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A trending problem of Extra Virgin Olive Oil (EVOO) adulteration is investigated using two analytical platforms, involving: (1) Near Infrared (NIR) spectroscopy, resulting in a two-way data set, and (2) Fluorescence Excitation-Emission Matrix (EEFM) spectroscopy, producing three-way data. The related instruments were employed to study genuine and adulterated samples. Each data set was first separately analyzed using the Data Driven-Soft Independent Modeling of Class Analogies (DD-SIMCA) method, based on Principal Component Analysis (for the two-way NIR data) and PARallel FACtor analysis (for the three-way EEFM data). The data sets were then processed together using the multi-block fusion method, based on the concept of Cumulative Analytical Signal (CAS). A comparison of the data processing methods in terms of sensitivity, specificity and selectivity showed the following order of excellence: NIR < EEFM < NIR + EEFM. This finding confirms the effectiveness of multi-block data fusion, which cumulatively improves the model performance.
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Contaminación de Alimentos , Aceite de Oliva , Espectroscopía Infrarroja Corta , Aceite de Oliva/química , Espectroscopía Infrarroja Corta/métodos , Contaminación de Alimentos/análisis , Espectrometría de Fluorescencia/métodos , Análisis de Componente PrincipalRESUMEN
The Zika disease caused by the Zika virus was declared a Public Health Emergency by the World Health Union (WHO), with microcephaly as the most critical consequence. Aiming to reduce the spread of the virus, biopharmaceutical organizations invest in vaccine research and production, based on multiple platforms. A crescent vaccine production approach is based on virus-like particles (VLP), for not having genetic material in its composition, hypoallergenic and non-mutant character. For bioprocess, it is essential to have means of real-time monitoring, which can be assessed using process analysis techniques such as Near-infrared (NIR) spectroscopy, that can be combined with chemometric methods, like Partial-Least Squares (PLS) and Artificial Neural Networks (ANN) for prediction of biochemical variables. This work proposes a biochemical Zika VLP upstream production at-line monitoring model using NIR spectroscopy comparing sampling conditions (with or without cells), analytical blank (air, ultrapure water), and spectra pre-processing approaches. Seven experiments in a benchtop bioreactor using recombinant baculovirus/Sf9 insect cell platform in serum-free medium were performed to obtain biochemical and spectral data for chemometrics modeling (PLS and ANN), composed by a random data split (80 % calibration, 20 % validation) for cross-validation of the PLS models and 70 % training, 15 % testing, 15 % validation for ANN. The best models generated in the present work presented an average absolute error of 1.59 × 105 cell/mL for density of viable cells, 2.37 % for cell viability, 0.25 g/L for glucose, 0.007 g/L for lactate, 0.138 g/L for glutamine, 0.18 g/L for glutamate, 0,003 g/L for ammonium, and 0.014 g/L for potassium.
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Candida auris and Candida haemulonii are two emerging opportunistic pathogens that have caused an increase in clinical cases in the recent years worldwide. The differentiation of some Candida species is highly laborious, difficult, costly, and time-consuming depending on the similarity between the species. Thus, this study aimed to develop a new, faster, and less expensive methodology for differentiating between C. auris and C. haemulonii based on near-infrared (NIR) spectroscopy and multivariate analysis. C. auris CBS10913 and C. haemulonii CH02 were separated in 15 plates per species, and three isolated colonies of each plate were selected for Fourier transform near-infrared (FT-NIR) analysis, totaling 90 spectra. Subsequently, principal component analysis (PCA) and variable selection algorithms, including the successive projections algorithm (SPA) and genetic algorithm (GA) coupled with linear discriminant analysis (LDA), were employed to discern distinctive patterns among the samples. The use of PCA, SPA, and GA algorithms associated with LDA achieved 100% sensitivity and specificity for the discriminations. The SPA-LDA and GA-LDA algorithms were essential in selecting the variables (infrared wavelengths) of most importance for the models, which could be attributed to binding of cell wall structures such as polysaccharides, peptides, proteins, or molecules resulting from yeasts' metabolism. These results show the high potential of combined FT-NIR and multivariate analysis techniques for the classification of Candida-like fungi, which can contribute to faster and more effective diagnosis and treatment of patients affected by these microorganisms.
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The glucose level in the blood is measured through invasive methods, causing discomfort in the patient, loss of sensitivity in the area where the sample is obtained, and healing problems. This article deals with the design, implementation, and evaluation of a device with an ESP-WROOM-32D microcontroller with the application of near-infrared photospectroscopy technology that uses a diode array that transmits between 830 nm and 940 nm to measure glucose levels in the blood. In addition, the system provides a webpage for the monitoring and control of diabetes mellitus for each patient; the webpage is hosted on a local Linux server with a MySQL database. The tests are conducted on 120 people with an age range of 35 to 85 years; each person undergoes two sample collections with the traditional method and two with the non-invasive method. The developed device complies with the ranges established by the American Diabetes Association: presenting a measurement error margin of close to 3% in relation to traditional blood glucose measurement devices. The purpose of the study is to design and evaluate a device that uses non-invasive technology to measure blood glucose levels. This involves constructing a non-invasive glucometer prototype that is then evaluated in a group of participants with diabetes.
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Automonitorización de la Glucosa Sanguínea , Glucemia , Diabetes Mellitus , Humanos , Anciano , Glucemia/análisis , Persona de Mediana Edad , Adulto , Automonitorización de la Glucosa Sanguínea/instrumentación , Automonitorización de la Glucosa Sanguínea/métodos , Diabetes Mellitus/sangre , Anciano de 80 o más Años , Masculino , Femenino , Espectroscopía Infrarroja Corta/métodos , Espectroscopía Infrarroja Corta/instrumentaciónRESUMEN
OBJECTIVES: Studies exploring variations in peripheral muscle oxygenation and pressure pain thresholds (PPT) of masticatory muscles in individuals with Temporomandibular Disorders (TMDs) are limited. The purpose of this study was to compare variations in peripheral oxygenation of the masseter muscle; PPT of the masseter and temporal muscles and correlate peripheral muscle oxygenation and PPT of the masseter muscle in individuals with different types of TMDs. MATERIALS AND METHODS: Cross-sectional study involving 116 participants classified into three groups: muscle group (MG, n = 32), joint group (JG, n = 30) and muscle-joint group (MJG, n = 54). Individuals aged 26.97 ± 6.93, 68.97% female, 31,03% males were included. All participants were evaluated using the Diagnostic Criteria for Temporomandibular Disorders, Near-infrared spectroscopy (NIRS) for peripheral muscle oxygenation and pressure algometer for PPT. RESULTS: There was no difference in masseter muscle oxygenation among groups. In the masseter muscle, a weakly positive correlation was observed between PPT and variation in tissue saturation index in the MG (rho = 0.365) and JG (rho = 0.317). In addition, the MJG expressed lower PPT (p = 0.004) than JG, demonstrating that MJG had more pain in this muscle. CONCLUSIONS: MJG have lower PPT in the masseter muscle. Although the PPT is dependent on the type of TMDs, the correlation between PPT and oxygenation is weak. All TMDs groups evaluated (MG, JG, MJG) showed hemodynamic similarities of the masseter muscle. CLINICAL RELEVANCE: Understanding pain thresholds and the hemodynamic behavior of the masticatory muscles contributes to a more assertive physiotherapeutic assessment in TMDs, serving as a basis for careful and individualized interventions.
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Músculo Masetero , Dimensión del Dolor , Umbral del Dolor , Espectroscopía Infrarroja Corta , Trastornos de la Articulación Temporomandibular , Humanos , Masculino , Trastornos de la Articulación Temporomandibular/fisiopatología , Femenino , Estudios Transversales , Adulto , Umbral del Dolor/fisiología , Músculo Masetero/fisiopatología , Dolor Facial/fisiopatología , Oxígeno/metabolismo , Músculo Temporal/fisiopatologíaRESUMEN
Near-infrared spectroscopy combined with vascular occlusion test (NIRS-VOT) is a reactive hyperemia technique for in vivo evaluation of skeletal muscle microvascular reactivity. Previous studies using NIRS-VOT have been shown to be able to detect impairments in microvascular function in high-risk cardiovascular disease populations, such as older individuals. It has been demonstrated that older individuals have slower reactive hyperemia compared with young individuals. Importantly, older individuals also show less desaturation during ischemia compared with young individuals. Based on these findings, it has been suggested that the slower reactive hyperemia observed in older individuals is explained by the lower desaturation during blood flow occlusion (reduced ischemic stimulus). This retrospective analysis compared reactive hyperemia in 36 young and 47 older tissue desaturation-matched individuals that underwent 5-min blood flow occlusion. Overall, we showed that older individuals have impaired reactive hyperemia compared with young when matching for the degree of desaturation and blood flow occlusion time. These findings provide evidence that lower tissue desaturation during ischemia is not a major determinant of impaired reactive hyperemia in older individuals.NEW & NOTEWORTHY Previous findings have suggested that aging-related impairment in skeletal muscle reactive hyperemia is majorly influenced by a lower degree of tissue desaturation during ischemia in older individuals compared with young individuals. In a retrospective analysis including 83 tissue desaturation-matched individuals, we show that the degree of tissue desaturation is not a major determinant of aging-related impairments in reactive hyperemia.
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Envejecimiento , Hiperemia , Microcirculación , Músculo Esquelético , Flujo Sanguíneo Regional , Espectroscopía Infrarroja Corta , Hiperemia/fisiopatología , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatología , Humanos , Estudios Retrospectivos , Masculino , Envejecimiento/metabolismo , Envejecimiento/fisiología , Anciano , Femenino , Adulto , Adulto Joven , Persona de Mediana Edad , Factores de Edad , Isquemia/fisiopatología , Isquemia/metabolismo , Oxígeno/sangre , Oxígeno/metabolismoRESUMEN
Gestational diabetes mellitus (GDM) is a hyperglycemic state that is typically diagnosed by an oral glucose tolerance test (OGTT), which is unpleasant, time-consuming, has low reproducibility, and results are tardy. The machine learning (ML) predictive models that have been proposed to improve GDM diagnosis are usually based on instrumental methods that take hours to produce a result. Near-infrared (NIR) spectroscopy is a simple, fast, and low-cost analytical technique that has never been assessed for the prediction of GDM. This study aims to develop ML predictive models for GDM based on NIR spectroscopy, and to evaluate their potential as early detection or alternative screening tools according to their predictive power and duration of analysis. Serum samples from the first trimester (before GDM diagnosis) and the second trimester (at the time of GDM diagnosis) of pregnancy were analyzed by NIR spectroscopy. Four spectral ranges were considered, and 80 mathematical pretreatments were tested for each. NIR data-based models were built with single- and multi-block ML techniques. Every model was subjected to double cross-validation. The best models for first and second trimester achieved areas under the receiver operating characteristic curve of 0.5768 ± 0.0635 and 0.8836 ± 0.0259, respectively. This is the first study reporting NIR-spectroscopy-based methods for the prediction of GDM. The developed methods allow for prediction of GDM from 10 µL of serum in only 32 min. They are simple, fast, and have a great potential for application in clinical practice, especially as alternative screening tools to the OGTT for GDM diagnosis.
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Significance: People with Parkinson's disease (PD) experience changes in fine motor skills, which is viewed as one of the hallmark signs of this disease. Due to its non-invasive nature and portability, functional near-infrared spectroscopy (fNIRS) is a promising tool for assessing changes related to fine motor skills. Aim: We aim to compare activation patterns in the primary motor cortex using fNIRS, comparing volunteers with PD and sex- and age-matched control participants during a fine motor task and walking. Moreover, inter and intrahemispheric functional connectivity (FC) was investigated during the resting state. Approach: We used fNIRS to measure the hemodynamic changes in the primary motor cortex elicited by a finger-tapping task in 20 PD patients and 20 controls matched for age, sex, education, and body mass index. In addition, a two-minute walking task was carried out. Resting-state FC was also assessed. Results: Patients with PD showed delayed hypoactivation in the motor cortex during the fine motor task with the dominant hand and delayed hyperactivation with the non-dominant hand. The findings also revealed significant correlations among various measures of hemodynamic activity in the motor cortex using fNIRS and different cognitive and clinical variables. There were no significant differences between patients with PD and controls during the walking task. However, there were significant differences in interhemispheric connectivity between PD patients and control participants, with a statistically significant decrease in PD patients compared with control participants. Conclusions: Decreased interhemispheric FC and delayed activity in the primary motor cortex elicited by a fine motor task may one day serve as one of the many potential neuroimaging biomarkers for diagnosing PD.
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The advent of miniaturized NIR instruments, also known as compact, portable, or handheld, is revolutionizing how technology can be employed in forensics. In-field analysis becomes feasible and affordable with these new instruments, and a series of methods has been developed to provide the police and official agents with objective, easy-to-use, tailored, and accurate qualitative and quantitative forensic results. This work discusses the main aspects and presents a comprehensive and critical review of compact NIR spectrophotometers associated with analytical protocols to produce information on forensic matters.
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INTRODUCTION: Previous functional near-infrared spectroscopy (fNIRS) studies using Go/No-Go (GNG) tasks have focused on brain activation in relation to cognitive processes, particularly inhibitory control (IC). The results of these studies commonly describe right hemispheric engagement of the dorsolateral, ventromedial, or inferior frontal regions of the prefrontal cortex. Considering that typical healthy cognitive development is negatively correlated with higher cortisol levels (which may alter brain development), the overarching aim of the current study was to investigate how elevated stress (due to unforeseeable events such as the pandemic) impacts early cognitive development. METHOD: In this study, we examined fNIRS data collected from a sample of children (aged 2-4 years) during a GNG task relative to the response to stressors measured via hair cortisol concentrations. We acquired data in an ecological setting (Early Childhood Education and Care) during the coronavirus pandemic. RESULTS: We found that children with higher stress levels and a less efficient IC recruited more neural terrain and our group-level analysis indicated activation in the left orbitofrontal area during IC performance. CONCLUSIONS: A contextual stressor may disrupt accuracy in the executive function of IC early in development. More research efforts are needed to understand better how an orbitofrontal network subserves goal-directed behavior.
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This study aimed to compare the intensity of deoxygenated haemoglobin concentration ([HHb]) and tissue saturation index (TSI) breakpoints ([HHb]-BP and TSI-BP) with maximal lactate steady state (MLSS) and critical power (CP), and to describe their association with 2000-m rowing ergometer performance. Fourteen male rowers performed on a rowing ergometer: I) a discontinuous incremental test with 3-min stages (INC3); II) a continuous incremental test with 1-min stages (INC1); III) constant workload tests to determine MLSS; and IV) performance tests of 500 m, 1000 m, 2000 m and 6000 m to determine CP.CP (257 ± 39 W; 3.79 ± 4.1 L · min-1) was higher than [HHb]-BP3 (205 ± 26 W; 3.48 ± 2.9 L · min-1), [HHb]-BP1 (207 ± 27 W; 3.27 ± 3.2 L · min-1), and TSI-BP3 (218 ± 31 W; 3.51 ± 3.0 L · min-1), but not higher than TSI-BP1 (222 ± 34 W; 3.43 ± 3.2 L · min-1). MLSS (187 ± 26 W; 3.33 ± 3.2 L · min-1) was lower than TSI-BP3 and TSI-BP1 for power output, but not different in any comparison for â©O2. The limits of agreement for power output and â©O2 suggest poor agreement among these thresholds. The low level of agreement compromises the use of [HHb]-BP and TSI-BP for estimating MLSS and CP; therefore, these thresholds should not be considered interchangeable.
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An increase in the delivery and use of oxygen to the musculature in physically active subjects are determinants of improving health-related aerobic capacity. Additional health benefits, such as an increase in the muscle mass and a decrease in fat mass, principally in the legs, could be achieved with weekly global physical activity levels of more than 300 min. The objective was to compare the muscle vascular and metabolic profiles of physically very active and inactive subjects. Twenty healthy men participated in the study; ten were assigned to the physically very active group (25.5 ± 4.2 years; 72.7 ± 8.1 kg; 173.7 ± 7.6 cm) and ten to the physically inactive group (30.0 ± 7.4 years; 74.9 ± 11.8 kg; 173.0 ± 6.4 cm). The level of physical activity was determined by the Global Physical Activity Questionnaire (GPAQ). A resting vascular occlusion test (5 min of an ischemic phase and 3 min of a reperfusion phase) was used, whereas a near-field infrared spectroscopy (NIRS) device was used to evaluate the muscle oxygenation in the right vastus lateralis of the quadriceps muscle. The area under the curve of the deoxyhemoglobin (HHb) during the ischemic phase and above the curve of the tissue saturation index (TSI) during the reperfusion phase were obtained to determine muscle metabolic and vascular responses, respectively. Physically very active group showed a higher absolute HHb (3331.9 ± 995.7 vs. 6182.7 ± 1632.5 mmol/s) and lower TSI (7615.0 ± 1111.9 vs. 5420.0 ± 781.4 %/s) and relative to body weight (46.3 ± 14.6 vs. 84.4 ± 27.1 mmol/s/kg and 106.0 ± 20.6 vs. 73.6 ± 13.8 %/s/kg, respectively), muscle mass (369.9 ± 122.2 vs. 707.5 ± 225.8 mmol/kg and 829.7 ± 163.4 vs. 611.9 ± 154.2 %/s/kg) and fat mass (1760.8 ± 522.9 vs. 2981.0 ± 1239.9 mmol/s/kg and 4160.0 ± 1257.3 vs. ±2638.4 ± 994.3 %/s/kg, respectively) than physically inactive subjects. A negative correlation was observed between HHb levels and TSI (r = -0.6; p < 0.05). Physically very active men (>300 min/week) present better muscle oxidative metabolism and perfusion and perform significantly more physical activity than physically inactive subjects. Extra benefits for vascular health and muscle oxidative metabolism are achieved when a subject becomes physically very active, as recommended by the World Health Organization. In addition, a higher level of physical activity determined by GPAQ is related to better vascular function and oxidative metabolism of the main locomotor musculature, i.e., the quadriceps.
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OBJECTIVE: This study aimed to delineate the recovery patterns of regional oxygen saturation (SrO2) in pediatric cardiac surgery patients subjected to remote ischemic preconditioning (RIPC), utilizing near-infrared spectroscopy (NIRS) for quantification. It also sought to establish the correlation between these perfusion patterns and postoperative clinical outcomes. DESIGN: A prospective longitudinal observational study. SETTING: The study was conducted at Fundación Valle Del Lili, a high-complexity service provider institution in Fundación Valle Del Lili. PARTICIPANTS: Pediatric patients (younger than 18 years of age) scheduled for elective cardiac surgery requiring cardiopulmonary bypass between August 2022 and July 2023. INTERVENTIONS: RIPC was performed after anesthetic induction, involving cycles of ischemia and reperfusion on a lower limb. Monitoring included SrO2 using NIRS. MEASUREMENTS AND MAIN RESULTS: The study identified 4 distinct patterns of SrO2 during RIPC. Findings demonstrated a significant association between the negative SrO2 pattern and increased postoperative adverse events, including extended hospital stays and higher mortality, while a positive pattern was associated with better outcomes. CONCLUSIONS: Specific patterns of SrO2 response to RIPC may serve as important indicators for risk stratification in congenital heart surgery. This study illustrated the potential of NIRS in detecting hypoxic states and predicting postoperative outcomes, emphasizing the need for standardized clinical interpretation of RIPC patterns.
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Procedimientos Quirúrgicos Cardíacos , Saturación de Oxígeno , Espectroscopía Infrarroja Corta , Humanos , Estudios Prospectivos , Masculino , Femenino , Procedimientos Quirúrgicos Cardíacos/métodos , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Lactante , Espectroscopía Infrarroja Corta/métodos , Saturación de Oxígeno/fisiología , Preescolar , Niño , Precondicionamiento Isquémico/métodos , Estudios Longitudinales , Adolescente , Resultado del Tratamiento , Cardiopatías Congénitas/cirugíaRESUMEN
Significance: Continuous-wave functional near-infrared spectroscopy has proved to be a valuable tool for assessing hemodynamic activity in the human brain in a non-invasively and inexpensive way. However, most of the current processing/analysis methods assume the head is a homogeneous medium, and hence do not appropriately correct for the signal coming from the scalp. This effect can be reduced by considering light propagation in a layered model of the human head, being the Monte Carlo (MC) simulations the gold standard to this end. However, this implies large computation times and demanding hardware capabilities. Aim: In this work, we study the feasibility of replacing the homogeneous model and the MC simulations by means of analytical multilayered models, combining in this way, the speed and simplicity of implementation of the former with the robustness and accuracy of the latter. Approach: Oxy- and deoxyhemoglobin (HbO and HbR, respectively) concentration changes were proposed in two different layers of a magnetic resonance imaging (MRI)-based meshed model of the human head, and then these changes were retrieved by means of (i) a typical homogeneous reconstruction and (ii) a theoretical layered reconstruction. Results: Results suggest that the use of analytical models of light propagation in layered models outperforms the results obtained using traditional homogeneous reconstruction algorithms, providing much more accurate results for both, the extra- and the cerebral tissues. We also compare the analytical layered reconstruction with MC-based reconstructions, achieving similar degrees of accuracy, especially in the gray matter layer, but much faster (between 4 and 5 orders of magnitude). Conclusions: We have successfully developed, implemented, and validated a method for retrieving chromophore concentration changes in the human brain, combining the simplicity and speed of the traditional homogeneous reconstruction algorithms with robustness and accuracy much more similar to those provided by MC simulations.
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Encéfalo , Fotones , Humanos , Simulación por Computador , Encéfalo/diagnóstico por imagen , Cuero Cabelludo/diagnóstico por imagen , Algoritmos , Imagen por Resonancia Magnética , Método de Montecarlo , Fantasmas de ImagenRESUMEN
This feasibility study evaluates a cleaning process designed to avoid the use of detergents and reduce operator exposure to the active pharmaceutical ingredient (API). The continuous manufacturing equipment was cleaned using excipients to displace ibuprofen residues from the system. The cleaning process was performed using 3.0 kg of Prosolv® and 3.0 kg of Tablettose® 70. The impact of different volumetric feed rates of the cleaning excipient was assessed. The displacement of API and blend residues was evaluated with in-line near infrared (NIR) spectroscopy. Principal component analysis (PCA) was performed to evaluate the cleaning progress as the Prosolv® flowed through the feeder, mixer and stream sampler. In-place Raman spectra were acquired from the material sticking to detect the ibuprofen residues. The study showed that Prosolv® and Tablettose® can remove ibuprofen residues effectively from the hopper, feeder screw, mixer paddles, shaft and stream sampler. The Process Analytical Technology (PAT) system can be utilized to detect API displacement during the cleaning process. However, dismantling and manual cleaning was required to remove material sticking at the surfaces adjacent to the rotating feeder screws and mixer paddles.
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Química Farmacéutica , Tecnología Farmacéutica , Tecnología Farmacéutica/métodos , Química Farmacéutica/métodos , Excipientes/química , Ibuprofeno/química , Polvos/química , Comprimidos , Composición de Medicamentos/métodosRESUMEN
BACKGROUND: The current techniques for determining carbon and nitrogen content to provide information about the nutritional status of plants are time-consuming and expensive. For this reason, the objective of this study was to develop an analytical method for the direct and simultaneous determination of nitrogen and carbon elemental content in soybean leaves using near-infrared spectroscopy and compare the performance of conventional (1100-2500 nm spectral range) and portable equipment (1100-1700 nm spectral range). Partial least-squares regression models were developed using 27 soybean leaf samples collected during the 2021 harvest and applied for the simultaneous determination of carbon and nitrogen in 13 samples collected during the 2022 harvest. RESULTS: The root-mean-square error of prediction values for nitrogen and carbon were low (2.42 g kg-1 and 4.37 g kg-1 respectively) for the benchtop method yielded low but higher for the portable method (3.82 g kg-1 and 10.7 g kg-1 respectively). The benchtop method did not show significant differences when compared with the reference method for determining nitrogen and carbon. In contrast, the portable methodology showed potential as a screening method for determining nitrogen levels, particularly in fieldwork. CONCLUSION: The methodologies evaluated in this study were implemented and evaluated under real crop monitoring conditions, using independent sets of calibration and prediction samples. Their utilization enables the acquisition of cost-effective, safe analytical data aligning with the principles of green analytical chemistry. © 2023 Society of Chemical Industry.
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Glycine max , Nitrógeno , Nitrógeno/análisis , Carbono/análisis , Hojas de la Planta/química , Análisis de los Mínimos Cuadrados , CalibraciónRESUMEN
First-line tuberculostatic agents, Rifampicin (RIF), Isoniazid (ISH), Ethambutol (ETB), and Pyrazinamide (PZA) are generally administered as a fixed-dose combination (FDC) for improving patient adherence. The major quality challenge of these FDC products is their variable bioavailability, where RIF and its solid state are key factors. In this work, the analysis of the impact of the polymorphism in the performance of RIF in RIF-ISH and PZA-RIF-ISH combined products was carried out by an overall approach that included the development and validation of two methodologies combining near-infrared (NIR) spectroscopy and partial least squares (PLS) to the further evaluation of commercial products. For NIR-PLS methods, training and validation sets were prepared with mixtures of Form I/Form II of RIF, and the appropriate amount of ISH (for double associations) or ISH-PZA (for triple associations). The corresponding matrix of the excipients was added to the mixture of APIs to simulate the environment of each FDC product. Four PLS factors, reduced spectral range, and the combination of standard normal variate and Savitzky-Golay 1st derivative (SNV-D') were selected as optimum data pre-treatment for both methods, yielding satisfactory recoveries during the analysis of validation sets (98.5±2.0%, and 98.7±1.8% for double- and triple-FDC products, respectively). The NIR-PLS model for RIF-ISH successfully estimated the polymorphic purity of Form II in double-FDC capsules (1.02 ± 0.02w/w). On the other hand, the NIR-PLS model for RIF-ISH-PZA detected a low purity of Form II in triple FDC tablets (0.800 ± 0.021w/w), these results were confirmed by X-ray powder diffraction. Nevertheless, the triple-FDC tablets showed good performance in the dissolution test (Q=99-102%), implying a Form II purity about of 80% is not low enough to affect the safety and efficacy of the product.
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Antituberculosos , Rifampin , Humanos , Rifampin/química , Antituberculosos/química , Isoniazida/química , Pirazinamida/química , Etambutol/química , Comprimidos/químicaRESUMEN
The Zika disease caused by the Zika virus was declared a Public Health Emergency by the World Health Union (WHO), with microcephaly as the most critical consequence. Aiming to reduce the spread of the virus, biopharmaceutical organizations invest in vaccine research and production, based on multiple platforms. A crescent vaccine production approach is based on virus-like particles (VLP), for not having genetic material in its composition, hypoallergenic and non-mutant character. For bioprocess, it is essential to have means of real-time monitoring, which can be assessed using process analysis techniques such as Near-infrared (NIR) spectroscopy, that can be combined with chemometric methods, like Partial-Least Squares (PLS) and Artificial Neural Networks (ANN) for prediction of biochemical variables. This work proposes a biochemical Zika VLP upstream production at-line monitoring model using NIR spectroscopy comparing sampling conditions (with or without cells), analytical blank (air, ultrapure water), and spectra pre-processing approaches. Seven experiments in a benchtop bioreactor using recombinant baculovirus/Sf9 insect cell platform in serum-free medium were performed to obtain biochemical and spectral data for chemometrics modeling (PLS and ANN), composed by a random data split (80 % calibration, 20 % validation) for cross-validation of the PLS models and 70 % training, 15 % testing, 15 % validation for ANN. The best models generated in the present work presented an average absolute error of 1.59 × 105 cell/mL for density of viable cells, 2.37 % for cell viability, 0.25 g/L for glucose, 0.007 g/L for lactate, 0.138 g/L for glutamine, 0.18 g/L for glutamate, 0,003 g/L for ammonium, and 0.014 g/L for potassium.
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Objective.MamoRef is an mammography device that uses near-infrared light, designed to provide clinically relevant information for the screening of diseases of the breast. Using low power continuous wave lasers and a high sensitivity CCD (Charge-coupled device) that captures a diffusely reflected image of the tissue, MamoRef results in a versatile diagnostic tool that aims to fulfill a complementary role in the diagnosis of breast cancer providing information about the relative hemoglobin concentrations as well as oxygen saturation.Approach.We present the design and development of an initial prototype of MamoRef. To ensure its effectiveness, we conducted validation tests on both the theoretical basis of the reconstruction algorithm and the hardware design. Furthermore, we initiated a clinical feasibility study involving patients diagnosed with breast disease, thus evaluating the practical application and potential benefits of MamoRef in a real-world setting.Main results.Our study demonstrates the effectiveness of the reconstruction algorithm in recovering relative concentration differences among various chromophores, as confirmed by Monte Carlo simulations. These simulations show that the recovered data correlates well with the ground truth, with SSIMs of 0.8 or more. Additionally, the phantom experiments validate the hardware implementation. The initial clinical findings exhibit highly promising outcomes regarding MamoRef's ability to differentiate between lesions.Significance.MamoRef aims to be an advancement in the field of breast pathology screening and diagnostics, providing complementary information to standard diagnostic techniques. One of its main advantages is the ability of determining oxy/deoxyhemoglobin concentrations and oxygen saturation; this constitutes valuable complementary information to standard diagnostic techniques. Besides, MamoRef is a portable and relatively inexpensive device, intended to be not only used in specific medical imaging facilities. Finally, its use does not require external compression of the breast. The findings of this study underscore the potential of MamoRef in fulfilling this crucial role.