Maximal Reduction Research Articles

Effect of Liraglutide in Different Abdominal Fat Layers Measured by Ultrasound: The Importance of Perirenal Fat Reduction

Introduction: Ultrasonography (US) in patients with obesity allows us to measure different layers of abdominal fat (superficial subcutaneous, deep subcutaneous, preperitoneal, omental, and perirenal), not assessable by DEXA or CT scan. Omental and perirenal fat depots are considered predictors of metabolic complications. Liraglutide is particularly effective in reducing weight in patients with insulin-resistance, but its direct impact on each abdominal fat layer is unknown. Methods: We measured, at the L4 level, all 5 abdominal fat depots in 860 patients with obesity (72.8% women, mean age 56.6 ± 1.5 years, BMI 34.4 ± 4.7 kg/m2, body fat 47 ± 2%, abdominal circumference 105.8 ± 3 cm), before and after 6 months of liraglutide treatment. Laboratory tests for glucose, insulin, and lipid profile were routinely done. T-student was used to compare intraindividual differences. Results: Weight loss was 7.5 ± 2.8 kg (7.96% from baseline), with no differences by sex/age/BMI. Greater loss was observed in patients with higher dosages and NAFLD. All US-measured fat layers showed a significant reduction (p < 0.05) at 6th months. Preperitoneal fat showed a −26 ± 5.5% reduction and 46% of the patients went below metabolic syndrome (MS) risk cut-off values. Omental fat was reduced by −17.8 ± 5% (67% of the patients below MS risk) and perirenal fat by −22.4 ± 4.4% (56% of the patients below MS). Both omental and perirenal fat reduction correlated with total and LDL cholesterol. Higher perirenal fat reduction (−28%) was seen among patients with obesity and hypertension. Perirenal fat also correlated with blood pressure reduction. Conclusion: Liraglutide induces greater fat loss in the layers involved with MS. However, the maximal reduction is seen at perirenal fat, which has been recently related with hypertension and could play an important role in modulating kidney’s expansion and intraglomerular pressure. US is a reproducible clinical tool to assess pathologic fat depots in patients living with obesity.

Optimizing network robustness via Krylov subspaces

We consider the problem of attaining either the maximal increase or reduction of the robustness of a complex network by means of a bounded modification of a subset of the edge weights. We propose two novel strategies combining Krylov subspace approximations with a greedy scheme and an interior point method employing either the Hessian or its approximation computed via the limited-memory Broyden-Fletcher-Goldfarb-Shanno algorithm (L-BFGS). The paper discusses the computational and modeling aspects of our methodology and illustrates the various optimization problems on networks that can be addressed within the proposed framework. Finally, in the numerical experiments we compare the performances of our algorithms with state-of-the-art techniques on synthetic and real-world networks.

Multi-Device Task-Oriented Communication via Maximal Coding Rate Reduction

Multi-Device Task-Oriented Communication via Maximal Coding Rate Reduction

Pediatric procedural sedation: a new protocol implemented

Pediatric procedural sedation is a difficult exercise aiming to find the balance between optimal quality of a medical imaging or act, and maximal reduction of risks for the patient. Harmlessness of chloral hydrate has been recently questioned, thus promoting the use of the dexmedetomidine for these kinds of procedures. In this context we decided to develop a new protocol at the CHUV. We tested different combinations of molecules until we found the best association and dosage. We present here the analysis of our patient cohort, attesting the efficiency, reliability, and safety of combined dexmedetomidine and midazolam given intranasal for pediatric MRI.

Classification of binding property of amyloid β to lipid membranes: Membranomic research using quartz crystal microbalance combined with the immobilization of lipid planar membranes

A biomembrane-related fibrillogenesis of Amyloid β from Alzheimer’ disease (Aβ) is closely related to its accumulation behavior. A binding property of Aβ peptides from Alzheimer’ disease to lipid membranes was then classified by a quartz crystal microbalance (QCM) method combined with an immobilization technique using thiol self-assembled membrane. The accumulated amounts of Aβ, Δfmax, was determined from the measurement of the maximal frequency reduction using QCM. The plots of Δfmax to Aβ concentration gave the slope and saturated value of Δfmax, (Δfmax)sat that are the parameters for binding property of Aβ to lipid membranes. Therefore, the Aβ-binding property on lipid membranes was classified by the slope and (Δfmax)sat. The plural lipid system was described as X + Y where X = L1, L1/L2, and L1/L2/L3. The slope and (Δfmax)sat values plotted as a function of mixing ratio of Y to X was classified on a basis of the lever principle (LP). The LP violation observed in both parameters resulted from the formation of the crevice or pothole, as Aβ-specific binding site, generated at the boundary between ld and lo phases. The LP violation observed only in the slope resulted from glycolipid-rich domain acting as Aβ-specific binding site. Furthermore, lipid planar membranes indicating strong LP violation favored strong fibrillogenesis. Especially, lipid planar membranes indicating the LP violation only in the slope induced lateral aggregated and spherulitic fibrillar aggregates. Thus, the classification of Aβ binding property on lipid membranes appeared to be related to the fibrillogenesis with a certain morphology.

Computational Comparison of the Mechanical Behavior of Aortic Stent-Grafts Derived from Auxetic Unit Cells

PurposeInappropriate stent-graft (SG) flexibility has been frequently associated with endovascular aortic repair (EVAR) complications such as endoleaks, kinks, and SG migration, especially in tortuous arteries. Stents derived from auxetic unit cells have shown some potential to address these issues as they offer an optimum trade-off between radial stiffness and bending flexibility.MethodsIn this study, we utilized an established finite element (FE)-based approach to replicate the mechanical response of a SG iliac limb derived from auxetic unit cells in a virtual tortuous iliac aneurysm using a combination of a 180° U-bend and intraluminal pressurization. This study aimed to compare the mechanical performance (flexibility and durability) of SG limbs derived from auxetic unit cells and two commercial SG limbs (Z-stented SG and circular-stented SG models) in a virtual tortuous iliac aneurysm. Maximal graft strain and maximum stress in stents were employed as criteria to estimate the durability of SGs, whereas the maximal luminal reduction rate and the bending stiffness were used to assess the flexibility of the SGs.ResultsSG limbs derived from auxetic unit cells demonstrated low luminal reduction (range 4–12%) with no kink, in contrast to Z-stented SG, which had a kink in its central area alongside a high luminal reduction (44%).ConclusionsSG limbs derived from auxetic unit cells show great promise for EVAR applications even at high angulations such as 180°, with acceptable levels of durability and flexibility.

Comparative Study of Organics Removal from Refinery Wastewater by Photocatalytic Fenton Reaction Coupled with Visible Light and Ultraviolet Irradiation

The study investigates photocatalytic advanced oxidation processes using iron-doped zeolite catalysts in heterogeneous Fenton reactions to degrade organic contents as chemical oxygen demand. The research revealed that the heterogenous photocatalytic Fenton process was the most successful treatment method under acidic circumstances and generated a greater rate of chemical oxygen demand degradation in a concise amount of radiation time. Compared to the heterogenous Fenton process with ultraviolet irradiation, it increased oxidation and was affected by catalyst load, power of hydrogen pH, hydrogen peroxide amounts, and temperature. The findings showed that the iron-doped zeolite catalyst, pH, and temperature significantly degraded the chemical oxygen demand. The experiment determined that the optimal conditions were obtained at a catalyst load of 0.07 g, pH of 3, with 20% excess of hydrogen peroxide, 40 °C in 2 hours for the ultraviolet/ iron-doped zeolite/hydrogen peroxide system that gave 99.84 % of the removal of the chemical oxygen demand. The heterogeneous photocatalytic Fenton method accompanied the reactions by hydroxyl radical production, which quickly reached its maximal reduction.

Primary cystic echinococcosis of the peritoneum: a case report

BackgroundPeritoneal cystic echinococcosis happens usually after traumatic rupture or after surgical treatment. Primary peritoneal cystic echinococcosis is a very rare case that constitutes a diagnostic and therapeutic challenge.Case reportA 30-year-old Tunisian man was admitted for hypogastric pain since 4 months. He has a 10 cm hypogastric mass. Biological-tests were normal. A computed tomography Scan showed a cystic mass on the pelvis measuring 13 × 17 cm without echinococcosis cyst in the liver.The patient was operated and we found a cystic mass of 17 cm located on the Douglas cul-de-sac that suggest a pelvic hydatid cyst. We have performed an aspiration of the cyst confirms the diagnosis followed by injection of hypertonic solution, extarction of the germinal layer and a maximal reduction of the pericyst. The postoperative course was uneventful.ConclusionTrough our case, we try to focus on the diagnosis and therapeutic options of this rare entity that we should think of in front of a patient with isolated peritoneal cyst especially in endemic country.

Prediction of CYP Down Regulation after Tusamitamab Ravtansine Administration (aDM4-Conjugate), Based on an In Vitro-In Vivo Extrapolation Approach.

Tusamitamab ravtansine is an antibody-drug conjugate (ADC) composed of a humanized monoclonal antibody (IgG1) and DM4 payload. Even if DM4 and its main metabolite methyl-DM4 (Me-DM4) circulate at low concentrations after ADC administration, their potential as perpetrators of cytochrome P450 mediated drug-drug interaction was assessed. In vitro studies in human hepatocytes indicated that Me-DM4 elicited a clear concentration-dependent down regulation of cytochrome P450 enzymes (CYP3A4, 1A2, and 2B6). Because DM4 was unstable under the incubation conditions studied, the in vitro constants could not be determined for this entity. Thus, to predict the clinical relevance of this observed downregulation, an in vitro-in vivo extrapolation (IVIVE) pharmacokinetic (PK) based approach was developed. To mitigate model prediction errors and because of their similar inhibitory effect on tubulin polymerization, the same downregulation constants were used for DM4 and Me-DM4. This approach describes the time course of decreasing CYP3A4, 1A2, and 2B6 enzyme amounts as a function of circulating concentrations of DM4 and Me-DM4 predicted from a population PK model. The developed IVIVE-PK model showed that the highest CYP abundance decrease was observed for CYP3A4, with a transient reduction of < 10% from baseline. The impact on midazolam exposure, as probe substrate of CYP3A, was then simulated based on a physiologically-based PK static method. The maximal CYP3A4 abundance reduction was associated with a predicted midazolam area under the curve (AUC) ratio of 1.14. To conclude, the observed in vitro downregulation of CYPs by Me-DM4 is not expected to have relevant clinical impact.

Exposure Assessment of Infectious Virus Particles in a Classroom Setting Using Computational Fluid Dynamics Model

Indoor air quality in classrooms directly affects comfort, focus, and academic performance. This research leveraged Computational Fluid Dynamics (CFD) to analyze the dispersion of infectious virus particles in classrooms. While Negative Pressure Systems (NPS) are often used at medical centers to inhibit virus particles’ dispersion, those are seldom applied in educational settings. The study aimed to pinpoint optimal ventilation and heating/AC flow rates to prevent virus particle spread. Results showed that prioritizing a higher flow rate at the ventilation unit over the heating/AC unit creates a negative pressure differential, decreasing virus dispersion by up to 93%. To establish negative pressure, the minimum flow rate ratio of ventilation to heating/AC should be 1.0. But for maximal virus particle reduction, a ratio of 2.8 is optimal. This research underscores CFD's value in understanding NPS dynamics and simulating virus behavior in classrooms. The findings suggest that NPS implementation in schools could significantly curb virus particle spread.

Durable Continuous Transfusion Independence (TI) with Imetelstat in IMerge Phase 3 for Patients with Heavily Transfused Non-Del(5q) Lower-Risk Myelodysplastic Syndromes (LR-MDS) Relapsed/Refractory (R/R) to or Ineligible for Erythropoiesis-Stimulating Agents (ESAs)

CONCLUSIONS MDS are serious life-threatening hematologic malignancies in which a heterogeneous group of clonal disorders results in ineffective hematopoiesis. An unmet need remains for new therapies for patients (pts) with LR-MDS who are red blood cell transfusion dependent (RBC-TD) and R/R to or ineligible for ESAs. Imetelstat, an oligonucleotide, is a first-in-class telomerase inhibitor that targets cells with high telomerase activity by direct binding to the RNA template of telomerase. In the IMerge phase 3 trial, imetelstat produced higher rates of TI for ≥8 weeks, ≥24 weeks, and ≥1 year (39.8%, 28.0%, and 17.8%) than placebo (15.0%, 3.3%, and 1.7%) in pts with non-del(5q) LR-MDS that was RBC-TD, R/R to/ineligible for ESAs, and naïve to lenalidomide or hypomethylating agents (HMAs; Platzbecker et al. EHA 2023. Abstr S165). We report characteristics and clinical benefit for pts with sustained TI for ≥1 year from this trial. IMerge (MDS3001, NCT02598661) is a global, double-blind, randomized, placebo-controlled, phase 3 trial of imetelstat in RBC-TD, ESA-R/R, non-del 5(q) lenalidomide/HMA-naïve LR-MDS. The primary end point was 8-week TI rate; secondary end points included safety, 24-week TI, duration of response, hematologic improvement, and MDS response. Exploratory end points included assessment of cytogenetic response and mutational status with clinical response. The proportion of pts with&amp;gt;1-year TI and other binary end points, were summarized with percentage and 95% 2-sided exact Clopper-Pearson CI. The Kaplan-Meier method was used to estimate the distribution of TI. Of 118 pts receiving imetelstat, 21 (17.8%; 95% CI, 11.4-25.9) achieved ≥1-year sustained TI, representing 45% of ≥8-week TI (21 of 47 pts) and 64% of ≥24-week TI (21 of 33 pts); of 60 pts receiving placebo plus supportive care, 1 (1.7%; 95% CI, 0-8.9) achieved ≥1-year TI. Of the ≥1-year TI imetelstat responders, 15/21 (71.4%) had ring sideroblasts, as did the 1 placebo pt. The median prior RBC transfusion burden was 6 U over 8 weeks (range, 4-9 U) for the imetelstat group and 5 U for the placebo pt. Additional baseline characteristics are in the table. Pts received imetelstat for a median of 101.1 weeks (range, 75.1-163.9 weeks) and a median of 24 cycles (range, 18-41 cycles). The median duration of TI for imetelstat ≥1-year TI responders was 123 weeks (95% CI, 80.4 to not evaluable); the median increase in hemoglobin during the longest TI interval was 5.18 g/dL (range, 2.67-13.76 g/dL) for the imetelstat group vs 1.67 g/dL for the placebo pt. After a median follow-up of 125 weeks, none of the patients with ≥1 year TI on either arm progressed to acute myeloid leukemia (AML). Of the pts receiving imetelstat, 7 had an abnormal karyotype at baseline, of which 6 had reduction in the cytogenetic abnormal clones (4 with cytogenetic complete response and 2 with cytogenetic partial response by independent review committee). Mutation data were available for 18 pts receiving imetelstat, all with SF3B1 mutations present at baseline, and multiple of these pts concurrently had TET2, DNMT3A, ASXL1, or JAK2 mutations. The maximal reduction ranged from −6% to −100% in SF3B1 variant allele frequency (VAF) in these pts, and 13 of 18 (72.2%) achieved ≥50% VAF reduction, including 7 with complete elimination of the VAF. Reduction in other concurrent mutations was also observed in these pts. Safety was consistent with that previously reported; most frequent adverse events were reversible grade 3 or 4 thrombocytopenia and neutropenia. At the time of data cutoff (May 10, 2023), 13 pts receiving imetelstat and the pt receiving placebo were ongoing (Figure); of the 8 who discontinued treatment, 7 had loss of response, and 1 was due to adverse event. Analyses for progression-free and overall survival were not evaluable as of this cutoff date (insufficient follow-up). Treatment with imetelstat resulted in ≥1-year sustained, continuous TI in 17.8% of pts in the IMerge phase 3 trial. In this ESA-R/R/ineligible population with a high prior transfusion burden, a reduction to 0 RBC transfusions for ≥1 year represents an opportunity to achieve relief from iron overload and other transfusion associated complications, and decreased demand on already limited blood product supply. Furthermore, durable TI and meaningful reductions in mutational burden suggest imetelstat may have disease-modifying activity.

Mechanisms underlying treatment effects of vestibular noise stimulation on postural instability in patients with bilateral vestibulopathy.

Previous studies indicate that imbalance in patients with bilateral vestibulopathy (BVP) may be reduced by treatment with low-intensity noisy galvanic vestibular stimulation (nGVS). To elucidate the potential mechanisms underlying this therapeutic effect. In particular, we determined whether nGVS-induced balance improvements in patients are compatible with stochastic resonance (SR)-a mechanism by which weak noise stimulation can paradoxically enhance sensory signal processing. Effects of nGVS of varying intensities (0-0.7mA) on body sway were examined in 19 patients with BVP standing with eye closed on a posturographic force plate. We assumed a bell-shaped response curve with maximal sway reductions at intermediate nGVS intensities to be indicative of SR. An established SR curve model was fitted on individual patient outcomes, and three experienced human raters had to judge whether responses to nGVS were consistent with the exhibition of SR. nGVS-induced reductions of body sway compatible with SR were found in 12 patients (63%) with optimal improvements of 31 ± 21%. In 10 patients (53%), nGVS-induced sway reductions exceeded the minimally important clinical difference (optimal improvement: 35 ± 21%), indicative of strong SR. This beneficial effect was more likely in patients with severe vestibular loss (i.e. lower video head impulse test gain; R = 0.663; p = 0.002) and considerable postural imbalance (baseline body sway; R = 0.616; p = 0.005). More than half of the assessed patients showed robust improvements in postural balance compatible with SR when treated with nGVS. In particular, patients with a higher burden of disease may benefit from the non-invasive and well-tolerated treatment with nGVS.

Phytoremediation for Nutrient Removal in an Environmentally Friendly Floating Cage System: A Field Experiment

Aquaculture is one of the efforts to optimize the utilization of water bodies. Aquaculture using floating net cages is detrimental to water, namely causing pollution from uneaten feed and fish excretion. Water quality would be degraded due to eutrophication, oxygen depletion, and uncontrolled growth of algae and aquatic plants. High concentrations of nitrogen and phosphorus mainly trigger water quality degradation and eutrophication. To reduce the negative impact of aquaculture activities in floating net cages in reservoir/lake waters, an environmentally friendly cage technology that is low waste is needed. The technology offered is a loop bio-phytoremediation system equipped with floating net cages, a water management system with recirculation, and plants. The floating net cage used is a double net where the upper net consists of two nets and a bottom net. The upper net is used for rearing carp fish, and the bottom net for tilapia. The plants used as phytoremediation agents were water spinach and vetiver grass. Moreover, the physical filter used for processed water before recirculating to the waterbody in the FNC consists of sand, palm fiber, and limestone layers. The results showed that the effectiveness of nutrient removal on water spinach hydroponic (HRT=15 h), vetiver grass wetland (HRT=36 h), and physical filters (HRT=2,4 h) in reducing nitrate was 83%, 86%, and 67%, respectively; maximal reduction of the organic matter reached 94%, 96%, and 96%, respectively; as well as the highest reduction in total phosphorus was 78%, 89%, and 82%, respectively.

A novel method to evaluate phase change materials' impact on buildings' energy, economic, and environmental performance via controlled natural ventilation

The construction industry consumes a significant portion of global energy, with space conditioning in buildings accounting for a substantial 34% of energy usage. Notably, the energy consumption of a building is significantly influenced by its envelope. Researchers widely acknowledge that incorporating phase change materials (PCM) into the building envelope is a promising way to enhance energy efficiency and mitigate CO2 emissions in the building sector, owing to their high latent heat capacity. However, PCM must be completely charged after each cycle to exploit its full potential. Natural ventilation is a viable technique to facilitate the charging and discharging cycle of PCM within a 24-h period. To this end, the present study utilized EnergyPlus simulations to optimize the cooling energy savings of a residential building incorporating PCM into its envelope for PCM melting temperatures, considering various ventilation strategies across 45 cities in 15 climate zones worldwide. In order to evaluate the latent heat utilization of PCM and its improvement facilitated by natural ventilation, two novel indicators, namely HS and HR, were formulated to represent the heat stored and released by PCM during a 24-h cycle, respectively. In addition, following an economic analysis of PCM integration, a comprehensive environmental evaluation was carried out, which included the carbon intensities (CI) of all fuel sources contributing to power generation. The study's findings reveal substantial energy savings across all climate zones when controlled natural ventilation is coupled with PCM, and the newly proposed indicators precisely quantify the performance of PCM in all scenarios evaluated. In the arid climate zone (A), combining PCM and natural ventilation enhances energy savings, albeit to a similar extent as using ventilation alone. However, the integration of PCM with temperature-controlled ventilation yields striking energy reductions of up to 72.8%, 85.3%, and 61% in arid (B), warm temperate (C), and snow (D) climate zones, respectively. The cost-benefit analysis reveals a minimal return period of as short as five years in climate zone C. In the same climate zone C, the in-depth environmental analysis reveals a maximal reduction of 42,004 CO2-e kg/year in carbon emissions. In conclusion, this research study demonstrated that integrating PCM with controlled natural ventilation offers a practical, sustainable, and cost-effective solution with eco-friendly and energy-efficient outcomes.

How might a Universal Basic Income influence UK mental health? A microsimulation modelling study

Abstract Background Universal Basic Income (UBI) may improve mental health (MH), but no studies have trialled or modelled UBI in whole populations. We simulated the MH effects of UBI on UK working-age adults. Methods Adults aged 25-64 were simulated from 2022-26 with the SimPaths microsimulation model, using data from the UK Household Longitudinal Study. SimPaths models short-term MH effects of UK tax/benefit policies via income, poverty and employment transitions. Three counterfactual UBI scenarios were modelled from 2023: ‘Partial’ (value equivalent to existing benefits), ‘Full’ (equivalent to the UK Minimum Income Standard) and ‘Full+’ (retained some means-tested benefits). Likely common mental disorder (CMD) was measured using the General Health Questionnaire (GHQ-12, score ≥4) and stratified by gender, education, and household structure. Simulations were run 1,000 times to generate 95% uncertainty intervals. Sensitivity analyses relaxed SimPaths assumptions about reduced employment resulting from Full/Full+ UBI. Results Partial UBI had little impact on poverty, employment or MH. Full UBI scenarios practically eradicated poverty, but decreased employment. Full+ UBI increased CMD prevalence by 0.38% points (0.13-0.69), equivalent to 157,951 additional CMD cases (54,036-286,805); effects were largest for men (0.63% [0.31-1.01]) and those with children (0.64% [0.18-1.14]). In our sensitivity analysis assuming minimal UBI-related employment impacts, CMD prevalence instead fell by 0.27% (-0.49, -0.05), a reduction of 112,228 cases (20,783-203,673); effects were largest for women (-0.32% [-0.65, 0.00]), those without children (-0.40 [-0.68, -0.15]) and those with least education (-0.42% [-0.97, 0.15]). MH effects waned by 2026 in all modelled scenarios. Conclusions UBI has potential to improve short-term population MH by reducing poverty, but impacts may be highly contingent on whether individuals choose to remain in employment following its introduction. Key messages • A UBI meeting living costs may slightly improve population mental health if people continue working after receiving the benefit, especially for women, the least educated, and those without children. • In a ‘worst-case scenario’, where the increased income led to maximal reductions in employment, UBI might instead worsen short-term mental health, especially for men and those with children.

Considerations of passive radiative cooling

Radiative cooling is a passive cooling method, which pumps the waste heat of terrestrial objects to the cold universe. Although much effort has been devoted to radiative cooling, the understanding of cooling properties should be further improved. This paper presents some considerations for radiative cooling to strengthen the understanding of the mechanism. First, it is generally recognized that the broadband cooler can get a higher maximal cooling power and the selective cooler can achieve a maximal temperature reduction, but this characteristic will be destroyed by non-radiative heat transfer between the cooler and surroundings, which means broadband materials will outperform selective materials across the board, violating the general viewpoint. Second, the maximal temperature reduction of the grey body cooler is independent of emissivity when the non-radiative heat transfer process is suppressed, indicating that only using maximal temperature reduction can not fully reflect the real cooling performance of the grey body cooler. Third, the thermal requirement of the potential applications should be highly considered during material design. If improving heat dissipation is always needed, the broadband cooler is the best choice. Otherwise, radiative cooler with dynamic emissivity modulation is the better one to adjust the dynamic requirement of heat dissipation and insulation.

Dielectric Characteristics and A.C. Conductivity of Pb3O4-Bi2O3-B2O3:CuO Glass Ceramics with CuBi2O4 Crystal Phase: A Possible Electrode Material for Ionic Batteries

In this study, we investigated the dielectric properties of Pb3O4-Bi2O3-B2O3 (PBB) glass ceramics doped with varying CuO concentrations across wide frequency and temperature ranges. The structural analysis involved XRD, SEM, XPS, DTA, FT-IR, ESR, and OA spectra, revealed the presence of anisotropic CuBi2O4 ferroelectric crystal phases with the size of a few microns in these glass ceramics. The glass-ceramics containing a higher content of CuO indicated a maximal reduction of Cu2+ to Cu+ ions that inhabit network-forming sites. Dielectric properties, including ε′, M,′ M″, Z, and σ ac , were studied as functions of CuO content. ε′ and σ ac were observed to decrease, while impedance was found to increase with CuO up to 0.8 mol%. Observed dipolar effects were quantitatively discussed with the identification of probable dipoles. The study indicated decreased ionic and increased polaronic contributions to σ ac with a rise of CuO from 0.2 to 0.8 mol%. In conclusion, glass ceramics with low CuO content are suitable as solid electrolytes, while higher CuO content serves as electrode materials in solid-state batteries.

Mannose-anchored solid lipid nanoparticles loaded with atorvastatin calcium and vinpocetine as targeted therapy for breast cancer

BackgroundThis study was aimed to design mannose-conjugated solid lipid nanoparticles (MSLNs) for the targeted delivery of Atorvastatin Calcium (ATS) and Vinpocetine (VIN) to augment its therapeutic efficacy against breast cancer. SLNs were prepared by hot emulsification ultra-probe sonication method and conjugated with mannose. In vitro cell line, in vivo pharmacokinetic and in vivo tumor regression studies were performed for MSLNs.ResultsMSLNs had an average particle size of 435.4 ± 3 nm with polydispersity index 0.298 ± 0.03 and a zeta potential of − 28.2 ± 1 emv. Entrapment efficiency was found to be 69.17 ± 0.92%, 71.18 ± 0.68% for ATS and VIN, respectively. The IC50 value of MSLNs was 1.46 µg/ml, which is efficient to control the growth of MDA MB231 cells as compared to the individual drugs and combinatorial SLNs. The combination index was found to be 0.7. MSLNs inhibited cell growth via necrosis by promoting to apoptosis through arresting SubG1 phase. The relative bioavailability of ATS and VIN loaded in MSLNs was 1.47 and 5.70, respectively, as compared to the marketed formulation. Maximal tumor volume reduction and higher survival rate was found for the MSLNs group (76.03%, P = 0.0001) as compared to the control group (P = 0.0364), individual drugs SLNs group.ConclusionThe results revealed that the MSLNs formulation augmented activity against breast cancer by inhibiting the cell growth. This promising drug delivery reduces the doses for both the drugs and attains minimal dose-associated side effects with synergism by reaching the specific target site, furthermore improving the therapeutic efficacy.

Acetazolamide and topiramate lower intracranial pressure through differential mechanisms: The effect of acute and chronic administration.

Diseases of raised intracranial pressure (ICP) cause severe morbidity and mortality. Multiple drugs are utilised to lower ICP including acetazolamide and topiramate. However, the evidence for their use is unclear. We aimed to assess the ICP modulatory effects and molecular effects at the choroid plexus (CP) of acetazolamide and topiramate. Female rats were implanted with telemetric ICP probes for physiological, freely moving 24/7 ICP recordings. Randomised cross-over studies were performed, where rats received acute (24 h) high doses of acetazolamide and topiramate, and chronic (10days) clinically equivalent doses of acetazolamide and topiramate, all via oral gavage. Cerebrospinal fluid (CSF) secretion assays, and RT-qPCR and western blots on in vitro and in vivo CP, were used to investigate drug actions. We demonstrate that acetazolamide and topiramate achieved maximal ICP reduction within 120 min of administration, and in combination doubled the ICP reduction over a 24-h period. Chronic administration of acetazolamide or topiramate lowered ICP by 25%. Topiramate decreased CSF secretion by 40%. Chronic topiramate increased the gene expression of Slc12a2 and Slc4a10 and protein expression of the sodium-dependent chloride/bicarbonate exchanger (NCBE), whereas chronic acetazolamide did not affect the expression of assessed genes. Acetazolamide and topiramate are effective at lowering ICP at therapeutic levels. We provide the first evidence that topiramate lowers CSF secretion and that acetazolamide and topiramate may lower ICP via distinct molecular mechanisms. Thus, the combination of acetazolamide and topiramate may have utility for treating raised ICP.

Bio-based synthesis of a sustainable Nano drag reducing agent for sprinkler irrigation systems

High-grade silica Nano particles were extracted from rice husk using a straightforward thermochemical method. The specifications of the isolated Nano particles were verified using a variety of material characterization techniques. Siloxane and silanol groups were notably visible in the spectra obtained using Fourier transform infrared spectroscopy. Scanning Electron Microscopy images revealed main Nano particles alongside secondary Micro particles. The size of the particles varied from 14.56 to 33.72 nm. The drag reduction experiments were took place in a facility that uses a forced closed loop. The extracted Nano silica was mixed with faucet water at a weight concentration of 50 to 400 mg/l to reduce drag. Records of pressure loss were obtained along a 186 cm carbon steel tube with internal diameters of 1.6 and 2.7 cm and variable flow rates of solutions at a comfortable temperature of 25 °C. The friction factor values were found to be around Blasuis asymptote for pure water but they were found to be near maximum drag reduction asymptotes when using the Nano material. A maximal drag reduction of nearly 68 % was achieved by using 400 ppm of Nano silica. It was observed that there is a crucial Reynolds number around 96000 that should not be surpassed since any additional increase results in a drop in drag reduction. Furthermore, a relationship between wall shear stress and velocity of the fluid was established.