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Urban air pollution is considered to be a critical environmental and public health issue, with the transportation sector being a major contributor. This study focuses on tailpipe pollutant emissions from light-duty vehicles in real driving conditions. Our principle objective was to identify primary factors that affect the emission rates under different driving styles, fuel grade, engine transmission, and checking/maintenance practices. We observed that emission rates were consistently lower with frequent acceleration and deceleration associated with aggressive driving (AD) compared to relaxed driving (RD) style. This indicates that vehicles driven in town (which are typically driven in a relaxed manner) may require more regular maintenance than vehicles driven on motorways (which are typically driven in an aggressive manner). All pollutant emissions were higher in manual transmission vehicles on both urban roads and motorways than in automatic transmission vehicles. The information generated from this research can help establish framework for pollution mitigation efforts, such as inspection and maintenance programs, and in developing traffic pollution management strategies for national use. © 2012 American Institute of Chemical Engineers Environ Prog, 32: 335-343, 2013 [ABSTRACT FROM AUTHOR]

Objective: Acoustic droplet vaporization (ADV) is the liquid-to-gas phase transition of perfluorocarbon (PFC) droplets to microbubbles upon ultrasound insonation. After ADV, gases dissolved in the surrounding fluid diffuse into microbubbles, enabling oxygen scavenging. Characterization of oxygen scavenging and transition efficiency (TE) in whole blood has so far been limited. In this work, oxygen scavenging and perfluorocarbon droplet TE in a saline buffer and whole bovine blood were evaluated using blood-gas analysis and flow cytometry., Methods: Oxygen scavenging from whole blood via ADV was determined using an in vitro flow phantom with droplets comprising a phospholipid shell and either a decafluorobutane (DFB) or a perfluoropentane (PFP) core. Fluorescent droplets were used to determine ADV TE in whole blood via flow cytometry. Finally, a mathematical model predicting oxygen scavenging from whole blood was developed based on the experimental TE values., Results: DFB droplets enabled greater oxygen scavenging and higher TE when compared with perfluoropentane droplets in both buffer and whole blood. Increasing the droplet concentration resulted in a greater amount of hemoglobin-bound and dissolved oxygen scavenging from whole blood. ADV of DFB droplets at a concentration of 5 × 10 -4 mL/mL yielded a total oxygen reduction of 913 μM. The TE decreased with increasing droplet concentration in both buffer and whole blood. Experimental oxygen scavenging data in whole blood aligned with the predicted values from the mathematical model., Conclusion: Increased oxygen scavenging and TE were achieved with DFB droplets relative to perfluoropentane droplets., Competing Interests: Conflict of Interest C.K.H. and K.J.H. have been consultants with Boston Scientific Inc. All other authors have no conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Long-acting crystal suspensions of active pharmaceutical ingredients (API) mostly comprised of an API, a suspension media (water) and excipients and provide sustained API release over time. Excipients are crucial for controlling particle size and to achieve the stability of the API crystals in suspension. A bottom-up process was designed to produce long-acting crystal suspensions whilst investigating the excipient requirements during the production process and the subsequent storage. PVP K30 emerged as the most effective excipient for generating stable naproxen crystals with the desired size of 1 to 15 μm, using ethanol as solvent and water as anti-solvent. Calculations, performed based on the crystal properties and assuming complete PVP K30 adsorption on the crystal surface, revealed lower PVP K30 requirements during storage compared to initial crystal generation. Consequently, a membrane-based diafiltration process was used to determine and fine-tune PVP K30 concentration in the suspension post-crystallization. A seven-stage diafiltration process removed 98 % of the PVP K30 present in the suspension thereby reducing the PVP-to-naproxen ratio from 1:2 to 1:39 without impacting the stability of naproxen crystals in suspension. This work provides insights into the excipient requirements at various production stages and introduce the membrane-based diafiltration for precise excipient control after crystallization., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Given that impurities may affect the quality and safety of drug products, impurity identification and profiling is an integral part of drug quality control and is particularly important for newly developed medications such as solriamfetol, which is used to treat excessive daytime sleepiness. Although the high-performance liquid chromatography analysis of commercial solriamfetol has revealed the presence of several impurities, their synthesis, structure elucidation, and chromatographic determination have not been reported yet. To bridge this gap, we herein identified, synthesized, and isolated eight process-related solriamfetol impurities, characterized them using spectroscopic and chromatographic techniques, and proposed plausible mechanisms of their formation. Moreover, we developed and validated a prompt impurity analysis method based on ultrahigh-performance liquid chromatography with UV detection, revealing that its selectivity, linearity, accuracy, precision, and quantitation limit meet the acceptance criteria of method validation stipulated by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use. Thus, the developed method was concluded to be suitable for the routine analysis of solriamfetol substances., Competing Interests: The authors declare that there are no conflicts of interest., (© 2023 The Authors.)

Acoustic droplet vaporization is the ultrasound-mediated phase change of liquid droplets into gas microbubbles. Following the phase change, oxygen diffuses from the surrounding fluid into the microbubble. An in vitro model was used to study the effects of droplet diameter, the presence of an ultrasound contrast agent, ultrasound duty cycle, and droplet concentration on the magnitude of oxygen scavenging in oxygenated deionized water. Perfluoropentane droplets were manufactured through a microfluidic approach at nominal diameters of 1, 3, 5, 7, 9, and 12 µm and studied at concentrations varying from 5.1 × 10 -5 to 6.3 × 10 -3 mL/mL. Droplets were exposed to an ultrasound transduced by an EkoSonic TM catheter (2.35 MHz, 47 W, and duty cycles of 1.70%, 2.34%, or 3.79%). Oxygen scavenging and the total volume of perfluoropentane that phase-transitioned increased with droplet concentration. The ADV transition efficiency decreased with increasing droplet concentration. The increasing duty cycle resulted in statistically significant increases in oxygen scavenging for 1, 3, 5, and 7 µm droplets, although the increase was smaller than when the droplet diameter or concentration were increased. Under the ultrasound conditions tested, droplet diameter and concentration had the greatest impact on the amount of ADV and subsequent oxygen scavenging occurred, which should be considered when using ADV-mediated oxygen scavenging in therapeutic ultrasounds.

A healthy condition is defined by complex human metabolic pathways that only function properly when fully satisfied by nutritional inputs. Poor nutritional intakes are associated with a number of metabolic diseases, such as diabetes, obesity, atherosclerosis, hypertension, and osteoporosis. In recent years, nutrition science has undergone an extraordinary transformation driven by the development of innovative software and analytical platforms. However, the complexity and variety of the chemical components present in different food types, and the diversity of interactions in the biochemical networks and biological systems, makes nutrition research a complicated field. Metabolomics science is an "-omic", joining proteomics, transcriptomics, and genomics in affording a global understanding of biological systems. In this review, we present the main metabolomics approaches, and highlight the applications and the potential for metabolomics approaches in advancing nutritional food research.

Objectives: Cancer survivorship status among patients evaluated for chest pain at the emergency department (ED) warrants high degree of suspicion. However, it remains unclear whether cancer survivorship is associated with different risk of major adverse cardiac events (MACE) compared to those with no history of cancer. Furthermore, while HEART score is widely used in ED evaluation, it is unclear whether it can adequately triage chest pain events in cancer survivors. We sought to compare the rate of MACE in patients with a recent history of cancer in remission evaluated for acute chest pain at the ED to those with no history of cancer, and compare the performance of a common chest pain risk stratification score (HEART) between the two groups., Methods: We performed a secondary analysis of a prospective observational cohort study of chest pain patients presenting to the EDs of three tertiary care hospitals in the USA. Cancer survivorship status, HEART scores, and the presence of MACE within 30 days of admission were retrospectively adjudicated from the charts. We defined patients with recent history of cancer in remission as those with a past history of cancer of less than 10 years, and currently cured or in remission., Results: The sample included 750 patients (age: 59 ± 17; 42% females, 40% Black), while 69 patients (9.1%) had recent history of cancer in remission. A cancer in remission status was associated with a higher comorbidity burden, older age, and female sex. There was no difference in risk of MACE between those with a cancer in remission and their counterparts in both univariate [17.4 vs. 19.5%, odds ratio (OR) = 0.87 (95% confidence interval (CI), 0.45-1.66], P = 0.67] and multivariable analysis adjusting for demographics and comorbidities [OR = 0.62 (95% CI, 0.31-1.25), P = 0.18]. Patients with cancer in remission had higher HEART score (4.6 ± 1.8 vs. 3.9 ± 2.0, P = 0.006), and a higher proportion triaged as intermediate risk [68 vs. 56%, OR = 1.67 (95% CI, 1.00-2.84), P = 0.05]; however, no difference in the performance of HEART score existed between the groups (area under the curve = 0.86 vs. 0.84, P = 0.76)., Conclusions: There was no difference in rate of MACE between those with recent history of cancer in remission compared to their counterparts. A higher proportion of patients with cancer in remission was triaged as intermediate risk by the HEART score, but we found no difference in the performance of the HEART score between the groups., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Traumatic diaphragmatic rupture (TDR) occurs in 0-5% of patients with major blunt thoraco-abdominal trauma, in most of them on the left side, and an early correct diagnosis is made in less than half of the cases (Meyers and McCabe, 1993; Ball et al., 1982)., Presentation of the Case: We report a case of a forty-eight years old man who had a pericardio-diaphragmatic rupture after a high-velocity blunt abdominal trauma that was diagnosed and treated successfully., Discussion: Pericardio-diaphragmatic rupture (PDR) is an uncommon problem that poses a diagnostic challenge to surgeons. The incidence of PDR is between 0.2% and 3.3% of cases with TDR (Sharma, 1999 [3])., Conclusion: PDR should be suspected in any patient with high velocity thoraco-abdominal trauma. Early diagnosis is essential and needs a high index of suspicion. Early Management is important in decreasing morbidity and mortality., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cell protection against different noxious stimuli like oxidative stress or chemical toxins plays a central role in the treatment of many diseases. The inducible heme oxygenase isoform, heme oxygenase-1 (HO-1), is known to protect cells against a variety of harmful conditions including apoptosis. Because a number of medium strong electrophiles from a series of α-X-substituted 2',3,4,4'-tetramethoxychalcones (α-X-TMCs, X = H, F, Cl, Br, I, CN, Me, p-NO2-C6H4, Ph, p-OMe-C6H4, NO2, CF3, COOEt, COOH) had proven to activate Nrf2 resulting in HO-1 induction and inhibit NF-κB downstream target genes, their protective effect against staurosporine induced apoptosis and reactive oxygen species (ROS) production was investigated. RAW264.7 macrophages treated with 19 different chalcones (15 α-X-TMCs, chalcone, 2'-hydroxychalcone, calythropsin and 2'-hydroxy-3,4,4'-trimethoxychalcone) prior to staurosporine treatment were analyzed for apoptosis and ROS production, as well as HO-1 protein expression and enzyme activity. Additionally, Nrf2 and NF-κB activity was assessed. We found that amongst all tested chalcones only E-α-(4-methoxyphenyl)-2',3,4,4'-tetramethoxychalcone (E-α-p-OMe-C6H4-TMC) demonstrated a distinct, statistically significant antiapoptotic effect in a dose dependent manner, showing no toxic effects, while its double bond isomer Z-α-p-OMe-C6H4-TMC displayed no significant activity. Also, E-α-p-OMe-C6H4-TMC induced HO-1 protein expression and increased HO-1 activity, whilst inhibition of HO-1 by SnPP-IX abolished its antiapoptotic effect. The only weakly electrophilic chalcone E-α-p-OMe-C6H4-TMC reduced the staurosporine triggered formation of ROS, while inducing the translocation of Nrf2 into the nucleus. Furthermore, staurosporine induced NF-κB activity was attenuated following E-α-p-OMe-C6H4-TMC treatment. Overall, E-α-p-OMe-C6H4-TMC demonstrated its effective cytoprotective potential via a non-toxic induction of HO-1 in RAW264.7 macrophages. The observed cytoprotective effect may partly be related to both, the activation of the Nrf2- and inhibition of the NF-κB pathway.

Inflammatory signaling pathways orchestrate the cellular response to infection and injury. These pathways are known to be modulated by compounds that alkylate cysteinyl thiols. One class of phytochemicals with strong thiol alkylating activity is the chalcones. In this study we tested fourteen chalcone derivatives, α-X-substituted 2',3,4,4'-tetramethoxychalcones (α-X-TMCs, X = H, F, Cl, Br, I, CN, Me, p-NO2-C6H4, Ph, p-OMe-C6H4, NO2, CF3, COOEt, COOH), for their ability to modulate inflammatory responses, as monitored by their influence on heme oxygenase-1 (HO-1) activity, inducible nitric oxide synthase (iNOS) activity, and cytokine expression levels. We confirmed that the transcriptional activity of Nrf2 was activated by α-X-TMCs while for NF-κB it was inhibited. For most α-X-TMCs, anti-inflammatory activity was positively correlated with thiol alkylating activity, i.e. stronger electrophiles (X = CF3, Br and Cl) being more potent. Notably, this correlation did not hold true for the strongest electrophiles (X = CN and NO2) which were found to be ineffective as anti-inflammatory compounds. These results emphasize the idea that chemical fine-tuning of electrophilicity is needed to achieve and optimize desired therapeutic effects.

Signal transducer and activator of transcription STAT5 and its upstream activating kinase JAK2 are essential mediators of cytokine signaling. Their activity is normally tightly regulated and transient. However, constitutive activation of STAT5 is found in numerous cancers and a driving force for malignant transformation. We describe here the identification of the synthetic chalcone α-Br-2',3,4,4'-tetramethoxychalcone (α-Br-TMC) as a novel JAK/STAT inhibitor. Using the non-transformed IL-3-dependent B cell line Ba/F3 and its oncogenic derivative Ba/F3-1*6 expressing constitutively activated STAT5, we show that α-Br-TMC targets the JAK/STAT pathway at multiple levels, inhibiting both JAK2 and STAT5 phosphorylation. Moreover, α-Br-TMC alters the mobility of STAT5A/B proteins in SDS-PAGE, indicating a change in their post-translational modification state. These alterations correlate with a decreased association of STAT5 and RNA polymerase II with STAT5 target genes in chromatin immunoprecipitation assays. Interestingly, expression of STAT5 target genes such as Cis and c-Myc was differentially regulated by α-Br-TMC in normal and cancer cells. While both genes were inhibited in IL-3-stimulated Ba/F3 cells, expression of the oncogene c-Myc was down-regulated and that of the tumor suppressor gene Cis was up-regulated in transformed Ba/F3-1*6 cells. The synthetic chalcone α-Br-TMC might therefore represent a promising novel anticancer agent for therapeutic intervention in STAT5-associated malignancies.

The present work investigates the efficacy of using Artemisia annua in traditional medicine in comparison with chemical extracts of its bioactive molecules. In addition, the effects of location (Egypt and Jericho) on the bioactivities of the plant were investigated. The results showed that water extracts of Artemisia annua from Jericho have stronger antibacterial activities than organic solvent extracts. In contrast, water and organic solvent extracts of the Artemisia annua from Egypt do not have anti-bacterial activity. Furthermore, while the methanol extract of EA displayed high anticancer affects, the water extract of Egypt and the extracts of Jericho did not show significant anticancer activity. Finally, the results showed that the methanol and water extracts of Jericho had the highest antioxidant activity, while the extracts of Egypt had none. The current results validate the scientific bases for the use of Artemisia annua in traditional medicine. In addition, our results suggest that the collection location of the Artemisia annua has an effect on its chemical composition and bioactivities.

Thiol-mediated processes play a key role to induce or inhibit inflammation proteins. Tailoring the reactivity of electrophiles can enhance the selectivity to address only certain surface cysteines. Fourteen 2',3,4,4'-tetramethoxychalcones with different α-X substituents (X=H, F, Cl, Br, I, CN, Me, p-NO2-C6H4, Ph, p-OMe-C6H4, NO2, CF3, COOEt, COOH) were synthesized, containing the potentially electrophilic α,β-unsaturated carbonyl unit. The assessment of their reactivity as electrophiles in thia-Michael additions with cysteamine shows a change in the reactivity of more than six orders of magnitude. Moreover, a clear correlation between their reactivity and an influence on the inflammation proteins heme oxygenase-1 (HO-1) and the inducible NO synthase (iNOS) is demonstrated. As the biologically most active compound, the α-CF3 -chalcone is shown to inhibit the NO production in RAW264.7 mouse macrophages in the nanomolar range., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The electrophilic nature of chalcones (1,3-diphenylprop-2-en-1-ones) and many other α,β-unsaturated carbonyl compounds is crucial for their biological activity, which is often based on thiol-mediated regulation processes. To better predict their biological activity a simple screening assay for the assessment of the second-order rate constants (k(2)) in thia-Michael additions was developed. Hence, a clear structure-activity relationship of 16 differentially decorated hydroxy-alkoxychalcones upon addition of cysteamine could be established. Moreover, amongst other naturally occurring α,β-unsaturated carbonyl compounds k(2) values for curcumin and cinnamaldehyde were gained while cinnamic acids or esters gave no or very slow reactions.