Combined approach for predicting the efficacy of nivolumab in head and neck carcinoma by tissue and soluble expressions of PD-L1 and PD-L2.

BACKGROUND: Predictive biomarkers for nivolumab in recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC) have not yet been established. METHODS: The tumor proportion score (TPS), combined positive score (CPS), and soluble forms of programmed cell death ligand-1 (PD-L1) and programmed cell death ligand-2 (PD-L2) were retrospectively analyzed in patients with RMHNSCC treated with nivolumab. RESULTS: The positivity rates for TPS (PD-L1), CPS (PD-L1), TPS (PD-L2), and CPS (PD-L2) were 73.8%, 78.2%, 56.4%, and 78.2%, respectively. Patients with high TPS (PD-L1), CPS (PD-L1), or CPS (PD-L1 and PD-L2) showed significantly prolonged progression-free survival. Favorable overall survival was associated with high CPS (PD-L1 and PD-L2) and low soluble PD-L1 and PD-L2 levels. The expressions of tissue and soluble PD-L1/2 were not correlated. CONCLUSIONS: Our study revealed that compared to PD-L1 expression alone, dual expression of PD-L1 and PD-L2 in tissue or soluble form could be feasible biomarkers in patients with RMHNSCC who received nivolumab.

Patterns and drivers of plant carbon, nitrogen, and phosphorus stoichiometry in a novel riparian ecosystem.

Carbon (C), nitrogen (N), and phosphorus (P) stoichiometry serve as valuable indices for plant nutrient utilization and biogeochemical cycling within ecosystems. However, the allocation of these nutrients among different plant organs and the underlying drivers in dynamic riparian ecosystems remain inadequately understood. In this study, we gathered plant samples from diverse life forms (annuals and perennials) and organs (leaves, stems, and roots) in the riparian zone of the Three Gorges Reservoir Region (TGRR) in China-a novel ecosystem subject to winter flooding. We used random forest analysis and structural equation modeling to find out how flooding, life forms, plant communities, and soil variables affect organs C, N, and P levels. Results showed that the mean concentrations of plant C, N, and P in the riparian zone of the TGRR were 386.65, 19.31, and 5.27 mg/g for leaves respectively, 404.02, 11.23, and 4.81 mg/g for stems respectively, and 388.22, 9.32, and 3.27 mg/g for roots respectively. The C:N, C:P and N:P ratios were 16.15, 191.7 and 5.56 for leaves respectively; 26.98, 273.72 and 4.6 for stems respectively; and 16.63, 223.06 and 4.77 for roots respectively. Riparian plants exhibited nitrogen limitation, with weak carbon sequestration, low nutrient utilization efficiency, and a high capacity for nutrient uptake. Plant C:N:P stoichiometry was significantly different across life forms and organs, with higher N and P concentrations in leaves than stems and roots, and higher in annuals than perennials. While flooding stress triggered distinct responses in the C, N, and P concentrations among annual and perennial plants, they maintained similar stoichiometric ratios along flooding gradients. Furthermore, our investigation identified soil properties and life forms as more influential factors than plant communities in shaping variations in C:N:P stoichiometry in organs. Flooding indirectly impacts plant C:N:P stoichiometry primarily through alterations in plant community composition and soil factors. This study underscores the potential for hydrologic changes to influence plant community composition and soil nutrient dynamics, and further alter plant ecological strategies and biogeochemical cycling in riparian ecosystems.

Effect of Verbal Encouragement on Performance and Affective Responses in Male Sport Science Students during Sprint Modalities.

This investigation aimed to examine the effect of verbal encouragement teacher to student (VETS) versus verbal encouragement student to student (VESS) on physical performance and affective responses during different modalities of sprint tests in active male students. In a randomized crossover design, twenty-two male sport science students (age: 21 ± 1.2 years, body height: 1.77 ± 0.3 m, body mass: 76.6 ± 2.1 kg, BMI: 22.9 ± 1.3 kg·m-2) performed linear and change-of-direction sprint tests under one of three conditions: (1) VETS; (2) VETS; (3) no verbal encouragement. In each condition, participants performed the 20 m sprint test, the 10 × 2 sprint test, and the L sprint test. The assessed parameters comprised physical performance, rating of perceived exertion (RPE), and a feeling scale. Post hoc test analysis indicates a significant increase in physical performance during VETS and VESS conditions compared to the control condition due to a decrease in sprint in line 20 m (VETS: p < 0.001, d = 0.55; VESS: p = 0.016, d = 0.41), sprint 10*2 (VETS: p < 0.001, d = 0.64; VESS: p = 0.05, d = 0.36), and sprint L (VETS: p = 0.001, d = 1.19) times compared to the control condition. Moreover, the feeling score was greater after VETS compared to other conditions (p = [<0.001-0.001], d = [0.77-1.18]). In addition, the RPE had no effect on sprint performance between the different conditions. It is indicated that VETS, rather than VESS, is a more significant and effective way to increase effort intensity and positive feelings during sprinting modalities.

Alpha-lipoic Acid: An Antioxidant with Anti-Aging Properties for Disease Therapy.

The anti-aging effects of alpha-lipoic acid (αLA), a natural antioxidant synthesized in human tissues, have attracted a growing interest in recent years. αLA is a short- -chain sulfur-containing fatty acid occurring in the mitochondria of all kinds of eukaryotic cells. Both the oxidized disulfide of αLA and its reduced form (dihydrolipoic acid, DHLA) exhibit prominent antioxidant function. The amount of αLA inside the human body gradually decreases with age resulting in various health disorders. Its lack can be compensated by supplying from external sources such as dietary supplements or medicinal dosage forms. The primary objectives of this study were the analysis of updated information on the latest two-decade research regarding the use of αLA from an anti-aging perspective. The information was collected from PubMed, Wiley Online Library, Scopus, ScienceDirect, SpringerLink, Google Scholar, and clinicaltrials.gov. Numerous in silico, in vitro, in vivo, and clinical studies revealed that αLA shows a protective role in biological systems by direct or indirect reactive oxygen/nitrogen species quenching. αLA demonstrated beneficial properties in the prevention and treatment of many age-related disorders such as neurodegeneration, metabolic disorders, different cancers, nephropathy, infertility, and skin senescence. Its preventive effects in case of Alzheimer's and Parkinson's diseases are of particular interest. Further mechanistic and clinical studies are highly recommended to evaluate the wide spectrum of αLA therapeutic potential that could optimize its dietary intake for prevention and alleviation disorders related to aging.

Multicomponent Amorphous Solid Forms of Telmisartan: Insights into Mechanochemical Activation and Physicochemical Attributes.

The present work aims to explore the new solid forms of telmisartan (TEL) with alpha-ketoglutaric acid (KGA) and glutamic acid (GA) as potential coformers using mechanochemical approach and their role in augmentation in physicochemical parameters over pure crystalline TEL. Mechanochemical synthesis was performed using 1:1 stoichiometric ratio of TEL and the selected coformers in the presence of catalytic amount of ethanol for 1 h. The ground product was characterized by PXRD, DSC, and FTIR. The new solid forms were evaluated for apparent solubility, intrinsic dissolution, and physical stability. Preliminary characterization revealed the amorphization of the mechanochemical product as an alternate outcome of cocrystallization screening. Mechanistic understanding of the amorphous phase highlights the formation of amorphous-mediated cocrystallization that involves three steps, viz., molecular recognition, intermediate amorphous phase, and product nucleation. The solubility curves of both multicomponent amorphous solid forms (TEL-KGA and TEL-GA) showed the spring-parachute effect and revealed significant augmentation in apparent solubility (8-10-folds), and intrinsic dissolution release (6-9-folds) as compared to the pure drug. Besides, surface anisotropy and differential elemental distributions in intrinsic dissolution compacts of both solid forms were confirmed by FESEM and EDX mapping. Therefore, amorphous phases prepared from mechanochemical synthesis can serve as a potential solid form for the investigation of a cocrystal through amorphous-mediated cocrystallization. This has greater implications in solubility kinetics wherein the rapid precipitation of the amorphous phase can be prevented by the metastable cocrystal phase and contribute to the significant augmentation in the physicochemical parameters.

Modeling of Styl'One Evolution Correction Factors for Multicomponent Mixtures Scaling-up to Roller Compaction.

Roll compaction (RC) is a cost-effective dry granulation method, widely implemented in the pharmaceutical industry. In early formulation development however, when the material availability is limited, being able to predict the most important parameters in RC, like gap width and specific compaction force (SCF), to obtain a target ribbon solid fraction (SF) would significantly improve the formulation development efficiency as it would avoid the need of performing experiments on the roller compactor itself. However, at the present state of things, experiments on RC mechanical simulators present an overestimation of the target SF, when compared to roller compactor SF values. Although numerous correction approaches have been developed to improve the predictive performance of different mathematical models applied to the simulation experimental results, no study has collected a database wide enough to demonstrate the validity of a correction factor that allows to accurately simulate the compaction behavior of multicomponent mixtures. Here, 25 different formulations at 40 % drug load are compacted at different SCFs, both on a RC mimicking device (Styl'One Evolution) and on an actual roller compactor (Gerteis Mini-Pactor): following a similar approach as Reimer et al. and implementing a simplified version of the Johanson's mathematical model, 4 different correction factors are calculated, depending on how their material properties and pressure dependencies are considered. In conclusion, one correction factor is identified as the optimal trade-off between the SF prediction accuracy on the Gerteis Mini-Pactor and its applicability to a wide range of formulations, as it is independent of the material properties. This finding is particularly relevant when applied to scale-up to this specific roller compactor or early development processes of new formulations that have not been mechanically characterized yet.

Unsolved morphogenesis problems and the hidden order.

In this work, the morphogenesis mechanisms are considered from the complexity perspective. It is shown that both morphogenesis and the functioning of organs should be unstable in the case of short-range interaction potentials. The repeatability of forms during evolution is a strong argument for its directionality. The formation of organs during evolution can occur only in the presence of a priori information about the structure of such an organ. The focus of the discussion is not merely on constraining potential possibilities but on the concept of directed evolution itself. A morphogenesis model was constructed based on nontrivial quantum effects. These interaction effects between biologically important molecules ensure the accurate synthesis of cells, tissues, and organs.

Flexible modelling of the dissolution performance of directly compressed tablets.

In this study, a compartmental disintegration and dissolution model is proposed for the prediction and evaluation of the dissolution performance of directly compressed tablets. This dissolution model uses three compartments (Bound, Disintegrated, and Dissolved) to describe the state of each particle of active pharmaceutical ingredient. The disintegration of the tablet is captured by three fitting parameters. Two disintegration parameters, ß0 and ßt,0, describe the initial disintegration rate and the change in disintegration rate, respectively. A third parameter, α, describes the effect of the volume of dissolved drug on the disintegration process. As the tablet disintegrates, particles become available for dissolution. The dissolution rate is determined by the Nernst-Brunner equation, whilst taking into account the hydrodynamic effects within the vessel of a USP II (paddle) apparatus. This model uses the raw material properties of the active pharmaceutical ingredient (solubility, particle size distribution, true density), lending it towards early development activities during which time the amount of drug substance available may be limited. Additionally, the strong correlations between the fitting parameters and the tablet porosity indicate the potential to isolate the manufacturing effects and thus implement the model as part of a real-time release testing strategy for a continuous direct compression line.

Factors influencing the increased 90Sr radioisotope migration in highly alkaline groundwater at Chornobyl NPP site.

This paper analyses the formation of high Sr2+ concentration in strong alkaline (pH = 9.5-12.5) groundwater using data of the 27 years of observations around the destroyed Chernobyl NPP Unit 4. It appears that the formation of strong alkaline groundwater in different monitoring wells is consistent with the distribution of 90Sr, pH and main ions. The reason for the increase in 90Sr concentrations is the process of its migration from the sources of contamination - leaks of highly active water localized in certain premises inside the «Shelter ¼ object. These computational experiments showed that for the groundwater in pH range 9.5-12.4, the concentration of strontium in the form of SrOH + increases and in the form of Sr2+ - decreases. In addition, the fraction of 90Sr in the form of a soluble neutral complex compound SrCO30, which is not sorbed, reaches 14-35%. Increased fractions of 90Sr in forms of SrOH+ and SrCO3 are factors which reduce the isotope ability to be sorbed by soils and therefore increase its migration ability. In strongly alkaline groundwater a sharp increase in 90Sr volumetric activity may also be caused by ionic strength (IS) increase above 5 mmol/L. Thus, the factors that influence the increase in 90Sr volumetric activity in strongly alkaline groundwater are the formation of its complex compounds and an increase in ionic strength (IS), which reduces the thickness of the double electric layer and, as a result, reduces the sorption capacity of soils.

Investigating foliar application of bulk and nanoparticles titanium dioxide on fennel productivity to mitigate the negative effects of saline irrigation water.

BACKGROUND: Fennel essential oils are fragrance compounds used in food and pharmaceutical sectors. One of the major impediments to expansion of fennel farming in Egypt's reclamation areas is saline water. Titanium dioxide (TiO2) or TiO2 nano particles (TiO2NP) can be utilized to boost the yield of aromatic plants cultivated under saline irrigation water. Saline water, particularly which contains sodium chloride can harm fennel plant; consequently, it was predicted that fennel production would fail in Egypt's reclaimed area, where the primary source of irrigation is groundwater consisting sodium chloride. This study sought to help fennel respond to sodium chloride by applying Ti forms to their leaves in order to reduce the detrimental effects of sodium chloride on them for expanding their production in the newly reclamation areas as a natural source of essential oil. Ti forms were applied as foliar application at 0, 0.1, 0.2 TiO2, 0.1 TiO2NP, and 0.2 TiO2NP, mM under irrigation with fresh water (0.4 dS m-1), or saline water (51.3 mM or 4.7 dS m-1). RESULTS: Plants exposed to 0.1 mM TiO2NP under fresh water resulted in the maximum values of morphological characters, estragole, oxygenated monoterpenes and photosynthetic pigments; while those subjected to 0.1 mM TiO2NP under saline water gave the greatest values of essential oil, proline, antioxidant enzymes and phenols. The greatest amounts of soluble sugars were recorded with 0.2 mM TiO2NP irrigated with saline water. Plants subjected to 0 mM TiO2 under saline water produced the greatest values of flavonoids, hydrogen peroxide and malondialdehyde. CONCLUSION: To mitigate the negative effects of salty irrigation water on fennel plant production, TiO2NP application is suggested as a potential strategy.

Decomposition of exotic versus native aquatic plant litter in a lake littoral zone: Stoichiometry and life form analyses.

The decomposition rates and stoichiometric characteristics of many aquatic plants remain unclear, and our understanding of material flow and nutrient cycles within freshwater ecosystems is limited. In this study, an in-situ experiment involving 23 aquatic plants (16 native and 7 exotic species) was carried out via the litter bag method for 63 days, during which time the mass loss and nutrient content (carbon (C), nitrogen (N), and phosphorus (P)) of plants were measured. Floating-leaved plants exhibited the highest decomposition rate (0.038 ± 0.002 day-1), followed by submerged plants and free-floating plants (0.029 ± 0.002 day-1), and emergent plants had the lowest decomposition rate (0.019 ± 0.001 day-1). Mass loss by aquatic plants correlated with stoichiometric characteristics; the decomposition rate increased with an increasing P content and with a decreasing C content, C:N ratio, and C:P ratio. Notably, the decomposition rate of submerged exotic plants (0.044 ± 0.002 day-1) significantly exceeded that of native plants (0.026 ± 0.004 day-1), while the decomposition rate of emergent exotic plants was 55 ± 4 % higher than that of native plants. The decomposition rates of floating-leaved and free-floating plants did not significantly differ between the native and exotic species. During decomposition, emergent plants displayed an increase in C content and a decrease in N content, contrary to patterns observed in other life forms. The P content decreased for submerged (128 ± 7 %), emergent (90 ± 5 %), floating-leaved (104 ± 6 %), and free-floating plants (32 ± 6 %). Exotic plants released more C and P but accumulated more N than did native plants. In conclusion, the decomposition of aquatic plants is closely linked to litter quality and influences nutrient cycling in freshwater ecosystems. Given these findings, the invasion of the littoral zone by submerged and emergent exotic plants deserves further attention.

Ethanol Content of Medications and Its Effect on Blood Alcohol Concentration in Pediatric Patients.

OBJECTIVE: Ethanol is a common excipient used in liquid medications to enhance solubility and inhibit -bacterial growth. While the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have released guidance for how much ethanol is acceptable in medicines, many medications contain more than the recommended amount. The objective of this study was to determine what effect these medications would have on blood alcohol concentration (BAC) for pediatric patients, defined as those medications that would increase the BAC by ≥2.5 mg/dL. METHODS: A list of medications dispensed to pediatric patients from a single hospital over a period of 4 months was obtained. The package inserts of these medications were reviewed to determine ethanol content. Typical doses were used to determine the amount of ethanol pediatric patients weighing 10, 20, and 40 kg would receive. The theoretical BAC was then calculated for each medication containing ethanol. RESULTS: Seven hundred ninety-six medications were dispensed for pediatric patients during the study period, of which 33 contained ethanol. Seven medications would be projected to increase the BAC above 2.5 mg/dL with a normal pediatric dose. CONCLUSION: While most medications do not contain ethanol, we found 7 that contained enough ethanol to potentially raise the BAC above 2.5 mg/dL. Health care practitioners should consider the ethanol content of medications prior to recommending them in children and when assessing overdoses.

Root and shoot phenology, architecture, and organ properties: an integrated trait network among 44 herbaceous wetland species.

Integrating traits across above- and belowground organs offers comprehensive insights into plant ecology, but their various functions also increase model complexity. This study aimed to illuminate the interspecific pattern of whole-plant trait correlations through a network lens, including a detailed analysis of the root system. Using a network algorithm that allows individual traits to belong to multiple modules, we characterize interrelations among 19 traits, spanning both shoot and root phenology, architecture, morphology, and tissue properties of 44 species, mostly herbaceous monocots from Northern Ontario wetlands, grown in a common garden. The resulting trait network shows three distinct yet partially overlapping modules. Two major trait modules indicate constraints of plant size and form, and resource economics, respectively. These modules highlight the interdependence between shoot size, root architecture and porosity, and a shoot-root coordination in phenology and dry-matter content. A third module depicts leaf biomechanical adaptations specific to wetland graminoids. All three modules overlap on shoot height, suggesting multifaceted constraints of plant stature. In the network, individual-level traits showed significantly higher centrality than tissue-level traits do, demonstrating a hierarchical trait integration. The presented whole-plant, integrated network suggests that trait covariation is essentially function-driven rather than organ-specific.

Genetic Evaluation for Monogenic Disorders of Low Bone Mass and Increased Bone Fragility: What Clinicians Need to Know.

PURPOSE OF REVIEW: The purpose of this review is to outline the principles of clinical genetic testing and to provide practical guidance to clinicians in navigating genetic testing for patients with suspected monogenic forms of osteoporosis. RECENT FINDINGS: Heritability assessments and genome-wide association studies have clearly shown the significant contributions of genetic variations to the pathogenesis of osteoporosis. Currently, over 50 monogenic disorders that present primarily with low bone mass and increased risk of fractures have been described. The widespread availability of clinical genetic testing offers a valuable opportunity to correctly diagnose individuals with monogenic forms of osteoporosis, thus instituting appropriate surveillance and treatment. Clinical genetic testing may identify the appropriate diagnosis in a subset of patients with low bone mass, multiple or unusual fractures, and severe or early-onset osteoporosis, and thus clinicians should be aware of how to incorporate such testing into their clinical practices.

Integration of an online application to optimise multi-disciplinary meetings: a retrospective analysis.

BACKGROUND: Multi-disciplinary Meetings (MDM) play a crucial role in complex patient care, involving input from various specialties to formulate evidence-based management plans. However, traditional unidirectional approaches and reliance on manual processes have led to inefficiencies in the MDM pathway. AIMS: This study identified and aimed to improve four critical moments where Information Communication Technologies (ICTs) could enhance the MDM process. Initial referral, information synthesis, meeting presentation and the creation of actionable/auditable items. METHODS: Microsoft Office Forms, a customisable survey platform, was implemented to streamline MDM processes. Forms were created to gather patient information, develop agendas, and track outcomes. Automation through Excel scripting further optimised data organisation and agenda creation. RESULTS: Referrals using Forms takes an average of 7 min and 21 s. Over 15 months the submission time has reduced and is trending towards under 5 min for each referral. The system's scalability has allowed 1744 cases to be discussed over a 15-month period. Active departments using Forms is expanding to seven from two prior to the pilot. CONCLUSION(S): Microsoft Office Forms proved to be a valuable and adaptable tool for MDMs, offering benefits such as streamlined information gathering, real-time collaboration, and scalability. The study highlights the potential of existing tools within Microsoft licenses for healthcare process optimisation, providing a cost-effective and customisable solution for MDM agendas. While recognising some limitations, the study concludes that leveraging Microsoft Office Forms can significantly improve system efficiency in a multi-disciplinary setting.

Growth, nutrient removal, and lipid productivity promotion of Chlorella sorokiniana by phosphate solubilizing bacteria Bacillus megatherium in swine wastewater: Performances and mechanisms.

Effects of a phosphorus-solubilizing bacteria (PSB) Bacillus megatherium on growth and lipid production of Chlorella sorokiniana were investigated in synthesized swine wastewater with dissolved inorganic phosphorus (DIP), insoluble inorganic phosphorus (IIP), and organic phosphorus (OP). The results showed that the PSB significantly promoted the algal growth in OP and IIP, by 1.10 and 1.78-fold, respectively. The algal lipid accumulation was also greatly triggered, respectively by 4.39, 1.68, and 1.38-fold in DIP, IIP, and OP. Moreover, compared with DIP, OP improved the oxidation stability of algal lipid by increasing the proportion of saturated fatty acids (43.8 % vs 27.9 %), while the PSB tended to adjust it to moderate ranges (30.2-41.6 %). Further, the transcriptome analysis verified the OP and/or PSB-induced up-regulated genes involving photosynthesis, lipid metabolism, signal transduction, etc. This study provided novel insights to enhance microalgae-based nutrient removal combined with biofuel production in practical wastewater, especially with complex forms of phosphorus.

[Effect of EDDS Application on Soil Cu/Cd Availability and Uptake/transport by Castor].

To investigate the effect of chelating agents on plant uptake of heavy metals, castor (Ricinus communis L.) was used as the test plant. Soil culture and pot experiments were conducted to study the effects of different concentrations of ethylenediamine disuccinic acid (EDDS) on the forms of Cu and Cd in soil and their absorption and transport by castor. The results showed that the application of EDDS significantly increased the content of available Cu and Cd. After 15 days of cultivation, the available Cu and Cd concentrations in the soil increased by 43.01%-103.55% and 51.78%-69.43%, respectively. EDDS promoted the conversion of reducible Cu to weak acid extractable and increased the mobility of Cu. Meanwhile, the application of EDDS promoted the absorption, transport, and enrichment of Cu in castor. Under the application of 2.5 mmol·kg-1 EDDS and 5.0 mmol·kg-1 EDDS, the Cu concentrations in the shoots were 4.88 times and 16.65 times higher than that of the control (P< 0.05), and the Cu concentrations in the roots were 2.89 times and 3.60 times higher than that of the control (P< 0.05), respectively. The Cu transport coefficient significantly increased by 72.73% and 381.82% when treated with EDDS 2.5 and EDDS 5.0. Simultaneously, the phytoextraction of Cu in shoots, roots, and their sum were 14.08, 2.16, and 4.70 times higher than that of the control (P<0.05), respectively, when treated with EDDS 5.0. Furthermore, EDDS significantly increased the Cd concentrations in castor. When treated with EDDS 2.5 the shoots and roots increased by 15.15% and 57.42%, respectively, and the phytoextraction of total Cd significantly increased by 13.44%. Generally, the EDDS treatment could increase the available Cu and Cd in soil, promote the uptake of Cu and Cd, and improve the phytoremediation efficiency of castor. Among them, the addition of 5.0 mmol·kg-1 EDDS had the best effect for Cu, whereas the addition of 2.5 mmol kg-1 EDDS had a higher increase in the phytoextraction of Cd.

The challenge of downstream processing of spray dried amorphous solid dispersions into minitablets designed for the paediatric population - A sustainable product development approach.

Poorly water-soluble drugs present a significant challenge in the development of oral solid dosage forms (OSDs). In formulation development the appropriate use of excipients to adjust solubility, and the choice of manufacturing method and pharmaceutical processes to obtain a dosage form to meet the needs of the patient group, is crucial. Preparing an amorphous solid dispersion (ASD) is a well-established method for solubility enhancement, and spray drying (SD) a common manufacturing method. However, the poor flowability of spray dried materials poses a significant challenge for downstream processing. Promoting sustainability in OSD development involves embracing a versatile formulation design, which enables a broader spectrum of patients to use the product, as opposed to altering existing dosage forms retrospectively. The objective of the current study was to develop a formulation of spray dried indomethacin ASD suited to the production, by direct compression, of instant release paediatric minitablets. Excipients evaluated were PVP or HPMCAS in solid dispersions at the preformulation phase, and MCC and lactose as a filler in direct compression. From the studied formulations, a 3:1 ratio blend of Vivapur 200/Pharmatose 200 M (MCC/lactose) with 0.5% (w/w) magnesium stearate was found to be the most promising in tableting, and minitablets containing a 6.22% content of spray-dried ASD of indomethacin/PVP K 29-32 could be obtained with desired tablet hardness and pharmaceutical quality, complying with tests of weight variation and fast disintegration in an aqueous environment. As a case example, this study provides a good foundation for further studies in harnessing a sustainable approach to the development of pharmaceutical formulations that can appropriately serve different patient sub-populations.

Importance of Considering Fed-State Gastrointestinal Physiology in Predicting the Reabsorption of Enterohepatic Circulation of Drugs.

PURPOSE: The purpose of this study was to develop a simulation model for the pharmacokinetics (PK) of drugs undergoing enterohepatic circulation (EHC) with consideration to the environment in the gastrointestinal tract in the fed state in humans. The investigation particularly focused on the necessity of compensating for the permeability rate constant in the reabsorption process in consideration of drug entrapment in bile micelles. METHODS: Meloxicam and ezetimibe were used as model drugs. The extent of the entrapment of drugs inside bile micelles was evaluated using the solubility ratio of Fed State Simulated Intestinal Fluid version 2 (FeSSIF-V2) to Fasted State Simulated Intestinal Fluid version 2 (FaSSIF-V2). Prediction accuracy was evaluated using the Mean Absolute Percentage Error (MAPE) value, calculated from the observed and predicted oral PK profiles. RESULTS: The solubilization of ezetimibe by bile micelles was clearly observed while that of meloxicam was not. Assuming that only drugs in the free fraction of micelles permeate through the intestinal membrane, PK simulation for ezetimibe was performed in both scenarios with and without compensation by the permeation rate constant. The MAPE value of Zetia® tablet, containing ezetimibe, was lower with compensation than without compensation. By contrast, Mobic® tablet, containing meloxicam, showed a relatively low MAPE value even without compensation. CONCLUSION: For drugs which undergo EHC and can be solubilized by bile micelles, compensating for the permeation rate constant in the reabsorption process based on the free fraction ratio appears an important factor in increasing the accuracy of PK profile prediction.

Roles of red mud in remediation of contaminated soil in mining areas: Mechanisms, advances and perspectives.

Red mud (RM) is a kind of strong alkaline solid waste produced from the aluminum industry, which contributes significantly to environmental pollution and can cause severe health issues.Currently, RM is widely recognized as a potential material for soil remediation because of its rich metal oxide content, such as Fe/Al oxides. However, there is no comprehensive description on the roles of RM in passivation remediation of contaminated soil in mining areas. This review summarizes the mechanisms of passivation of heavy metals (HMs) in contaminated soil by RM, including precipitation, adsorption and ion exchange. Besides the effects of adding RM on soil physicochemical properties, heavy metal forms and ecological environment are further elaborated. Moreover, using the co-hydrothermal carbonization of RM and biomass for enhancing the efficiency of contaminated soil remediation is proposed as the main prospective research. This paper provides technical references for the resource utilization of RM and the treatment of heavy metal-contaminated soil.