Blood Alcohol Research Articles

520 Use of Phenobarbital for Alcohol Withdrawal in Small Burn Patients: Evaluation of a Pilot Protocol

Abstract Introduction Phenobarbital is a long-acting barbiturate that has primarily been used an antiepileptic in clinical practice. However its use as a sedative has seen a resurgence recently especially for the prevention and/or treatment of alcohol withdrawal. It has several characteristics that make it appealing for this indication, including its long half-life and its distinct binding to GABAA receptors that, unlike benzodiazepines, does not depend on endogenous GABA to produce its effects. Several recent studies have evaluated its use for the treatment of alcohol withdrawal both inside and outside of the ICU setting, however reports of its use in patients with burn injury are sparse. A pilot treatment protocol utilizing phenobarbital for patients with less than 20% TBSA burns at high risk of alcohol withdrawal was formulated and put into practice at our center in January of 2022. We sought to evaluate the safety and efficacy of this protocol for quality improvement. Methods This was a retrospective chart review of patients admitted from January to August 2022 with less than 20% TBSA burns who received treatment with phenobarbital for alcohol withdrawal at a major burn center in North Central Florida. There were no exclusion criteria. This project was registered as a Quality Improvement Project with the institution. Results Ten patients were included in the evaluation. Median age was 63 yo, 90% were male, and 70% were Caucasian. Median % TBSA burn was 6.5% (range 0.5-12%) and median length of stay was 16 days (range 9-50 days). Most patients were injured by Fire/Flame (80%). Most patients had a history of binge drinking (70%), and most reported drinking at least 3-4 alcoholic drinks 4 or more times per week (70%). Of those that had a detectable blood alcohol concentration on admission, the median was 163 mg/dL (range 44-325 mcg/dL). Over half of the patients (60%) received an IV bolus (either 5 or 10 mg/kg based on ideal body weight) of phenobarbital followed by an oral taper, with the remaining 40% having received an oral taper without a bolus dose. Median RASS prior to initiation of the protocol was +1, and the majority of patients remained RASS +1 or less throughout the duration of the protocol (70%). No rescue benzodiazepines were needed, no seizures were identified, and no intubations occurred while patients were on the protocol. Conclusions The phenobarbital protocol was well tolerated and controlled agitation in the majority of the patients who received it. No obvious safety concerns were identified during this review. Although this was a small sample size, these results are encouraging and support continued use of phenobarbital in preventing and controlling symptoms of alcohol withdrawal in patients with less than 20% TBSA burns. Applicability of Research to Practice Phenobarbital may be a safe and effective benzodiazepine-free option for preventing and/or treating alcohol withdrawal in small burn patients.

701 Impact of Alcohol and Methamphetamine Use on Burn Resuscitation

Abstract Introduction Mortality associated with burn injuries is declining with improved critical care, including resuscitation. However, patients admitted with concurrent substance use have increased risk of complications and poor outcomes. The impact of alcohol and methamphetamine use on acute burn resuscitation has been described in single center studies, however, has not been studied since implementation of computerized decision support for resuscitation. The purpose of this study was to evaluate resuscitation volumes for patients with alcohol and methamphetamine use within a large prospective observational trial at 5 major US burn centers. Methods We performed an observational trial across five institutions with > 20% total body surface area (TBSA) burn, weighing >40kg that were resuscitated utilizing computerized decision support. Patients were evaluated based presence of alcohol, with a minimum blood alcohol level of 0.10, or positive methamphetamines on urine drug screen. Fluid volumes and urine output were examined over 48 hours and Wilcoxon Method was utilized to compare patient groups. Results A total of 296 patients were analyzed. 37 (12.5%) were positive for methamphetamine use, 50 (16.9%) were positive for alcohol use, and 209 (70.1%) with negative for both. Patients positive for methamphetamine received a mean of 5.30 ±2.63 cc/kg/TBSA, patients positive for alcohol received a mean of 5.41 ± 2.49 cc/kg/TBSA, and patients with neither received a mean 4.33 ± 1.79 cc/kg/TBSA. Patients with methamphetamine or alcohol use had significantly higher fluid requirements than those who were negative for both substances. In the first 6 hours patients with alcohol use had significantly higher urinary output in comparison to patients with methamphetamine use which had similar output to patients negative for both substances. Conclusions This study demonstrated that patients with alcohol and methamphetamine use had statistically significantly larger fluid resuscitation requirements compared to patients without. The effects of alcohol as a diuretic align with previous literature. However, patients with methamphetamine lack the increased urinary output as a cause for their increased fluid requirements. Methamphetamine’s neurologic and cardiovascular effects due to increased release of dopamine, serotonin, and norepinephrine are known. Further investigation is required to better understand the mechanism underlying the need for increased resuscitation after burn injury in patients positive for methamphetamines. Applicability of Research to Practice The impact of alcohol and illicit substances on burn care, especially during the initial resuscitation, aids providers in guiding early critical care.

Rate of alcohol-induced blackout experience and its negative consequences among Korean university students

An alcohol-induced blackout suggested to be related to a rapid increase in blood alcohol concentration and it is closely related to long-term memory creation. Blackout has been experienced by 35% of the general population and over 50% of university student population. In addition, it has been shown that blackout could be a precursor of injury risk. However, the rate of blackout and blackout related negative consequences in Korean university students have rarely been studied. Therefore, the objective of this study was to determine the blackout experience rate and its negative consequences among students from four universities in Korea. A survey was conducted among university students located in Pusan, Korea in 2013. Demographic and blackout related information were collected through self-report questionnaire, including blackout experience, age of first blackout, and negative consequences of blackout. Descriptive statistical analysis was performed for collected data. Of a total of 470 subjects (Male = 217, Female = 253) surveyed, 190 (40.4%) subjects had experienced a blackout at some points in their lives. The majority (86.3%) of them experienced the first blackout between 20–25 years old. Among those who had experienced a blackout, 57.0% reported that they could not remember how they went home at the end of the night, 8.1%, 7.6%, 3.1%, and 2.2% reported that they had bodily injuries, argument, physical or personal fight, and sexual-related incidences, respectively. This study shows that many Korean university students have experienced blackouts and related negative events. These results suggest that more systematic drinking control strategy is required for Korean university students.

The comparative and correlation study of postmortem ethanol levels between axillosubclavian blood and femoral venous blood in forensic autopsy cases at Thammasat University Hospital, Thailand

BackgroundFemoral venous blood (FVB) is accepted as a standard sample for postmortem ethanol analysis, but owing to the nature of unnatural death cases, FVB may not always be obtainable, and subclavian blood might be used for alternative specimens. This study investigated the correlation between postmortem ethanol concentrations in FVB and axillosubclavian blood (ASB) from autopsy cases in the tropical climate of Central Thailand. Two other factors potentially affecting the correlation, the time of death and ethanol absorption state, were also investigated. FVB, ASB, and vitreous humor were collected from 100 subjects between May 2021 and May 2022. Subjects with decomposition signs and large open wounds were excluded. ASB was drawn from the axillosubclavian vein at the thoracic outlet. Ethanol concentrations in all samples were measured by headspace GC-FID.ResultsEthanol concentrations in ASB were statistically identical to those in FVB (p = 0.6761) and their relationship was statistically correlated (r = 0.9818, p < 0.001). The correlation was not statistically influenced by time since death or absorptive statuses. The diagnostic study to assess the practical application of ASB instead of FVB at a cut-off concentration above 50 mg/dL yielded an area under the ROC curve of 0.96.ConclusionsOur study indicated that ASB can be used as an alternative specimen for postmortem ethanol analysis when FVB is unavailable in dead bodies that are in a tropical climate.

G protein-coupled receptor 158 modulates sensitivity to the sedative-hypnotic effect of ethanol in male mice.

Sensitivity to ethanol provides an index of the predisposition to recover from unconsciousness induced by a dose of ethanol. The role of the G protein-coupled receptor 158 (GPR158) in modulating sensitivity to the sedative-hypnotic effect of ethanol has not been investigated. Loss of righting reflex (LORR) is a behavioral indicator of hypnosis in rodents. In this study, Gpr158-/- mice and wild-type (WT) littermates (n = 8/genotype) were tested using LORR induced by a dose of 3.5 g/kg ethanol, an open-field test (OFT), and a measure of blood ethanol concentration. The OFT was used to examine the role of GPR158 in the ethanol effect on motor activity in Gpr158-/- mice (n = 6/genotype). We also tested CamK2A-Cre;Gpr158fl/fl (n = 9) and Vgat-Cre;Gpr158fl/fl mice (n = 10) using the LORR test and OFT to compare with controls (n = 9 and 8, respectively). Gpr158 deficiency prolonged the LORR duration by 110.6%, t(14) = -5.241, p = 0.0001, without altering spontaneous activity, t(14) = -0.718, p = 0.485, or ethanol metabolism, F(1, 8) = 0.259, p = 0.625. Gpr158 knockout did not change the ethanol effect on locomotion, F(1, 10) = 0.262, p = 0.62. The LORR duration increased by 69% in the conditional knockouts of Gpr158 within calcium/calmodulin-dependent protein kinase II alpha-positive (CamK2A+ ) neurons, t(16) = -2.914, p = 0.01, and by 92% in the vesicular GABA transporter-positive (Vgat+ ) neurons, t(9.802) = -2.519, p = 0.023. Locomotion was not altered in Camk2A-Cre;Gpr158fl/fl , t(16) = 0.49, p = 0.631 or Vgat-Cre;Gpr158fl/fl mice, t(16) = 0.035, p = 0.972. This study reveals the key role of neuronal GPR158 in shaping sensitivity to the sedative-hypnotic effect of ethanol. These findings contribute to our understanding of the neurobiology of ethanol intoxication.

Walnut (Juglans regia L.) Oligopeptides Alleviate Alcohol-Induced Acute Liver Injury through the Inhibition of Inflammation and Oxidative Stress in Rats.

The study was aimed at investigating the effects of walnut oligopeptides (WOPs) on alcohol-induced acute liver injury and its underlying mechanisms. Male Sprague Dawley (SD) rats were randomly assigned to six groups: normal control, alcohol control, whey protein (440 mg/kg.bw), and three WOPs (220 mg/kg.bw, 440 mg/kg.bw, 880 mg/kg.bw) groups. After 30 days of gavage, ethanol with a volume fraction of 50%, administered at a dose of 7 g/kg.bw., caused acute liver injury. A righting reflex experiment and a blood ethanol concentration evaluation were then performed. Serum biochemical parameters, inflammatory cytokines, liver alcohol metabolism enzymes, oxidative stress biomarkers, liver nuclear factor-κB (NF-κB p65), and cytochrome P4502E1 expression were determined. The results revealed that the intervention of 440 mg/kg and 880 mg/kg WOPs could alleviate the degree of intoxication, decrease blood ethanol concentration, alleviate alcohol-induced hepatic steatosis, enhance the activity of hepatic ethanol metabolizing enzymes and antioxidant capacity, reduce lipid oxidation products and pro-inflammatory factor contents, and inhibit the expression of NF-κBp65 in the livers of rats. The outcomes of the study suggest that WOPs have beneficial effects on liver damage caused by acute ethanol binge drinking, with the high-dose WOPs (880 mg/kg.bw) exerting the most pronounced hepatoprotective effect.

Association of cerebellar and pre-motor cortex gray matter density with subjective intoxication and subjective response following acute alcohol intake

Acute alcohol intake produces subjective intoxication (SI) and response (SR; e.g., valanced stimulation and sedation), which has important implications for alcohol-related risk. Individuals who experience less SI may be more likely to engage in risky behaviors while drinking. Gray matter morphometry in brain regions underlying cognitive and affective processes may help to inform individual differences in subjective intoxication and response. The subjective effects of alcohol vary between limbs of the blood alcohol concentration (BAC) curve (i.e., whether BAC is rising or falling; acute tolerance). We examined the relationship between gray matter density (GMD) and SI/SR as a function of BAC limb. Healthy social drinkers (N = 89; 55 women) completed an alcohol challenge paradigm (target BAC = 0.08 g/dL) and structural magnetic resonance imaging (MRI). Participants completed measures of SR and SI on ascending and descending BAC limbs. Association between GMD and SI/SR on each limb were assessed using whole-brain, voxel-wise general linear models. GMD estimates were extracted from significant clusters. Differences in association of GMD and SI/SR between limbs were assessed using hierarchical regression. Significant associations of SI with GMD on the ascending limb were observed in the cerebellum. A significant association between SR and GMD on the descending limb were observed in the pre-motor cortex (BA6) and cerebellum. We identified common and unique associations among cerebellum and pre-central gyrus structures with SI and SR between BAC limbs. Functional imaging studies may further clarify unique dimensions of subjective alcohol effects linked to the observed structural associations.

A multi-sensor based emergency healthcare monitoring system integrating heart status, stress, and alcohol detections

PurposeUbiquitous health-care monitoring systems can provide continuous surveillance to a person using various sensors, including wearables and implantable and fabric-woven sensors. By assessing the state of many physiological characteristics of the patient’s body, continuous monitoring can assist in preparing for the impending emergency. To address this issue, this study aims to propose a health-care system that integrates the treatment of the impending heart, stress and alcohol emergencies. For this purpose, this study uses readings from sensors used for electrocardiography, heart rate, respiration rate, blood alcohol content percentage and blood pressure of a patient’s body.Design/methodology/approachFor heart status, stress level and alcohol detection, the parametric values obtained from these sensors are preprocessed and further divided into four, five and six phases, respectively. A final integrated emergency stage is derived from the stages that were interpreted to examine at a person’s state of emergency. A thorough analysis of the proposed model is carried out using four classification techniques, including decision trees, support vector machines, k nearest neighbors and ensemble classifiers. For all of the aforementioned detections, four metrics are used to evaluate performance: classification accuracy, precision, recall and fmeasure.FindingsEventually, results are validated against the existing health-care systems. The empirical results received reveal that the proposed model outperforms the existing health-care models in the context of metrics above for different detections taken into consideration.Originality/valueThis study proposes a health-care system capable of performing data processing using wearable sensors. It is of great importance for real-time systems. This study assures the originality of the proposed system.

Alcohol and driving—How bad is the combination? A meta-analysis

Objective The objective of this study was to summarize existing knowledge on the association between driving under the influence of alcohol and road safety outcomes and to assess factors that may explain why these estimates vary. Methods Based on studies of the association between blood alcohol concentration (BAC) levels and crashes, we used multilevel metaregression to calculate summary effects of BAC level and analyze potential moderators of the association. Results Based on 60 studies and 393 effect estimates, we found that BAC level, outcome severity, use of hospital data, and geographical region contributed to heterogeneity in results. Conclusion The effect of BAC on crash and injury risk and culpability is stronger at higher BAC levels and for more serious outcomes. The relationship between BAC level and outcome is approximately exponential. The relationship is stronger in studies from Nordic countries than in studies from other countries, possibly because of the relatively low level of drunk driving in these countries. Studies based on hospital data and studies using non-crash-involved control groups find smaller effects on average.

Differential expression of adipocyte and myotube extracellular vesicle miRNA cargo in chronic binge alcohol-administered SIV-infected male macaques.

Our studies in chronic binge alcohol (CBA) -treated simian immunodeficiency virus (SIV)-infected macaques and in people living with HIV (PLWH) show significant alterations in metabolic homeostasis. CBA promotes a profibrotic phenotype in adipose tissue and skeletal muscle (SKM) and decreases adipose-derived stem cell and myoblast differentiation, making adipose and SKM potential drivers in metabolic dysregulation. Furthermore, we have shown that the differential expression of microRNAs (miRs) in SKM contributes to impaired myoblast differentiation potential. Beyond modulation of intracellular responses, miRs can be transported in extracellular vesicles (EVs) to mediate numerous cellular responses through intercellular and interorgan communication. This study tested the hypothesis that CBA alters concentration and miR cargo of EVs derived from adipocytes and myotubes isolated from SIV-infected male macaques. Fourteen male rhesus macaques received either CBA (2.5g/kg/day) or sucrose (VEH) for 14.5 months. Three months following the initiation of CBA/VEH, all animals were infected with SIVmac251 and 2.5 months later were initiated on antiretroviral therapy. SKM and adipose tissue samples were collected at the study endpoint (blood alcohol concentration=0mM). EVs were isolated by ultracentrifugation of myotube and adipocyte cell culture supernatant. Nanoparticle tracking revealed no differences in concentration or size of particles between VEH and CBA groups. Adipocyte-derived EVs from CBA animals showed decreased miR-let-7a expression (p=0.03). Myotube-derived EVs from CBA animals had decreased miR-16 (p=0.04) and increased miR-133a and miR-133b (both p=0.04) expression. These results indicate that CBA administration differentially regulates EV miR content but does not alter the number of EVs from adipocytes or myotubes. Future studies are warranted to determine the functional relevance of CBA-altered EV miR cargo and their role in intercellular and interorgan communication and metabolic dysregulation.

MicroRNA-206 improves alcohol-mediated decreased myoblast differentiation

Background: With recent advances in antiretroviral therapy (ART), people living with HIV (PLWH) have a near-normal life expectancy but have higher risk for aging-related comorbidities, such as metabolic disorders and frailty earlier in life than the general population. At-risk alcohol use is twice as likely in PLWH compared to the general population and alcohol-related myopathy occurs in 40- 60% of people with alcohol use disorder. Previous studies demonstrated that in vivo chronic binge alcohol (CBA) administration in simian immunodeficiency virus (SIV)-infected male rhesus macaques decreased myoblast differentiation and downregulated microRNA-206 (miR-206) expression in skeletal muscle. We hypothesized that increasing miR-206 expression would increase differentiation in CBA-derived primary macaque myoblasts. Methods: Eight SIV-infected female rhesus macaques received either water (VEH) or CBA (13- 14 g/kg/week) for 14.5 months. Three months into either VEH or CBA administration, animals were vaginally infected with SIVmac251, and ART was started 2.5 months later. Animals were sacrificed after 9 months, and primary myoblasts isolated from vastus lateralis muscle 24 hours after the last dose of alcohol (blood alcohol=0 mM). Myoblasts at passage 4 (VEH &amp; CBA) were proliferated for three days. Cells were then transfected with either miR-206 mimic or control (miR scramble). Four experimental groups were studied at day 5 of differentiation: VEH+scramble, CBA+scramble, VEH+miR-206, and CBA+miR-206. Expression of miR-206 was determined by qPCR. Myoblast differentiation was determined by myotube density, calculated as the average number of myotubes per frame, and fusion index calculated as the percentage of myonuclei that fused into myotubes. Results: In non-transfected CBA-derived cells, myotube density and miR-206 expression was lower compared to VEH-derived myotubes (p&lt;0.001 and p&lt;0.05, respectively). miR-206 transfection resulted in over 150-fold higher miR-206 expression compared to VEH-scramble (p&lt;0.05) in CBA- and VEH-derived cells. miR-206 overexpression significantly increased myotube fusion index (p&lt;0.05) compared to myoblasts transfected with miR scramble in CBA-derived cells. Conclusions: Data show significant improvement of alcohol-mediated decreased myoblast differentiation with miR-206 overexpression. These findings suggest that increasing muscle miR-206 can potentially be used as a therapeutic strategy to improve regenerative capacity in response to muscle injury or atrophy. (Supported by: T35AA021097, F30AA029358, P60AA009803, K01AA024494) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Injunctive and descriptive normative feedback for college drinking prevention: Is the whole greater than the sum of its parts?

Single-component personalized normative feedback (PNF) interventions and multicomponent personalized feedback interventions (PFI) have been shown to reduce alcohol consumption among college students. The present study compared the efficacy of PNF interventions targeting descriptive norms alone (descriptive PNF), injunctive norms alone (injunctive PNF), or their combination (combined PNF), against a multicomponent PFI and an attention control condition. Undergraduates (N = 1,137) across two universities who reported a minimum of one past-month episode of heavy episodic drinking (i.e., 4 +/5 + drinks on a single occasion for females/males) completed assessments at baseline and 3, 6, and 12 months postintervention. Relative to the attention control, participants in each of the four intervention conditions showed greater reductions in perceived descriptive/injunctive norms, total drinks per week, and alcohol-related consequences. Peak estimated blood alcohol concentration was also reduced in the injunctive PNF, combined PNF, and multicomponent PFI conditions, with the latter two conditions showing an advantage for duration of effects. The multicomponent PFI condition also evidenced greater reductions than the injunctive PNF in descriptive norms at 3-month and injunctive norms at 6- and 12-month follow-ups. No other group comparisons on any outcome were significant. Each intervention has merit for use in college student harm reduction efforts. Single-component or combined PNF could be considered a potential starting point, as PNF is less burdensome than a multicomponent PFI when considering ease and length of delivery. Results can inform optimization of norms-based interventions and guide recommendations on efficacious components for reducing alcohol use and harms on college campuses. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Acceptability and validity of using the BACtrack skyn wrist-worn transdermal alcohol concentration sensor to capture alcohol use across 28 days under naturalistic conditions - A pilot study.

Wrist-worn transdermal alcohol concentration (TAC) sensors have the potential to provide detailed information about day-level features of alcohol use but have rarely been used in field-based research or in early adulthood (i.e., 26-40 years) alcohol users. This pilot study assessed the acceptability, user burden, and validity of using the BACtrack Skyn across 28 days in individuals' natural settings. Adults aged 26-37 (N=11, Mage=31.2, 55% female, 73% non-Hispanic white) participated in a study including retrospective surveys, a 28-day field protocol wearing Skyn and SCRAM sensors and completing ecological momentary assessments (EMA) of alcohol use and duration (daily morning reports and participant-initiated start/stop drinking EMAs), and follow-up interviews. Day-level features of alcohol use extracted from self-reports and/or sensors included drinks consumed, estimated Blood Alcohol Concentration (eBAC), drinking duration, peak TAC, area under the curve (AUC), rise rate, and fall rate. Repeated-measures correlations (rrm) tested within-person associations between day-level features of alcohol use from the Skyn versus self-report or the SCRAM. Participants preferred wearing the Skyn over the SCRAM [t (10)=-6.79, p<.001, d=2.74]. Skyn data were available for 5614 (74.2%) out of 7566h, with 20.7% of data lost due to syncing/charging issues and 5.1% lost due to device removal. Skyn agreement for detecting drinking days was 55.5% and 70.3% when compared to self-report and the SCRAM, respectively. Correlations for drinking intensity between self-report and the Skyn were 0.35 for peak TAC, 0.52 for AUC, and 0.30 for eBAC, which were smaller than correlations between self-report and SCRAM, at 0.78 for peak TAC, 0.79 for AUC, and 0.61 for eBAC. Correlations for drinking duration were larger when comparing self-report to the Skyn (rrm=0.36) versus comparing self-report to the SCRAM (rrm=0.31). The Skyn showed moderate-to-large, significant correlations with the SCRAM for peak TAC (rrm=0.54), AUC (rrm=0.80), and drinking duration (rrm=0.63). Our findings support the acceptability and validity of using the Skyn for assessing alcohol use across an extended time frame (i.e., 28 days) in individuals' natural settings, and for providing useful information about day-level features of alcohol use.

Mealtime alcohol consumption suppresses skeletal muscle mTORC1 signaling in female mice.

To determine whether alcohol consumed within the meal influences the feeding induced increase in mTORC1 signaling. Alcohol provided in the liquid diet was consumed by alcohol naïve, fasted, C57BL/6Hsd female mice and gastrocnemius was collected 1hr after the refeeding. Subsequent experiments determined the extent to which changes in mTORC1 signaling persisted across the day. Compared with control mice, protein synthesis, mTORC1 (Ser2448), 4EBP1 (Ser65), S6K1 (Thr389), rpS6 (Ser240/244), Akt (Thr308), and ULK1 (Ser757) were lower in EtOH. Similar suppressive patterns were observed in the hours following consumption of alcohol containing food throughout the dark cycle. Higher peak blood alcohol concentrations induced by intraperitoneal injection of alcohol extended the time and magnitude of mTORC1 pathway suppression. Alcohol administered as part of the meal results in lower skeletal muscle mTORC1 signaling while subsequent models show that alcohol may influence this pathway across the day.

A clinical experience-based Chinese herbal formula improves ethanol-induced drunken behavior and hepatic steatohepatitis in mice models

BackgroundBao-Gan-Xing-Jiu-Wan (BGXJW) is a clinical experience-based Chinese herbal formula. Its efficacy, pharmacological safety, targeted function, process quality, and other aspects have met the evaluation standards and the latest requirements of preparations. It could prevent and alleviate the symptoms of drunkenness and alcoholic liver injury clinically. The present work aims to elucidate whether BGXJW could protect against drunkenness and alcoholic liver disease in mice and explore the associated mechanism.Material and methodsWe used acute-on-chronic (NIAAA) mice model to induce alcoholic steatosis, and alcohol binge-drinking model to reappear the drunk condition. BGXJW at indicated doses were administered by oral gavage respectively to analyze its effects on alcoholic liver injury and the associated molecular mechanisms.ResultsBGXJW had no cardiac, hepatic, renal, or intestinal toxicity in mice. Alcoholic liver injury and steatosis in the NIAAA mode were effectively prevented by BGXJW treatment. BGXJW increased the expression of alcohol metabolizing enzymes ADH, CYP2E1, and ALDH2 to enhance alcohol metabolism, inhibited steatosis through regulating lipid metabolism, counteracted alcohol-induced upregulation of lipid synthesis related proteins SREBP1, FASN, and SCD1, meanwhile it enhanced fatty acids β-oxidation related proteins PPAR-α and CPT1A. Alcohol taken enhanced pro-inflammatory TNF-α, IL-6 and down-regulated the anti-inflammatory IL-10 expression in the liver, which were also reversed by BGXJW administration. Moreover, BGXJW significantly decreased the blood ethanol concentration and alleviated drunkenness in the alcohol binge-drinking mice model.ConclusionsBGXJW could effectively relieve drunkenness and prevent alcoholic liver disease by regulating lipid metabolism, inflammatory response, and alcohol metabolism.Graphical

Predicting Intoxication Using Motorcycle and Head Movements of Riders Wearing Alcohol Intoxication Goggles

The movement of a motorcycle is one of the critical factors that influences the stability of the ride. It has been established that the gait patterns of drunk and sober people are distinct. However, drunk motorcycle (MC) drivers’ balance has not been investigated as a predictor of intoxication. This paper characterized and used MC and head movements, such as pitch and roll, to predict intoxication while riding. Two separate experiments were conducted to monitor MC and head movement. Male participants were recruited between the ages of 23 and 50 to participate in the study. Participants used alcohol intoxication goggles (AIG) to simulate blood alcohol content (BAC) while driving on a straight path. Placebo goggles were used for control. Results showed that pitch and roll amplitudes of the MC could distinguish drivers wearing placebo and AIGs, as well as the pitch and roll frequency of the head. Deep learning can be used to predict the intoxication of MC riders. The predictive accuracy of the algorithm shows a viable opportunity for the use of movement to monitor drunk riders on the road.

Optimal designs for a non-linear model for the pharmacokinetics of ethanol elimination in the human body

The equation most commonly used to estimate a person’s blood alcohol concentration after consuming alcoholic drinks assumes zero-order kinetics in the ethanol elimination phase. This implies that the elimination process occurs in the body at a uniform rate as a function of the ethyl-oxidation constant. The model, formulated by Widmark, does not consider the phase of increase in concentration, and approximates the phase of elimination in a linear way, which may be insufficient if the tests are carried out in the first phases of alcohol intake. In this paper, a non-linear model that fits the different phases of the pharmacokinetic process of ethanol in the human body (absorption, distribution, metabolism, and elimination) is proposed. Optimal experimental designs methods are used in order to find the most informative observation times for the estimation of the parameters of the model.

The influence of alcohol and automation on drivers’ visual behavior during test track driving

BackgroundDriving under the influence of alcohol severely increases crash risk. Impairment detection during driving is therefore key to improve traffic safety. However, future detection systems need to capture impairment for more reasons than alcohol intoxication and must also function in all driving modes (manual, assisted, autonomous). Driver Monitoring Systems (DMS) are promising candidates for such broader impairment detection. MethodA test track study investigated the effects of alcohol intoxication on drivers’ visual behavior both when just driving and when engaged in a non-driving related task. Twenty-six participants performed two drives: 1) sober baseline, 2) with a target blood alcohol concentration of 0.1%. The participants drove in either manual, assisted, or autonomous drive (AD) mode. ResultsIntoxication influenced glance behavior in all driving modes. It was most evident during visually demanding non-driving related tasks where it resulted in longer single and total off-path glance durations. Additionally, when just driving in manual mode, almost one third of the drivers displayed gaze concentration to the forward roadway when intoxicated. For sober driving, the difference in visual behavior between manual and assisted mode were moderate. In contrast, there was a huge shift towards longer off-path glances, lower percent road center, and lower off-path glance frequency in AD mode. ConclusionsIntoxication clearly affects drivers’ on/off road glance behavior. However, it is necessary to account for both driving mode and engagement in non-driving related tasks to reliably distinguish sober from drunk driving. Glance metrics has the potential to serve as a sub-set of indicators for a broader DMS-based detection of impaired driving, which can inform the decisions on when to activate in-vehicle countermeasures.

Evaluation of blood alcohol levels in samples taken from medico-legal cases in Manaus, Northern Brazil

Historically, the alcohol consumption has been associated to occurrence of different crimes, including homicides, rapes and sexual assault, among others. Hence, the aim of this study was to evaluate the blood alcohol levels (BAC) in samples taken from medico- legal cases in Manaus, northern Brazil. An observational retrospective study covering May-2018 through April-2019 was carried out and the database of the referral center was employed. In total, 142 cases were evaluated. The mean age of participants was 36.2 ± 10.9 years (range 18-78 years, CI 95% 34.34-38.42) and the majority of them was male (87.32%), single (66.20%), attended the secondary school level (47.89%) and living in the city of Manaus at the time of the incidence (61.70%). The mean BAC was 0.20 ± 0.08 g/dL (range 0.1-0.64 g/dL, CI 95% 0.10-0.15). In relation to the incident, the weekday with most cases was Sunday (30.28%) and in the early morning (24 to 06 hours; 40.14%). Only a small percent was alive before the blood draw (7.04%) and traffic accidents were the most registered occurrence (61.27%). Cocaine was also found in some cases (4.23%). Highest BAC levels were observed for the homicide cases whereas lowest BAC values were attained for the suicide cases (p=0.01). Furthermore, there was a weak positive correlation between age and BAC (r=0.27; p=0.01). For the first time, the study of BAC in samples taken from medico-legal cases was performed in Manaus. Taking into account the results, authorities may develop dedicated strategies to deal with this problem.

Formation of phosphatidylethanol and ethylglucuronide after low to moderate alcohol consumption in volunteers with a previous three-week alcohol abstinence.

Phosphatidylethanol (PEth) is only formed when ethanol is present in blood. This direct alcohol marker has been widely discussed, including the minimum amount of ethanol being necessary to form as much PEth as to exceed the threshold of 20ng/mL in previously PEth negative subjects. In order to corroborate hitherto existing results, a drinking study including 18 participants after a 3-week alcohol abstinence was performed. They consumed a pre-calculated amount of ethanol to reach a blood alcohol concentration (BAC) of at least 0.6g/kg. Blood was drawn before and periodically seven times after alcohol administration on day 1. Blood and urine were also collected the next morning. Dried blood spots (DBS) were prepared immediately from collected venous blood. BAC was determined by head space gas chromatography and the concentrations of both PEth (16:0/18:1, 16:0/18:2 and five additional homologues) and ethyl glucuronide (EtG) were analysed using liquid chromatography-tandem mass spectrometry. Out of 18, 5 participants had concentrations of PEth 16:0/18:1 above the threshold of 20ng/mL, and 11 out of the 18 subjects had concentrations between 10 and 20ng/mL. In addition, four persons had PEth 16:0/18:2 concentrations above 20ng/mL the following morning. All test subjects tested positive for EtG in DBS (≥ 3ng/mL) and urine (≥100ng/mL) upon 20-21h after alcohol administration. By combining both a lower cutoff of 10ng/mL and the homologue PEth 16:0/18:2, the sensitivity to detect a single alcohol intake after a 3-week abstinence increases to 72.2%.