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Caffeine naturally occurs in tea and cocoa, which is also used as an additive in beverages and has pharmacological effects such as refreshing, antidepressant, and digestion promotion, but excessive caffeine can cause harm to the human body. In this work, based on the specific response between nano zinc 5, 10, 15, 20-tetra(4-pyridyl)-21H-23H-porphine (nano ZnTPyP)-CdTe quantum dots (QDs) and caffeine, combined with chemometrics, a visual paper-based sensor was constructed for rapid and on-site detection of caffeine. The fluorescence of QDs can be quenched by nano ZnTPyP. When caffeine is added to the system, it can pull nano ZnTPyP off the surface of the QDs to achieve fluorescence recovery through electrostatic attraction and nitrogen/zinc coordination. The detection range is 5 × 10 -11 ~3 × 10 -9  mol L -1 , and the detection limit is 1.53 × 10 -11  mol L -1 (R 2  = 0.9990) (S/N = 3). The paper-based sensor constructed exhibits good results in real samples, such as tea water, cell culture fluid, newborn bovine serum, and human plasma. Therefore, the sensor is expected to be applied to the rapid instrument-free detection of caffeine in food and biological samples.Graphical abstract.

The International Conference on Cognitive Modeling brings together researchers from around the world whose main goal is to build computational systems that reflect the internal processes of the mind. In this issue, we present the five best representative papers on this work from our 19th meeting, ICCM 2021, which was held virtually from July 3 to July 9, 2021. Three of these papers provide new techniques for refining computational models, giving better methods for taking empirical data and producing accurate computational models of the cognitive systems that produce them. The other two papers focus on explanation: using models to elucidate the underlying processes affecting cognition in such diverse domains as logical reasoning and the effects of caffeine., (© 2022 Cognitive Science Society LLC.)

A fast method for the determination of methylxanthines in cocoa products and drugs based on PS-MS/MS under MRM condition has been developed. Analyte ions were generated by applying a high voltage on a paper substrate drenched of sample extract using a small volume (∼15 μL) of spray solvent. The gas phase chemistry of the molecules under investigation has been elucidated. The accuracy values of the methodology ranged from 95 to 110%, while the analytical parameters LOQ, LOD, recovery and reproducibility, calculated analyzing spiked samples, confirmed the consistency of the proposed method. Furthermore, real samples have been analyzed both by the developed methodology and by using a classical HPLC-UV approach obtaining comparable values., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

A simple and fast method based on paper spray mass spectrometry for the determination of caffeine in commercial beverages and drugs has been developed; the analyses were carried out in MRM mode, monitoring the transitions m/z 195 → m/z 138 for caffeine and m/z 198 → m/z 140 for the labeled internal standard. To verify the reliability of the proposed approach, a spiked sample (soda drink and paracetamol tablet) with a known amount of caffeine has been prepared and analyzed by PS-MS, providing accuracy values about 100 %; the LOQ and LOD values were calculated at 1.2 and 1.6 μg/mL, respectively. Both beverages and drugs were also analyzed with the classic analytical method based on LC-UV measurements, showing consistent results between the two approaches, thus confirming the reliability of the developed ambient MS determination. Graphical Abstract The assay of caffeine by paper mass spectrometry.

Paper substrate room temperature phosphorescence (RTP) of theobromine (TB), caffeine (CF) and theophylline (TP) were investigated. The method is based on fast speed quantitative filter paper as substrate and KI-NaAc as heavy atom perturber. Various factors affecting their RTP were discussed in detail. Under the optimum experimental conditions, the linear dynamic range, limit of detection (LOD), and relative standard deviation (R.S.D.) were 14.41 approximately 576.54 ng per spot, 1.14 ng per spot, 4.8% for TB, 5.44 approximately 699.08 ng per spot, 0.78 ng per spot, 1.56% for CF, 7.21 approximately 360.34 ng per spot, 1.80 ng per spot, 3.80% for TP, respectively. The first analytical application for the determination of these compounds was developed. The recovery of standard samples added to commercial products chocolate, tea, coffee and aminophylline is in the range 92.80-106.08%. The proposed method was successfully applied to real sample analysis without separation.

The photocatalytic decomposition of caffeine under UV-light irradiation was observed for the first time in a matrix of synthetic urine using granules of hydrogenated and iron-exchanged natural zeolite, coated with two loadings of TiO 2 . A natural clinoptilolite-mordenite blend was used to prepare photocatalytic adsorbents coated with TiO 2 nanoparticles. The performance of the obtained materials was tested in the photodegradation of caffeine, a water contaminant of emerging concern. The photocatalytic activity was better in the urine matrix, due to the formation of surface complexes on the TiO 2 coating, cation exchange performed by the zeolite support, and use of the carrier electrons in the reduction of ions, affecting recombination of the electrons and holes during photocatalysis. The composite granules maintained photocatalytic activity for at least four cycles, with more than 50% of caffeine removal in the synthetic urine matrix., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We report an assay method for the determination of salivary caffeine concentrations by high-performance liquid chromatography. A simple, new method for collecting mixed saliva using a piece of filter paper has been developed. An arbitrary amount of saliva is absorbed and a fixed amount of internal standard is added. The mean coefficient of variation of measurements repeated by changing both volumes absorbed and caffeine concentrations of saliva was 5.6% with this method. The detection limit was determined to be 0.5 microgram/ml. Precision of measurements and recoveries did not depend upon the volume of saliva absorbed. Four volunteers were given a capsule of 230 mg caffeine, and saliva was collected by the ordinary method using chemical stimulation with citric acid and by our filter paper absorption methods; the methods were compared. Salivary caffeine concentrations were always lower than plasma concentrations, and there were no big differences between two methods, although salivary concentrations measured by our method was higher, with a significant difference at 1.5 h after dosing. From the practical viewpoint this method would be convenient and sufficiently accurate.

Submariners face many environmental and operational challenges to maintaining good sleep, including suboptimal lighting, shift work, and frequent interruptions. Anecdotally, many Sailors consume caffeine to alleviate the effects of poor sleep on alertness, mood, and performance; however, caffeine itself may also degrade sleep quantity and/or quality. This study provides the first exploration of the potential relationship between caffeine use and sleep onboard submarines. Objective measures (wrist actigraphy, available from 45 participants), self-report sleep metrics, and self-reported caffeine consumption were collected from 58 US Navy Sailors before and during a routine submarine underway at sea lasting 30 days. Contrary to expectations, less caffeine was reportedly consumed at sea (232.8 ± 241.1 mg) than on land prior to the underway (M = 284.4 ± 251.7 mg; X 2 (1) = 7.43, p = 0.006), positive rather than negative relationships were observed between caffeine consumption and sleep efficiency (F = 6.11, p = 0.02), and negative relationships were observed between caffeine consumption and wake after sleep onset (F = 9.36, p = 0.004) and sleep fragmentation (F = 24.73, p < 0.0001). However, in contrast, higher caffeine consumption was also negatively related to self-reported sleep duration while at sea (F = 4.73, p = 0.03). This observational study is the first to measure relationships between caffeine consumption and sleep quantity and/or quality in a submarine environment. We propose that the unique submarine environment and the unique caffeine consumption patterns of submariners should be considered in the development of potential countermeasures for sleepiness., (Published 2023. This article is a U.S. Government work and is in the public domain in the USA. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

We describe the use of ambient ionization mass spectrometry in a freshman-level undergraduate class for the detection of caffeine and other components in several commercially available energy drinks (5-hour Energy, Starbucks Refreshers, Red Bull Sugarfree, and Coca Cola Classic). We use the technique of paper-spray mass spectrometry where a filter paper is used as a substrate on which a sample is directly applied and a high voltage is used to generate an electrospray of ions in ambient conditions which are then detected by a mass spectrometer. The purpose of this laboratory exercise is twofold: 1) to use the paper-spray method to determine the chemical composition of different types of commercially available energy drinks and 2) to perform tandem mass spectrometry (MS/MS) to demonstrate that the mass spectrometer can be used for structural analysis. This laboratory serves as an excellent means of introducing the beginning student to the concepts of charge, mass, and molecular structure. In addition to the freshmen general chemistry class, we also incorporated this lab into the introductory analytical chemistry class taught at the sophomore level with the inclusion of a third exercise where the usefulness of mass spectrometry for quantitative analysis is demonstrated by determining the concentration of caffeine in the energy drinks with deuterated caffeine as an internal standard. [ABSTRACT FROM AUTHOR]

Purpose: To propose a two-compartment renal perfusion model for calculating glomerular blood transfer rate ( INLINEMATH ) as a new measure of renal function., Theory: The renal perfusion signal was divided into preglomerular and postglomerular flows according to flow velocity. By analyzing perfusion signals acquired with and without diffusion gradients, we estimated INLINEMATH , the blood transfer rate from the afferent arterioles into the glomerulus., Methods: A multislice multidelay diffusion-weighted arterial spin labeling sequence was applied to subjects with no history of renal dysfunctions. In the multiple b-value experiment, images were acquired with seven b-values to validate the bi-exponential decays of the renal perfusion signal and to determine the appropriate b-value for suppressing preglomerular flow. In the caffeine challenge, six subjects were scanned twice on the caffeine day and the control day. The INLINEMATH values of the two dates were compared., Results: The perfusion signal showed a bi-exponential decay with b-values. There was no significant difference in renal blood flow and arterial transit time between caffeine and control days. In contrast, cortical INLINEMATH ). These results were consistent with those from the literature., Conclusion: We showed that the perfusion signal consists of two compartments of preglomerular flow and postglomerular flow. The proposed diffusion-weighted arterial spin labeling could measure the glomerular blood transfer rate ( INLINEMATH ), which was sensitive enough to noninvasively monitor the caffeine-induced vasodilation of afferent arterioles., (© 2022 International Society for Magnetic Resonance in Medicine.)

Most computational theories of cognition lack a representation of physiology. Understanding the cognitive effects of compounds present in the environment is important for explaining and predicting changes in cognition and behavior given exposure to toxins, pharmaceuticals, or the deprivation of critical compounds like oxygen. This research integrates physiologically based pharmacokinetic (PBPK) model predictions of caffeine concentrations in blood and tissues with ACT-R's fatigue module to predict the effects of caffeine on fatigue. Mapping between the PBPK model parameters and ACT-R model parameters is informed by the neurophysiological literature and established associations between ACT-R modules and brain regions. The results from three such parameter mappings are explored to explain observed data from sleep-deprived participants performing the psychomotor vigilance test with and without caffeine. Predicted caffeine concentrations in the brain are used to modulate procedural parameters in the fatigue module to explain caffeine's effects on multiple performance metrics., (© 2022 Cognitive Science Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Coffee wastewater contains large amounts of caffeine which affects microflora and seed development to great extent. Although several physio-chemical methods available for caffeine degradation, they are not preferred for large-scale treatment. In this study, we optimized induced cell concentration, aeration and agitation rate for maximizing caffeine degradation rate in bioreactor using Uniform design. Maximum caffeine degradation rate of 23·59 mg L -1  h -1 was achieved. The reduction in chemical oxygen demand, biological oxygen demand and total organic carbon removal were found to be 72, 78 and 72% respectively. Mathematical model was developed through regression analysis and predicted maximum caffeine degradation rate of 24·2 mg L -1  h -1 under optimal conditions of 0·35 g L -1 biomass, 395 rev min -1 and 1·62 vvm. Experimental validation at optimum condition resulted in 22 mg L -1  h -1 of caffeine degradation rate. This is the first-ever bioreactor study showing highest caffeine degradation rate in synthetic coffee wastewater with limited experimental runs., (© 2022 The Society for Applied Microbiology.)

The addition of caffeine caused the accumulation of a new nucleotide compound simultaneously with the rigid inhibition of ribofalvin production in non-growing cells of Eremothecium ashbyii. In the present study we tried to identify the structure of the nucleotide compound using non-growing cells of the mold. 1) It became possible to obtain a large amount of mycelia by masscultivation in a reagent tank. 2) A new nucleotide compound, referred to as compound A in the paper, was extracted with perchloric acid solution and purified by the following subsequent procedures: 1) Dowex 1 x 2 (HCOO-) column, 2) charcoal treatment, 3) DEAE-Sephadex A25 (CI-) column, 4) Dowex 1 x 2 (C1-) column, and 5) DEAE-Sephadex A25 (HCO3-) column. 3) The structure of the new nucleotide compound was proved to be guanine ribonucleotidyl-(3'-5')-adenosine (GpA) from the results of the following analyses: 1) alkaline degradation, 2) UV-spectra, IR-spectra and NMR-spectra, and 3) enzymatic treatments with RNase T2 and phosphodiesterase. 4) The roles of caffeine and guanine ribonucleotidyl-(3'-5')-adenosine in connection with flavinogenesis of this mold were discussed.

Since their introduction in 1987, energy drinks have become increasingly popular and the energy drink market has grown at record pace into a multibillion-dollar global industry. Young people, students, office workers, athletes, weekend warriors, and service members frequently consume energy drinks. Both health care providers and consumers must recognize the difference between energy drinks, traditional beverages (e.g., coffee, tea, soft drinks/sodas, juices, or flavored water), and sports drinks. The research about energy drinks safety and efficacy is often contradictory, given the disparate protocols and types of products consumed: this makes it difficult to draw firm conclusions. Also, much of the available literature is industry-sponsored. After reports of adverse events associated with energy drink consumption, concerns including trouble sleeping, anxiety, cardiovascular events, seizures, and even death, have been raised about their safety. This article will focus on energy drinks, their ingredients, side effects associated with their consumption, and suggested recommendations, which call for education, regulatory actions, changes in marketing, and additional research. [ABSTRACT FROM AUTHOR]

Objectives: Coffee, green tea, and caffeine are potential preventive factors for dementia, but the underlying evidence is insufficient. This study aimed to examine associations between the consumption of coffee, green tea, and caffeine and dementia risk in middle-aged and older people., Methods: This was a cohort study with an 8.0-year follow-up. Participants were community-dwelling individuals (n = 13,757) aged 40-74 years. A self-administered questionnaire survey was conducted in 2011-2013. Predictors were the consumption of coffee/green tea, from which caffeine consumption was estimated. The outcome was incident dementia obtained from the long-term care insurance database. Covariates were demographic factors, body mass index, physical activity, energy, smoking, drinking, and disease history. Adjusted hazard ratios (HRs) were calculated using Cox proportional hazards models. HRs were also calculated using a Cox model with delayed entry., Results: The number of dementia cases during the study period was 309. Participants with higher coffee consumption had lower HRs (adjusted p for trend = 0.0014), with the fifth quintile (≥326 ml/day) having a significantly lower HR (0.49, 95% confidence interval [CI]: 0.30-0.79) than the first quintile (<26 ml/day, reference). Similarly, participants with higher caffeine consumption had a significantly lower HR (adjusted p for trend = 0.0004) than the reference. The Cox model with delayed entry yielded similar results. These associations were significant in men, but not in women. Moreover, participants who consumed 2-2.9 cups/day and ≥3 cups/day of coffee had lower HRs (0.69, 95% CI: 0.48-0.98 and 0.53, 95% CI: 0.31-0.89, respectively) than those who consumed 0 cup/day. The association between green tea consumption and reduced dementia risk was significant (adjusted p for trend = 0.0146) only in the 60-69 years age subgroup., Conclusions: High levels of coffee and caffeine consumption were significantly associated with a reduced dementia risk in a dose-dependent manner, especially in men. Moreover, coffee consumption of ≥3 cups/day was associated with a 50% reduction in dementia risk., (© 2021 The American Geriatrics Society.)

Ginoid hydrolipodystrophy (HDLG) or "cellulite" involves alteration of the cutaneous relief and occurs in 80-90% of the female population. Several topical treatments are available with the use of substances capable of stimulating lipolysis, such as caffeine. However, the effectiveness of topical therapy is related to the processes of release and permeation of the active in skin cells. In this sense, ionic liquids, such as choline geranate, are considered to facilitate topical permeation agents. In this way, the aim of this research was to develop and evaluation of the effectiveness of a cosmetic product for topical treatment of cellulite with caffeine in association with choline geranate. The choline geranate was synthesized by the reaction between geranic acid and choline hydroxide [1: 2]. The gel was prepared using 2% Carpobol 940®, 5% caffeine, and 1% choline geranate. Preliminary and accelerated stability tests were performed by checking pH, spreadability, and organoleptic characteristics. The transdermal permeation capacity of caffeine in vitro was evaluated by the Franz cell permeation assay, and the gel cytotoxicity by the MTS method. To prove the efficacy in the treatment of cellulite, a pilot type 1 clinical trial was carried out. The formulation was considered stable and the product maintained your characteristics during 180 days of storage. The product showed moderate cytotoxicity and high skin permeation capacity. In the clinical trial, it showed results superior to the caffeine gel without ionic liquid. The developed gel favored the cutaneous permeation of caffeine, showing a promising product in the treatment of cellulite.

Natural and synthetic alkaloids are widely used for several applications, ranging from clinical purposes to criminal activities. Presumptive color tests are considered a leading tool to reveal on-scene substance identification via rapid chemical reactions that result in visual color changes. Colorimetric tests are popular due to their inherent simplicity, low cost, promptitude and portability; however, in many cases the results of such tests may not be predictable, partly because of the interference from similar species. In this proof-of-concept study, we present a paper-based microfluidic optoelectronic tongue – the so-called μOPTO – comprised of 6 indicators in lieu of one specific test and capable of discriminating 8 different alkaloid drugs (i.e. scopolamine, atropine, cocaine, morphine, ephedrine, caffeine, dipyrone and alprazolam) used for recreational, criminal and medical purposes. The wax printing method was employed to fabricate the microfluidic analytical device with six circular spots for reagent accommodation connected to a centered spot to enable simultaneous reactions with one sample injection. Digital images were obtained using an ordinary flatbed scanner, and the RGB information from before and after sample exposure was extracted using appropriate software. The color changes related to each spot were used to build differential maps with a unique fingerprint for each drug. The chemometric tools (i.e. PCA and HCA) showed suitable discrimination of all studied alkaloids in different quantities. To demonstrate a practical application, different alcoholic beverages spiked with scopolamine – a famous substance that causes drug abuse – were analyzed using the optoelectronic tongue. The results showed that small quantities of the drug were identified in different beverages, demonstrating that our device has the potential to be used in situ to prevent ingestion of contaminated samples. [Display omitted] • A microfluidic paper-based optoelectronic tongue for the discrimination of eight alkaloids is presented. • The array was comprised of 6 chemoresponsive reagents. • The color change after reaction enabled the creation of a unique fingerprint for each alkaloid. • Chemometric tools allowed useful discrimination of the drugs. • The μOPTO was applied to identify contaminated alcoholic beverages. [ABSTRACT FROM AUTHOR]

Aims: The purpose of this scoping review was to map out the existing literature on caffeine intake and lower urinary tract symptoms (LUTS) in adults., Methods: In this scoping review, we searched for all studies available until June 2019 in MEDLINE, Embase, CINAHL, Cochrane Central Register, PsycINFO, LILACS, LiSSa, Web of Science, and Joanna Briggs Institute electronic databases, in addition to a hand search of the bibliographies of all relevant articles and a gray literature search. Both intervention studies on the effects of caffeine reduction in adults with LUTS and observational studies on the association between caffeine intake and LUTS-related outcomes in adults were included and assessed for methodological quality by two independent reviewers., Results: Fourteen intervention and 12 observational studies were included. Overall, there was a decrease in urgency episodes (level of evidence 2, grade of recommendation B) and nocturnal enuresis episodes (4, C) with caffeine reduction. Observational studies reported an unclear association between caffeine intake and LUTS-related outcomes. Most importantly, this present review highlighted high heterogeneity in the studied populations, caffeine measures, and reported outcomes. There was also unknown or high risk of bias in most identified studies., Conclusions: Caffeine reduction appears to reduce LUTS. Future studies on caffeine reduction interventions should target populations with urgency and urge urinary incontinence, which show the most promising results, and include valid and reliable measures of caffeine intake and LUTS. Finally, future studies should also use reporting guidelines to ensure lower risk of bias., (© 2020 Wiley Periodicals, Inc.)

Frogs have permeable skin, so transdermal delivery provides a practical alternative to traditional dosing routes. However, little is known about how frog skin permeability differs interspecifically, and there are different reported clinical outcomes following topical application of the same chemical in different frog species. This study collated in vitro absorption kinetic data previously reported for two frog species: the green tree frog (Litoria caerulea) and the cane toad (Rhinella marina), and used linear mixed-effects modelling to produce a model of absorption. Histology of skin samples from each species was performed to observe morphological differences that may affect absorption. Absorption kinetics differed significantly between species, with the logP of the applied chemical a better predictor of permeability than molecular weight. Application site also influenced permeability, with dorsal permeability consistently higher in cane toads. Ventral permeability was more consistent between species. Skin thickness differed between species and skin regions, and this may explain the differences in absorption kinetics. Guidelines for selecting chemicals and dosing site when treating frogs are presented. The permeability differences identified may explain the poor reproducibility reported in the treatment of disease across frog species, and reinforces the importance of considering interspecies differences when designing therapeutic treatments for frogs., (© 2019 John Wiley & Sons Ltd.)

Thin layer chromatography (TLC) is a simple and inexpensive type of chromatography that is extensively used in forensic laboratories for drugs of abuse analysis. In this work, TLC is optimized to analyze cocaine and its adulterants (caffeine, benzocaine, lidocaine and phenacetin) in which the sensitivity (visual determination of LOD from 0.5 to 14mgmL(-1)) and the selectivity (from the study of three different eluents: CHCl3:CH3OH:HCOOHglacial (75:20:5v%), (C2H5)2O:CHCl3 (50:50v%) and CH3OH:NH4OH (100:1.5v%)) were evaluated. Aiming to improve these figures of merit, the TLC spots were identified and quantified (linearity with R(2)>0.98) by the paper spray ionization mass spectrometry (PS-MS), reaching now lower LOD values (>1.0μgmL(-1)). The method developed in this work open up perspective of enhancing the reliability of traditional and routine TLC analysis employed in the criminal expertise units. Higher sensitivity, selectivity and rapidity can be provided in forensic reports, besides the possibility of quantitative analysis. Due to the great simplicity, the PS(+)-MS technique can also be coupled directly to other separation techniques such as the paper chromatography and can still be used in analyses of LSD blotter, documents and synthetic drugs. [ABSTRACT FROM AUTHOR]

The paper provides a demonstration of how UV/VIS imaging can be employed to evaluate the crushing strength, friability, disintegration time and dissolution profile of tablets comprised of solely white components. The samples were produced using different levels of compression force and API content of anhydrous caffeine. Images were acquired from both sides of the samples using UV illumination for the API content prediction, while the other parameters were assessed using VIS illumination. Based on the color histograms of the UV images, API content was predicted with 5.6 % relative error. Textural analysis of the VIS images yielded crushing strength predictions under 10 % relative error. Regarding friability, three groups were established according to the weight loss of the samples. Likewise, the evaluation of disintegration time led to the identification of three groups: <10 s, 11-35 s, and over 36 s. Successful classification of the samples was achieved with machine learning algorithms. Finally, immediate release dissolution profiles were accurately predicted under 5 % of RMSE with an artificial neural network. The 50 ms exposition time during image acquisition and the resulting outcomes underscore the practicality of machine vision for real-time quality control in solid dosage forms, regardless of the color of the API., 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.)

Caffeine, a methylxanthine alkaloid, works as a nonselective adenosine receptor antagonist. It is the most widely used psychostimulant drug worldwide. However, caffeine overdose can lead to acute intoxication, posing a clinical problem. Hyperthermia and hyperactivity are associated issues with acute caffeine intoxication; however, no definitive treatment exists. This study aimed to assess the ability of risperidone to attenuate caffeine-induced hyperthermia and hyperactivity while elucidating the unknown mechanisms of caffeine intoxication. The rats received intraperitoneal injections of saline, risperidone (0.25 mg/kg, 0.5 mg/kg), WAY-100635, ketanserin, haloperidol, sulpiride, or SCH 23390, 5 min after the administration of caffeine (25 mg/kg). Subcutaneous temperature and activity counts were measured using nano tag ® for up to 90 min. In vivo microdialysis was used to determine the effect of risperidone on caffeine-induced elevation of dopamine (DA), serotonin (5-HT), and noradrenaline (NA) concentrations in the anterior hypothalamus. Rats were injected with caffeine (25 mg/kg), followed by saline or risperidone (0.5 mg/kg) 5 min later. The levels of DA, 5-HT, and noradrenaline were measured every 15 min for up to 90 min after caffeine administration. Risperidone and 5-HT2A receptor antagonist ketanserin attenuated caffeine-induced hyperthermia and hyperactivity. Haloperidol and dopamine D1 antagonist SCH-23390 exacerbated hyperthermia without any effect on the hyperactivity. In the microdialysis study, risperidone treatment further attenuated caffeine-induced 5-HT elevation, but not DA and NA. Our results indicate that risperidone attenuates caffeine-induced hyperthermia and hyperactivity by blocking 5-HT2A receptor activity and may be potentially useful for treating caffeine intoxication., 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 Elsevier B.V. All rights reserved.)

Waste-derived organics introduced to soils along with pharmaceutical active compounds (PhAC) are a crude mixture of compounds occurring in various size and polarity fractions. They affect the sorption of PhACs to soil; however, the relevant knowledge is still insufficient. The effects of different size and polarity fractions of manure-derived mobile organic matter (<63 µm) on the sorption of sulfadiazine, caffeine and atenolol to five topsoils were investigated. Mobilization of the PhACs was strongest in the presence of dissolved organic matter (mDOM, <0.45 µm), with a reduction of K d of sulfadiazine, caffeine and atenolol by mean factors of 0.66, 0.57 and 0.41, respectively. The mobilizing effects of colloidal organic matter (0.45-10 µm) were slightly smaller. Fine particulate organic matter (10-63 µm) reduced the sorption of the PhACs in slightly acidic soils (pH 6.0), but increased it in strongly acidic soil (pH 4.3). Furthermore, hydrophobic (HO-mDOM) and hydrophilic (HI-mDOM) fractions of mDOM reduced the sorption capacity but increased the sorption nonlinearity of PhACs in soils. Effects of HO-mDOM and HI-mDOM were PhAC specific. It is suggested to consider the varying impacts of mobile fractions in animal manure and/or treated wastewater in evaluating the fate and environmental relevance of associated PhACs., 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 Authors. Published by Elsevier B.V. All rights reserved.)

Participants completed two sessions of an auditory attention task and intermittently responded to thought probes asking about their level of mind-wandering. After the first session one group received 200 mg of caffeinated chewing gum (n = 61) and another group received regular (placebo) chewing gum (n = 66). The gum was chewed for 20-minutes and then disposed of before beginning the second session. Participants who received caffeine showed a performance benefit as well as reported being more on task and fewer instances of spontaneous mind-wandering compared to those in the placebo group. Participants who received caffeine also reported greater positive affect and arousal, as well as less feelings of boredom, sleepiness, and mental effort required to stay on task compared to those who received placebo. These results suggest that caffeine may benefit attentional engagement as well as performance during a sustained attention task., 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 Authors. Published by Elsevier Inc. All rights reserved.)

Background: The association between coffee and caffeine intake and the risk of COPD and lung function has not been thoroughly discussed in Americans, with subgroup and threshold effects remaining unclear., Objectives: This study investigated the association between coffee and caffeine consumption and the risk of chronic obstructive pulmonary disease (COPD) as well as lung function utilizing data from the NHANES 2007-2012., Methods: We assessed the associations of coffee and caffeine consumption with the risk of COPD and lung function parameters, including FEV1 and FVC, adjusting for common demographic and disease characteristics in a cross-sectional analysis of NHANES data., Results: A total of 9763 participants were included in the study, and 592 were diagnosed with COPD. Multivariate regression models revealed positive associations between coffee and caffeine consumption and the risk of COPD and lung function. Subgroup analyses stratified by sex, DM, hypertension status, and smoking habits identified potential effect modifiers as well as inflection points from threshold effect examinations., Conclusions: The results of this cross-sectional study indicated significant positive correlations between coffee and caffeine consumption and the risk of COPD. Additionally, positive correlations between exposure variables and FEV1 and FVC were detected. Among the stratification factors, smoking status exhibited the most potential for modifying effects. Future practices and research are needed to validate the results and explore the underlying mechanisms., 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. Published by Elsevier Inc.)

In aquatic ecosystems, the presence of pharmaceuticals, particularly caffeine (CAF), has been linked to wastewater discharge, hospital waste, and the disposal of expired pharmaceutical products containing CAF. Additionally, rising temperatures due to climate change are anticipated in aquatic environments. This study aimed to assess the toxicity of various CAF concentrations under current (17 °C) and projected (21 °C) temperature conditions, using the mussel Mytilus galloprovincialis as a bioindicator species. Subcellular impacts were evaluated following 28 days of exposure to four CAF concentrations (0.5; 1.0; 5.0; 10.0 μg/L) at the control temperature (17 °C). Only effects at an environmentally relevant CAF concentration (5.0 μg/L) were assessed at the highest temperature (21 °C). The overall biochemical response of mussels was evaluated using non-metric Multidimensional Scaling (MDS) and the Integrated Biomarker Response (IBR) index, while the Independent Action (IA) model was used to compare observed and predicted responses. Results showed that at 17 °C, increased CAF concentrations were associated with higher metabolism and biotransformation capacity, accompanied by cellular damage at the highest concentration. Conversely, under warming conditions (21 °C), the induction of antioxidant enzymes was observed, although insufficient to prevent cellular damage compared to the control temperature. Regarding neurotoxicity, at 17 °C, the activity of the acetylcholinesterase enzyme was inhibited up to 5.0 μg/L; however, at 10.0 μg/L, activity increased, possibly due to CAF competition for adenosine receptors. The IA model identified a synergistic response for most parameters when CAF and warming acted together, aligning with observed results, albeit with slightly lower magnitudes., 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 Authors. Published by Elsevier B.V. All rights reserved.)

Caffeine and anabolic-androgenic steroids (AAS) are commonly used to improve muscle mass and athletic performance. Nandrolone Decanoate (ND) is one of the most abused AAS worldwide, leading to behavioral changes in both humans and rodents. Caffeine, the most widely consumed psychostimulant globally, is present in various thermogenic and gym supplements. Low and moderate doses of caffeine antagonize adenosine receptors and have been linked to improved memory and pain relief. We have previously demonstrated that consuming caffeine prevents the risk-taking behavior triggered by nandrolone. In this study, we aimed to investigate the long-term effects of ND and caffeine, either alone or in combination, on passive avoidance memory and nociception. We used the step-down and hot-plate tasks in male and female Lister Hooded rats. Our results confirmed the antinociceptive effect of caffeine and indicated that chronic administration of the ND-caffeine association promotes the evocation of aversive memory in female rats., 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 Elsevier B.V. All rights reserved.)

Caffeine, a nonselective adenosine receptor antagonist, is the major component of coffee and the most consumed psychostimulant at nontoxic doses in the world. It has been identified that caffeine consumption reduces the risk of several neurological diseases. However, the mechanisms by which it impacts the pathophysiology of neurological diseases remain to be elucidated. In this study, we investigated whether caffeine exerts anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation and depression in vivo and explored the potential mechanism of caffeine through LPS-induced brain injury. Adult male Sprague-Dawley (SD) rats were intraperitoneal injected with various concentrations of LPS to induce the neuroinflammation and depressive-like behavior. Then SD rats were treated with caffeine in the presence or absence of LPS. Open-filed and closed-field tests were applied to detect the behaviors of SD rats, while western blot was performed to measure the phosphorylation level of protein kinase B (p-AKT) and nuclear factor κB (NF-κB) in the cortex after caffeine was orally administered. Our findings indicated that caffeine markedly improved the neuroinflammation and depressive-like behavior of LPS-treated SD rats. Mechanistic investigations demonstrated that caffeine down-regulated the expression of p-AKT and NF-κB in LPS-induced SD rats cortex. Taken together, these results indicated that caffeine, a potential agent for preventing inflammatory diseases, may suppress LPS-induced inflammatory and depressive responses by regulating AKT phosphorylation and NF-κB., 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 Elsevier B.V. All rights reserved.)

Coffee plants contain well-known xanthines as caffeine. Three Coffea species grown in a controlled greenhouse environment were the focus of this research. Coffea arabica and C. canephora are two first principal commercial species and commonly known as arabica and robusta, respectively. Originating in Central Africa, C. anthonyi is a novel species with small leaves. The xanthine metabolites in flower, fruit and leaf extracts were compared using both targeted and untargeted metabolomics approaches. We evaluated how the xanthine derivatives and FQA isomers relate to the expression of biosynthetic genes encoding N- and O-methyltransferases. Theobromine built up in leaves of C. anthonyi because caffeine biosynthesis was hindered in the absence of synthase gene expression. Despite this, green fruits expressed these genes and they produced caffeine. Given that C. anthonyi evolved successfully over time, these findings put into question the defensive role of caffeine in leaves. An overview of the histolocalisation of xanthines in the different flower parts of Coffea arabica was also provided. The gynoecium contained more theobromine than the flower buds or petals. This could be attributed to increased caffeine biosynthesis before fructification. The presence of theophylline and the absence of theobromine in the petals indicate that caffeine is catabolized more in the petals than in the gynoecium., 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 Elsevier B.V. All rights reserved.)

Pollution from regularly used substances such as pharmaceuticals, cleaning agents, and even food and beverages is an increasing problem in the environment. Caffeine, a commonly ingested stimulant, is one such contaminant that has been detected in aquatic environments worldwide. Yet, little is known about how ecologically relevant concentrations of caffeine influence the morphology, behaviour, and physiology of exposed organisms. To address this knowledge gap, we exposed fathead minnow (Pimephales promelas) to three caffeine treatments: a freshwater control (nominal: 0 ng/L), a low (nominal: 1,000 ng/L) and high environmentally relevant dose (nominal: 10,000 ng/L), for 35 days. We tested the learning abilities, anxiety, metabolic rates, and morphological features of exposed vs. control fish. Caffeine exposure did not affect the ability of fish to learn but did influence anxiety levels. Over the course of repeated anxiety testing, unexposed control fish visited a black square more often while fish exposed to low levels of caffeine did not, potentially indicating that these fish remained in a more anxious state. While caffeine did not impact metabolism, fish growth, or body size, it was associated with lower liver investment-although this response was only observed in our low caffeine treatment. Overall, our results suggest that even relatively low concentrations of caffeine may impact the liver size and anxiety of exposed fish, but further research is needed to assess how extended exposure to caffeine impacts fitness. Given the increase in anthropogenic contaminants in aquatic environments, it is important that we continue to investigate their effects on the organisms exposed to them., 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. Published by Elsevier B.V.)

The objective of the present research was to develop chitosan-coated nanoliposomes using a modified heating method as a delivery system for simultaneous encapsulation of caffeine and roselle anthocyanin to fortify beverage. Response surface methodology was used to ascertain the optimized formulation, aiming to maximize the encapsulation efficiency, minimize the particle size, and maximize the zeta potential. The liposomes fabricated under the optimized conditions (lecithin to cholesterol ratio of 13 and wall to core ratio of 2.16) showed encapsulation efficiency values of 66.73 % for caffeine and 97.03 % for anthocyanin, with a size of 268.1 nm and a zeta potential of -39.11 mV. Fourier transform infrared spectroscopy confirmed the formation of hydrogen bonds between the polar sites of lecithin and the loaded core compounds. Thermal analysis suggested the successful encapsulation of the caffeine and anthocyanin. Transmission and scanning electron microscopy images confirmed a uniform spherical shape with a smooth surface. Fortifying the model beverage with the liposome and the chitosan-coated nanoliposome revealed higher values of encapsulation efficiency of anthocyanin (70.33 ± 3.11 %), caffeine (86.37 ± 2.17 %) and smaller size (280.5 ± 0.74 nm) of the chitosan-coated nanoliposomes at the end of 60th e days. A hedonic sensory test of the fortified beverage with chitosan-coated nanoliposomes confirmed an improvement in the organoleptic properties of the beverage by masking its bitterness (receiving three more sensory scores in perceiving the bitterness intensity). Overall, our study indicates that the high potential of the chitosan-coated nanoliposomes for the simultaneous loading of the caffeine and anthocyanin, as well as their possible application in food and beverage formulations., 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 Elsevier B.V. All rights reserved.)

The astringency of green tea is an integrated result of the synergic and antagonistic effects of individual tea components, whose mechanism is highly complex and not completely understood. Herein, we used an epigallocatechin gallate (EGCG)/caffeine (CAF)/saliva model to simulate the oral conditions during tea drinking. The effect of CAF on the interaction between EGCG and salivary proteins was first investigated using molecular docking and isothermal titration calorimetry (ITC). Then, the rheological properties and the micro-network structure of saliva were studied to relate the molecular interactions and perceived astringency. The results revealed that CAF partially occupied the binding sites of EGCG to salivary proteins, inhibiting their interaction and causing changes in the elastic network structure of the salivary film, thereby reducing astringency., 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 Elsevier Ltd. All rights reserved.)

Modifications to the small intestine and liver are known to occur during the symptomatic disease period of amyotrophic lateral sclerosis (ALS), a member of the motor neuron disease (MND) family of neurodegenerative disorders. How these modifications impact on oral absorption and pharmacokinetics of drugs remains unknown. In this study, model drugs representing different mechanisms of intestinal transport (caffeine for passive diffusion, digoxin for P-glycoprotein efflux, and sulfasalazine for breast cancer resistance protein efflux) were administered via oral gavage to postnatal day 114-120 male and female SOD1 G93A mice (model of familial ALS) and wild-type (WT) littermates. Samples of blood, brain and spinal cord were taken at either 15, 30, 60 or 180 min after administration. In addition, the in vivo gastric emptying of 70 kDa fluorescein isothiocyanate-dextran (FITC-dextran) and the ex vivo intestinal permeability of caffeine were assessed. The area under the plasma concentration-time curves (AUC plasma ) of digoxin and sulfasalazine were not significantly different between SOD1 G93A and WT mice for both sexes. However, the AUC plasma of caffeine was significantly lower (female: 0.79-fold, male: 0.76-fold) in SOD1 G93A compared to WT mice, which was associated with lower AUC brain (female: 0.76-fold, male: 0.80-fold) and AUC spinal cord (female: 0.81-fold, male: 0.82-fold). The AUC stomach of caffeine was significantly higher (female: 1.5-fold, male: 1.9-fold) in SOD1 G93A compared to WT mice, suggesting reduced gastric emptying in SOD1 G93A mice. In addition, there was a significant reduction in gastric emptying of FITC-dextran (0.66-fold) and ex vivo intestinal permeability of caffeine (0.52-fold) in male SOD1 G93A compared to WT mice. Reduced systemic and brain/spinal cord exposure of caffeine in SOD1 G93A mice may therefore result from alterations to gastric emptying and small intestinal permeability. Specific dosing requirements may therefore be required for certain medicines in ALS to ensure that they remain in a safe and effective concentration range., 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 Authors. Published by Elsevier B.V. All rights reserved.)