BACKGROUND: Prenatal alcohol exposure causes a variety of impairments to the fetus called Fetal Alcohol Spectrum Disorders (FASD). Since it is very difficult to identify women that consume alcohol during pregnancy, different methods have been studied to evaluate alcohol exposure. Ethyl Glucuronide (EtG) and Fatty Acid Ethyl Esters (FAEEs) are commonly used to measure alcohol consumption in individuals at-risk for alcohol abuse, including pregnant women.
METHODS: We conducted a study of two cohorts of 1.5 year-old infants (of mothers without a history of alcohol abuse) with or without meconium samples positive to both EtG and FAEEs and we evaluated their cognitive-behavioral development by the Griffiths Mental Developmental Scale (GMDS) method. Our protocol included 8 infants with meconium positive to alcohol metabolites (EtG and FAEEs) and 7 with meconium negative to alcohol metabolites.
RESULTS: None of the 8 alcohol metabolites positive meconium infants exhibited distinctive facial features and growth retardation of severe FASD, showing that other factors may contribute to the FASD onset but elevations in EtG and FAEEs in the meconium were significantly associated with disrupted neurodevelopment and adaptive functions within the first year and a half of life. Indeed, we found out that infants with meconium positive for both EtG and FAEEs, although without displaying any FASD morphological features, had a delay in the fine regulation of their own locomotory capabilities.
CONCLUSIONS: Further analyses and larger studies are needed to estimate the right link between prenatal alcohol exposure and the different range of disorders connected but this study provides an additional step in the field of FASD in order to suggest early treatments for at-risk newborns and infants.

OBJECTIVE: Ethyl glucuronide (EtG) in hair is a direct biomarker proven to be useful for the detection of chronic excessive alcohol use. This study investigated the association of self-reported alcohol consumption with traditional biomarkers: GGT, AST, ALT, CDT, and MCV in blood and a direct biomarker, hair EtG, in a total of 122 patients with alcohol dependence syndrome. The diagnostic accuracy of the biomarkers to differentiate heavy from non-heavy drinkers was also evaluated.
METHODS: GGT, AST, and ALT in serum were measured by Automated Chemistry Analyzer, MCV in blood was measured by Haematology Analyzer, serum CDT was analyzed by ELISA, and EtG in hair was evaluated by gas chromatography-mass spectrometry. The association between the biomarkers and the amount of alcohol consumed (self-reported) was determined using Spearman\'s rank correlation.
RESULTS: All participants showed EtG level above the cut-off (0.03 ng/mg). Hair EtG showed a statistically significant linear and positive correlation with the amounts (in grams) of alcohol consumed (r = 0.60; p < 0.001). No correlation was observed among the traditional biomarkers and the quantity of alcohol consumed. Also, EtG showed an excellent receiver operating characteristic (ROC) curve (98%) with good sensitivity (85%) and specificity (60%) to classify heavy drinkers among individuals with alcohol dependence syndrome.
CONCLUSIONS: Hair EtG can be helpful to estimate retrospective alcohol consumption in long-term chronic alcohol consumption cases. Hair EtG also provides a reliable diagnostic test to detect heavy drinkers among individuals with alcohol dependence syndrome.

The serotonin transporter (SERT) mRNA was previously reported to be a quantitative and pathophysiology-based biomarker of heavy drinking in 5HTTLPR:LL genotype-carriers treated with ondansetron. Here, we validated the potential use of SERT mRNA for quantitative prediction of recent alcohol consumption (in the absence of treatment) and compared it with the known biomarkers ethyl glucuronide (EtG) and ethyl sulfate (EtS).
Binge drinking men and women of European ancestry aged 21 to 65 years were enrolled in a 12-day, in-patient, randomized, double-blind, crossover study, where they were administered three beverage doses (placebo, 0.5 g/kg [0.4 g/kg] ethanol, and 1 g/kg [0.9 g/kg] ethanol for men [women]) individually in three 4-day periods (experiments), separated by minimum 7-day washout period. Diet, sleep, and physical activity were controlled throughout the inpatient experiments. Twenty-nine participants were randomized to receive beverage doses counterbalancing the sequence of treatment and gender within subgroups stratified by SERT genotypes 5HTTLPR:LL+rs25531:AA (LA LA ) versus 5HTTLPR:LS/SS. Peripheral venous blood was collected daily for (1) quantification of SERT mRNA (the primary outcome measure) using qRT-PCR and (2) plasma EtG and EtS levels using tandem mass-spectrometry.
The association between administered beverage dose and SERT mRNA from completers of at least one 4-day experiment (N = 18) assessed by a linear mixed model was not statistically significant. Significant positive associations were found with beverage dose and plasma EtG, EtS and EtG/EtS ratio (β = 5.8, SE = 1.2, p < 0.0001; β = 1.3, SE = 0.6, p = 0.023; and β = 3.0, SE = 0.7, p < 0.0001, respectively; the C-statistics for discriminating outcomes were 0.97, 0.8, and 0.92, respectively). Additionally, we observed a sequence effect with a greater placebo effect on SERT mRNA when it was administered during the first experiment (p = 0.0009), but not on EtG/EtS measures.
The findings do not validate the use of SERT as a biomarker of heavy drinking. Larger and more innovative studies addressing the effects of placebo, race, gender, and response to treatment with serotonergic agents are needed to fully assess the utility of SERT as a biomarker of heavy and binge drinking.

The Identifying Depression Early in Adolescence Risk Score (IDEA-RS) has been externally assessed in samples from four continents, but North America is lacking. Our aim here was to evaluate the performance of the IDEA-RS in predicting future onset of Major Depressive Disorder (MDD) in an adolescent population-based sample in the United States of America - the Great Smoky Mountains Study (GSMS). We applied the intercept and weights of the original IDEA-RS model developed in Brazil to generate individual probabilities for each participant of the GSMS at age 15 (N = 1029). We then evaluated the performance of such predictions against the diagnosis of MDD at age 19 using simple, case-mix corrected and refitted models. Furthermore, we compared how prioritizing the information provided by parents or by adolescents affected performance. The IDEA-RS exhibited a C-statistic of 0.63 (95% CI 0.53-0.74) to predict MDD in the GSMS when applying uncorrected weights. Case-mix corrected and refitted models enhanced performance to 0.69 and 0.67, respectively. No significant difference was found in performance by prioritizing the reports of adolescents or their parents. The IDEA-RS was able to parse out adolescents at risk for a later onset of depression in the GSMS cohort with above chance discrimination. The IDEA-RS has now showed above-chance performance in five continents.

OBJECTIVE: Pharmacokinetics may be of relevance for the risk of clozapine discontinuation. We compared metabolite profiles, accounting for smoking habits, in patients switching versus maintaining clozapine treatment at therapeutic concentrations.
METHODS: Adult patients with clozapine serum levels above 1070 nmol/L (350 ng/mL) were retrospectively included from a Norwegian therapeutic drug monitoring service during 2018-2020. Inclusion criteria were (1) known smoking habits, (2) blood sample drawn within 10 to 30 hours after last clozapine intake, and (3) detectable levels of N -desmethylclozapine, clozapine -N -oxide, clozapine-5 N -glucuronide, or clozapine- N + - glucuronide. Patients comedicated with cytochrome P450 enzyme inducers, inhibitors, or valproic acid were excluded. The high-resolution mass spectrometry assay enabled detection of 21 clozapine metabolites. Metabolite profiles were compared between patients switching treatment (switchers), measured as clozapine being replaced by another antipsychotic drug in blood samples, versus maintaining clozapine treatment (nonswitchers) during the study period.
RESULTS: Of the 84 patients fulfilling the study criteria, 7 patients (8.3%) were identified as clozapine switchers. After correcting for smoking habits, the clozapine-5 N -glucuronide/clozapine ratio was 69% lower ( P < 0.001), while the clozapine- N + -glucuronide/clozapine-5 N -glucuronide ratio was 143% higher ( P = 0.026), respectively, in switchers versus nonswitchers. The other metabolite ratios did not significantly differ between switchers and nonswitchers.
CONCLUSIONS: The present study found a significantly reduced 5 N -glucuronidation phenotype in patients switching from clozapine at therapeutic serum concentrations (>1070 nmol/L) to other antipsychotic drugs. This may indicate that glucuronidation, as a potential detoxification mechanism, is related to clozapine tolerability. However, the causality of this observation needs to be investigated in future studies with larger patient populations.

This study evaluated the chemoprotective effect of scutellarin (SC) in vitro and in vivo against gastric carcinogenesis in rats and celllines and examined the underlying mechanism. Gastric cancer celllines (AGS) was used for the in vitro study and lactate dehydrogenase (LDH) profile, histone deacetylase (HDAC) assay, cell cycle & apoptosis ratio and antioxidant parameters were measured. N-methyl-N\'-nitro-N-nitrosoguanidine (MNNG) was used to induce gastric carcinogenesis in rats and the rats received the different doses of SC (10, 20 and 30 mg/kg). The body weight and tumor incidence were measured at regular time intervals. The antioxidant and pro-inflammatory cytokines were estimated. The finding of data showed that the drug was effective against AGS cell line. Supplementation of scutellarin revealed an upregulation in body weight compared with the MNNG group rats. Moreover, it also reduced the incidence of tumor. It also altered the significant DNA density, LDH content, mucus content and acidity. Scutellarin treated rats showed improved activity in enzymatic and non-enzymatic antioxidant profile and reversed the content of cytokines compared with MNNG induced gastric cancer group rats. This research reveals the chemoprotective property of the scutellarin and highlights the promising role of drug by alteration of inflammatory pathway by minimizing its adverse effect.

BACKGROUND: Surgical site infection (SSI) is a common complication of gastrointestinal surgery. Olanexidine gluconate (OLG) is a novel skin antiseptic that is effective against a wide range of bacteria. The purpose of this study was to evaluate the bactericidal efficacy of OLG in gastrointestinal cancer surgery.
METHODS: This retrospective study included a total of 281 patients who underwent gastrointestinal cancer surgery (stomach or colon). The patients were divided into two groups: 223 patients were treated with OLG (OLG group), and 58 patients were treated with povidone-iodine (PVP-I) (control group). The efficacy and safety outcomes were measured as the rate of SSI within 30 days after surgery. In addition, we conducted subgroup analyses according to the surgical approach (open or laparoscopic) or primary lesion (stomach or colon).
RESULTS: There was a significant difference in the rate of SSI between the control group and OLG group (10.3% vs. 2.7%; p = 0.02). There was a significant difference in the SSI rate in terms of superficial infection (8.6% vs. 2.2%; p = 0.0345) but not in deep infection (1.7% vs. 0.5%; p = 0.371). There was no significant difference between the control group and OLG group in the overall rate of adverse skin reactions (5.2% vs. 1.8%; p = 0.157).
CONCLUSIONS: This retrospective study demonstrates that OLG is more effective than PVP-I in preventing SSI during gastrointestinal cancer surgery.

The evaluation of drinking behaviors can help in limiting high-risk situation, such as driving under the influence (DUI). We investigate ethyl glucuronide in hair (hEtG) levels to evaluate alcohol consumption behavior in subjects followed up after having been charged for DUI of psychoactive substances and/or alcohol. We performed a retrospective observational cohort study on 4328 subjects over 18 years old who underwent hEtG analysis in the period 2015-2019 in the Italian Province of Pavia. hEtG level was used as a proxy for the alcohol consumption behavior. Effects of age, sex, and district on alcohol drinking behavior were investigated with an ordinal logit model. A state sequence analysis was used to study people\'s alcohol consumption behavior over time. hEtG was found ≥7.0 pg/mg in 22.2% of the drivers (of which 7% has an hEtG ≥30.0 pg/mg). Among positive cases, a prevalence of males (96.3%) aged 35-44 (32.6%), coming from main city and hinterland (38.2%), was observed. The propensity to drink was higher for males (odds ratio [OR] ≈ 2.28, p < 0.001) and for subject coming from the district devoted to the cultivation of vineyards. Young age classes have a reduced drinking risk if compared to the drivers over 55 years old (p < 0.001). A general decreasing trend over time in hEtG values was observed. Being male, age ≥ 55 years, and coming from rural areas are potential risk factors related to alcohol drinking habits among drivers. Ethyl glucuronide in hair test in the driving license reissuing protocol contributed to decrease alcohol misuse behaviors.

BACKGROUND: Excessive use of alcohol increases the risk to be involved in a road traffic accident. According to many legislations, certain maximal blood-alcohol-concentrations (BAC) have to be respected to be allowed to drive on public roads. Acute alcohol intoxication is evaluated by blood analysis or analysis of the exhaled alveolar air. In many cases, evaluation of the alcohol consumption during the past months can be useful. In this light, ethyl glucuronide (EtG), a direct alcohol biomarker which can be found in keratinized matrices (hair, nails) is valuable and can be used for the long-term follow-up of alcohol consumption.
OBJECTIVE: To compare the EtG concentration in hair and fingernails from teetotalers, and to propose a cut-off value for EtG in fingernails for alcohol abstinence.
METHODS: Paired samples of hair and nails were collected from participants, with a minimum age of 18 years. They all stated alcohol abstinence for at least 6 months. Participants were asked to complete a questionnaire about age, gender and the use of hair care products and nail polish. Analysis of EtG in the nail and hair samples were conducted following a validated analytical method.
RESULTS: From 126 participants a hair and nail sample were collected. Of this group, 15 participants were finally not included in the study because of insufficient amount of hair or nails collected. There were more female participants (65%) and the average age of participants was 39 years. The EtG concentration in hair was below the limit of detection of 2.1 pg/mg in all but 4 samples (2.1, 2.1, 2.9, and 3.5 pg/mg). The EtG concentration in nails was below the limit of detection in 97 of the 111 samples. The concentrations in nails ranged between 2.3 and 23 pg/mg.
CONCLUSIONS: In a population of 111 teetotalers, the 97.5% percentile of EtG concentrations in fingernails is 7.6 pg/mg. The highest EtG concentration observed was 23 pg/mg. These results suggest that the cut-off value for alcohol abstinence may be lower than the previous suggested 59 pg/mg and 37 pg/mg.

The present research aimed to elucidate a convenient, safe and economic approach to induce the growth of endogenous bone tissue and bone regeneration. S-UNL-E was prepared using reverse-phase evaporation, and scutellarin encapsulation was subsequently compared. Meanwhile, the optimal preparation scheme was developed using an orthogonal method, and the particle size was determined using laser light scattering. In osteoblasts cultured in vitro, methyl thiazolyl tetrazolium (MTT), alkaline phosphatase (ALP) staining and alizarin red staining were used to detect the osteogenic effects of S-UNL-E. The results indicated that the optimal process conditions for S-UNL-E included mass ratios of phospholipid-cholesterol, phospholipid-breviscapine, phospholipid-sodium cholate, and phospholipid-stearamide were 2:1, 15:1, 7:1 and 7:1, respectively, and the mass of ethylenediamine tetramethylphosphonic acid (EDTMP) was 30 mg. The average particle size of S-UNL-E was 156.67 ± 1.76 nm, and Zeta potential was -28.77 ± 0.66 mv. S-UNL-E substantially increased the expression of ALP osteoblasts, elevated the content of osteocalcin protein and promoted the formation of mineralized nodules. Cells in the S-UNL-E group were densely distributed with integrated cell structure, and the actin filaments were clear and obvious. The findings demonstrated that S-UNL-E greatly promoted the differentiation and maturation of osteoblasts, and S-UNL-E (2.5 × 108) produced the most favorable effect in differentiation promotion. In conclusion, the present study successfully constructed an S-UNL-E material characterized by high encapsulation and high stability, which could effectively promote osteogenic differentiation and bone formation.