Method For Accurate Quantification Research Articles

A U-Net architecture as a surrogate model combined with a geostatistical spectral algorithm for transient groundwater flow inverse problems

Characterizing groundwater flow parameters is crucial for understanding complex aquifer systems, and inverse techniques play a fundamental role in modeling hydrogeological parameters and assessing their uncertainties. Nonetheless, the use of a forward model in these methods can be highly time-consuming, especially with an increasing number of model parameters. To address this issue, we propose a surrogate model based on a U-Net architecture that replaces the transient groundwater flow model, reducing runtime and enabling a fast quantification of uncertainties related to key parameters, including heterogeneous hydraulic conductivity, boundary conditions, specific storage, and pumping rate. The surrogate is trained using limited evaluations of the forward model to learn the physical relationship between hydraulic conductivity fields and transient hydraulic heads measured on-site. The physical principles of the studied problem, including boundary conditions, specific storage, and source terms, are also mapped and introduced as inputs to the model to enhance its understanding of the governing equation of transient groundwater flow. To speed up learning using image–image regression, the previously predicted transient hydraulic heads also serve as an input to predict the transient heads at the current time step. Once the model is trained, we use a spectral geostatistical method to solve the inverse problem, a pumping test of 12 h, using the surrogate model in place of the forward model. Our study demonstrates that the trained U-Net accurately reproduces the state variables corresponding to a specific parameter field, and in terms of computational demand, using U-Net as a surrogate model reduces the required computational time by approximately an order of magnitude for the defined problem. The proposed approach offers an efficient and accurate method for groundwater flow parameter characterization and uncertainty quantification in complex aquifer systems.

A novel method for accurate and real-time quantification of radiopharmaceutical activity in automated dose dispensers

In recent years, there has been a rapid growth in new technologies within nuclear medicine and PET diagnostics, particularly in the field of radiopharmaceutical dose preparation. These advancements are driven by the integration of automatic algorithms into the process. This evolution has brought about significant improvements in the efficiency and accuracy of radiopharmaceutical dose preparation. These automatic algorithms utilize state-of-the-art technologies to streamline the process and ensure precise and tailored doses for patients. The integration of these advanced technologies has revolutionized the field, allowing for more effective and personalized treatment options in nuclear medicine and PET diagnostics. By employing automatic radiopharmaceutical dose dispensers (ARDDs), radiation exposure to technologists is minimized while also mitigating the risk of potential infections for patients. Ionization chambers are currently the most used detectors to measure the activity of radiopharmaceuticals in ARDDs. However, they present certain limitations, including size constraints. This study is part of an international endeavor to develop a new approach for evaluating radiopharmaceutical activity in an ARDD named KARl 100. A new approach was used to develop a scintillation detector by linking a PVT detector to a SiPMs array consisting of four elements, each having an active surface of 6 × 6 mm with a bias voltage of 30 V. The detection system's amplified output was then fed to a single-channel analyzer called Enviro, developed by Tema Sinergie S.p.A in Italy. The counts per second (CPS) detected by the detector were studied using WinTAM software allowing for the radionuclide’s activity concentration to be read out at run-time. Three widely used medical radioisotopes, 18F, 11C and 68Ga, were used to evaluate the performance of the detector in terms of linearity and repeatability of the measurements. Half-life and linear response were evaluated over a wide range of activities with different decay schemes. Data analysis was conducted, resulting in half-lives of the 18F, 11C and 68Ga radioisotopes of 109.75 ± 0.35, 20.62 ± 0.34 and 67.82 ± 0.25 min, respectively, with calculated deviations of 0.0167%, 1.00% and 0.29% from expected values. The linear response of the detector over the entire range of desired activity concentrations was confirmed after data correction for the detector dead time. Calibration of the detector combined with the dispenser system was carried out in parallel investigations to provide the required device properties for reference applications in nuclear medicine. Furthermore, Monte Carlo simulations using FLUKA code were performed to investigate the contribution of beta particles in addition to gamma radiations to assess the influence of beta particles on the calibration factors. For better accuracy, a shielding was designed to prevent any beta particles from reaching the detector.

Synergistic quantification of mixed insulin preparations using time domain NMR techniques

Diabetes patients often rely on tailored insulin therapies, necessitating precise blends of various insulin types to achieve optimal pharmacokinetic profiles, including the quantity and action duration of insulin absorption into the bloodstream. This study aimed to develop an accurate quantification method for mixed insulin preparations, consisting of Insulin-NPH and Insulin Regular in ratios varying between 0:100–100:0. Time Domain NMR (TD-NMR) techniques, T2 relaxation times, and T1T2 maps were used to analyze the mixtures. Individually, neither technique provided a reliable determination of insulin ratios. However, the integration of both methods through chemometrics has been proven to be a synergistic approach, yielding a robust quantification technique suitable for quality control in the assessment of mixed insulin drugs. This innovative combined TD-NMR method is non-invasive, cost-effective, and user-friendly, offering at the same time a significant potential for preventing health complications associated with improper insulin dosing. Furthermore, our work elucidates the broader applicability of converging multiple TD-NMR techniques for analyzing intricate mixtures.

Development of a TaqMan Real-Time PCR for Early and Accurate Detection of Anthracnose Pathogen Colletotrichum siamense in Pachira glabra.

Anthracnose, caused by Colletotrichum siamense, is a destructive disease of Pachira glabra in southern China. Early and proper monitoring and quantification of C. siamense is of importance for disease control. A calmodulin (CAL) gene-based TaqMan real-time PCR assay was developed for efficient detection and quantification of C. siamense, which reliably detected as low as 5 pg of genomic DNA and 12.8 fg (5800 copies) of target DNA. This method could specifically recognize all tested C. siamense isolates, while no amplification was observed in other closely related Colletotrichum species. The assay could still detect C. siamense in plant mixes, of which only 0.01% of the tissue was infected. A dynamic change in the amount of C. siamense population was observed during infection, suggesting that this real-time PCR assay can be used to monitor the fungal growth progression in the whole disease process. Moreover, the method enabled the detection of C. siamense in naturally infected and symptomless leaves of P. glabra trees in fields. Taken together, this specific TaqMan real-time PCR provides a rapid and accurate method for detection and quantification of C. siamense colonization in P. glabra, and will be useful for prediction of the disease to reduce the epidemic risk.

Chiral liquid chromatography-tandem mass spectrometry for enantiomeric profiling of ten alkaloids in tobacco: Assessing interconversion in precursor materials and aerosol

Multiple chiral enantiomer separation poses challenges in analyzing complex matrices like natural plant materials. Currently, there is no straightforward method for simultaneous separation and analysis of ten alkaloids and enantiomers, mainly due to most of their low levels. Here, we present an improved chiral liquid chromatography-tandem mass spectrometry method for accurate quantification of ten alkaloids and enantiomers. This method exhibits recoveries of 92.3 to 118.1 %, intra-day precisions of 0.6 to 4.7 %, and inter-day precisions of 1.2 to 4.5 %, with detection limits ranging from 0.03 to 3.0 ng/mL. Successfully applied to the ten alkaloids and enantiomers quantification in precursor tobacco materials and aerosols from traditional cigarettes and heated tobacco products, our results show higher concentrations of ten alkaloids in traditional cigarette aerosol compared to heated tobacco products aerosol. During aerosol formation, (R)-cotinine, N-methylanabasine, and β-nornicotyrine were produced. Notably, high temperatures during aerosol formation favored the (R)-enantiomer of several chiral alkaloids, and lead to the formation of new secondary alkaloids. This proposed mechanism represents the first attempt to elucidate the interconversion of alkaloids during aerosol formation.

Cyanobacteria and Macroinvertebrate Relationships in Freshwater Benthic Communities beyond Cytotoxicity.

Cyanobacteria are harmful algae that are monitored worldwide to prevent the effects of the toxins that they can produce. Most research efforts have focused on direct or indirect effects on human populations, with a view to gain easy accurate detection and quantification methods, mainly in planktic communities, but with increasing interest shown in benthos. However, cyanobacteria have played a fundamental role from the very beginning in both the development of our planet's biodiversity and the construction of new habitats. These organisms have colonized almost every possible planktic or benthic environment on earth, including the most extreme ones, and display a vast number of adaptations. All this explains why they are the most important or the only phototrophs in some habitats. The negative effects of cyanotoxins on macroinvertebrates have been demonstrated, but usually under conditions that are far from natural, and on forms of exposure, toxin concentration, or composition. The cohabitation of cyanobacteria with most invertebrate groups is long-standing and has probably contributed to the development of detoxification means, which would explain the survival of some species inside cyanobacteria colonies. This review focuses on benthic cyanobacteria, their capacity to produce several types of toxins, and their relationships with benthic macroinvertebrates beyond toxicity.

Simultaneous quantitation of 15 bioactive components in Yupingfeng granules by LC-MS/MS.

Yupingfeng granules (YPFG) is commonly used in the treatment of immunological diseases, inflammations, and pulmonary diseases. Several studies have found that chromones, flavones, and saponins were the major bioactive compounds of YPFG. However, few studies have reported accurate quantification methods of these compounds. This study aimed to establish a simple and rapid method by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine 15 bioactive compounds in YPFG. The experimental parameters including extraction methods, extraction solvents, extraction time, solid-liquid ratio, and LC-MS/MS condition were optimized. The linearity, precision, repeatability, stability, and recovery of the established method were evaluated. The contents of 15 bioactive compounds in seven batches of YPFG samples were analyzed by the established method and the results were compared with the values determined by HPLC. The optimal extraction condition was to extract 0.1 g of YPFG by ultrasound with 50 mL 50% ethanol for 30 min. A Waters ACQUITY UPLCBEH C18 column using the 0.1% formic acid water solution and acetonitrile as mobile phase with a gradient elution was applied to the chromatographic separation. The linearity, precision, repeatability, stability, and recovery of the method were within acceptable ranges. Compared with HPLC analysis methods in Chinese Pharmacopoeia and literature, the established method was faster, simpler, more accurate, and more reliable. The method of simultaneous determination of 15 components in YPFG by LC-MS might provide a basis for the study of the bioactive compounds and the improvement of the quality standard of YPFG.

Profiling of 1-aminocyclopropane-1-carboxylic acid and selected phytohormones in Arabidopsis using liquid chromatography-tandem mass spectrometry

BackgroundGaseous phytohormone ethylene levels are directly influenced by the production of its immediate non-volatile precursor 1-aminocyclopropane-1-carboxylic acid (ACC). Owing to the strongly acidic character of the ACC molecule, its quantification has been difficult to perform. Here, we present a simple and straightforward validated method for accurate quantification of not only ACC levels, but also major members of other important phytohormonal classes – auxins, cytokinins, jasmonic acid, abscisic acid and salicylic acid from the same biological sample.ResultsThe presented technique facilitates the analysis of 15 compounds by liquid chromatography coupled with tandem mass spectrometry. It was optimized and validated for 10 mg of fresh weight plant material. The extraction procedure is composed of a minimal amount of necessary steps. Accuracy and precision were the basis for evaluating the method, together with process efficiency, recovery and matrix effects as validation parameters. The examined compounds comprise important groups of phytohormones, their active forms and some of their metabolites, including six cytokinins, four auxins, two jasmonates, abscisic acid, salicylic acid and 1-aminocyclopropane-1-carboxylic acid. The resulting method was used to examine their contents in selected Arabidopsis thaliana mutant lines.ConclusionThis profiling method enables a very straightforward approach for indirect ethylene study and explores how it interacts, based on content levels, with other phytohormonal groups in plants.

LC-MS/MS-BASED QUANTITATIVE PROFILING OF PAPAIN ENZYME IN CARICA PAPAYA L.: METHOD DEVELOPMENT AND VALIDATION

Objective: To develop and validate a sensitive Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) method for quantifying the Papain enzyme in Carica papaya L. plant extracts. Methods: As an internal standard (IS), Papain was procured. A gradient-based LC-MS/MS method was developed using the Quasar C18, 150 mm × 2.1 mm, 3 µm column; the drug separation was accomplished using a gradient elution mode with a mobile phase consisting of 0.2% formic acid in water (A) and a 98:2% ratio of formic acid in acetonitrile (B). The mobile phase was injected with a volume of 10 µl at a flow rate of 0.5 ml/min. Results: Matrix-matched calibration adhering to SANCO guidelines was employed for accurate quantification, covering a concentration range of 1 to 2000 ng/ml. The method's selectivity and linearity were confirmed with an R2 correlation value of 0.990. Limits of detection (LOD) and quantification (LOQ) were determined as 170.5 ng/ml and 516.8 ng/ml, respectively. The developed LC-MS/MS method demonstrated robust analytical performance, providing a solid basis for quantifying Papain enzyme levels in Carica papaya L. plant extracts. The matrix-matched calibration approach, with a well-defined standard calibration curve, showcased the method's selectivity and linearity. The LOD and LOQ values further underscored the method's sensitivity. Conclusion: This study successfully establishes and validates a gradient-based LC-MS/MS method for accurate quantification of Papain enzyme levels in Carica papaya L. plant extracts. The demonstrated precision, accuracy, and sensitivity support the reliability of this analytical approach, offering a valuable tool for future investigations into the biological effects of Papain.

Enhancing 2-Pyrone Synthase Efficiency by High-Throughput Mass-Spectrometric Quantification and In Vitro/In Vivo Catalytic Performance Correlation.

Engineering efficient biocatalysts is essential for metabolic engineering to produce valuable bioproducts from renewable resources. However, due to the complexity of cellular metabolic networks, it is challenging to translate success in vitro into high performance in cells. To meet such a challenge, an accurate and efficient quantification method is necessary to screen a large set of mutants from complex cell culture and a careful correlation between the catalysis parameters in vitro and performance in cells is required. In this study, we employed a mass-spectrometry based high-throughput quantitative method to screen new mutants of 2-pyrone synthase (2PS) for triacetic acid lactone (TAL) biosynthesis through directed evolution in E. coli. From the process, we discovered two mutants with the highest improvement (46 fold) in titer and the fastest kcat (44 fold) over the wild type 2PS, respectively, among those reported in the literature. A careful examination of the correlation between intracellular substrate concentration, Michaelis-Menten parameters and TAL titer for these two mutants reveals that a fast reaction rate under limiting intracellular substrate concentrations is important for in-cell biocatalysis. Such properties can be tuned by protein engineering and synthetic biology to adopt these engineered proteins for the maximum activities in different intracellular environments.

Quantitative assessment of corneal elasticity distribution after FS-LASIK using optical coherence elastography.

Quantifying corneal elasticity after femtosecond laser-assisted in situ keratomileusis (FS-LASIK) procedure plays an important role in improving surgical safety and quality, since some latent complications may occur ascribing to changes in postoperative corneal biomechanics. Nevertheless, it is suggested that current research has been severely constrained due to the lack of an accurate quantification method to obtain postoperative corneal elasticity distribution. In this paper, an acoustic radiation force optical coherence elastography system combined with the improved phase velocity algorithm was utilized to realize elasticity distribution images of the in vivo rabbit cornea after FS-LASIK under various intraocular pressure levels. As a result, elasticity variations within and between the regions of interest could be identified precisely. This is the first time that elasticity imaging of in vivo cornea after FS-LASIK surgery was demonstrated, and the results suggested that this technology may hold promise in further exploring corneal biomechanical properties after refractive surgery.

Rapid monitoring of heavy metal-ammonia complexes in solutions by UV–vis/ATR-FTIR spectroscopy and chemometric models

Ammonia can form stable chemical complexes with heavy metal ions, which significantly affect the treatment efficiency of these wastewaters. Thus, accurately determining the concentration of heavy metal ammonia complex ions is crucial to understanding the complex decomposition mechanism. The current study predicted the composition of copper ammonia solution through thermodynamic calculations. The mid-infrared first derivative spectra obtained from density functional theory (DFT) calculation and measurements of the simulated solutions were compared, which indicated that [Cu(NH3)4]2+ was the primary form of complexes in solution. The acquired FTIR spectra and UV–vis spectra demonstrated a strong correlation with the [Cu(NH3)4]2+ concentrations; whereas a principal component regression (PCR) model was implemented for concentration computation. The UV–vis-PCR model was found to be a fast and accurate method for quantification of copper-ammonia complex concentration, and its detection limit and quantification limit could reach 5 mg·L−1 and 10 mg·L−1, respectively, in the 5–200 mg·L−1 range. This study established qualitative and quantitative methods for analyzing copper ammonia complex in water, which provided the feasibility for rapid real-time monitoring of copper ammonia complex.

An LC-MS/MS-based platform for the quantification of multiple amyloid beta peptides in surrogate cerebrospinal fluid

IntroductionThe accurate quantification of amyloid beta (Aβ) peptides in cerebrospinal fluid (CSF) is crucial for Alzheimer's disease (AD) research, particularly in terms of preclinical and biomarker studies. Traditional methods, such as the enzyme-linked immunosorbent assay (ELISA), have limitations. These include high costs, labor intensity, lengthy processes, and the possibility of cross-reactivity. ObjectivesThe primary objectives of this research were twofold: to comprehensively characterize Aβ peptides and to develop a reliable and accurate method for the simultaneous quantification of Aβ 1–40 and Aβ 1–42 peptides in surrogate CSF that is traceable to the International System of Units (SI). MethodsWe developed a novel method that combined solid phase extraction (SPE) with isotope dilution liquid chromatography/tandem mass spectrometry (ID-LC/MSMS). SPE was employed to efficiently eliminate matrix interferences, while [15N] Aβ1-40 and [15N] Aβ1-42 served as internal standards to improve accuracy. In addition, we introduced Peptide Impurity Corrected Amino Acid Analysis (PICAA) to ensure traceability to the SI and reliable quantification of Aβ peptides. ResultsThe developed platform demonstrated a linear calibration range of 300–20000 pg/ml for both Aβ1-42 and Aβ1-40 peptides, accompanied by strong correlation coefficients greater than 0.995. Quality Control (QC) samples demonstrated an accuracy of at least 90.0 %. ConclusionThe enhanced specificity and flexibility of the developed platform potentially have implications for Alzheimer's disease diagnosis and future investigations of novel Aβ peptide biomarkers.

Benzenepoly(carboxylic acid)s as Exclusive Intrinsic Markers to Assess Riverine Export of Dissolved Black Carbon.

Landscape fires annually generate large quantities of black carbon. The water-soluble fraction of black carbon (i.e., dissolved black carbon/DBC) is an important constituent of the dissolved organic carbon (DOC) pool, playing a crucial role in the global budget of refractory carbon and climate change. A key challenge in constraining the flux and fate of riverine DBC is to develop targeted and accurate quantification methods. Herein, we report that benzenepentacarboxylic acid (B5CA) intrinsically present in DBC can be used as an exclusive and holistic marker (representing both condensed aromatics and less-/nonaromatic fractions) for DBC quantification. B5CA was universally detected in water extractions of biochar and fire-affected soils with relatively large abundance but not produced by nonthermogenic processes. It has good mobility in the environment as it is not readily precipitated by cations or adsorbed by common geosorbents. B5CA also represents the recalcitrant components of DBC with excellent stability against photodegradation and biodegradation. Applying B5CA as the DBC marker in surface waters of the Changjiang River (i.e., the third largest river in the world), we calculate the DBC concentration in the downstream Changjiang River to be 4.8 ± 5.5% of the DOC flux. Our work provides a simple and reliable approach for the accurate quantification and source tracking of DBC in the soil and aquatic carbon pools.

An UHPLC-QE-Orbitrap-MS Method for Accurate Quantification of Short-Chain Fatty Acids in Serum From an Older Chinese Population

An UHPLC-QE-Orbitrap-MS Method for Accurate Quantification of Short-Chain Fatty Acids in Serum From an Older Chinese Population

Quantification of Gabapentin, Lacosamide, Perampanel, Pregabalin, Rufinamide, and Vigabatrin in Serum Using Liquid Chromatography-Tandem Mass Spectrometry.

Antiepileptic drugs (AEDs) have been used to control epilepsy. More than 17 new AEDs, including gabapentin (GPN), lacosamide (LCM), perampanel (PER), pregabalin (PRG), rufinamide (RFM), and vigabatrin (VGB) have been approved and marketed since 1989. Accurate measurement of serum concentration of the antiepileptic drugs is crucial to achieve optimal efficacy and avoid adverse events. We describe an accurate and precise liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of GPN, LCM, PER, PRG, RFM, and VGB in serum. The method requires a small volume of sample (10μL) and has a total chromatographic run time of 4min for simultaneous measurement of these drugs. The method showed good accuracy with a bias of -0.2-5%. The intra- and inter-day imprecision were less than 5.0% for all the analytes. The linear assay ranges were 0.3-26μg/mL for GPN, 0.15-24μg/mL for LCM, 7.4-1881ng/mL for PER, 0.03-13μg/mL for PRG, 0.78-90μg/mL for RFM, and 0.3-43μg/mL for VGB.

Validating noninvasive techniques for 11C‐ER176 PET quantification in controls and Alzheimer’s disease patients

AbstractBackgroundNoninvasive yet accurate PET quantification methods are crucial for safe yet meaningful PET studies. [11C]ER176 is a PET radioligand that images neuroinflammation via the 18‐kDa translocator protein (TSPO), which is upregulated in activated microglia and has previously been a PET target in Alzheimer’s disease research. Currently, the gold‐standard method for quantifying ER176 PET is kinetic modeling of the dynamic PET data using the arterial input function (AIF), which is invasive and expensive. The current study explores a pseudo‐reference region (RR) technique to noninvasively quantify ER176 scans to facilitate clinical PET studies.MethodDynamic 90‐min [11C]ER176 PET scans were acquired in 11 participants, 5 controls (5M/0F) and 6 patients (3 MCI‐3M/0F; 3 AD‐2M/1F). Arterial blood data were collected throughout the duration of the scan and were used along with the dynamic imaging data to determine regional total volume of distribution (V T) using the two‐tissue compartment model. Standardized Uptake Value Ratio (SUVR) was calculated by normalizing the radioactivity in each region by that of the reference region (cerebellar gray matter). We explored differences across methods (AIF‐derived V T vs. RR‐derived SUVR) and across groups (controls vs. patients).ResultWithin each group, the outcome measures from AIF and RR methods were well correlated (Controls: R2 = 0.986, p < 0.001; Patients: R2 = 0.983, p < 0.001; Figure 1). Both methods showed greater TSPO expression in patients compared to controls, with mean differences in the medial temporal cortex of 14.99% between groups for V T and 10.65% between groups for SUVR, but lower variance for SUVR compared to V T (Figure 2). Both quantification methods showed similar regional patterns of percent differences between groups, corresponding to tau progression along Braak staging (Figure 3).ConclusionResults suggest that using the cerebellum, which does not accumulate amyloid plaques or tau aggregates until end‐stage disease, as a reference region for [11C]ER176 may be a valid method for quantifying differences between AD patients and controls compared to gold‐standard methodology. Regional increases in neuroinflammation are more reliable for SUVR than V T in AD‐related regions. Ongoing work includes a larger sample size to further validate noninvasive PET quantification.

Validating noninvasive techniques for 11C‐ER176 PET quantification in controls and Alzheimer’s disease patients

AbstractBackgroundNoninvasive yet accurate PET quantification methods are crucial for safe yet meaningful PET studies. [11C]ER176 is a PET radioligand that images neuroinflammation via the 18‐kDa translocator protein (TSPO), which is upregulated in activated microglia and has previously been a PET target in Alzheimer’s disease research. Currently, the gold‐standard method for quantifying ER176 PET is kinetic modeling of the dynamic PET data using the arterial input function (AIF), which is invasive and expensive. The current study explores a pseudo‐reference region (RR) technique to noninvasively quantify ER176 scans to facilitate clinical PET studies.MethodDynamic 90‐min [11C]ER176 PET scans were acquired in 11 participants, 5 controls (5M/0F) and 6 patients (3 MCI‐3M/0F; 3 AD‐2M/1F). Arterial blood data were collected throughout the duration of the scan and were used along with the dynamic imaging data to determine regional total volume of distribution (VT) using the two‐tissue compartment model. Standardized Uptake Value Ratio (SUVR) was calculated by normalizing the radioactivity in each region by that of the reference region (cerebellar gray matter). We explored differences across methods (AIF‐derived VT vs. RR‐derived SUVR) and across groups (controls vs. patients).ResultWithin each group, the outcome measures from AIF and RR methods were well correlated (Controls: R2 = 0.986, p < 0.001; Patients: R2 = 0.983, p < 0.001; Figure 1). Both methods showed greater TSPO expression in patients compared to controls, with mean differences in the medial temporal cortex of 14.99% between groups for VT and 10.65% between groups for SUVR, but lower variance for SUVR compared to VT (Figure 2). Both quantification methods showed similar regional patterns of percent differences between groups, corresponding to tau progression along Braak staging (Figure 3).ConclusionResults suggest that using the cerebellum, which does not accumulate amyloid plaques or tau aggregates until end‐stage disease, as a reference region for [11C]ER176 may be a valid method for quantifying differences between AD patients and controls compared to gold‐standard methodology. Regional increases in neuroinflammation are more reliable for SUVR than VT in AD‐related regions. Ongoing work includes a larger sample size to further validate noninvasive PET quantification.

Utility of N-Bromosuccinimide-Water Combination as a Green Reagents for a Validated Indirect Spectrophotometric Determination of Some Antihypertensive Drugs: An Application to Their Monitoring in Marketed Tablets and Capsules.

Analytical tests were conducted to investigate the use of N-bromosuccinimide (NBS) as an important, safe analytical reagent for the spectrophotometric detection of therapeutically significant dihydropyridine-based calcium antagonists (DHP), namely nifedipine (NIF) and amlodipine (AML), which have been demonstrated to possess antioxidant activity in vivo and to reduce the intracellular production of reactive oxygen species (ROS). Following the reaction of DHP and NBS in acidic media, the excess NBS was evaluated for the first time by its interaction with P-aminophenol (PAP), which produced a violet-colored product that was detected at 556 nm. The analytical method was performed and validated since different variables disturbing the reaction (concentration of reagent, type and concentration of the selected acid, reaction time and the diluting solvents) were carefully studied and optimized. The stoichiometry of the applied reaction was determined by Job's method of continuous variation. Monitoring of these drug dosage forms' content uniformity is a first tool or evidence for their efficacy and safety after their administration. Beer's law was obeyed in the concentration range 1.25-11.0 µg/mL for NIF and 1.25-10.0 µg/mL for AML. The calculated limit of detection (LODs) and limit of quantification (LOQs) for NIF and AML were 0.220, 0.155 µg/mL and 0.519, 0.735 µg/mL, respectively. The precision of the applied method was satisfactory; the RSDs did not exceed 2%. Two greenness assessment tools, the Green Analytical Procedure Index (GAPI) and Analytical Greenness Metric for Sample Preparation (AGREEprep) were used for measuring the environmental friendliness of the recommended method. The micro-determinations of content uniformity for NIF and AML in their pharmaceutical dosage forms were extremely comparable with those from official and validated procedures. A validated indirect spectrophotometric method for accurate quantification of some 1,4-dihydropyridine drugs using NBS with the aid of PAP. Monitoring of NIF and AML dosage forms' content uniformity as a first tool or evidence for their efficacy and safety after their administration. Greenness evaluation tools, GAPI and AGREEprep, for measuring the environmental friendliness of the recommended method.

Non-Invasive Diagnostic of NAFLD in Type 2 Diabetes Mellitus and Risk Stratification: Strengths and Limitations.

The progressive potential of liver damage in type 2 diabetes mellitus (T2DM) towards advanced fibrosis, end-stage liver disease, and hepatocarcinoma has led to increased concern for quantifying liver injury and individual risk assessment. The combination of blood-based markers and imaging techniques is recommended for the initial evaluation in NAFLD and for regular monitoring to evaluate disease progression. Continued development of ultrasonographic and magnetic resonance imaging methods for accurate quantification of liver steatosis and fibrosis, as well as promising tools for the detection of high-risk NASH, have been noted. In this review, we aim to summarize available evidence regarding the usefulness of non-invasive methods for the assessment of NAFLD in T2DM. We focus on the power and limitations of various methods for diagnosis, risk stratification, and patient monitoring that support their implementation in clinical setting or in research field.