Graphene Multiplexed Sensor for Point-of-Need Viral Wastewater-Based Epidemiology.

Wastewater-based epidemiology (WBE) can help mitigate the spread of respiratory infections through the early detection of viruses, pathogens, and other biomarkers in human waste. The need for sample collection, shipping, and testing facilities drives up the cost of WBE and hinders its use for rapid detection and isolation in environments with small populations and in low-resource settings. Given the ubiquitousness and regular outbreaks of respiratory syncytial virus, SARS-CoV-2, and various influenza strains, there is a rising need for a low-cost and easy-to-use biosensing platform to detect these viruses locally before outbreaks can occur and monitor their progression. To this end, we have developed an easy-to-use, cost-effective, multiplexed platform able to detect viral loads in wastewater with several orders of magnitude lower limit of detection than that of mass spectrometry. This is enabled by wafer-scale production and aptamers preattached with linker molecules, producing 44 chips at once. Each chip can simultaneously detect four target analytes using 20 transistors segregated into four sets of five for each analyte to allow for immediate statistical analysis. We show our platform's ability to rapidly detect three virus proteins (SARS-CoV-2, RSV, and Influenza A) and a population normalization molecule (caffeine) in wastewater. Going forward, turning these devices into hand-held systems would enable wastewater epidemiology in low-resource settings and be instrumental for rapid, local outbreak prevention.

Coffee consumption and cardiometabolic health: a comprehensive review of the evidence.

This review provides a comprehensive synthesis of longitudinal observational and interventional studies on the cardiometabolic effects of coffee consumption. It explores biological mechanisms, and clinical and policy implications, and highlights gaps in the evidence while suggesting future research directions. It also reviews evidence on the causal relationships between coffee consumption and cardiometabolic outcomes from Mendelian randomization (MR) studies. Findings indicate that while coffee may cause short-term increases in blood pressure, it does not contribute to long-term hypertension risk. There is limited evidence indicating that coffee intake might reduce the risk of metabolic syndrome and non-alcoholic fatty liver disease. Furthermore, coffee consumption is consistently linked with reduced risks of type 2 diabetes (T2D) and chronic kidney disease (CKD), showing dose-response relationships. The relationship between coffee and cardiovascular disease is complex, showing potential stroke prevention benefits but ambiguous effects on coronary heart disease. Moderate coffee consumption, typically ranging from 1 to 5 cups per day, is linked to a reduced risk of heart failure, while its impact on atrial fibrillation remains inconclusive. Furthermore, coffee consumption is associated with a lower risk of all-cause mortality, following a U-shaped pattern, with the largest risk reduction observed at moderate consumption levels. Except for T2D and CKD, MR studies do not robustly support a causal link between coffee consumption and adverse cardiometabolic outcomes. The potential beneficial effects of coffee on cardiometabolic health are consistent across age, sex, geographical regions, and coffee subtypes and are multi-dimensional, involving antioxidative, anti-inflammatory, lipid-modulating, insulin-sensitizing, and thermogenic effects. Based on its beneficial effects on cardiometabolic health and fundamental biological processes involved in aging, moderate coffee consumption has the potential to contribute to extending the healthspan and increasing longevity. The findings underscore the need for future research to understand the underlying mechanisms and refine health recommendations regarding coffee consumption.

Associations between prenatal caffeine exposure and child development: Longitudinal results from the Adolescent Brain Cognitive Development (ABCD) Study.

Objective: Though caffeine use during pregnancy is common, its longitudinal associations with child behavioral and physical health outcomes remain poorly understood. Here, we estimated associations between prenatal caffeine exposure, body mass index (BMI), and behavior as children enter adolescence. Method: Longitudinal data and caregiver-reported prenatal caffeine exposure were obtained from the ongoing Adolescent Brain and Cognitive Development (ABCD) SM Study, which recruited 11,875 children aged 9-11 years at baseline from 21 sites across the United States starting June 1, 2016. Prenatal caffeine exposure was analyzed as a 4-level categorical variable, and further group contrasts were used to characterize "any exposure" and "daily exposure" groups. Outcomes included psychopathology characteristics in children, sleep problems, and BMI. Potentially confounding covariates included familial (e.g., income, familial psychopathology), pregnancy (e.g., prenatal substance exposure), and child (e.g., caffeine use) variables. Results: Among 10,873 children (5,686 boys [52.3%]; mean [SD] age, 9.9 [0.6] years) with nonmissing prenatal caffeine exposure data, 6,560 (60%) were exposed to caffeine prenatally. Relative to no exposure, daily caffeine exposure was associated with higher child BMI (ß=0.08; FDR-corrected p=0.02), but was not associated with child behavior. Those exposed to two or more cups of caffeine daily (n=1,028) had greater sleep problems than those with lower/no exposure (ß>0.92; FDR-corrected p<0.04). Conclusion: Daily prenatal caffeine exposure is associated with heightened childhood BMI, and when used multiple times a day greater sleep problems even after accounting for potential confounds. Whether this relationship is a consequence of prenatal caffeine exposure or its correlated factors remains unknown.

Caffeine Consumption and Interaction with ADORA2A, CYP1A2 and NOS1 Variants Do Not Influence Age at Onset of Machado-Joseph Disease.

BACKGROUND: The age at onset (AO) of Machado-Joseph disease (SCA3/MJD), a disorder due to an expanded CAG repeat (CAGexp) in ATXN3, is quite variable and the role of environmental factors is still unknown. Caffeine was associated with protective effects against other neurodegenerative diseases, and against SCA3/MJD in transgenic mouse models. We aimed to evaluate whether caffeine consumption and its interaction with variants of caffeine signaling/metabolization genes impact the AO of this disease. METHODS: a questionnaire on caffeine consumption was applied to adult patients and unrelated controls living in Rio Grande do Sul, Brazil. AO and CAGexp were previously determined. SNPs rs5751876 (ADORA2A), rs2298383 (ADORA2A), rs762551 (CYP1A2) and rs478597 (NOS1) were genotyped. AO of subgroups were compared, adjusting the CAGexp to 75 repeats (p < 0.05). RESULTS: 171/179 cases and 98/100 controls consumed caffeine. Cases with high and low caffeine consumption (more or less than 314.5 mg of caffeine/day) had mean (SD) AO of 35.05 (11.44) and 35.43 (10.08) years (p = 0.40). The mean (SD) AO of the subgroups produced by the presence or absence of caffeine-enhancing alleles in ADORA2A (T allele at rs5751876 and rs2298383), CYP1A2 (C allele) and NOS1 (C allele) were all similar (p between 0.069 and 0.516). DISCUSSION: Caffeine consumption was not related to changes in the AO of SCA3/MJD, either alone or in interaction with protective genotypes at ADORA2A, CYP1A2 and NOS1.

Updating 'Data on the determination of human epidermis integrity in skin permeation experiments by electrical resistance' with Data on pig ear skin.

The data presented in this article are an update of the dataset provided by Musazzi et al. [1] and are related to the research article entitled "Equivalence assessment of creams with quali-quantitative differences in light of the EMA and FDA regulatory framework" [2]. In vitro permeation study (IVPT) is typically conducted using the method of Franz's diffusion cell for assessing the biopharmaceutical performance of topically applied products. While the human epidermis is considered the benchmark, various animal models (for instance, pig ear) have been accepted as a permeation membrane. Nonetheless, it is crucial to evaluate the integrity of the membrane to ensure the quality of the experiments. The methods employed for this assessment vary, and the outcomes are heavily reliant on the operational conditions, and the model membrane. The article contributes to the existing dataset by providing data on the electrical resistance values of pig ear skin samples and their correlation with the in vitro permeability fluxes of caffeine and benzoic acid. This data is utilized to determine a suitable cut-off for verifying the skin integrity of such an animal model. This information could be beneficial for facilitating critical or comprehensive analyses, contributing to the creation of a standard method.

Ad libitum caffeine consumption, cognitive performance, and sleep in special forces soldiers during a 96-h combat exercise.

Introduction: This observational study investigated the effects of sleep deprivation and ad libitum caffeine consumption on cognitive performance, risk behavior, and mood among 28 Israeli Special Forces (SF) soldiers (mean age: 20.57 ± 0.92 years) during a 96-hour combat exercise. Methods: Actigraphy was used to monitor sleep and activity; cognitive function, risk-taking propensity, mood states, and self-reported sleepiness were assessed using the Psychomotor Vigilance Task (PVT), Evaluation of Risks Scale (EVAR), Profile of Mood States (POMS), Karolinska Sleepiness Scale (KSS); and caffeine consumption by questionnaire at 0, 50, and 96 hours. For analyses, participants were divided into Low (<400 mg) and High (≥400 mg) caffeine consumption groups. Results: The soldiers hiked 108.5 ± 0.52 km and slept for 12.7 ± 0.5 h, with a notable transition from multiple short sleep epochs in the initial 50 hours to a consolidated 5-hour sleep period subsequently. In the High caffeine group, PVT reaction time was faster (p = 0.024) compared to the Low caffeine group, with fewer premature response errors (p = 0.026). However, this group showed increased risk-taking (p = 0.037), particularly reduced Self-Control (p = 0.010). No significant impact of ad libitum caffeine intake on mood was observed. However, degradation over the course of the exercise in both groups in mood states, including anger, fatigue, tension, and vigor, was noted (p < 0.05). KSS scores increased significantly at 50 and 96 h (p < 0.001). Discussion: These results suggest that while caffeine enhances cognitive function, its ad libitum consumption did not consistently improve these measures in this cohort of SF soldiers. The study highlights the complex relationship between sleep deprivation and caffeine intake and their combined effects on soldiers' cognitive and behavioral functions, indicating a need for evidence-based caffeine use guidelines for using caffeine in military settings.

Development of an HPLC method using relative molar sensitivity for the measurement of blood concentrations of nine pharmaceutical compounds.

We developed a reliable high-performance liquid chromatographic analysis method using a relative molar sensitivity (RMS) technique that does not require an authentic, identical reference analyte material to quantify blood serum carbamazepine, phenytoin, voriconazole, lamotrigine, meropenem, mycophenolic acid, linezolid, vancomycin, and caffeine levels for routine blood concentration measurements. Carbamazepine and caffeine were also used as non-analyte reference materials to calculate the RMS of each analyte. The RMS was calculated from the ratio of the slope of the calibration equation (analyte/non-analyte reference material), then used to quantify analytes in control serum samples spiked with carbamazepine, phenytoin, voriconazole, meropenem, mycophenolic acid, linezolid or vancomycin. In addition, the concentrations of these six drugs in control serum samples determined by the proposed RMS method agreed well with that obtained using a conventional method. The proposed RMS method is a promising tool for the clinical determination of nine drugs, given the accuracy, precision, and efficiency of quantifying these analytes.

[Investigation of Mechanism of Creming-down Phenomenon and Development of High-order Functions Using Tea Catechins].

An aqueous solution of 2,3-cis gallate type catechin (-)-epigallocatechin-3-O-gallate (EGCg) and caffeine afforded a precipitate of Creaming-down Phenomenon, which crystallized slowly for about three months to give a colorless block crystal. By X-ray crystallographic analysis, the crystal was determined to be a 2 : 2 complex of EGCg and caffeine, in which caffeine molecules were captured in a hydrophobic space formed with three aromatic A, B, and B' rings of EGCg. It was considered that the solubility of the 2 : 2 complex in water rapidly decreased and the 2 : 2 complex precipitated from aqueous solution. The hydrophobic spaces of EGCg captured a variety of heterocyclic compounds, and the molecular capture abilities of heterocyclic compounds using EGCg from the aqueous solutions were evaluated. Since the C ring of EGCg has two chiral carbon atoms, C2 and C3, the hydrophobic space of EGCg was a chiral space. EGCg captured diketopiperazine cyclo(Pro-Xxx) (Xxx=Phe, Tyr) and pharmaceuticals with a xanthine skeleton, proxyphylline and diprophylline, in the hydrophobic space, and recognized their chirality.

Interaction between caffeine consumption & genetic susceptibility in Parkinson's disease: A systematic review.

BACKGROUND: Caffeine is one of the most consumed psychoactive substances globally. Caffeine-gene interactions in Parkinson's disease (PD) has not been systematically examined. OBJECTIVES: To conduct a systematic review on the interaction between caffeine consumption and genetic susceptibility to PD. METHODOLOGY: We conducted PubMed and Embase search using terms "Genetic association studies", "Caffeine", "polymorphism" and "Parkinson's disease", from inception till 2023. Of the initial 2391 studies, 21 case-control studies were included. The demographic, genetic and clinical data were extracted and analyzed. RESULTS: We identified 21 studies which involved a total of 607,074 study subjects and 17 gene loci (SNCA, MAPT, HLA-DRA, NOS1, NOS3, GBA, ApoE, BST1, ESR2, NAT2, SLC2A13, LRRK2, NOS2A, GRIN2A, CYP1A2, ESR1, ADORA2A) have been investigated for the effect of gene-caffeine interaction and PD risk. The genes were identified through PD GWAS or involved in caffeine or related metabolism pathways. Based on the genetic association and interaction studies, only MAPT, SLC2A13, LRRK2, ApoE, NOS2A, GRIN2A, CYP1A2, and ADORA2A have been shown by at least one study to have a positive caffeine-gene interaction influencing the risk of PD. CONCLUSION: Studies have shown an interaction between caffeine with genetic variants of MAPT, SLC2A13, LRRK2, ApoE, NOS2A, GRIN2A, CYP1A2, and ADORA2A in modulating the risk of PD. Due to the potential limitations of these discovery/pilot studies, further independent replication studies are needed. Better designed genetic association studies in multi-ancestry and admixed cohorts to identify potential shared or unique multivariate gene-environmental interactions, as well as functional studies of gene-caffeine interactions will be useful.

Sudden cardiac arrest occurring in temporal proximity to consumption of energy drinks.

BACKGROUND: Energy drinks potentially can trigger life-threatening cardiac arrhythmias. It has been postulated that the highly stimulating and unregulated ingredients alter heart rate, blood pressure, cardiac contractility, and cardiac repolarization in a potentially proarrhythmic manner. OBJECTIVE: The purpose of this study was to describe our experience regarding sudden cardiac arrest (SCA) occurring in proximity to energy drink consumption in patients with underlying genetic heart diseases. METHODS: The electronic medical records of all SCA survivors with proven arrhythmias referred to the Mayo Clinic Windland Smith Rice Genetic Heart Rhythm Clinic for evaluation were reviewed to identify those who consumed an energy drink before their event. Patient demographics, clinical characteristics, documented energy drink consumption, and temporal relationship of energy drink consumption to SCA were obtained. RESULTS: Among 144 SCA survivors, 7 (5%; 6 female; mean age at SCA 29 ± 8 years) experienced an unexplained SCA associated temporally with energy drink consumption. Of these individuals, 2 had long QT syndrome and 2 had catecholaminergic polymorphic ventricular tachycardia; the remaining 3 were diagnosed with idiopathic ventricular fibrillation. Three patients (43%) consumed energy drinks regularly. Six patients (86%) required a rescue shock, and 1 (14%) was resuscitated manually. All SCA survivors have quit consuming energy drinks and have been event-free since. CONCLUSION: Overall, 5% of SCA survivors experienced SCA in proximity to consuming an energy drink. Although larger cohort studies are needed to elucidate the incidence/prevalence and quantify its precise risk, it seems prudent to sound an early warning on this potential risk.

Loss-of-function W4645R mutation in the RyR2-caffeine binding site: implications for synchrony and arrhythmogenesis.

AIMS: Previous studies have identified RyR2 W4645R mutation, located in the caffeine-binding site, to associate with CPVT1 pathology. Caffeine binding to its site is thought to displace the carboxyl-terminal domain to Ca2+-binding, allowing the tryptophan residue (W4645) to regulate Ca2+ sensitivity of RyR2. To gain insights into regulation of RyR2 Ca2+-binding and its interaction with caffeine-binding site, we introduced W4645R-RyR2 point mutation via CRISPR/Cas9 gene-editing in human induced pluripotent stem cell-derived cardiomyocytes (hiPSCCMs) and characterized their Ca2+-signaling phenotype compared to WT hiPSCCMs. METHODS AND RESULTS: W4645R-RyR2 cardiomyocytes had: (1) no significant change in ICa magnitude or voltage-dependence; (2) slightly reduced CICR; (3) altered relaxation kinetics of Ca2+-transients with no change in isoproterenol sensitivity; (4) complete loss of caffeine-triggered Ca2+ release; (5) larger SR Ca2+ leak resulting in 40 % lower SR Ca2+ content, as determined by myocytes' response to 4-CmC; (6) lower incidence of calcium sparks and asynchronous spontaneous SR Ca2+ releases. CONCLUSIONS: W4645R-RyR2 mutation induces loss of caffeine-triggered SR Ca2+ release and enhances SR Ca2+ leak that underlie asynchronous spontaneous Ca2+ releases, triggering arrhythmia and impairing cardiac function.

Chronic administration of caffeine, modafinil, AVL-3288 and CX516 induces time-dependent complex effects on cognition and mood in an animal model of sleep deprivation.

OBJECTIVE: Caffeine and modafinil are used to reverse effects of sleep deprivation. Nicotinic alpha-7 receptor and AMPA receptor positive allosteric modulators (PAM) are also potential substances in this context. Our objective is to evaluate the effects of caffeine, modafinil, AVL-3288 (nicotinic alpha-7 PAM) and CX516 (AMPA receptor PAM) on cognition and mood in a model of sleep deprivation. METHOD: Modified multiple platform model is used to sleep-deprive mice for 24 days, for 8 h/day. Vehicle, Modafinil (40 mg/kg), Caffeine (5 mg/kg), CX516 (10 mg/kg), and AVL3288 (1 mg/kg) were administered intraperitoneally daily. A cognitive test battery was applied every six days for four times. The battery that included elevated plus maze, novel object recognition, and sucrose preference tests was administered on consecutive days. RESULTS: Sleep deprivation decreased novel object recognition skill, but no significant difference was found in anxiety and depressive mood. Caffeine administration decreased anxiety-like behavior in short term, but this effect disappeared in chronic administration. Caffeine administration increased memory performance in chronic period. AVL group showed better memory performance in short term, but this effect disappeared in the rest of experiment. Although, in the modafinil group, no significant change in mood and memory was observed, anhedonia was observed in the chronic period in vehicle, caffeine and modafinil groups, but not in AVL-3288 and CX-516 groups. CONCLUSION: Caffeine has anxiolytic effect in acute administration. The improvement of memory in chronic period may be associated with the neuroprotective effects of caffeine. AVL-3288 had a short-term positive effect on memory, but tolerance to these effects developed over time. Furthermore, no anhedonia was observed in AVL-3288 and CX516 groups in contrast to vehicle, caffeine and modafinil groups. This indicates that AVL-3288 and CX516 may show protective effect against depression.

Escalating caffeine dose-dependently increases alcohol consumption in adult male, but not female, C57BL/6J mice.

Although previous research has illustrated the effects of the consumption of alcohol and caffeine individually, less research has focused on the popular combination of the two drugs. The increase in alcohol consumption when combined with caffeine has led to the idea that the stimulant effects of caffeine may mask the depressant effects of alcohol, and this may contribute to increased binge drinking as the individual feels more awake and stimulated. Preclinical research has shown various effects of combined alcohol and caffeine where several studies show decreased alcohol consumption and others show increased alcohol consumption and even binge-like drinking. Results from a previous study in our lab indicate that intermittent access (IA) to steady levels of low (0.015 %) but not moderate (0.03 %) caffeine increased alcohol consumption in male C57BL/6J mice. The current studies further investigated the sex and dose differences in adult mice receiving varying concentrations of caffeine on combined alcohol intake. In Experiment 1, adult mice (n = 50, 25 males and 25 females) had IA to one of the following experimental bottles throughout the 4 week period: water, alcohol (10 % v/v), caffeine (0.015 % w/v), or 10 % alcohol +0.015 % caffeine. In Experiment 2, adult mice (n = 70, 35 males and 35 females) were given IA to one of the following experimental bottles: water, alcohol (10 % v/v; steady, maintained throughout the 4 weeks), caffeine (increasing 0.01 % to 0.015 % to 0.02 % to 0.03 % weekly), or 10 % alcohol+increasing caffeine (at the previously mentioned concentrations). When both caffeine and alcohol concentrations remained steady throughout the 4 weeks, there was no change in alcohol consumption. Chronic exposure to IA caffeine led to increased locomotor activity and decreased freezing episodes when tested in the open field test approximately 6 h after removal of the bottles. In Experiment 2, caffeine dose-dependently increased alcohol co-consumption in male mice whereas female mice consumed less alcohol when it was presented in conjunction with caffeine. The results in males are in line with clinical literature suggesting that the combination of alcohol and caffeine may lead to increased stimulation and alcohol drinking. Additionally, these studies provide evidence that the escalation of caffeine is crucial when investigating alcohol and caffeine co-consumption using the IA paradigm.

The combined effect of lifestyle factors and polygenic scores on age at onset in Parkinson's disease.

The objective of this study was to investigate the association between a Parkinson's disease (PD)-specific polygenic score (PGS) and protective lifestyle factors on age at onset (AAO) in PD. We included data from 4367 patients with idiopathic PD, 159 patients with GBA1-PD, and 3090 healthy controls of European ancestry from AMP-PD, PPMI, and Fox Insight cohorts. The association between PGS and lifestyle factors on AAO was assessed with linear and Cox proportional hazards models. The PGS showed a negative association with AAO (ß = - 1.07, p = 6 × 10-7) in patients with idiopathic PD. The use of one, two, or three of the protective lifestyle factors showed a reduction in the hazard ratio by 21% (p = 0.0001), 44% (p < 2 × 10-16), and 55% (p < 2 × 10-16), compared to no use. An additive effect of aspirin (ß = 7.62, p = 9 × 10-7) and PGS (ß = - 1.58, p = 0.0149) was found for AAO without an interaction (p = 0.9993) in the linear regressions, and similar effects were seen for tobacco. In contrast, no association between aspirin intake and AAO was found in GBA1-PD (p > 0.05). In our cohort, coffee, tobacco, aspirin, and PGS are independent predictors of PD AAO. Additionally, lifestyle factors seem to have a greater influence on AAO than common genetic risk variants with aspirin presenting the largest effect.

The relationship between coffee-related factors and cortical and hippocampal structure: a triangulation of evidence approach and Mendelian randomization research.

Objective: Existing studies have reported sustained changes in the cortical structure of rats due to coffee-related factors, which are speculated to occur in the human body. However, there is a lack of research on this topic. Additionally, previous observational studies have found the impact of diseases on cortical structure and the potential therapeutic effects of coffee on these diseases. Our aim was to study the causal effects of coffee-related factors on the human brain using SNPs (single nucleotide polymorphisms). We will connect these discovered causal effects to the impact of diseases on the brain. Through triangulating evidence, we will reveal the potential active areas of coffee in preventing diseases. Methods: We utilized GWAS data from multiple cohorts and their databases, selecting instrumental variables for genetic prediction of coffee intake and plasma levels of caffeine and its direct metabolites. We applied these instrumental variables to individual data on cortical thickness and surface area, as well as hippocampal volume, from the ENIGMA and CHARGE consortium for Mendelian randomization analysis (MR). Triangular evidence was obtained by integrating existing evidence through a specified retrieval strategy, calculating the overlap between coffee's effects on brain regions and disease-related brain regions to identify potential regions of action. Results: The MR analysis yielded 93 positive results for 9 exposures, among which theobromine, a metabolite in the caffeine pathway, was found to be associated with increased hippocampal volume. For cortical structure, theobromine in the caffeine pathway was associated with a decrease in total surface area, while theobromine and caffeine in the pathway were associated with an increase in total thickness. The overlap rate of triangular evidence showed no difference in both overall and subgroup analyses, indicating a high overlap between the effects of coffee on brain regions and disease. Conclusions: From predicted outcomes from causal effects, coffee intake-related factors may have lasting effects on cortical structure. Additionally, theobromine and theophylline have the greatest impact on certain brain gyri, rather than caffeine. Triangulation evidence indicates that disease and coffee intake-related factors act on the same cortical regions, suggesting the presence of potential shared or antagonistic pathways.

Management of androgenic alopecia: a systematic review of the literature.

We aimed to determine the efficacy of the various available oral, topical, and procedural treatment options for hair loss in individuals with androgenic alopecia. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review of the National Library of Medicine was performed. Overall, 141 unique studies met our inclusion criteria. We demonstrate that many over the counter (e.g. topical minoxidil, supplements, low-level light treatment), prescription (e.g. oral minoxidil, finasteride, dutasteride), and procedural (e.g. platelet-rich plasma, fractionated lasers, hair transplantation) treatments successfully promote hair growth, highlighting the superiority of a multifaceted and individualized approach to management.

Adenosine A2A and dopamine D2 receptor interaction controls fatigue resistance.

Introduction: Caffeine and the selective A2A receptor antagonist SCH58261 both have ergogenic properties, effectively reducing fatigue and enhancing exercise capacity. This study investigates in male Swiss mice the interaction between adenosine A2A receptors and dopamine D2 receptors controlling central fatigue, with a focus on the striatum where these receptors are most abundant. Methods: We employed DPCPX and SCH58261 to antagonize A1 and A2A receptors, caffeine as a non-competitive antagonist for both receptors, and haloperidol as a D2 receptor antagonist; all compounds were tested upon systemic application and caffeine and SCH58261 were also directly applied in the striatum. Behavioral assessments using the open field, grip strength, and treadmill tests allowed estimating the effect of treatments on fatigue. Results and discussion: The results suggested a complex interplay between the dopamine and adenosine systems. While systemic DPCPX had little effect on motor performance or fatigue, the application of either caffeine or SCH58261 was ergogenic, and these effects were attenuated by haloperidol. The intra-striatal administration of caffeine or SCH58261 was also ergogenic, but these effects were unaffected by haloperidol. These findings confirm a role of striatal A2A receptors in the control of central fatigue but suggest that the D2 receptor-mediated control of the ergogenic effects of caffeine and of A2A receptor antagonists might occur outside the striatum. This prompts the need of additional efforts to unveil the role of different brain regions in the control of fatigue.

Prevalence of fatigue and consumption of energy drinks consumption among nursing students studying part-time.

Background: Professional nurses who study part-time are faced with demanding tasks, demanding routine, having to cope with their studies and family commitments. Some nurses try different tactics to cope with their demanding tasks, such as the consumption of energy drinks, to alleviate tiredness and fatigue. Although these energy drinks can alleviate fatigue and boost their energy levels, they have adverse effects to their health such as migraines, insomnia, seizures, arrhythmias and other cardiovascular complications. Aim: To determine the health effects of energy drinks among nurses studying part-time. Setting: Selected university in the Gauteng province, South Africa. Methods: Descriptive, quantitative method that was contextual in nature was used. Self-administered questionnaire was used to collect data from a conveniently sampled population to determine the health effects of the use of energy drinks. Data analysis were done by means of descriptive statistics using the Statistical package for Social Sciences version 26. Results: Findings indicated that nurses studying part-time experience fatigue (n = 86; 49%). To alleviate fatigue (n = 91; 52%), they use energy drinks. Conclusion: Use of energy drinks is prevalent among the nurses because of fatigue caused by studying while working. To reduce the use of energy drinks, the participants need study leave and to be supported by their families and employers. Contribution: The study encourages reduction or prevent the use of energy drinks by nurses who work and study part-time. Participants must use time management as a coping mechanism.