Sequential purification of cannabidiol by two-dimensional liquid chromatography combined with modeling and simulation of elution profiles.

Cannabidiol (CBD) has garnered significant attention for its neuroprotective properties, and research on its therapeutic effects has increased dramatically in recent years. However, the systematic purification of CBD through scalable processes has remained bottleneck due to the structural similarities of the cannabinoids. Although preparative chromatography is considered as a potential solution, it is usually time-consuming and expensive. Therefore, the development of scalable strategy via fast and accurate optimization approach is crucial. The present study aimed to develop a sequential process for the scalable purification of CBD through an eco-friendly ethanolic extraction using ultrasonic assisted extraction, decarboxylation of cannabidiolic acid optimized by response surface methodology, followed by the development of off-line two-dimensional semi-preparative chromatography, boosted with stacked injection overloading. In the first dimension, a column packed with macroporous resin allows to enrich the target substance and then, the behavior of resin column for scale-up procedure were predicted and optimized by developed mathematical model. A C18 column was used in the second dimension. The CBD purity and recovery obtained were 94.3 and 82.1 %, respectively. A robust and reliable method was employed for CBD enrichment/purification, which can be generalized to other bioactive compounds in complex matrices.

Computational fluid dynamics simulation of a jet crystallizer for continuous crystallization of lovastatin.

Continuous crystallization of lovastatin from a lovastatin-methanol solution and water as the anti-solvent in an impinging jet crystallizer is investigated using a computational fluid dynamics model. To capture the important phenomena, the model is coupled with micro-mixing, population balance, and related energy balance equations. It is implemented in OpenFOAM and validated against experimental data, where a fairly good agreement is found. The effects of key process parameters on the crystallization performance are also studied using the validated model. The results show that increasing the inlet jet velocity from 1 to 4 m/s yields a much narrower size distribution and 70% reduction in the mean crystal size. The four-fold increase in the inlet jet velocity also reduces the crystal production rate by one order of magnitude. Also, it is found that increasing the inlet supersaturation ratio from 6.8 to 8.8 nearly doubles the mean crystal size. Moreover, it results in a wider size distribution and a six-fold increase in the crystal production rate. The simulations also confirm that lower solution to anti-solvent mass flow ratios yield a wider size distribution, a larger mean crystal size and a higher crystal production rate. Increasing this ratio from 0.5 to 2 reduces the production rate by two orders of magnitude.

Comparison of the High Cycle Fatigue Behavior of the Orthodontic NiTi Wires: An in Vitro Study

Abstract Objective: To compare the high-cycle fatigue behavior of four commercially available NiTi orthodontic wires. Material and Methods: Twelve NiTi orthodontic wires, round, 0.016-in, three per brand, were selected and divided into four groups: G1 - Heat-activated NiTi, G2 - Superelastic NiTi, G3 - Therma-Ti, and G4 - CopperNiTi. The atomic absorption spectrometry method was used to determine the chemical composition of investigated NiTi wires. We also performed a fatigue test at three-point bending using a universal testing machine for 1000 cycles in a 35 °C water bath. For the first and thousandth cycle, the average plateau load and the plateau length were determined in the unloading area of the force versus displacement diagram. In addition, we calculated the difference between the average plateau load of the first and thousandth cycle (∆F), as well as the difference between the plateau length of both cases (∆L). Results: According to our results, there were no significant differences between the average plateau load of the first and thousandth cycles of each group (p>0.05) and in the plateau length of the first and thousandth cycles of the groups (p>0.05). Conclusion: There were no significant differences between the groups changing the superelasticity property after high-cycle fatigue.

Comparison of the Effect of Nifedipine Alone and the Combination of Nifedipine and Sildenafil in Delaying Preterm Labor: A Randomized Clinical Trial.

Objective: Recently, sildenafil as a drug effective in relaxing smooth muscles can be used as an adjunct to delay the onset of uterine contractions and therefore the occurrence of preterm labor. The aim of this study was to evaluate the effect of nifedipine combination with sildenafil on preterm delivery compared with nifedipine alone. Materials and methods: This randomized double-blinded clinical trial was performed on pregnant women with a gestational age of 26-34 weeks with singleton pregnancy and symptoms of preterm delivery. The mothers were randomly assigned into two groups receiving nifedipine plus sildenafil or those receiving nifedipine alone. The time of delivery, maternal and neonatal complications were compared between the two groups. Results: Mothers who received the combination therapy experienced significantly lower preterm delivery within 72 hours of intervention compared to nifedipine alone (4.5% versus 27.3%, p = 0.002). The rate of delivery during the first 7 days after discharge was 7.6% and 31.8% in nifedipine plus sildenafil and nifedipine alone, respectively (P = 0.001). The prevalence of neonatal respiratory distress syndrome (RDS) as well as mean birth weight was higher in the nifedipine group alone. Treatment protocol with nifedipine and sildenafil compared with nifedipine alone was associated with a significant increase in preterm delivery delay (beta =-5.819, p = 0.001). Conclusion: The use of sildenafil in addition to nifedipine causes more delay in delivery in cases of preterm labor, followed by lower risk for RDS, reduces neonatal intensive care unit (NICU) admission, and preserves neonatal birth weight.

Extreme heat events heighten soil respiration.

In the wake of climate change, extreme events such as heatwaves are considered to be key players in the terrestrial biosphere. In the past decades, the frequency and severity of heatwaves have risen substantially, and they are projected to continue to intensify in the future. One key question is therefore: how do changes in extreme heatwaves affect the carbon cycle? Although soil respiration (Rs) is the second largest contributor to the carbon cycle, the impacts of heatwaves on Rs have not been fully understood. Using a unique set of continuous high frequency in-situ measurements from our field site, we characterize the relationship between Rs and heatwaves. We further compare the Rs response to heatwaves across ten additional sites spanning the contiguous United States (CONUS). Applying a probabilistic framework, we conclude that during heatwaves Rs rates increase significantly, on average, by ~ 26% relative to that of non-heatwave conditions over the CONUS. Since previous in-situ observations have not measured the Rs response to heatwaves (e.g., rate, amount) at the high frequency that we present here, the terrestrial feedback to the carbon cycle may be underestimated without capturing these high frequency extreme heatwave events.

Tissue Sampling through Endoscopic Ultrasound-Guided Fine Needle Aspiration versus Endoscopic Retrograde Cholangiopancreatographic Brushing Cytology Technique in Suspicious Malignant Biliary Stricture.

BACKGROUND Differentiation of benign and malignant biliary strictures plays a pivotal role in managing biliary strictures. Brush cytology via endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) are two diagnostic methods. In the present study, we aimed to compare the accuracy of the results of EUS-FNA and ERCP-based sampling of biliary strictures. METHODS In a prospective study, between January 2019 and March 2020, patients with indeterminate biliary strictures who had no history of hepatobiliary surgery, opium usage, cancer of pancratobiliary system, and acute liver disease were selected. They underwent EUS and ERCP in the same session. They were followed up for 6 months, and the sensitivity, specificity, positive and negative predictive values, and accuracy of these imaging modalities were compared. RESULTS A total of 60 patients were enrolled. 28 lesions were located in the distal and 32 lesions in the proximal parts of the biliary tree. 55 malignant and 5 benign lesions were diagnosed. The sensitivity and accuracy of EUS-FNA and ERCP tissue sampling were 78.2% and 80.0% versus 50.9% and 55.0%, respectively (p = 0.024). The combination of both methods improved the sensitivity and accuracy to 85.5% and 86.7%, respectively. Regarding the location, EUS-FNA is superior to ERCP-brush cytology in diagnosing proximal lesions with sensitivity and specificity of 73.3% and 75.0% vs. 50.0% and 53.1%, respectively (p = 0.04). CONCLUSION EUS-FNA is superior to ERCP brushing in the diagnosis of indeterminate biliary strictures, particularly in distal lesions. Combining ERCP brushing and EUS-FNA improves the diagnosis accuracy.

Simulation of pellet coating in Wurster coaters.

A combination of computational fluid dynamics (CFD), discrete element method (DEM), and discrete droplet method (DDM), i.e., a CFD-DEM-DDM model, was developed to simulate coating of pellets in a Wurster coater. The model equations were implemented in parallel using an approach that uses the computational resources of both CPU and GPU. Effects of the gas flow pattern, inlet gas temperature, partition gap, and spray characteristics were studied on the process. Decreasing the peripheral gas velocity, increasing the central jet velocity, and reducing the partition gap caused more uniform distributions of the circulation time and draft tube time, while the inlet gas temperature had negligible effect on them. Very high jet velocity caused a wider distribution of the circulation time. The dynamics of the spray and its interaction with pellets had significant effects on the coating mass distribution. Widening the spray angle while maintaining the droplet size constant caused the most uniform coating mass distribution and the highest deposition rate. Heat and mass transfer conditions as well as the deposition pattern changed the distributions of the solvent content and temperature of the pellets.

Incidence and risk factors of retinopathy of prematurity and utility of the national screening criteria in a tertiary center in Iran.

AIM: To determine the incidence and risk factors of retinopathy of prematurity (ROP) and the sensitivity of current screening criteria in a tertiary eye center in Tehran, Iran. METHODS: In a cross-sectional observational study, neonates weighing ≤2000 grams at birth or born <34wk gestational age (GA) and all other infants at risk of ROP admitted to the neonatal intensive care unit (NICU) or referred to our ROP clinic were investigated. The incidence of ROP and severe ROP (i.e. patients needing treatment) were determined. The associations between risk factors and the development and severity of ROP were assessed. We also examined the sensitivity of the current national screening guideline in Iran. RESULTS: Among 207 infants, the incidence of ROP and severe ROP was 33.3% and 11.1%, respectively. Mean GA and birth weight (BW) were significantly lower in ROP vs non-ROP infants (29±2wk vs 33±3wk, P<0.001; 1274±489 g vs 1916±550 g, P<0.001, respectively). Univariate analysis displayed significant association between ROP incidence and GA, BW, NICU admission period, blood transfusion, surfactant usage, sepsis, intraventricular hemorrhage and patent ductus arteriosus (P<0.05 for all). BW [relative risk (RR): 0.857 (0.711-0.873), P<0.001], GA [RR: 0.788 (0.711-0.873), P<0.001] and blood transfusion [RR: 1.888 (0.995-3.583), P=0.052] were independent ROP risk factors. The sensitivity of country-specific screening guidelines was 95.7% and 100% for overall and severe ROP detection, respectively. CONCLUSION: ROP incidence is relatively high in Iran. Identifying ROP risk factors results in more accurate screening and reduces the risk of irreversible vision loss. The ROP screening criteria utilized in Iran are efficient at the present time.

Development and modeling of two-dimensional fast protein liquid chromatography for producing nonstructural protein-free food-and-mouth diseases virus vaccine.

Concerns for the use of non-purified or incompletely purified inactivated foot-and-mouth disease (FMD) vaccine, like difficulties for differentiation vaccinated from infected animals, can be a motivation in order to develop methods based on size exclusion chromatography (SEC). In this study, a two dimensional size exclusion chromatography (2D-SEC) system was successfully constructed using two different SEC column media to achieve a high-throughput purification system for the cell culture-derived foot and mouth diseases virus (FMDV). A mathematical model was also utilized to predict and to get a better insight into the separation process. Column and the packing particles characteristics such as column void volume, total column volume, particle porosity and accessible particle porosity was acquired experimentally. Retention times and elution profile of two different molecules, blue dextran and bovine serum albumin, were used for evaluating the capability of SEC media for separating two critical impurities (residual DNA (rDNA) and non-structural protein (NSP)) from active ingredient of vaccine (FMDV particle). Experiments were carried out with two different commercial columns (XK 26/60) and (XK 16/100) and with four different packing media superdex 200 prep grade, sephacryl S-500 HR, Sephacryl S-400 HR and Sephacryl S-300HR. The mathematical model was first validated by experimental chromatographic data of different SEC media and was then used to propose the best 2D-SEC system for downstream processing of the FMDV vaccine. The loading capacity of the constructed 2D-SEC sample was increased to 12.5% of total column volume and the purity of the final product was more than 90%. The entire purification process was performed with 77% FMDV recovery and 79.1% virus yield. Based on the high-performance size exclusion chromatography (HPSEC), the purity of the final NSP-free FMDV was about 90% and over 94.6% of host cell DNA was removed. Analyses of the purified FMDV by HPSEC, transmission electron microscopy (TEM) and dynamic light scattering (DLS) indicated that the final product had spherical shape with mean size about 30 nm and their structure remained intact.

Assessing the effectiveness of Landsat 8 chlorophyll a retrieval algorithms for regional freshwater monitoring.

Predicting algal blooms has become a priority for scientists, municipalities, businesses, and citizens. Remote sensing offers solutions to the spatial and temporal challenges facing existing lake research and monitoring programs that rely primarily on high-investment, in situ measurements. Techniques to remotely measure chlorophyll a (chl a) as a proxy for algal biomass have been limited to specific large water bodies in particular seasons and narrow chl a ranges. Thus, a first step toward prediction of algal blooms is generating regionally robust algorithms using in situ and remote sensing data. This study explores the relationship between in-lake measured chl a data from Maine and New Hampshire, USA lakes and remotely sensed chl a retrieval algorithm outputs. Landsat 8 images were obtained and then processed after required atmospheric and radiometric corrections. Six previously developed algorithms were tested on a regional scale on 11 scenes from 2013 to 2015 covering 192 lakes. The best performing algorithm across data from both states had a 0.16 correlation coefficient (R2 ) and P ≤ 0.05 when Landsat 8 images within 5 d, and improved to R2 of 0.25 when data from Maine only were used. The strength of the correlation varied with the specificity of the time window in relation to the in-situ sampling date, explaining up to 27% of the variation in the data across several scenes. Two previously published algorithms using Landsat 8's Bands 1-4 were best correlated with chl a, and for particular late-summer scenes, they accounted for up to 69% of the variation in in-situ measurements. A sensitivity analysis revealed that a longer time difference between in situ measurements and the satellite image increased uncertainty in the models, and an effect of the time of year on several indices was demonstrated. A regional model based on the best performing remote sensing algorithm was developed and was validated using independent in situ measurements and satellite images. These results suggest that, despite challenges including seasonal effects and low chl a thresholds, remote sensing could be an effective and accessible regional-scale tool for chl a monitoring programs in lakes.

Vitamin B12 Deficiency as a Cause of Neurotrophic Keratopathy.

INTRODUCTION: Neurotrophic keratitis is a rare degenerative corneal disease caused by an impairment of trigeminal corneal innervation, leading to a decrease or absence of corneal sensation. Here, we present a case of neurotrophic keratopathy caused by B12 deficiency in a 34 years old man who had a progressive decrease in visual acuity and corneal involvement since 3 months before being referred to our ophthalmology clinic. RESULT AND DISCUSSION: Based on our clinical findings and with the diagnosis of B12 deficiency we started B12 treatment for the patient. After 3 weeks the patient showed a dramatic response with corneal sensation reversal, an increase of visual acuity, improved neurotrophic keratopathy and significantly improved neurological findings. To the best of our knowledge, there is no report regarding vitamin B12 deficiency induced keratopathy and this is the first report that describes this aspect of vitamin B12 deficiency.

Laser in situ keratomileusis for correction of induced astigmatism from cataract surgery.

PURPOSE: To evaluate the efficacy, predictability, stability, and safety of laser in situ keratomileusis (LASIK) to correct residual astigmatism after cataract surgery. METHODS: LASIK was performed on 20 eyes of 20 patients with refractive myopic or mixed astigmatism (3.00 to 6.00 D) at least 1 year after extracapsular cataract extraction with posterior chamber intraocular lens implantation without complication. Each eye received bitoric LASIK with the Nidek EC-5000 excimer laser and the Automated Corneal Shaper microkeratome. RESULTS: At 6 months after LASIK, mean refractive cylinder decreased from 4.64+/-0.63 D to 0.44+/-0.24 D (P<.001). Mean percent reduction of astigmatism was 90.4+/-5.0% (range 80% to 100%). Mean spherical equivalent refraction decreased from -2.19+/-0.88 D (range -1.00 to -3.88 D) to -0.32+/-0.34 D (range -1.25 to +0.38 D) (P<.001). Vector analysis showed that the mean amount of axis deviation was 0.7+/-1.2 degrees (range 0 degrees to 4.3 degrees) and the mean percent correction of preoperative astigmatism was 92.1+/-5.9% (range 85.6% to 108%). Eighty-five percent of all eyes had a mean spherical equivalent refraction and mean cylinder within +/-0.50 D of emmetropia. Change in spherical equivalent refraction and cylinder from 2 weeks to 6 months was < or = 0.50 D in 90% (18 eyes) and 95% (19 eyes), respectively. Spectacle-corrected visual acuity was not reduced in any eye. Diffuse lamellar keratitis occurred in three eyes (15%) after LASIK, and were treated successfully with eyedrops. CONCLUSION: LASIK was an effective, predictable, stable, and safe procedure for correction of residual myopic or mixed astigmatism ranging from 3.00 to 6.00 D with a low spherical component after cataract surgery.