Analytical description of adolescent binge drinking patients.

BACKGROUND: Binge drinking is a widespread health compromising behavior among adolescents and young adults, leading to significant health problems, injuries and mortality. However, data on alcohol consumption is often unreliable, as it is mainly based on self-reporting surveys. In this five-year study (2014-2019) at the University Children's Hospital Zurich, we analyzed blood samples from adolescent binge drinking patients to investigate blood alcohol concentrations (BACs), co-ingestion of drugs, assess compliance between self-reported and measured substance use, and test for genetic components of innate alcohol tolerance. Furthermore, hair analysis was performed to retrospectively access drug exposure and to evaluate the potential of hair analysis to assess binge drinking. METHODS: In a prospective, single-center study, patients with alcohol intoxications aged 16 years and younger were included. Blood and hair samples were analyzed by sensitive liquid chromatography - tandem mass spectrometry drug analysis. HTTLPR genotyping was performed with PCR and fragment analysis. RESULTS: Among 72 cases, 72 blood and 13 hair samples were analyzed. BACs ranged from 0.08-3.20‰ (mean 1.63‰, median 1.60‰), while a mean concentration of 3.64 pg/mg hair (median 3.0 pg/mg) of the alcohol marker ethyl glucuronide (EtG) was detected in eleven hair samples, providing no evidence of chronic excessive drinking. In 47% of the cases, co-ingested drugs were qualitatively detected next to ethanol, but only 9% of the detected drugs had blood concentrations classified as pharmacologically active. Cannabis consumption (22%) and stimulant intake (16%) were the most frequently observed drugs. Compliance between patients' statements and measured substances matched well. Although we investigated the genetic contribution to innate alcohol tolerance via the 5-HTTLPR polymorphism, the diverse genetic background of the cohort and small sample size did not allow any conclusions to be drawn. CONCLUSION: Almost half of our binge drinking patients tested positive for other substances, primarily cannabis. We anticipate that our study enhances understanding of consumption behavior of young people and encourage continued efforts to address the harmful effects of binge drinking and co-occurring substance use.

Determination of the Time since Deposition of blood-traces in a forensic context: Application of untargeted LC-HR-MS/MS metabolomics profiling.

Being able to attest when a bloodstain was deposited at a crime scene can be invaluable to a prosecution process, and methods to provide that information have long been desired. Determining the Time since Deposition (TsD) of a trace would allow placing a subject both in space and time to the crime scene-or prove that a trace left by that person was unrelated to it because it was deposited before or after the time the crime had occurred. To this day, no method for TsD determination has made its way into routine forensic casework, mainly because of the numerous challenges that await when trying to understand and account for all the influencing and confounding factors that affect the aging process (such as, e.g., temperature, UV-light exposure, or humidity). Here, we present an untargeted metabolomics-based study using liquid chromatography high-resolution mass spectrometry (LC-HR-MS) and data-dependent acquisition to analyze blood samples aged under two distinctly different storage conditions over 48 weeks. Global differences in age- and storage-dependent changes in blood metabolomes were described, and TsD-classification strategies based on qualitative and quantitative assessment of molecular features (MFs) have been proposed. Based on the selected criteria to best predict the TsD, the dipeptide Phenylalanylalanine (PheAla) can be considered as a promising candidate for TsD prediction. In essence, changes in the blood metabolome dynamics showed a strong association with increasing TsD, but significant differences depending on storage conditioning were observed, facilitating the need to study further the influence of individual influencing factors on TsD determination.

Metabolomics-based Sleepiness Markers for Risk Prevention and Traffic Safety (ME-SMART): a monocentric, controlled, randomized, crossover trial.

BACKGROUND: Too little sleep and the consequences thereof are a heavy burden in modern societies. In contrast to alcohol or illicit drug use, there are no quick roadside or workplace tests for objective biomarkers for sleepiness. We hypothesize that changes in physiological functions (such as sleep-wake regulation) are reflected in changes of endogenous metabolism and should therefore be detectable as a change in metabolic profiles. This study will allow for creating a reliable and objective panel of candidate biomarkers being indicative for sleepiness and its behavioral outcomes. METHODS: This is a monocentric, controlled, randomized, crossover, clinical study to detect potential biomarkers. Each of the anticipated 24 participants will be allocated in randomized order to each of the three study arms (control, sleep restriction, and sleep deprivation). These only differ in the amount of hours slept per night. In the control condition, participants will adhere to a 16/8 h wake/sleep regime. In both sleep restriction and sleep deprivation conditions, participants will accumulate a total sleep deficit of 8 h, achieved by different wake/sleep regimes that simulate real-life scenarios. The primary outcome is changes in the metabolic profile (i.e., metabolome) in oral fluid. Secondary outcome measures will include driving performance, psychomotor vigilance test, d2 Test of Attention, visual attention test, subjective (situational) sleepiness, electroencephalographic changes, behavioral markers of sleepiness, changes in metabolite concentrations in exhaled breath and finger sweat, and correlation of metabolic changes among biological matrices. DISCUSSION: This is the first trial of its kind that investigates complete metabolic profiles combined with performance monitoring in humans over a multi-day period involving different sleep-wake schedules. Hereby, we aim to establish a candidate biomarker panel being indicative for sleepiness and its behavioral outcomes. To date, there are no robust and easily accessible biomarkers for the detection of sleepiness, even though the vast damage on society is well known. Thus, our findings will be of high value for many related disciplines. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT05585515, released on 18.10.2022; Swiss National Clinical Trial Portal SNCTP000005089, registered on 12 August 2022.

Aldosterone deficiency in mice burdens respiration and accentuates diet-induced hyperinsulinemia and obesity.

Aldosterone synthase inhibitors (ASIs) should alleviate obesity-related cardiovascular and renal problems resulting partly from aldosterone excess, but their clinical use may have limitations. To improve knowledge for the use of ASIs, we investigated physiology in aldosterone synthase-knockout (ASKO) mice. On regular chow diet (CD), ASKO mice ate more and weighed less than WT mice, largely because they hyperventilated to eliminate acid as CO2. Replacing CD with high-fat diet (HFD) lessened the respiratory burden in ASKO mice, as did 12- to 15-hour fasting. The latter eliminated the genotype differences in respiratory workload and energy expenditure (EE). Thus, aldosterone deficiency burdened the organism more when the animals ate carbohydrate-rich chow than when they ate a HFD. Chronic HFD exposure further promoted hyperinsulinemia in ASKO mice that contributed to visceral fat accumulation accompanied by reduced lipolysis, thermogenic reprogramming, and the absence of weight-gain-related EE increases. Intracerebroventricular aldosterone supplementation in ASKO mice attenuated the HFD-induced hyperinsulinemia, but did not affect EE, suggesting that the presence of aldosterone increased the body's energetic efficiency, thus counteracting the EE-increasing effect of low insulin. ASIs may therefore cause acid-overload-induced respiratory burden and promote obesity. Their use in patients with preexisting renal and cardiopulmonary diseases might be contraindicated.