Artificial Intelligence-Based Screening System for Diabetic Retinopathy in Primary Care.

BACKGROUND: This study aimed to test an artificial intelligence-based reading system (AIRS) capable of reading retinographies of type 2 diabetic (T2DM) patients and a predictive algorithm (DRPA) that predicts the risk of each patient with T2DM of developing diabetic retinopathy (DR). METHODS: We tested the ability of the AIRS to read and classify 15,297 retinal photographs from our database of diabetics and 1200 retinal images taken with Messidor-2 into the different DR categories. We tested the DRPA in a sample of 40,129 T2DM patients. The results obtained by the AIRS and the DRPA were then compared with those provided by four retina specialists regarding sensitivity (S), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), accuracy (ACC), and area under the curve (AUC). RESULTS: The results of testing the AIRS for identifying referral DR (RDR) in our database were ACC = 98.6, S = 96.7, SP = 99.8, PPV = 99.0, NPV = 98.0, and AUC = 0.958, and in Messidor-2 were ACC = 96.78%, S = 94.64%, SP = 99.14%, PPV = 90.54%, NPV = 99.53%, and AUC = 0.918. The results of our DRPA when predicting the presence of any type of DR were ACC = 0.97, S = 0.89, SP = 0.98, PPV = 0.79, NPV = 0.98, and AUC = 0.92. CONCLUSIONS: The AIRS performed well when reading and classifying the retinographies of T2DM patients with RDR. The DRPA performed well in predicting the absence of DR based on some clinical variables.

Whole-genome analysis of plasma fibrinogen reveals population-differentiated genetic regulators with putative liver roles.

Genetic studies have identified numerous regions associated with plasma fibrinogen levels in Europeans, yet missing heritability and limited inclusion of non-Europeans necessitates further studies with improved power and sensitivity. Compared with array-based genotyping, whole genome sequencing (WGS) data provides better coverage of the genome and better representation of non-European variants. To better understand the genetic landscape regulating plasma fibrinogen levels, we meta-analyzed WGS data from the NHLBI's Trans-Omics for Precision Medicine (TOPMed) program (n=32,572), with array-based genotype data from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium (n=131,340) imputed to the TOPMed or Haplotype Reference Consortium panel. We identified 18 loci that have not been identified in prior genetic studies of fibrinogen. Of these, four are driven by common variants of small effect with reported MAF at least 10 percentage points higher in African populations. Three signals (SERPINA1, ZFP36L2, and TLR10) contain predicted deleterious missense variants. Two loci, SOCS3 and HPN, each harbor two conditionally distinct, non-coding variants. The gene region encoding the fibrinogen protein chain subunits (FGG;FGB;FGA), contains 7 distinct signals, including one novel signal driven by rs28577061, a variant common in African ancestry populations but extremely rare in Europeans (MAFAFR=0.180; MAFEUR=0.008). Through phenome-wide association studies in the VA Million Veteran Program, we found associations between fibrinogen polygenic risk scores and thrombotic and inflammatory disease phenotypes, including an association with gout. Our findings demonstrate the utility of WGS to augment genetic discovery in diverse populations and offer new insights for putative mechanisms of fibrinogen regulation.

Impact of sediment mobilization on trace elements release in Galician Rías (NW Iberian Peninsula): insights into aquaculture.

In the latest years, the concentration levels of certain metals and metalloids in the sediments of the Galician Rías have shown an increasing trend (e.g., As, Zn, Cu, Pb, Hg). These areas are also characterized by their richness in nutrients and their great aquaculture or mariculture activity, with the presence of more than 3500 mussel rafts in the Rías Baixas. The inner areas of the Galician Rías are subjected to activities that resuspend the sediment such as high levels of maritime traffic and dredging or cleaning operations. It is likely that a transfer of these elements to the water column happens during the resuspension of sediments caused by natural events or anthropogenic activities. In this study, selected samples of surface sediments of the Ría de Pontevedra (NW Spain) were subjected to a procedure of aerobic oxidation to determine the concentration of some elements (Fe, Mn, Cu, Cr, Pb, Hg, and Zn) released from the sediment to the aqueous phase. The experiment was carried out within 5 days. Measurements of pH and total concentration were taken both in water and sediment samples. Furthermore, speciation of trace elements was carried out in the sediment samples. Trace element concentrations were lower in the sediments during aerobic oxidation, being released to the aqueous phase. From an environmental point of view, Cu was the only trace element released in quantities that may be toxic for the organisms in the area. This problem of sediment oxidation related to dredging activities or natural storm conditions should be considered in environmental impact studies and transferred to stakeholders.

Can Functional Motor Capacity Influence Mortality in Advanced Chronic Kidney Disease Patients?

Alterations in the body's nutritional status or composition may be observed as the kidney disease advances, which could influence the kidney's functional capacity and, consequently, could increase the risk of mortality. The aim of the study is to determine the influence of functional capacity on mortality assessed by different functional tests in patients with advanced chronic kidney disease (ACKD). A prospective observational study was designed, which included 225 patients followed for 8 years in a CKD clinic. The study assessed functional capacity by using a range of tests, which included the Short Physical Performance Battery, the 6 minutes walking gait test, the timed up and go, and the four versions of the sit-to-stand test. Additionally, body composition and nutritional conditions were considered, taking into consideration various biochemical indicators such as albumin, prealbumin, c-reactive protein (CRP), lymphocytes, and transferrin, muscle strength, comorbidity, and frailty. The relationship between functionality and all-cause mortality was investigated using a Cox proportional hazard model. A total of fifty patients died during the duration of the study. Patients who performed worse on the function and muscle strength tests showed a worse body composition and nutritional status, and exhibited a reduced life expectancy. Inflammation (CRP) was associated with an increased risk of mortality (model 1: hazard ratio (HR) = 1.246; 95% confidence interval (95% CI = 1.014-1.531; model 2: HR = 1.333; 95% CI = 1.104-1.610). Good functional capacity as determined by the SPPB test decreased the risk of mortality (model 1: HR = 0.764; 95% CI = 0.683-0.855; model 2 HR = 0.778; 95% CI = 0.695-0.872). Cut-off points of maximum sensitivity and specificity for mortality were obtained with different tests. The study demonstrated that functional capacity influences mortality in patients with ACKD, being higher in those patients with impaired functionality regardless of the test used, although the SPPB allows a larger number of patients to be assessed. Therefore, it is essential to incorporate the assessment of functionality into the comprehensive care of patients with CKD.

Tracing nerve fibers with volume electron microscopy to quantitatively analyze brain connectivity.

The highly complex structure of the brain requires an approach that can unravel its connectivity. Using volume electron microscopy and a dedicated software we can trace and measure all nerve fibers present within different samples of brain tissue. With this software tool, individual dendrites and axons are traced, obtaining a simplified "skeleton" of each fiber, which is linked to its corresponding synaptic contacts. The result is an intricate meshwork of axons and dendrites interconnected by a cloud of synaptic junctions. To test this methodology, we apply it to the stratum radiatum of the hippocampus and layers 1 and 3 of the somatosensory cortex of the mouse. We find that nerve fibers are densely packed in the neuropil, reaching up to 9 kilometers per cubic mm. We obtain the number of synapses, the number and lengths of dendrites and axons, the linear densities of synapses established by dendrites and axons, and their location on dendritic spines and shafts. The quantitative data obtained through this method enable us to identify subtle traits and differences in the synaptic organization of the samples, which might have been overlooked in a qualitative analysis.

Social interaction-induced fear memory reduction: exploring the influence of dopamine and oxytocin receptors on memory updating.

It has been well established that a consolidated memory can be updated during the plastic state induced by reactivation. This updating process opens the possibility to modify maladaptive memory. In the present study, we evaluated whether fear memory could be updated to less-aversive level by incorporating hedonic information during reactivation. Thus, male rats were fear conditioned and, during retrieval, a female was presented as a social rewarding stimulus. We found that memory reactivation with a female (but not a male) reduces fear expression within-session and in the test, without presenting reinstatement or spontaneous recovery. Interestingly, this intervention impaired extinction. Finally, we demonstrated that this emotional remodeling to eliminate fear expression requires the activation of dopamine and oxytocin receptors during retrieval. Hence, these results shed new lights on the memory updating process and suggests that the exposure to natural rewarding information such as a female during retrieval reduces a previously consolidated fear memory.

Exercise in cancer patients: assistance levels and referral pathways-a position statement from the Spanish Society of Medical Oncology.

There is growing evidence about how physical activity can improve cancer care. Unfortunately, exercise is still not widely prescribed to oncology patients, despite the benefit it brings. For this to occur, it is necessary for a multidisciplinary approach involving different types of healthcare professionals, given that each treatment be tailored for each single case. Besides incorporating appropriate infrastructures and referral pathways, we need to integrate exercise into healthcare practice, which ameliorates patients' quality of life and treatment side effects. From the Spanish Society of Medical Oncology (SEOM), and through the Exercise and Cancer Working Group, we indicate considerations, analyze patient care scenarios, and propose a referral pathway algorithm for exercise prescription, taking in account the patient's needs. In later sections of this paper, we describe how this algorithm could be implemented, and how the exercise programs should be built, including the physical activity contents, the settings, and the delivery mode. We conclude that professionals, infrastructures, and organizations should be available at every assistance level to create programs providing adequate exercise training for cancer patients.

Body weight change during a smoking cessation intervention for individuals with overweight or obesity.

INTRODUCTION: A more comprehensive understanding of the factors regarding weight control in individuals with overweight or obesity after quitting smoking is needed. The study aimed to analyze the changes of in-treatment variables during a smoking cessation intervention and examine their impact on weight. METHODS: A total of 120 individuals who smoke with overweight or obesity (MBMI = 31.75 ± 4.31; 54.16 % female) participated in a cognitive-behavioral therapy for smoking cessation and weight control or the same treatment plus contingency management. Weight, smoking variables (cotinine and continuous abstinence), eating behaviors (appetite, grazing), exercise, and sleep were assessed weekly throughout the treatment. RESULTS: More participants gained weight over time with reduced nicotine use or abstinence. There was a tendency during treatment to increase appetite and exercise time, while grazing episodes and sleeping hours remained stable. Higher baseline weight (p < .001), greater cotinine reduction (p = .021) and time (p = .009) were associated with greater weight gain, while more hours of exercise (p = .003), no appetite changes (p = .003) and diminished appetite (p < .001) were associated with less gain over the treatment. Both treatment conditions showed similar results in all in-treatment variables. DISCUSSION: Individuals with overweight and obesity with higher baseline weight and higher baseline cotinine levels during smoking cessation interventions may require special attention to improve weight outcomes. Exercise and appetite regulation may be useful for mitigating weight gain in smoking cessation interventions for individuals with overweight or obesity.

International Cost-Effectiveness Analysis of Durvalumab in Stage III Non-Small Cell Lung Cancer.

Importance: Standard of care for unresectable locally advanced non-small cell lung cancer (NSCLC) involves definitive chemoradiotherapy followed by maintenance therapy with durvalumab. However, the cost of durvalumab has been cited as a barrier to its use in various health systems. Objective: To evaluate the cost-effectiveness of durvalumab vs placebo as maintenance therapy in patients with unresectable stage III NSCLC from 4 international payer perspectives (US, Brazil, Singapore, and Spain). Design, Setting, and Participants: In this economic evaluation, a Markov model was designed to compare the lifetime cost-effectiveness of maintenance durvalumab for unresectable stage III NSCLC with that of placebo, using 5-year outcomes data from the PACIFIC randomized placebo-controlled trial. Individual patient data were extracted from the PACIFIC, KEYNOTE-189, ADAURA, ALEX, and REVEL randomized clinical trials to develop a decision-analytic model to determine the cost-effectiveness of durvalumab compared with placebo maintenance therapy over a 10-year time horizon. Direct costs, adverse events, and patient characteristics were based on country-specific payer perspectives and demographic characteristics. The study was conducted from June 1, 2022, through December 27, 2023. Main Outcomes and Measures: Life-years, quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs) were estimated at country-specific willingness-to-pay thresholds ([data reported in US$] US: $150 000 per QALY; Brazil: $22 251 per QALY; Singapore: $55 288 per QALY, and Spain: $107 069 per QALY). One-way and probabilistic sensitivity analyses were performed to account for parameters of uncertainty. A cost-threshold analysis was also performed. Results: The US base-case model found that treatment with durvalumab was associated with an increased cost of $114 394 and improved effectiveness of 0.50 QALYs compared with placebo, leading to an ICER of $228 788 per QALY. Incremental cost-effectiveness ratios, according to base-case models, were $141 146 for Brazil, $153 461 for Singapore, and $125 193 for Spain. Durvalumab price adjustments to the PACIFIC data improved cost-effectiveness in Singapore, with an ICER of $45 164. The model was most sensitive to the utility of durvalumab. Conclusions and Relevance: In this cost-effectiveness analysis of durvalumab as maintenance therapy for unresectable stage III NSCLC, the therapy was found to be cost-prohibitive from the perspective of various international payers according to country-specific willingness-to-pay thresholds per QALY. The findings of the study suggest that discounted durvalumab acquisition costs, as possible in Singapore, might improve cost-effectiveness globally.

Hungry bone syndrome following thyroid surgery.

The diagnosis of hypocalcemia-induced tetany following a total thyroidectomy is not common. However, there is a higher risk in patients with a history of gastric bypass surgery due to their malabsorption condition. This case describes postoperative hungry bone syndrome resulting from chronic malabsorption in a patient with a history of bariatric surgery. It is important to consider alternative treatment options if the initial management proves ineffective. Typically, this is a temporary condition, but it's crucial to prioritize prevention in high-risk patients by providing perioperative calcium and vitamin D supplementation.

Depletion forces in dense mixtures of spheres and rods.

We evaluate depletion forces in molecular dynamics simulation of a binary mixture of spheres (depleted particles) and rods (depletant particles) for a wide range of densities for both species. This evaluation was carried out using a recently proposed least squares fitting algorithm. We found that the restriction of the rods' rotational degrees of freedom, when the distance between two spheres is less than the rods length, creates a shallow, and apparently linear, attractive force ramp. For intersphere distances smaller than the rods' diameter, a much stronger attractive force is found, and a large repulsive barrier appears between these aforementioned regimes, roughly at the distance of the rods' thickness. The evaluated forces are validated via a comparison of the pairwise correlation functions obtained from molecular dynamics simulation of a mono-disperse sphere fluid, using the evaluated effective forces, against the original (full system) pairwise correlation functions. Agreement is excellent. We also record the angular pairwise correlation function, using the P2(x) Legendre polynomial, and find that for high densities of both species, a local nematic ordering starts to appear. This nematic order may be a factor in the small differences found between original and effective pairwise correlation functions at high densities of rods.

Unambiguous identification of asymmetric and symmetric synapses using volume electron microscopy.

The brain contains thousands of millions of synapses, exhibiting diverse structural, molecular, and functional characteristics. However, synapses can be classified into two primary morphological types: Gray's type I and type II, corresponding to Colonnier's asymmetric (AS) and symmetric (SS) synapses, respectively. AS and SS have a thick and thin postsynaptic density, respectively. In the cerebral cortex, since most AS are excitatory (glutamatergic), and SS are inhibitory (GABAergic), determining the distribution, size, density, and proportion of the two major cortical types of synapses is critical, not only to better understand synaptic organization in terms of connectivity, but also from a functional perspective. However, several technical challenges complicate the study of synapses. Potassium ferrocyanide has been utilized in recent volume electron microscope studies to enhance electron density in cellular membranes. However, identifying synaptic junctions, especially SS, becomes more challenging as the postsynaptic densities become thinner with increasing concentrations of potassium ferrocyanide. Here we describe a protocol employing Focused Ion Beam Milling and Scanning Electron Microscopy for studying brain tissue. The focus is on the unequivocal identification of AS and SS types. To validate SS observed using this protocol as GABAergic, experiments with immunocytochemistry for the vesicular GABA transporter were conducted on fixed mouse brain tissue sections. This material was processed with different concentrations of potassium ferrocyanide, aiming to determine its optimal concentration. We demonstrate that using a low concentration of potassium ferrocyanide (0.1%) improves membrane visualization while allowing unequivocal identification of synapses as AS or SS.

Contingency management for smoking cessation for individuals with overweight or obesity: A randomized controlled trial.

BACKGROUND: Interventions for quitting smoking and weight control among individuals with excess weight are scarce. Our study evaluated the effectiveness of cognitive behavioral therapy (CBT) plus contingency management (CM) in this population, and examined whether CM for smoking cessation improved CBT treatment outcomes at end of treatment (EOT) and at 1-, 3-, 6-, and 12-month follow-ups (FU). METHODS: In an 8-week randomized clinical trial, 120 adults who smoke with overweight or obesity (54.16% females; MBMI = 31.75 ± 4.31) were randomly assigned to CBT for both quitting smoking and weight control (n = 60) or the same treatment plus CM for smoking cessation (n = 60). Outcome variables were compared (i.e., treatment completion, smoking abstinence, weight change and secondary outcomes). RESULTS: At EOT, the CBT + CM group achieved 78.33% 7-day point-prevalence abstinence rates compared to 61.67% in the CBT group (p = .073), and rates declined over time (12-month FU: 18% vs 12%). Participants who attained abstinence weighed more compared to baseline at EOT (Mkg = 1.07; SD = 1.88) and over time (12-month FU: Mkg = 4.19; SD = 4.31). No differences were found between the two groups in outcome variables. CONCLUSIONS: Both interventions were effective in promoting abstinence and reducing tobacco use over time. Combining CBT with CM for smoking cessation did not improve treatment outcomes in individuals with overweight or obesity compared to CBT only. Future studies should evaluate whether implementing CM for weight maintenance helps control post-cessation weight gain in this population.

Dynamical arrest transition of a bidisperse two-patchy colloidal dispersion: A dynamic Monte Carlo study.

During the last few years, patchy colloidal dispersions have emerged as ideal candidates of glass-formers of systems composed of particles that interact with non-isotropic potentials. However, from the computational point of view, the characterization of their dynamical properties close to the glass transition via any kind of molecular dynamics simulation technique can be very difficult due to the slowing down of both the rotational and translational dynamics. Although a plethora of dynamical techniques have been developed to account for the dynamics of patchy colloids, new and complementary simulation techniques are required to explore, much faster and more efficiently, the dynamical arrest transition of patchy colloidal dispersions when computer simulation consists of a large number of particles and, due to the slow particle dynamics at the glass transition, an extended time window is explicitly required. Then, in this contribution, by means of the so-called dynamic-Monte Carlo method, we report on the dynamical arrest transition, both rotational and translational, of a bidisperse patchy colloidal dispersion, following three different paths along the density-temperature plane, including high densities and low temperatures. Although this method has not been extensively tested at extreme thermodynamic conditions, we show that even at the dynamical arrest transition, it allows us to extract good dynamical data from a complex system. Therefore, it turns out to be a promising technique to explore the onset of vitrification of anisotropic colloidal particles.

Neural circuits for the adaptive regulation of fear and extinction memory.

The regulation of fear memories is critical for adaptive behaviors and dysregulation of these processes is implicated in trauma- and stress-related disorders. Treatments for these disorders include pharmacological interventions as well as exposure-based therapies, which rely upon extinction learning. Considerable attention has been directed toward elucidating the neural mechanisms underlying fear and extinction learning. In this review, we will discuss historic discoveries and emerging evidence on the neural mechanisms of the adaptive regulation of fear and extinction memories. We will focus on neural circuits regulating the acquisition and extinction of Pavlovian fear conditioning in rodent models, particularly the role of the medial prefrontal cortex and hippocampus in the contextual control of extinguished fear memories. We will also consider new work revealing an important role for the thalamic nucleus reuniens in the modulation of prefrontal-hippocampal interactions in extinction learning and memory. Finally, we will explore the effects of stress on this circuit and the clinical implications of these findings.

A genetic association study of circulating coagulation factor VIII and von Willebrand factor levels.

ABSTRACT: Coagulation factor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are critical to coagulation and platelet aggregation. We leveraged whole-genome sequence data from the Trans-Omics for Precision Medicine (TOPMed) program along with TOPMed-based imputation of genotypes in additional samples to identify genetic associations with circulating FVIII and VWF levels in a single-variant meta-analysis, including up to 45 289 participants. Gene-based aggregate tests were implemented in TOPMed. We identified 3 candidate causal genes and tested their functional effect on FVIII release from human liver endothelial cells (HLECs) and VWF release from human umbilical vein endothelial cells. Mendelian randomization was also performed to provide evidence for causal associations of FVIII and VWF with thrombotic outcomes. We identified associations (P < 5 × 10-9) at 7 new loci for FVIII (ST3GAL4, CLEC4M, B3GNT2, ASGR1, F12, KNG1, and TREM1/NCR2) and 1 for VWF (B3GNT2). VWF, ABO, and STAB2 were associated with FVIII and VWF in gene-based analyses. Multiphenotype analysis of FVIII and VWF identified another 3 new loci, including PDIA3. Silencing of B3GNT2 and the previously reported CD36 gene decreased release of FVIII by HLECs, whereas silencing of B3GNT2, CD36, and PDIA3 decreased release of VWF by HVECs. Mendelian randomization supports causal association of higher FVIII and VWF with increased risk of thrombotic outcomes. Seven new loci were identified for FVIII and 1 for VWF, with evidence supporting causal associations of FVIII and VWF with thrombotic outcomes. B3GNT2, CD36, and PDIA3 modulate the release of FVIII and/or VWF in vitro.

The Broad Autism Phenotype-International Test (BAP-IT): A two-domain-based test for the assessment of the broad autism phenotype.

LAY ABSTRACT: The broad autism phenotype refers to a group of behaviors related to autism spectrum disorder, but that appear to a lesser extent. Its assessment has been performed through outdated broad autism phenotype/autism spectrum disorder definitions and tests. To address this problem, this study presents the development of a new test, the Broad Autism Phenotype-International Test, a 20-item measure consisting of two dimensions, SOCIAL-BAP and RIRE-BAP, targeting the two-domain operationalization of autism spectrum disorder in Spain and the United Kingdom. Unlike the Broad Autism Phenotype Questionnaire, this test received empirical support as a quick and effective broad autism phenotype measure that can facilitate both broad autism phenotype/autism spectrum disorder research and interventions. This is the first step to studying the BAP in several Spanish and English-speaking countries.

The role of the differential outcomes procedure and schizotypy in the recognition of dynamic facial expressions of emotions.

Emotional facial expression recognition is a key ability for adequate social functioning. The current study aims to test if the differential outcomes procedure (DOP) may improve the recognition of dynamic facial expressions of emotions and to further explore whether schizotypal personality traits may have any effect on performance. 183 undergraduate students completed a task where a face morphed from a neutral expression to one of the six basic emotions at full intensity over 10 s. Participants had to press spacebar as soon as they identified the emotion and choose which had appeared. In the first block, participants received no outcomes. In the second block, a group received specific outcomes associated to each emotion (DOP group), while another group received non-differential outcomes after correctly responding (NOP group). Employing generalized linear models (GLMs) and Bayesian inference we estimated different parameters to answer our research goals. Schizotypal personality traits did not seem to affect dynamic emotional facial expression recognition. Participants of the DOP group were less likely to respond incorrectly to faces showing Fear and Surprise at fewer intensity levels. This may suggest that the DOP could lead to better identification of the main features that differentiate each facial expression of emotion.

Prevalence of energy drink consumption world-wide: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The increasing market for energy drinks (EDs) in recent years, as well as the health risks caused by their consumption, prompt calls to estimate the prevalence of ED use among different countries. This systematic review and meta-analysis aimed to synthesize the prevalence of ED use in different continents and age groups. METHOD: We searched two databases (i.e. PubMed and PsycInfo) on 31 March 2023 to identify studies reporting the prevalence of ED use. A total of 192 studies (196 distinct samples; n = 1 120 613; 53.37% males) from the United States, Europe, Asia, Oceania and Africa were included in the analysis. A random-effects model was applied to estimate the overall pooled prevalence at several time-periods. Subgroup analyses were performed to provide prevalence based on continent and age group. The quality of articles was assessed using Joana Brigg's Institute (JBI) critical appraisal checklist. Measurements included prevalence of ED use (i.e. life-time, past 12 months, past 30 days, past 7 days and daily use), continent and age group (i.e. children, adolescents, young adults and adults). RESULTS: The life-time ED use world-wide-pooled prevalence was estimated to be 54.7% [95% confidence interval (CI) = 48.8-60.6; I2 = 99.80], 43.4% (95% CI = 36.1-50.6; I2 = 99.92) in the past 12 months, 32.3% (95% CI = 28.8-35.8; I2  = 99.82) in the past 30 days, 21.6% (95% CI = 18.7-24.5; I2 = 99.95) in the past 7 days and 8.82% (95% CI = 6.3-11.4; I2 = 99.95) daily ED use. Subgroups analyses showed significant differences in ED life-time use within age groups (P = 0.002) and continents (P = 0.035). CONCLUSIONS: The world-wide prevalence of energy drink use appears to be high, particularly among adolescents and young adults.

Accessing gold p-acid reactivity under electrochemical anode oxidation (EAO) through oxidation relay.

The gold π-acid activation under electrochemical conditions is achieved. While EAO allows easy access to gold(III) intermediates over alternative chemical oxidation under mild conditions, the reported examples so far are limited to coupling reactions due to the rapid AuIII reductive elimination. Using aryl hydrazine-HOTf salt as precursors, the π-activation reaction mode was realized through oxidation relay. Both alkene and alkyne di-functionalization were achieved with excellent functional group compatibility and regioselectivity, which extended the versatility and utility of electrochemical gold redox chemistry for future applications.