Facile synthesis of a novel CeCO3OH@(H/C-CdS) catalyst with synergistic effect of heterophase junction and heterojunction for enhanced visible-light photocatalytic degradation efficiency at room temperature.

A new CeCO3OH@(hexagonal/cubic phases-CdS) (CeCO3OH@(H/C-CdS)) composite catalyst was facilely synthesized by a simple microinjection titration-stirring method, in which CdS nanoparticles were dispersed on the surface of CeCO3OH nanolines. The optimal conditions for the preparation of composite catalysts with high photocatalytic performance were determined by single-factor experiments and response surface experiments. Under these conditions, the degradation rate of 30 mL 2.000 g/L rhodamine B (Rh B) by CeCO3OH@(H/C-CdS) in a photocatalytic reaction for 1 h at 25 °C was up to 86.81 % and its degradation rate in a photocatalytic reaction for 150 min was up to 99.62 %. The degradation rate could be maintained above 80 % even after six times recycling. Especially, the photocatalytic degradation efficiency of 2.000 g/L Rh B on the composite catalyst under sunlight and at room temperature for 30 min reached 97.66 %. Meanwhile, the large size of CeCO3OH considerably alleviated the agglomeration of CdS, providing more adsorption and active sites for visible light-mediated degradation of Rh B. Importantly, the Z-scheme charge transfer realized by CdS and CeCO3OH enhanced the efficient separation of photogenerated electrons and holes, and successfully inhibited the recombination of photogenerated electrons with holes. At the same time, owing to the low energy band difference between the two phases of CdS, charge was transferred between the hexagonal and cubic phases, leaving more effective photogenerated charge to participate in the degradation of Rh B. The synergism of the heterophase junction and heterojunction and the presence of oxygen and sulfur vacancies considerably enhanced the degradation performance of the catalyst. Thus, this study provides a new strategy for the modification and enhanced visible-light catalysis performance of CdS-based catalysts.

Quantifying kinetically relevant species on Zr-SiO2 materials for MPV reduction.

On supported metal catalysts such as Zr-SiO2, it can be challenging to isolate characteristics that result from intrinsic properties of the active site from those that result from the environment surrounding the active site. In this report, we utilize in situ titration of Lewis acid sites with phosphonic acid to accurately and quantitatively describe kinetically relevant Zr species on Zr-SiO2 materials for the MPV reduction of cyclohexanone. We find that rate of MPV reduction on Zr-SiO2 materials can be described as a combination of rate over titratable Zr, that is likely well dispersed Zr, and rate over non-titratable Zr, that is likely supported ZrOx. The fraction of Zr that is well dispersed on the SiO2 is dependent on the surface density at which Zr is grafted but not the choice of Zr precursor. We demonstrate that phosphonic acid titration can offer a more relevant, quantitative description of Zr dispersion than UV-vis and can be used to quantitatively describe changes that occur to the material during regeneration.

Elucidation of the mechanisms of fluconazole resistance and repurposing treatment options against urinary Candida spp. isolated from hospitalized patients in Alexandria, Egypt.

BACKGROUND: The incidence of fungal urinary tract infections (UTIs) has dramatically increased in the past decades, with Candida arising as the predominant etiological agent. Managing these infections poses a serious challenge to clinicians, especially with the emergence of fluconazole-resistant (FLC-R) Candida species. In this study, we aimed to determine the mechanisms of fluconazole resistance in urinary Candida spp. isolated from hospitalized patients in Alexandria, Egypt, assess the correlation between fluconazole resistance and virulence, and explore potential treatment options for UTIs caused by FLC-R Candida strains. RESULTS: Fluconazole susceptibility testing of 34 urinary Candida isolates indicated that 76.5% were FLC-R, with a higher prevalence of resistance recorded in non-albicans Candida spp. (88.9%) than in Candida albicans (62.5%). The calculated Spearman's correlation coefficients implied significant positive correlations between fluconazole minimum inhibitory concentrations and both biofilm formation and phospholipase production. Real-time PCR results revealed that most FLC-R isolates (60%) significantly overexpressed at least one efflux pump gene, while 42.3% significantly upregulated the ERG11 gene. The most prevalent mutation detected upon ERG11 sequencing was G464S, which is conclusively linked to fluconazole resistance. The five repurposed agents: amikacin, colistin, dexamethasone, ketorolac, and sulfamethoxazole demonstrated variable fluconazole-sensitizing activities in vitro, with amikacin, dexamethasone, and colistin being the most effective. However, the fluconazole/colistin combination produced a notable reduction (49.1%) in bladder bioburden, a 50% decrease in the inflammatory response, and tripled the median survival span relative to the untreated murine models. CONCLUSIONS: The fluconazole/colistin combination offers a promising treatment option for UTIs caused by FLC-R Candida, providing an alternative to the high-cost, tedious process of novel antifungal drug discovery in the battle against antifungal resistance.

Prognostic impact of outpatient loop diuretic reduction patterns in patients with chronic heart failure.

Background: The relationship between patterns of outpatient oral loop diuretic (LD) dose reduction and prognosis in patients with heart failure (HF) remains unclear. Methods: We evaluated 679 patients with HF-prescribed LDs at baseline between September 2015 and August 2019. Dose reduction was defined as a change to a lower LD dose than the previous outpatient dose. Dose intensification was defined as a change to a higher LD dose than the previous outpatient dose. Patients were classified into no-reduction (no LD dose reduction during follow-up) and reduction groups (categorized into successive-reduction [≥2 successive LD dose reductions without intervening LD dose intensification] and single-reduction [LD dose reduction without successive dose reduction] groups). The primary outcomes were all-cause death, HF hospitalization (HFH), and the composite of cardiovascular death (CVD) or HFH. Results: Within a median follow-up of 53.7 (range, 2.6-99.1) months, 156 deaths were recorded: 121 (29 %), 31 (15 %), and three (4 %) patients in the no-reduction (n = 411), single-reduction (n = 195), and successive-reduction (n = 73) groups, respectively. After adjusting for cofounders, the reduction group had a lower risk of primary outcomes than the no reduction group (all-cause death: hazard ratio (HR) = 0.65, 95 % confidence interval (CI) = 0.44-0.96; CVD or HFH: HR=0.69, 95 %CI=0.52-0.93; HFH: HR=0.69, 95 % CI=0.52-0.93). The successive-reduction group had a lower risk of the composite of CVD or HFH (HR=0.26, 95 % CI: 0.10-0.67) and HFH (HR=0.34, 95 % CI=0.13-0.86) than the single-reduction group. Conclusions: Outpatient LD dose reduction patterns can be indicators of good prognosis in HF patients.

Low-dose methadone added to another opioid for cancer pain: a multicentre prospective study.

CONTEXT: The use of methadone for cancer pain management is gaining wider acceptance. However, switching to methadone treatment can still pose challenges. Consequently, there is ongoing development of its use in low doses in combination with other opioids, despite a lack of clinical evidence regarding its efficacy and safety. OBJECTIVES: This study aimed to evaluate the efficacy and tolerability of low-dose methadone in combination with another opioid in patients with moderate-to-severe cancer-related pain in a clinical setting. PATIENTS AND METHODS: This was a prospective, open-label study conducted in 19 pain and/or palliative care centres treating patients with cancer-related pain. Pain intensity, patients' global impression of change, and adverse effects were assessed on day 7 and day 14. The main outcome measure was the proportion of responders. RESULTS: The study included 92 patients. The daily dose of methadone was 3 [3-6] mg at baseline, 9 [4-10] mg on day 7 and 10 [6-15] mg on day 14. The NRS pain ratings significantly decreased from 7 [6-8] at baseline to 5 [3-6] on visit 2 (p < .0001) and 4 [3-6] on visit 3 (p < .0001). Similarly, the VRS pain ratings decreased from 3 [3-3] at baseline to 2 [2-3] on visit 2 (p = 0.026) and 2 [1-3] (p < 0.001) on visit 3. At Visits 1 and 2, half of the patients were considered Responders. Of those responders, 73.5% were High-Responders at Visit 1 and 58.7% were High-Responders at Visit 2. No adverse events related to the risk of QT prolongation, overdose, or drug interactions were reported. CONCLUSION: For patients experiencing moderate to severe cancer-related pain despite initial opioid treatment, our study found that low-dose methadone, when used in combination with another opioid, was both safe and effective. This supports the use of methadone as an adjunct to opioid-based treatment for cancer pain.

Smartphone-deployable and all-in-one machine vision for visual quantification analysis based on distance readout of electrophoresis titration biosensor.

As a class of point-of-care (POC) assays with visible distance readout (thermometer style), the electrophoresis titration (ET) biosensor affords high robustness, versatility, and simplicity for point-of-care quantification. However, naked-eye observation of the distance readout is unreliable in POC settings and manual processing of distance readout is time-consuming. Herein, we developed a smartphone-deployable and all-in-one machine vision for four ET biosensors (bovine serum albumin, melamine, uric acid, glutathione) to classify and quantify the samples simultaneously. To ensure accurate and rapid quantification on the smartphone, we customized the decolorization methods and edge detection operators to balance the region of interest (ROI) extraction performance and processing speed. We then established a dataset of 180 distance readout images to endow our machine vision with the ability to classify four sample types. Consequently, our machine vision demonstrated high accuracy in determining the sample type (>97.2%) and concentration (>97.3%). Moreover, expanding its applications to other targets was readily achieved by including distance readout images of other ET biosensors (e.g., hemoglobin A1c) in the dataset. Therefore, our strategy of constructing machine vision is compatible with the versatile ET biosensor technique, suggesting that the same strategy can be used for other thermometer-style POC assays.

Computational Insights Into the Mechanism of EGCG's Binding and Inhibition of the TDP-43 Aggregation.

Misfolding and aggregation of TAR DNA-binding protein, TDP-43, is linked to devastating proteinopathies such as ALS. Therefore, targeting TDP-43's aggregation is significant for therapeutics. Recently, green tea polyphenol, EGCG, was observed to promote non-toxic TDP-43 oligomer formation disallowing TDP-43 aggregation. Here, we investigated if the anti-aggregation effect of EGCG is mediated via EGCG's binding to TDP-43. In silico molecular docking and molecular dynamics (MD) simulation suggest a strong binding of EGCG with TDP-43's aggregation-prone C-terminal domain (CTD). Three replicas, each having 800 ns MD simulation of the EGCG-TDP-43-CTD complex, yielded a high negative binding free energy (ΔG) inferring a stable complex formation. Simulation snapshots show that EGCG forms close and long-lasting contacts with TDP-43's Phe-313 and Ala-341 residues, which were previously identified for monomer recruitment in CTD's aggregation. Notably, stable physical interactions between TDP-43 and EGCG were also detected in vitro using TTC staining and isothermal titration calorimetry which revealed a high-affinity binding site of EGCG on TDP-43 (Kd, 7.8 µM; ΔG, -6.9 kcal/mol). Additionally, TDP-43 co-incubated with EGCG was non-cytotoxic when added to HEK293 cells. In summary, EGCG's binding to TDP-43 and blocking of residues important for aggregation can be a possible mechanism of its anti-aggregation effects on TDP-43.

Exploring the Impact of Subtle Differences in the Chemical Structure of 1-Alkylsulfates and 1-Alkylsulfonates on Their Interactions with Human Serum Albumin.

The objective of this study was to examine the interactions between anionic surfactants, specifically 1-alkylsulfonates (KXS) and 1-alkylsulfates (SXS) ions, with human serum albumin (HSA). A combination of experimental techniques, including isothermal titration calorimetry (ITC), steady-state fluorescence spectroscopy (SF), and molecular dynamics-based approaches was employed to gain a comprehensive understanding of these processes. It has been demonstrated that the subtle variations in the charge distribution on the anionic surfactant headgroups have a significant impact on the number of binding sites, the stoichiometry of the resulting complexes, and the strength of the interactions between the surfactants and the protein. Additionally, we established that the affinity of the investigated ligands to specific regions on the protein surface is governed by both the charge of the surfactant headgroup and the length of the aliphatic hydrocarbon chain. In summary, the findings highlight the crucial role of charge distribution on surfactant functional groups in the binding mode and the thermodynamic stability of surfactant-protein complexes.

Ligand-Induced Folding in a Dopamine-Binding DNA Aptamer.

Aptamers are often employed as molecular recognition elements in the development of different types of biosensors. Many of these biosensors take advantage of the aptamer having a ligand-induced structure-formation binding mechanism. However, this binding mechanism is poorly understood. Here we use isothermal titration calorimetry, circular dichroism spectroscopy and NMR spectroscopy to study the binding and ligand-induced structural change exhibited by a dopamine-binding DNA aptamer. We analysed a series of aptamers where we shorten the terminal stem that contains the 5´ and 3´termini of the aptamer sequence. All aptamers bind dopamine in an enthalpically driven process coupled with an unfavorable entropy. A general trend of the aptamer having a weaker binding affinity is observed as the terminal stem is shortened. For all aptamers studied, numerous signals appear in the imino region of the 1H NMR spectrum indicating that new structure forms with ligand binding. However, it is only when this region of structure formation in the aptamer is brought close to the sensor surface that we obtain a functional electrochemical aptamer-based biosensor.

Real-world experience in initiation of treatment with the selective cardiomyosin inhibitor mavacamten in an outpatient clinic cohort during the 12-week titration period.

INTRODUCTION: Lately, mavacamten emerged as a new therapeutic option for symptomatic patients with obstructive hypertrophic cardiomyopathy (oHCM). Clinical trials revealed reduction of serum biomarkers, and left ventricular outflow tract (LVOT) obstruction, as well as an improvement in clinical symptoms and exercise capacity. Nevertheless, clinical experience and manageability of patients in a real-world setting is still lacking. MATERIAL AND METHODS: 22 patients with symptomatic oHCM (54.5% male, age 58.5 ± 16.2 years) and elevated LVOT gradients were started on mavacamten between March 2023 and June 2024. All patients were New York Heart Association (NYHA) class II or higher. Seven patients were excluded from primary analysis due to comedication with Angiotensin-converting-enzyme-inhibitors or Angiotensin-II receptor blockers. Cardiac imaging, laboratory work-up and clinical evaluation were assessed at three visits during the 12 weeks initiation phase; Dosing of mavacamten was adjusted according to manufacturer's recommendations. RESULTS: At 12 weeks, the majority of patients described a significant improvement of their quality of life. Work-up at 12 weeks revealed a significant reduction of serum biomarkers and LVOT gradients. In four patients, mavacamten needed to be temporarily paused due to clinical complaints or transient left ventricular ejection fraction deterioration below 50% with subsequent full recovery. CONCLUSION: We provide first insights into the usage of mavacamten in oHCM patients during the titration period in a real-world setting. Clinical findings are in line with previous clinical trials. In accordance with current recommendations, we highlight the need for standardized follow-up of patients on mavacamten treatment.

Concentration Scales and Solvation Thermodynamics: Some Theoretical and Experimental Observations Regarding Spontaneity and the Partition Ratio.

The solvation thermodynamics (ST) formalism proposed by A. Ben-Naim is a mathematically rigorous and physically grounded theory for describing properties related to solvation. It considers the solvation process as the transfer of a molecule ("solute") from a fixed position in the ideal gas phase to a fixed position within the solution. Thus, it removes any contribution to the solvation process that is not related to the interactions between this molecule and its environment in the solution. Because ST is based on statistical thermodynamics, the natural variable is number density, which leads to the amount (or "molar") concentration scale. However, this choice of concentration scale is not unique in classical thermodynamics and the solvation properties can be different for commonly used concentration scales. We proposed and performed experiments with diethylamine in a water/hexadecane heterogeneous mixture to confront the predictions of the ST, based on the amount (or "molar") concentration scale, and the Fowler-Guggenheim formalism, based on the mole fraction scale. By means of simple acid-base titration and 1H NMR measurements, it was established that the predictions of differences in the solvation Gibbs energy and the partition ratio (or "partition coefficient") of diethylamine between water and hexadecane are consistent with the ST formalism. Additionally, with current literature data, we have shown additional experimental support for the ST. However, due to the arbitrariness of the relative amount of solvents in the partition ratio, the choice of a single concentration scale within the classical thermodynamics is still not possible.

Challenge Dose Titration in a Mycobacterium bovis Infection Model in Goats.

Goats are natural hosts of Mycobacterium (M.) bovis, and affected herds can be the cause of significant economic losses. Similarites in disease course and lesions of M. bovis infections in goats and M. tuberculosis in humans make goats good models for human tuberculosis. The aim of this investigation was to characterize M. bovis challenge models in goats. For this, goats were endobronchially inoculated with three doses of M. bovis or culture medium. Clinical signs, shedding, and immune responses were monitored until 146 days post inoculation (dpi). At necropsy, lesions were examined by computed tomography, histology, and bacteriological culture. Infected goats did not develop clinical signs. M. bovis was cultured from feces, but never from nasal swabs. IGRAs were positive from 28 dpi onwards, antibodies at 140 dpi, and SICCT at 146 dpi. The increase in CD25+, IFN-γ+, and IFN-γ-releasing T-cell subpopulations was time-related, but not dose-dependent. All infected goats developed paucibacillary granulomas in the lungs and regional lymph nodes. M. bovis was regularly cultured. Dose-dependent effects included the size of pulmonary lesions, caverns, intestinal lesions, and early generalization in the high-dose group. In summary, reproducible challenge models with dose-dependent differences in lesions were established, which may serve for testing vaccines for veterinary or medical use.

An SMS-Guided Basal Insulin Titration in People with Type 2 Diabetes New on Insulin.

INTRODUCTION: The shortage of general practitioners (GPs) and the increasing prevalence of type 2 diabetes create significant pressure on primary healthcare services. To enable that medical services are available to all that need it, innovative solutions are needed. One of those, a Short Message Service (SMS)-supported basal insulin titration service is investigated in this study. The primary objective was to determine the percentage of subjects who achieved stable fasting blood glucose (FBG) within their individual target range with this service after week 16. METHODS: This single-arm, 16-week study aimed to enroll 111 adults diagnosed with type 2 diabetes that needed insulin. The study subjects measured their FBG 4 consecutive days to establish a baseline, then received SMS prompts for daily FBG measurements and evening insulin injections until their FBG stabilized within the target range. Adjusting the insulin based on the FBG. Once stabilization was achieved, subjects continued with their optimal insulin dose for the remainder of the study. Sixteen weeks after the baseline, subjects measured FBG for 4 days before visit 4, where these values were read by the healthcare provider. RESULTS: Out of the planned 111 subjects, only 30 were enrolled, with one withdrawal prior to service activation. Challenges in subject recruitment were attributed to the COVID-19 outbreak, limited eligibility, competing studies, and new medications delaying insulin initiation. Subjects were on average 59.97 years old, had an HbA1c of 9.29% a FBG of 205.64 mg/dl, and had diabetes for 10 years. Among the 29 subjects who started the service, 72% achieved successful titration at visit 4, with a median time of 49 days. Notable improvements were observed in HbA1c levels (decreased by 1.58%) and FBG levels (decreased by 64 mg/dl) over the 16-week study period. No adverse events or device-related issues were reported. CONCLUSIONS: Despite recruitment challenges, guided basal insulin titration holds promise for insulin therapy initiation in individuals. The findings emphasize the potential of tele-medical approaches, specifically through remote messaging, in managing diabetes and improving therapy adherence.

Thermodynamic origin of the affinity, selectivity, and domain specificity of metallothionein for essential and toxic metal ions.

The small Cys-rich protein metallothionein (MT) binds several metal ions in clusters within two domains. While the affinity of MT for both toxic and essential metals has been well studied, the thermodynamics of this binding has not. We have used isothermal titration calorimetry measurements to quantify the change in enthalpy (ΔH) and change in entropy (ΔS) when metal ions bind to the two ubiquitous isoforms of MT. The seven Zn2+ that bind sequentially at pH 7.4 do so in two populations with different coordination thermodynamics, an initial four that bind randomly with individual tetra-thiolate coordination and a subsequent three that bind with bridging thiolate coordination to assemble the metal clusters. The high affinity of MT for both populations is due to a very favourable binding entropy that far outweighs an unfavourable binding enthalpy. This originates from a net enthalpic penalty for Zn2+ displacement of protons from the Cys thiols and a favourable entropic contribution from the displaced protons. The thermodynamics of other metal ions binding to MT were determined by their displacement of Zn2+ from Zn7MT and subtraction of the Zn2+-binding thermodynamics. Toxic Cd2+, Pb2+, and Ag+, and essential Cu+, also bind to MT with a very favourable binding entropy but a net binding enthalpy that becomes increasingly favourable as the metal ion becomes a softer Lewis acid. These thermodynamics are the origin of the high affinity, selectivity, and domain specificity of MT for these metal ions and the molecular basis for their in vivo binding competition.

[Preliminary evaluation of the interest of a therapeutic optimization cell on the titration of treatments for heart failure with reduced left ventricular ejection fraction and the quality of life of patients]. / Évaluation préliminaire de l'intérêt d'une cellule d'optimisation thérapeutique sur la titration des traitements de l'insuffisance cardiaque à fraction d'éjection ventriculaire gauche réduite et la qualité de vie des patients.

INTRODUCTION: A multidisciplinary therapeutic optimization unit (COT) was created in January 2023 at Versailles Hospital, aimed at therapeutic optimisation of patients with chronic heart failure with reduced left ventricular ejection fraction. The objective of the study was to assess the impact of the first year of COT activity on the sequential implementation and titration of heart failure treatments, the clinical evolution, and improvement of patients' quality of life. METHODS: This prospective study included consecutive patients treated by the COT after hospitalisation for acute heart failure, from January to December 2023. Clinical, biological, titration, and tolerance data were analysed. Quality of life was assessed at baseline and at the end of the follow-up by COT, using standardized SF-12 and EQ-5D questionnaires. RESULTS: We included 90 patients (men 73%, mean age 67 years). The mean left ventricular ejection fraction was 34 ± 10 %. At final visit (median number of visits 4 ; median follow-up duration 156 days), 76.7% of patients achieved optimisation with respect to maximum individually tolerated doses, but only 13.3% with respect to theoretical maximum doses for the four therapeutic classes. At 1-year follow up, total mortality was 4.4% (4/90), and 9 patients (10%) were rehospitalised unplanned for acute heart failure. COT monitoring was associated with significant improvement in NYHA class, left ventricular ejection fraction, and SF-12 and EQ-5D-5L quality of life scores. CONCLUSION: Although titration of heart failure treatments remained suboptimal, significant improvement was observed for NYHA class, left ventricular ejection fraction, and patient quality of life parameters.

Structure and Characterization of Catanionic Complexes and Biocompatible Vesicles of N-Acyltaurine and Sarcosine Alkyl Ester: Encapsulation and Release Studies with 5-Fluorouracil.

Hydrated dispersions containing equimolar mixtures of cationic and anionic amphiphiles, referred to as catanionic systems, exhibit synergistic physicochemical properties, and mixing single-chain cationic and anionic lipids can lead to the spontaneous formation of vesicles as well as other phase structures. In the present work, we have characterized two catanionic systems prepared by mixing N-acyltaurines (NATs) and sarcosine alkyl esters (SAEs) bearing 11 and 12 C atoms in the acyl/alkyl chains. Turbidimetric and isothermal titration calorimetric studies revealed that both NATs form equimolar complexes with SAEs having matching acyl/alkyl chains. The three-dimensional structure of the sarcosine lauryl ester (lauryl sarcosinate, LS)-N-lauroyltaurine (NLT) equimolar complex has been determined by single-crystal X-ray diffraction. The LS-NLT equimolar complex is stabilized by electrostatic attraction and multiple hydrogen bonds, including classical, strong N-H···O hydrogen bonds as well as several C-H···O hydrogen bonds between the two amphiphiles. DSC studies showed that both equimolar complexes show single sharp phase transitions. Transmission electron microscopy and dynamic light scattering studies have demonstrated that the LS-NLT catanionic complex assemblies yield stable medium-sized vesicles (diameter 280-350 nm). These liposomes were disrupted at high pH, suggesting that the designed catanionic complexes can be used to develop base-labile drug delivery systems. In vitro studies with these catanionic liposomes showed efficient entrapment (73% loading) and release of the anticancer drug 5-fluorouracil in the physiologically relevant pH range of 6.0-8.0. The release rate was highest at pH 8.0, reaching about 78%, 90%, and 100% drug release at 2, 6, and 12 h, respectively. These observations indicate that LS-NLT catanionic vesicles will be useful for designing drug delivery systems, particularly for targeting organs such as the colon, which are inherently at basic pH.

Clinical challenges in the dosing and titration of cariprazine.

The introduction of a new psychopharmaceutical medication instead of the previous one always poses a certain challenge. In the case of antipsychotics (AP), these problems are considerably more complicated and are mainly caused by the question of dose equivalents, but also by the pharmacokinetic properties of the drug. In the case of partial dopamine D2 agonists, an additional issue is the possibility of deterioration when switching from the previous D2 antagonists to these drugs. Cross-titration is therefore generally recommended. Finally, due to the capsule form, it is not possible to increase the dose of cariprazine by less than 1.5 mg during titration. In this paper, we have presented our proposal to replace the most commonly used second-generation APs with the third-generation AP cariprazine. We have taken into account the dose equivalents, the pharmacological forms of the drugs and their pharmacokinetic and pharmacodynamic properties.

Analysis of the Thermal Aging Kinetics of Tallow, Chicken Oil, Lard, and Sheep Oil.

Understanding the thermal aging kinetics of animal oils is of vital importance in the storage and applications of animal oils. In this work, we use four different techniques, including UV-Vis spectrometry, viscometry, impedance spectroscopy, and acid-base titration, to study the thermal aging kinetics of tallow, chicken oil, lard, and sheep oil in the temperature range from 120 °C to 180 °C. The evolutions of the UV-Vis absorbance, dynamic viscosity, electric impedance, and acid titration are discussed with the defect kinetics. The evolutions of the color centers, defects for dynamic viscosity, and electric dipoles follow second-order, first-order, and zero-order kinetics, respectively. The temperature dependence of rate constants for the evolutions of the UV-Vis absorbance, dynamic viscosity, electric impedance, and acid titration satisfies the Arrhenius equation with the same activation energy for individual animal oils. The activation energies are ~43.1, ~23.8, ~39.1, and ~37.5 kJ/mol for tallow, chicken oil, lard, and sheep oil, respectively. The thermal aging kinetics of the animal oils are attributed to the oxidation of triglycerides.