation in Parkinson's disease.

High-frequency, conventional deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD) is usually applied bilaterally under the assumption of additive effects due to interhemispheric crosstalk. Theta burst stimulation (TBS-DBS) represents a new patterned stimulation mode with 5 Hz interburst and 200 Hz intraburst frequency, whose stimulation effects in a bilateral mode compared to unilateral are unknown. This single-center study evaluated acute motor effects of the most affected, contralateral body side in 17 PD patients with unilateral subthalamic TBS-DBS and 11 PD patients with bilateral TBS-DBS. Compared to therapy absence, both unilateral and bilateral TBS-DBS significantly improved (p < 0.05) lateralized Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) scores. Bilateral TBS-DBS revealed only slight, but not significant additional effects in comparison to unilateral TBS-DBS on total lateralized motor scores, but on the subitem lower limb rigidity. These results indicate that bilateral TBS-DBS has limited additive beneficial effects compared to unilateral TBS-DBS in the short term.

Towards reducing tension-compression yield and cyclic asymmetry in pure magnesium and magnesium-aluminum alloy with cerium addition

In this study, we report the effect of cerium (Ce) addition on the tension-compression yield and cyclic asymmetry in commercially pure magnesium (Cp-Mg) and Mg–Al alloy at room temperature (RT). The investigated materials Cp-Mg, Mg-0.5Ce, and Mg–3Al-0.5Ce were extruded at 400 °C, followed by annealing at the same temperature for 1 h. Incorporating 0.5 wt% Ce in pure Mg results in the weakening of its basal texture, uniform distribution of Mg12Ce precipitates, and grain size refinement. Consequently, the tensile yield strength and ductility of pure Mg increased, and tension-compression yield asymmetry was eliminated. However, the presence of 3 wt% Al in Mg suppresses the beneficial effects of Ce addition. The formation of non-uniformly distributed complex precipitates, such as Mg–Al–Ce and Al11Ce3, limits the weakening of the basal texture, reduction in grain size, improvement in ductility, and elimination of tension-compression yield asymmetry observed in Mg-0.5Ce. Nevertheless, Al contributes to the solid solution strengthening in Mg and possibly lowers the critical stress required for twinning in Mg, resulting in the highest tensile strength of Mg–3Al-0.5Ce. Finally, the addition of 0.5 wt% Ce enhances the cyclic strength, stabilizes cyclic stress response, reduces inelastic strain, and minimizes cyclic asymmetry in both pure Mg and Mg–Al alloy while maintaining a comparable fatigue life. Overall, Ce addition positively impacts the microstructure and mechanical behavior of pure Mg and its investigated alloy. The reasons for these improvements are discussed in detail.

Metabolic and cardiovascular benefits and risks of 4-hydroxy guanabenz hydrochloride: α2-adrenoceptor and trace amine-associated receptor 1 ligand

Backgroundα2-adrenoceptor ligands have been investigated as potential therapeutic agents for the treatment of obesity. Our previous studies have shown that guanabenz reduces the body weight of obese rats, presumably through its anorectic action. This demonstrates an additional beneficial effect on selected metabolic parameters, including glucose levels. The purpose of this present research was to determine the activity of guanabenz's metabolite—4-hydroxy guanabenz hydrochloride (4-OH-Guanabenz).MethodsWe performed in silico analyses, involving molecular docking to targets of specific interest as well as other potential biological targets. In vitro investigations were conducted to assess the selectivity profile of 4-OH-Guanabenz binding to α-adrenoceptors, along with intrinsic activity studies involving α2-adrenoceptors and trace amine-associated receptor 1 (TAAR1). Additionally, the effects of 4-OH-Guanabenz on the body weight of rats and selected metabolic parameters were evaluated using the diet-induced obesity model. Basic safety and pharmacokinetic parameters were also examined.Results4-OH-guanabenz is a partial agonist of α2A-adrenoceptor. The calculated EC50 value for it is 316.3 nM. It shows weak agonistic activity at TAAR1 too. The EC50 value for 4-OH-Guanabenz calculated after computer simulation is 330.6 µM. Its primary mode of action is peripheral. The penetration of 4-OH-Guanabenz into the brain is fast (tmax = 15 min), however, with a low maximum concentration of 64.5 ng/g. 4-OH-Guanabenz administered ip at a dose of 5 mg/kg b.w. to rats fed a high-fat diet causes a significant decrease in body weight (approximately 14.8% compared to the baseline weight before treatment), reduces the number of calories consumed by rats, and decreases plasma glucose and triglyceride levels.ConclusionsThe precise sequence of molecular events within the organism, linking the impact of 4-OH-Guanabenz on α2A-adrenoceptor and TAAR1 with weight reduction and the amelioration of metabolic disturbances, remains an unresolved matter necessitating further investigation. Undoubtedly, the fact that 4-OH-Guanabenz is a metabolite of a well-known drug has considerable importance, which is beneficial from an economic point of view and towards its further development as a drug candidate.

High-pressure drop rates in solid-state batch one-step scCO2 foaming of acrylic polymers: A way to stabilize the structure of micro-nano foams

One-step solid-state batch scCO2 foaming is used with the target of achieving acrylic polymer micro-nano foams. Foaming is triggered by an average pressure drop (APDR), covering two decades, from 0.3 to 30 MPa.s−1. This study principally addresses the combined beneficial effects of block copolymer addition (BCP, here denoted as MAM) and high APDR. Numerous subtle kinetic parameters actually interplay and compete in the production of the final foams. In particular, the material effective temperature, the effective glass transition temperature of the plasticized system and the instantaneous PDR are physical quantities each having their own kinetics during foaming. The resulting foam morphologies are quantified by SEM microscopy and image analysis. A high APDR and the presence of BCP are shown to play a key role in the final structure of the foams. Over the scrutinized range of saturation temperature (40 °C to 60 °C i.e. rather ‘low’ temperatures in the CO2 supercritical state), the APDR is the main factor for significantly reducing cell size and increasing nuclei density in foams from neat PMMA. In the block copolymer approach, increasing the APDR is of secondary importance as the targeted reduction of the porosity dimensions and augmentation of nuclei density are mostly the consequence of MAM presence. In this latter case, increasing the APDR still promotes the ‘efficiency’ of the BCP nucleants. A real efficient nucleation activity of MAM additive is observed at a very high APDR (30 MPa.s−1), leading to monomodal homogeneous distribution of tiny pores in nearly nanosized foams. At lower APDR, an interesting reproducible double porosity (foams containing intra-wall and inter-wall pores) is detected in PMMA/MAM systems. In such double porosity foams, benefits from the Knudsen effect achieved within well expanded local domains (showing micron-sized pores) may remain meaningful thanks to a locally poorly expanded nanoporous thick solid skeleton encapsulating these local domains. Thereby, the radiative thermal conduction can be minimized and does not override the conductive component at the sample scale. This work provides further insight on acrylic polymer BCP foams influenced by different kinetics.

The Gulf Achievement of Cholesterol Targets in Out-Patients Study (GULF ACTION): Design, Rationale, and Preliminary Results.

To assess the current dyslipidemia management in the Arabian Gulf region by describing the demographics, study design, and preliminary results of out-patients who achieved low-density lipoprotein cholesterol (LDL-C) goals at the time of the survey. The Arabian Gulf population is at high risk for atherosclerotic cardiovascular disease at younger ages. There is no up-to-date study regarding dyslipidemia management in this region, especially given the recent guideline-recommended LDL-C targets. Up-to-date comprehensive assessment of the current dyslipidemia management in the Arabian Gulf region, particularly in view of the recent evidence of the additive beneficial effects of ezetimibe and proprotein convertase subtilisin/kexin-9 (PCSK-9) inhibitors on LDL-C levels and cardiovascular outcomes. The Gulf Achievement of Cholesterol Targets in Out-Patients (GULF ACTION) is an ongoing national observational longitudinal registry of 3000 patients. In this study, adults ≥18 years on lipid-lowering drugs for over three months from out-patients of five Gulf countries were enrolled between January 2020 and May 2022 with planned six-month and one-year follow-ups. Of the 1015 patients enrolled, 71% were male, aged 57.9±12 years. In addition, 68% had atherosclerotic cardiovascular disease (ASCVD), 25% of these patients achieved the LDL-C target, and 26% of the cohort were treated using combined lipid-lowering drugs, including statins. The preliminary results of this cohort revealed that only one-fourth of ASCVD patients achieved LDL-C targets. Therefore, GULF ACTION shall improve our understanding of current dyslipidemia management and "guideline gaps" in the Arabian Gulf region.

Comparison of Two Different Doses of Nalbuphine With Isobaric Ropivacaine in Patients Undergoing Lower Segment Cesarean Section Under Subarachnoid Block: A Randomized Controlled Trial.

Obstetric analgesia and anesthesia is a challenge in itself. It requires an understanding of the physiological changes during pregnancy and labor and the effect of anesthetic agents on the fetus and newborn. Because neuraxial techniques provide superior analgesia and materno-fetal benefits, their use have increased significantly over the past three decades or so. A combination of local anesthetics like ropivacaine with opioids like nalbuphine has been shown to have additive beneficial effects in subarachnoid block (SAB) in lower segment cesarean section (LSCS). However, the optimal dose combination of ropivacaine and nalbuphine to maximize their benefits and minimize side effects remains to be established. Our study has compared the clinical efficacy and safety of 0.75% isobaric ropivacaine (15 mg) with two different doses of nalbuphine (0.4 mg and 0.6 mg) when given intrathecally for LSCS in terms of quality of sensory and motor blocks, hemodynamic parameters, duration of effective analgesia, Apgar score in newborn, and associated side effects. In this prospective, randomized, double-blind study, a total of 69 parturients between the age of 20-45 years, belonging to American Society of Anesthesiologists (ASA) grade I and II, undergoing cesarean section under SAB were evaluated. Patients were randomly allocated into three groups of 23 each by using the draw-of-lots technique. The patient and the observer were kept blinded as to which dose of drug (intrathecal) was being given to the patient. Patients in Group A received 0.75% isobaric ropivacaine 15 mg (2 ml) + 0.3 ml normal saline; patients in Group B received 0.75% isobaric ropivacaine 15 mg (2 ml) + 0.4 mg of nalbuphine (0.2 ml) + 0.1 ml normal saline; patients in Group C received 0.75% isobaric ropivacaine 15 mg (2 ml) + 0.6 mg of nalbuphine (0.3 ml). The total volume of drug solution in all three groups was 2.3 ml. We found that the time to onset of sensory block was shortest in Group A (5.87±1.290 minutes) followed by Group C (6.00±1.087 minutes) and Group B (6.17±1.696 minutes); time to two-segment regression of sensory block was longest in Group C (101.74±8.996 minutes) followed by Group B (85.87±15.348 minutes) and Group A (65.00±7.071 minutes); duration of effective analgesia was longest in Group C (206.09±18.766 minutes) followed by Group B (183.91±15.880 minutes) and Group A (121.74±11.833 minutes); and time from SAB to complete regression of motor block was longest in Group C (216.52±15.553 minutes) followed by Group B (203.48±20.138 minutes) and Group A (174.78±14.731 minutes). Side effectswere comparable among all three groups. The optimal dose combination in SAB for cesarean section was 15 mg of 0.75% isobaric ropivacaine + 0.6 mg nalbuphine, with minimal side effects.

Effect of pelvic floor muscle training on reports of urinary incontinence in obese women undergoing a low-calorie diet before bariatric surgery — protocol of a randomized controlled trial

BackgroundObesity represents a growing threat to health with multiple negative impacts including urinary incontinence. Pelvic floor muscle training (PFMT) is the first line of treatment for urinary incontinence. Both surgical and conservative weight loss results in improvement of urinary incontinence reports in obese women and we hypothesize that a low-calorie diet in combination with PFMT would result in additional beneficial effects to urinary symptoms in women with UI compared would with weight loss alone.ObjectiveTo assess the effect of a low-calorie diet plus PFMT protocol in obese women’s urinary incontinence reports.MethodsThis is a protocol for a randomized controlled trial that will include obese women reporting UI and being able to contract their pelvic floor muscles. The participants will be randomly allocated in two groups: group 1 will participate in a 12-week protocol of low-calorie diet delivered by a multi-professional team at a tertiary hospital; group II will receive the same low-calorie diet protocol during 12 weeks and will additionally participate in 6 group sessions of supervised PFMT delivered by a physiotherapist. The primary outcome of the study is self-reported UI, and severity and impact of UI on women’s quality of life will be assessed by the ICIQ-SF score. The secondary outcomes will be adherence to the protocols assessed using a home diary, pelvic floor muscle function assessed by bidigital vaginal palpation and the modified Oxford grading scale, and women’s self-perception of their PFM contraction using a questionnaire. Satisfaction with treatments will be assessed using a visual analog scale. The statistical analysis will be performed by intention to treat and multivariate analysis of mixed effects will be used to compare outcomes. The complier average causal effects (CACE) method will be used to assess adherence. There is an urgent need for a high-quality RCT to investigate if the association of a low-calorie diet and PFMT can provide a larger effect in the improvement of urinary incontinence reports in women with obesity.Trial registrationClinical Trials NCT04159467. Registered on 08/28/2021.

Long-term properties of self-cleaning alkali-activated slag-based mortars with titanium dioxide nanoparticles

Titanium dioxide (TiO2) is considered one of the most efficient photocatalysis to produce self-cleaning cementitious materials. At the same time, alkali activated binders have become one of the most interesting low-carbon alternatives to Portland cement. For this, the addition of titanium dioxide nanoparticles in one-part alkali-activated slag-based (AAS) mortars was analyzed to evaluate the effect on the rheological and mechanical properties, dirt pick-up resistance as well as self-cleaning capability. This paper reports a two-year campaign of outdoor exposure in an industrial environment in Northern Italy to investigate the natural photoactivity of the mortars doped with different TiO2 dosages. The experimental results indicated limited effect of nanoparticles on the rheology and mechanical properties of AAS mortars. It was also highlighted the beneficial effect of TiO2 addition in self-cleaning capability under natural and accelerated conditions and the fundamental role in photocatalytic efficiency of the alkali content.