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Background/Objectives: Recurrent shoulder instability following Bankart lesion repair often necessitates surgical revision. This systematic review aims to understand the failure rates of arthroscopic revision Bankart repair. Methods: Following the PRISMA guidelines and registered on PROSPERO, this systematic review examined twenty-five articles written between 2000 and 2024. Two independent reviewers assessed eligibility across three databases, focusing on recurrent instability as the primary endpoint, while also noting functional measures, adverse events, revision operations, and return-to-sport rates when available. Results: The key surgical techniques for recurrent instability post-Bankart repair were identified, with revision arthroscopic Bankart being the most common (685/1032). A comparative analysis revealed a significantly lower recurrence for open coracoid transfer compared to arthroscopic revision Bankart repair (9.67% vs. 17.14%; p < 0.001), while no significant difference was observed between remplissage plus Bankart repair and Bankart repair alone (23.75% vs. 17.14%; p = 0.24). The majority of studies did not include supracritical glenoid bone loss or engaging Hill–Sachs lesions, and neither subcritical nor non-engaging lesions significantly influenced recurrence rates (p = 0.85 and p = 0.80, respectively). Conclusions: Revision arthroscopic Bankart repair remains a viable option in the absence of bipolar bone loss; however, open coracoid transfer appears to have lower recurrence rates than arthroscopic Bankart repair, consistent with prior evidence. Further studies should define cutoffs and investigate the roles of critical glenoid bone loss and off-track Hill–Sachs lesions. Preoperative measurements of GBL on three-dimensional computed tomography and characterizing lesions based on glenoid track will help surgeons to choose ideal candidates for arthroscopic revision Bankart repair. [ABSTRACT FROM AUTHOR]

The central axis of the didactic proposal described in this contribution is the educational approach to the question: are microbes good or bad? Schoolchildren of all levels suffer a constant family, social and, especially media, bombardment about the dangers of microbes and the need to eliminate them. This generates an oversized biophobia towards microbes, which is not counteracted by the meager content of microbiology in educational curricula. Given this situation, it is necessary to develop new innovative educational materials for the teaching of microorganisms and their relationship (both positive and negative) with human beings. This contribution describes a didactic board game on microbiology, which addresses, in addition to viruses, different types of microorganisms, both beneficial and harmful, and opportunistic, as well as their characteristics and their relationship with humans. This relationship is addressed through a series of events that include vaccines, antibiotics, sex, hygiene, food, environment, biotechnology, etc. It is a versatile educational resource, easily adaptable to different levels of education, with which it is possible to approach microorganisms from Primary Education to Higher Education, including initial teacher training. [ABSTRACT FROM AUTHOR]

Rationale: Regular consumption of gamma-hydroxybutyrate (GHB) may result in a dependence syndrome that can lead to withdrawal symptoms. There are limited data on medications to manage GHB withdrawal. Objectives: To examine characteristics associated with delirium and discharge against medical advice (DAMA), in the context of implementing a GHB withdrawal management protocol at an inner-city hospital in 2020. Methods: We retrospectively reviewed records (01 January 2017–31 March 2021), and included admissions that were ≥ 18 years of age, admitted for GHB withdrawal, and with documented recent GHB use. Admissions were assessed for demographics, medications administered, features of delirium, ICU admission, and DAMA. Exploratory analyses were conducted to examine factors associated (p < 0.2) with features of delirium and DAMA. Results: We identified 135 admissions amongst 91 patients. Medications administered included diazepam (133 admissions, 98.5%), antipsychotics (olanzapine [70 admissions, 51.9%]), baclofen (114 admissions, 84%), and phenobarbital (8 admissions, 5.9%). Features of delirium were diagnosed in 21 (16%) admissions. Delirium was associated with higher daily GHB consumption prior to admission, while duration of GHB use, time from presentation to first dose of diazepam, and concomitant methamphetamine use were inversely associated with delirium. DAMA occurred amongst 41 (30%) admissions, and was associated with a longer time from presentation to first dose of baclofen, while being female and receiving a loading dose of diazepam were inversely associated. Conclusions: This study adds to the literature in support of the safety and feasibility of diazepam and baclofen for the management of GHB withdrawal. Prospective, randomised trials are required. [ABSTRACT FROM AUTHOR]

[Display omitted] Solution crystallization techniques of hybrid lead halides for perovskite photovoltaics, while remaining the most common method for fabricating solar cells, are inevitably complicated by the formation of numerous intermediate solvates that predetermine the morphology and properties of the final perovskite light-harvesting layer. Here, for the first time, a chemical classification of known solvates is proposed based on a comprehensive analysis of their structural features and relationships with possible structural types. [ABSTRACT FROM AUTHOR]

[Display omitted] • Fast, simple and direct determination of GBL in adulterated beverages. • GBL prediction capability statistically comparable in all samples evaluated. • Suitable methodology for in-situ forensic Analytical Chemistry without solvent and reagents. • Developed procedure in good agreement with the principles of Green Analytical Chemistry. • Simplicity in calibration model required. A green partial least square (PLS) attenuated total reflectance infrared spectroscopy (ATR-FTIR) method has been developed for the prediction of the γ-butyrolactone (GBL) in all type of soft and alcoholic beverages. The method involves the use of a drop (less than 5 µL) of sample and a single calibration model based on aqueous and alcoholic solutions of GBL and beverages free from GBL. A selected wavenumber range from 1225 to 1171 cm−1 and from 999 to 972 cm−1 of the second derivative (SD) spectra of samples and standards were employed. The validation set provided root mean square error of prediction (RMSEP) of the order of 300 µg g−1 GBL with a ratio of standard error of performance to standard deviation value (RPD) of 13.4. The prediction of unknown samples not considered in the calibration nor in the validation sets offered accuracy relative errors between −1.0 and 2.9 % GBL. The proposed PLS-FTIR based method allows a fast and direct determination of GBL in all type of beverages, in less than 2 min and avoiding the use of neither reagents nor solvents, without any sample treatment required, being in agreement with the principles of Green Analytical Chemistry. [ABSTRACT FROM AUTHOR]

[Display omitted] • Highly viscous electrolyte has been applied in dye-sensitized solar cells (DSSCs). • The best efficiency was gained by the cell with dimethylformamide (DMF) as solvent. • DSSC with DMF-based electrolyte produces low charge transfer resistance. • The best cell exhibited small reduction in efficiency after 4 weeks of storage. Dye-sensitized solar cell (DSSC) performance with a liquid electrolyte depends strongly on the choice of electrolyte solvent. Acetonitrile (AN) is the most widely used organic solvent due to its low viscosity and good solubility to dissolve iodide salts. However, the stability has become critical due to the high vapor pressure of AN. In this study, the efficiency and stability of DSSC using iodide-based electrolyte were observed by using high viscosity solvents namely dimethylformamide (DMF) and γ-butyrolactone (GBL). The cell using DMF shows the best performance with an efficiency of 7.69 %, higher than that of the cell with commercial AN-based electrolyte with an efficiency of 7.14 %. Impedance spectroscopy measurement to the cell using DMF reveals a relatively low charge transfer resistance, both at TiO 2 -dye/electrolyte and counter electrode/electrolyte interfaces, compared to other solvents. Furthermore, the efficiency is retained at 76 % after 4 weeks of storage under ambient air, the best among various solvents tested in the present study. [ABSTRACT FROM AUTHOR]

Total Vaporization Solid‐Phase Microextraction (TV‐SPME) relies on the same technique as standard SPME but completely vaporizes a sample extract, and analytes are sorbed directly from the vapor phase. On‐fiber derivatization may also be performed using TV‐SPME, where the fiber is first exposed to the headspace of a vial containing the derivatization agent, then exposed to a new vial containing the sample. ɣ‐Hydroxybutyric acid (GHB) and ɣ‐butyrolactone (GBL) are drugs of concern in that they may be used in drug facilitated sexual assault by surreptitiously spiking them into a victim's beverage. These drugs cause sedation, memory loss, and are difficult to detect in biological samples. One challenge in their analysis is that they can interconvert in aqueous samples, which was demonstrated in samples allowed to stand at room temperature for long periods. A volume study of GBL in water was performed with volumes ranging from 1 to 10,000 µl to compare the efficacy of TV‐SPME, headspace SPME, and immersion SPME. Lastly, water, beer, wine, liquor, and mixed drinks were spiked with either GHB or GBL with realistic concentrations (mg/ml) and microliter quantities were analyzed using a TV‐SPME Gas Chromatography‐Mass Spectrometry method. The GBL volume study demonstrated an increased sensitivity in GBL detection when TV‐SPME was utilized. Additionally, GHB and GBL were identified in various beverages at realistic concentrations. Overall, TV‐SPME is beneficial because it requires no sample preparation and uses smaller sample volumes than immersion and headspace SPME. [ABSTRACT FROM AUTHOR]

Streptomyces )-butyrolactones (GBLs) are quorum sensing communication signals triggering antibiotic production. The GBL system of Streptomyces filipinensis, the producer of the antifungal agent filipin, has been investigated. Inactivation of sfbR (for S. filipinensis )-butyrolactone receptor), a GBL receptor, resulted in a strong decrease in production of filipin, and deletion of sfbR2, a pseudo-receptor, boosted it, in agreement with lower and higher levels of transcription of filipin biosynthetic genes, respectively. It is noteworthy that none of the mutations affected growth or morphological development. While no ARE (autoregulatory element)-like sequences were found in the promoters of filipin genes, suggesting indirect control of production, five ARE sequences were found in five genes of the GBL cluster, whose transcription has been shown to be controlled by both S. filipinensis SfbR and SfbR2. In vitro binding of recombinant SfbR and SfbR2 to such sequences indicated that such control is direct. Transcription start points were identified by 5= rapid amplification of cDNA ends, and precise binding regions were investigated by the use of DNase I protection studies. Binding of both regulators took place in the promoter of target genes and at the same sites. Information content analysis of protected sequences in target promoters yielded an 18-nucleotide consensus ARE sequence. Quantitative transcriptional analyses revealed that both regulators are self-regulated and that each represses the transcription of the other as well as that of the remaining target genes. Unlike other GBL receptor homologues, SfbR activates its own transcription whereas SfbR2 has a canonical autorepression profile. Additionally, SfbR2 was found here to bind the antifungal antimycin A as a way to modulate its DNA-binding activity. [ABSTRACT FROM AUTHOR]

• Co-ingestion of ethanol increases the adverse effects of patients intoxicated by GHB/GBL. • The most common features were reduction in consciousness. • Patients with ethanol co-ingestion had a higher frequencies of arrivals by ambulance, reduction in consciousness, need for treatment in the ED, use of sedatives, admission to critical care units, and prolonged hospital stay. Ethanol intake can increase the sedative effects of gamma-hydroxybutyrate / gamma-butyrolactone (GHB/GBL), although the real clinical impact is unknown. We studied the clinical impact of the co-ingestion of ethanol in patients presenting to the Emergency Department (ED) with acute toxicity related to GHB/GBL use. We performed a secondary analysis of the Euro-DEN Plus Registry (14 countries, 22 EDs) which includes 17,371 consecutive patients presenting to the ED with acute recreational drug toxicity over 39 consecutive months (October 2013 – December 2016). We compared the epidemiological and clinical characteristics and ED management of patients identified as presenting with acute toxicity related to lone GHB/GBL (Group A) or GHB/GBL combined with ethanol (Group B) without other concomitant drugs. A total of 609 patients were included (age 32 (8) years; 116 women (19%); Group A: 183 patients and Group B: 426). The most common features were reduction in consciousness (defined as Glasgow Coma Score <13 points: 56.1%) and agitation/aggressiveness (33.6%). Those with ethanol co-ingestion were younger patients (Group A/B: 31.5/33.1 years, p = 0.029) and ethanol co-ingestion was associated with a lower frequency of bradycardia (23.5%/15.7%, p = 0.027) and more frequent arrival at the ED by ambulance (68.3/86.6%; p < 0.001), reduction in consciousness (58.9%/49.1%; p = 0.031), need for treatment in the ED (49.2%/60.4%; p = 0.011), use of sedatives (20.1%/12.8%; p = 0.034), admission to critical care units (22.4%/55.3%; p < 0.001), and longer hospital stay (stay longer than 6 h: 16.9%/28.4%; p = 0.003). Co-ingestion of ethanol increases the adverse effects of patients intoxicated by GHB/GBL, leading to greater depression of consciousness, need for treatment, admission to the ICU and longer hospital stay. [ABSTRACT FROM AUTHOR]

The authors examine the determinants of the effective implementation of game-based learning (GBL) for experiential learning. They focus on the successful GBL initiative called Management Game (MG) and adopt the theory-driven deductive thematic analysis approach of Boyatzis along with the Matsuo model as theoretical rationale. Overall, the findings show that MG is an effective GBL that addresses the five seminal factors of the Matsuo model. Further, the study sheds light on the optimal structure of the successful GBL that allows learners to effectively acquire knowledge and skills. Several implications of the study are discussed in the conclusion together with the limitations of the study. [ABSTRACT FROM AUTHOR]

Γ-valerolactone (GVL), marketed online as "Tranquilli-G" and "excellent Valium", is used as a legal substitute for γ-hydroxybutyric acid (GHB); however, until now, GVL has only been connected to one Drug-Facilitated Sexual Assault (DFSA) case. Moreover, the pharmaco-toxicological effects of GVL are poorly studied. The aim of this study was to investigate the 1) in vivo effects of gavage administration of GVL (100–3000 mg/kg) on neurological (myoclonia, convulsions), sensorimotor (visual, acoustic, and overall tactile) responses, righting reflex, thermoregulation, motor activity (bar, drag, and accelerod test) and cardiorespiratory changes (heart rate, breath rate, oxygen saturation, and pulse distension) in CD-1 male mice and the 2) in silico ADMET profile of GVL in comparison to GHB and the open active form γ-hydroxyvaleric acid (GHV). The present study demonstrates that GVL inhibits, in a dose-dependent manner, sensorimotor and motor responses and induces cardiorespiratory depression (at a dose of 3000 mg/kg) in mice. The determination of the ED 50 in sensorimotor and motor responses revealed that GVL is about 4–5 times less potent than GHB. In silico prediction of ADMET profiles revealed toxicokinetic similarities between GHB and GHV, and differences with GVL. These results suggest that GVL could be used as a substitute for GHB and should be added to forensic toxicology screenings. • GVL inhibits sensorimotor, motor and cardiorespiratory responses in mice. • GVL is about 4–5 times less potent than GHB. • In silico ADMET prediction reveals toxicokinetic differences between GVL and GHB. [ABSTRACT FROM AUTHOR]

Highlights • Laboratory rat strains differ in response to gamma butyrolactone (GBL) evoked spike-and-wave discharges. • Long Evans rats display greater sensitivity to GBL than do Sprague-Dawley or Wistar rats. • Responses to GBL differ as a function of sex and estrus cycle. Abstract Childhood absence epilepsy (CAE) is the most common pediatric epilepsy syndrome and is characterized by typical absence seizures (AS). AS are non-convulsive epileptic seizures characterized by a sudden loss of awareness and bilaterally generalized synchronous 2.5–4 Hz spike and slow-wave discharges (SWD). Gamma butyrolactone (GBL) is an acute pharmacological model of AS and induces bilaterally synchronous SWDs and behavioral arrest. Despite the long use of this model, little is known about its strain and sex-dependent features. We compared the dose-response profile of GBL-evoked SWDs in three rat strains (Long Evans, Sprague-Dawley, and Wistar), and examined the modulatory effects of estrous cycle on SWDs in female Wistar rats. We evaluated the number of seizures, the cumulative time seizing, and the average seizure duration as a function of dose, strain, and sex/estrous phase. Long Evans rats displayed the greatest sensitivity to GBL, followed by Wistar rats, and then by Sprague-Dawley rats. GBL-evoked SWDs were modulated by estrous cycle in female rats, with the lowest sensitivity to GBL occurring during metestrus. Wistar rats showed the greatest variability as a function of dose, and the least variability within dose; these features make this strain desirable for interventional studies. Moreover, our finding that the SWD response to GBL differs as a function of estrous cycle underscores the importance of cycle monitoring in studies examining female animals using this model. Together, these strain and sex-dependent findings provide guidance for future studies. [ABSTRACT FROM AUTHOR]

The problematic use of psychoactive substances has adverse consequences for people’s lives and requires on-going investigation of experiences of onset, course and resolution in order to better inform theoretical understanding, particularly with regard to the use of club drugs and novel psychoactive substances. In turn, this may influence treatment approaches. GHB/GBL, frequently termed ‘G’, is one such substance, with problematic use resulting in increased presentations at A&E departments and at substance dependence clinics across Europe. The aim of the present study was to explore problematic G use as experienced by people who had presented for treatment, in Ireland, using interpretative phenomenological analysis (IPA). IPA was selected in recognition of the lack of previous research on the experience of problematic use of G and in the context of an evolving understanding of what constitutes problematic substance use. A purposive and homogenous sample of seven people, five gay males and two straight females, who had presented for treatment for ‘G’ substance use disorder to a community-based drug team, participated in semi-structured interviews. Three superordinate themes reflecting the participants chronological development of problematic ‘G’ use and early recovery were fully developed and presented—(1) early use: “I was part of that gang that took G”; (2) daily use: “It’s like insidious; it just weaves into your everyday life”; and (3) early recovery: “my priorities are changing”. This study supports the interactive role of community, self-identity, personal vulnerability and substance effects in the development, maintenance and recovery from problematic G use. Findings are discussed in the context of gay community health, the role of chemsex in problematic substance use and the need for public health providers to engage with novel psychoactive substance use and the health and well-being effects of chemsex. [ABSTRACT FROM AUTHOR]

Background. Although the effectiveness of game-based learning (GBL) is well-supported, much less is known about the process underlying it. Nevertheless, developing a mental model that matches the game system, which in turn models a real-world system, is a promising proposed process.Aim. This article explores the first steps in model matching: identifying the entities and (complex) relations in a game system.Method. Participants (N = 30) played the analog game DOMINION and completed a multi-step mental model mapping exercise. Categories of entities in mental model maps were inductively identified with grounded theory coding, while complex relations in mental model maps were identified via content analysis.Results. Participants described formal game entities, player actions, sociality, learning processes, and subjective experience in their mental model maps. Participants identified very few complex relations—and no feedback loops—in their mental model maps.Conclusions. Games—and analog games specifically—provide a breadth of resources for model matching and GBL. Through gameplay, learners come to affix conceptual meanings to material objects, a process dubbed lamination. [ABSTRACT FROM AUTHOR]

Objective To study the profile of European gamma-hydroxybutyrate (GHB) and gammabutyrolactone (GBL) intoxication and analyse the differences in the clinical manifestations produced by intoxication by GHB/GBL alone and in combination with other substances of abuse. Method We prospectively collected data on all the patients attended in the Emergency Departments (ED) of the centres participating in the Euro-DEN network over 12 months (October 2013 to September 2014) with a primary presenting complaint of drug intoxication (excluding ethanol alone) and registered the epidemiological and clinical data and outcomes. Results We included 710 cases (83% males, mean age 31 years), representing 12.6% of the total cases attended for drug intoxication. Of these, 73.5% arrived at the ED by ambulance, predominantly during weekend, and 71.7% consumed GHB/GBL in combination with other substances of abuse, the most frequent additional agents being ethanol (50%), amphetamine derivatives (36%), cocaine (12%) and cannabis (8%). Among 15 clinical features pre-defined in the project database, the 3 most frequently identified were altered behaviour (39%), reduced consciousness (34%) and anxiety (14%). The severity ranged from mild cases requiring no treatment (308 cases, 43.4%) to severe cases requiring admission to intensive care (103 cases, 14.6%) and mechanical ventilation (49 cases, 6.9%). No deaths were reported. In comparison with only GHB/GBL consumption, patients consuming GHB/GBL with co-intoxicants presented more vomiting (15% vs. 3%, p < 0.001) and cardiovascular symptoms (5.3% vs. 1.5%, p < 0.05), a greater need for treatment (59.8% vs. 48.3%, p < 0.01) and a longer ED stay (11.3% vs. 3.6% patients with ED stay >12 h, p < 0.01). Conclusions The profile of the typical GHB/GBL-intoxicated European is a young male, requiring care for altered behaviour and reduced level of consciousness, mainly during the weekend. The clinical features are more severe when GHB is consumed in combination with other substances of abuse. [ABSTRACT FROM AUTHOR]

Innovation in learning and teaching is an everyday requirement in contemporary higher education (HE), especially in challenging subjects such as mathematics. Teaching mathematics to students with limited experience of formal mathematical instruction is a good example of a demanding pedagogical undertaking where innovatory practice can help HE teachers rise to the challenge. This paper presents an innovative game-based learning approach to the teaching of basic mathematics in HE through the example of a first-year mathematics module of the BSc Computer Science course offered by the Aberystwyth University (UK). Excellent examination results and positive student feedback concerning the learning experience point to the value-addedness of this approach in HE and it is, therefore, offered here as an example of good teaching practice to be disseminated more widely in the sector. [ABSTRACT FROM AUTHOR]

TylP is one of five regulatory proteins involved in the regulation of antibiotic (tylosin) production, morphological and physiological differentiation in Streptomyces fradiae. Its function is similar to those of various γ-butyrolactone receptor proteins. In this report, N-terminally His-tagged recombinant TylP protein (rTylP) was overproduced in Escherichia coli and purified to homogeneity. The rTylP protein was crystallized from a reservoir solution comprising 34%( v/ v) ethylene glycol and 5%( v/ v) glycerol. The protein crystals diffracted X-rays to 3.05 Å resolution and belonged to the trigonal space group P3121, with unit-cell parameters a = b = 126.62, c = 95.63 Å. [ABSTRACT FROM AUTHOR]

Background: GHB (gamma-hydroxybutyrate) and its pro-drugs GBL (gamma-butyrolactone) and 1,4-butanediol (1,4-BD) are central nervous system depressants whose street names include 'G' and 'liquid ecstasy'. They are used recreationally predominately for their stimulant and pro-sexual effects or for sedation to help with sleep and/or to 'come down' after using stimulant recreational drugs. Although overall population prevalence is low (0.1 %), in some groups such as men who have sex with men, GHB/GBL use may reach 20 %. GHB/GBL dependence may be associated with severe withdrawal with individuals presenting either acutely to emergency departments or to addiction services for support. Benzodiazepines are currently prescribed for GHB/GBL detoxification but do not prevent all complications, such as behavioural disinhibition, that may require hospitalisation or admission to a high dependency/intensive care unit. The GABAB receptor mediates most effects of GHB/GBL and the GABAB agonist, baclofen, has shown promise as an adjunct to benzodiazepines in reducing withdrawal severity when prescribed both during withdrawal and as a 2-day 'preload' prior to detoxification. The key aim of this feasibility study is provide information about recruitment and characteristics of the proposed outcome measure (symptom severity, complications including delirium and treatment escalation) to inform an application for a definitive randomised placebo controlled trial to determine the role of baclofen in the management of GHB/GBL withdrawal and whether starting baclofen 2 days earlier improves outcomes further. Methods/design: This is a prospective, randomised, double-blind, placebo-controlled feasibility study that will recruit participants (aged over 18 years) who are GHB/GBL-dependent and wish to undergo planned GHB/GBL detoxification or are at risk of acute withdrawal and are inpatients requiring unplanned withdrawal. We aim to recruit 88 participants: 28 unplanned inpatients and 60 planned outpatients. During detoxification we will compare baclofen 10 mg three times a day with placebo as an adjunct to the usual benzodiazepine regimen. In the planned outpatient arm, we will also compare a 2-day preload of baclofen 10 mg three times a day with placebo. Ratings of GHB/GBL withdrawal, sleep, depression, anxiety as well as GHB/GBL use will be collected. The main data analyses will be descriptive about recruitment and characterising the impact of adding baclofen to the usual benzodiazepine regimen on measures and outcomes of GHB/GBL withdrawal to provide estimates of variability and effect size. A qualitative approach will evaluate research participant and clinician acceptability and data collected to inform cost-effectiveness. Discussion: This feasibility study will inform a randomised controlled trial to establish whether adding baclofen to a benzodiazepine regimen reduces the severity and complications of GHB/GBL withdrawal. [ABSTRACT FROM AUTHOR]

Misuse of gamma hydroxybutrate (GHB) and gamma butyrolactone (GBL) has increased greatly since the early 1990s, being implicated in a rising number of deaths. This paper reviews knowledge on GHB and derivatives, and explores the largest series of deaths associated with their non-medical use. Descriptive analyses of cases associated with GHB/GBL and 1,4-butanediol (1,4-BD) use extracted from the UK's National Programme on Substance Abuse Deaths database. From 1995 to September 2013, 159 GHB/GBL-associated fatalities were reported. Typical victims: White (92%); young (mean age 32 years); male (82%); with a drug misuse history (70%). Most deaths (79%) were accidental or related to drug use, the remainder (potential) suicides. GHB/GBL alone was implicated in 37%; alcohol 14%; other drugs 28%; other drugs and alcohol 15%. Its endogenous nature and rapid elimination limit toxicological detection. Post-mortem blood levels: mean 482 (range 0–6500; SD 758) mg/L. Results suggest significant caution is needed when ingesting GHB/GBL, particularly with alcohol, benzodiazepines, opiates, stimulants, and ketamine. More awareness is needed about risks associated with consumption. [ABSTRACT FROM AUTHOR]

Summary: Typical and atypical seizures of absence epilepsy are thought to be generated by a rhythmogenic interplay between the cortex and the thalamus. However, the question remains as to which other subcortical and extrathalamic structures are involved in the pathophysiology of typical and atypical absence epilepsy. Limbic structures are not thought to be involved in typical absence seizures, since in animal models and human patients there is no evidence for the occurrence of spike-and-wave discharges of absence seizures in the limbic regions. However, there are a number of observations from animal models of absence epilepsy that point to a possibly important link between absence seizure mechanisms and limbic structures. Atypical absence seizures are distinct in many ways from typical absence seizures although they bear considerable clinical, EEG, and pharmacological resemblance to typical absence seizures. The differences between typical and atypical seizures of absence epilepsy appear to be circuitry dependent. While both typical and atypical absence seizures involve the cortico-thalamo-cortical circuitry, they each engage different neuronal networks within that circuitry. This review examines the involvement of limbic structures in typical and atypical absence seizures, shows that limbic circuitry forms an integral component of the absence epilepsy network and concludes that further knowledge of this component is important for understanding the complex relationships involved in absence epilepsy. [Copyright &y& Elsevier]

Abstract: Gamma-hydroxybutyrate (GHB), and its precursors 1,4-butanediol (1,4-BD) and gamma-butyrolactone (GBL) are known drugs of abuse. The ability of acute and chronic administration of equimolar doses of GHB (200mg/kg), 1,4-BD (174mg/kg) and GBL (166mg/kg) to produce catalepsy in male Swiss Webster mice was examined. GHB, 1,4-BD, GBL produced catalepsy when injected acutely. Drug treatment was then continued for 14days. Tolerance development was determined on days 6, 14, and challenged with a higher dose on day 15 in those chronically pretreated mice, and compared with naïve mice. Chronic GHB produced tolerance to catalepsy, as evidenced from area under the curve (AUC) of catalepsy versus time (min–sec) on days 6 (678±254), 14 (272±247), which were less than those on day 1 (1923±269). However, less tolerance was seen from GBL or 1,4-BD, as AUCs on days 6 and 14 were not significantly lower than that of day 1. In conclusion, although equimolar doses were used, expecting similar levels of GHB in the body, 1,4-BD and GBL shared only some of the in vivo effects of GHB. The rate of metabolic conversion of 1,4-BD and GBL into GHB might be responsible for the differences in the tolerance development to these drugs. [Copyright &y& Elsevier]

This article focuses on "G" in the United Kingdom (UK), G being the collective term for gamma-hydroxybutyrate (GHB) and gamma-butyrolactone (GBL). Drawing on empirical data and taking a critical drug studies perspective, we use G as a case study in how drug cultures move through phases whereby a diffuse and contested network of emergent practices, agencies, and processes become progressively ordered into a more stable and conventional set of problems and actors, here G and the "G problem." The production of former "legal high" G as a particular kind of drug in this network has shaped its relative neglect within UK research, policy, and practice as compared to mephedrone, another former legal high. Our case study supports the longstanding observation that researchers, policy makers and practitioners contribute to the performative and material constitution of "drugs" and "drug problems," upon which we reflect in our conclusion. [ABSTRACT FROM AUTHOR]

Abstract: The Dutch Minister of Health requested the Coordination point Assessment and Monitoring new drugs (CAM) to re-assess the overall risk of GHB. The present paper is a extended redraft of a state of art report used in the risk evaluation procedure. The prevalence of GHB use is low, but the relative proportion of GHB intoxications compared to other illicit drugs is high resulting in a substantial number of GHB related incidents. In recent years the number of GHB intoxications has increased because many inexperienced users seemed unaware of the potential adverse effects, like ‘passing out’ upon overdosing, a condition where the user is unconsciousness (or comatose) for several hours. The dependence potential of frequent GHB use is now judged by the CAM to be rather high, but users appear not well informed about this risk. In the Netherlands, last month prevalence of GHB use is relatively low (0.2%) and treatment demand is limited (524 of a total of 76,295 referrals to the addiction treatment services in 2010). So far, no public nuisance or criminality associated with GHB use has been reported. The CAM estimated the overall risk potential of GHB use as moderate to high. The Dutch Minister of Health endorsed this conclusion and decided to upgrade GHB to Schedule I (hard drugs) of the Dutch Opium Act. [Copyright &y& Elsevier]

Introduction: Since 1999, gamma-hydroxybutyric acid (GHB) is a prescription drug only for hospital use for intra-venous injection. It is classified as a narcotic if used orally. Scheduling GHB led the users to use mainly one of its chemical precursors, the gamma-butyrolactone (GBL) which is not classified. The use of GHB/GBL in a purpose of drug facilitated sexual assault remains rare. The main diverted usage is for entertaining purpose, but as the therapeutic range is narrow, thus its consumption may be life-threatening, particularly if alcohol is taken concurrently. Cases and methods: The toxicological investigations of the presented cases were performed on preserved peripheral blood, and when available, urine by GC-MS. When hair was available; analysis were performed by GC-MS/MS. In three cases analyses were undertaken on seized products. In seven cases of mono-intoxication by GHB/GBL, the blood concentrations ranged from 285 to 815 mg/L for fatal cases (n=4), and from 74 to 158 mg/L for non-fatal cases (n=3). In four non-fatal cases of GHB/GBL intoxication together with alcohol, MDMA, cannabis and/or methadone taken concurrently, the blood concentrations of GHB ranged from 86 to 184 mg/L. In two cases, hair analysis showed a GHB peak on the segment corresponding to the events at respectively 9.8 ng/mg and 9.6 ng/mg, typical of a single intake, in correlation with the presence of exogenous GHB in the blood and the urine at the time of the event. In one case GHB concentration was 62 ng/g in pubic hair and 105 ng/mg in nails, corresponding to a chronic use of GHB/GBL. Conclusion: GHB/GBL use can be lethal. An erratic consumption may be detected by segmental analysis of hair, but should be evidence among other proofs (urine concentration, seized products). A chronic consumption is easily detected in hair and nails. The use of GBL has been proved by the concurrent analysis of seized products. [ABSTRACT FROM AUTHOR]

Abstract: The demand of high throughput methods for the determination of gamma-hydroxybutyrate (GHB) and its precursors gamma-butyrolactone (GBL) and 1,4-butane-diol (1,4BD) as well as for pregabalin is increasing. Here we present two analytical methods using ultra-high pressure liquid chromatography (UPLC) and tandem mass spectrometric (MS/MS) detection for the determination of GHB, beta-hydroxybutyrate (BHB), pregabalin, 1,4BD and GBL in whole blood and urine. Using the 96-well formate, the whole blood method is a simple high-throughput method suitable for screening of large sample amounts. With an easy sample preparation for urine including only dilution and filtration of the sample, the method is suitable for fast screening of urine samples. Both methods showed acceptable linearity, acceptable limits of detection, and limits of quantification. The within-day and between-day precisions of all analytes were lower than 10% RSD. The analytes were extracted from matrices with recoveries near 100%, and no major matrix effects were observed. Both methods have been used as routine screening analyses of whole blood and urine samples since January 2010. [Copyright &y& Elsevier]

The analysis of gamma-hydroxybutyric acid (GHB) is problematic because it is hygroscopic, it lacks a good UV chromophore, and it undergoes heat-induced cyclization. This paper presents a new method utilizing ion-exchange chromatography (IC) with conductivity detection. The simple sample preparation, rapid analysis time, and inorganic anion detection capabilities are all advantages over the current methods. The detection of inorganic salts (formed during GHB synthesis) gives insight into the synthetic route utilized and can aid in drug seizure comparison. The developed method has a detection limit for GHB anions of 0.57 mg/L and chloride of 0.22 mg/L. A comparison of this technique with a current gas chromatography-mass spectrometry technique is presented, and a t-test found that the two methods' results are not statistically different at the 99.9% confidence level demonstrating the merits of this fast, simple, and informative IC method as a routine screening tool. [ABSTRACT FROM AUTHOR]

To describe morbidity associated with gamma-butyrolactone (GBL) dependence, and outcomes of withdrawal. Case series. Specialist out-patient clinic and affiliated in-patient detoxification unit. Patients with home support were offered the option of out-patient withdrawal management, based on high-dose diazepam and baclofen, titrated against withdrawal severity in an initial session lasting approximately 4 hours. Patients were then reviewed daily during the first 3 days of treatment, offered weekly follow-up for 4 weeks, and telephoned 2-4 months later. People dependent on GBL seeking detoxification. Drug history and social functioning were obtained by self-report in clinical interviews with a single clinician. Treatment completion, outcomes and adverse events associated with withdrawal are reported. Patients reported impaired social functioning associated with GBL dependence and difficulty in accessing treatment. Nineteen patients commenced detoxification; 17 initially declined admission and were treated as out-patients. Mean diazepam dose in the first 24 hours was 75 mg (range 40-110 mg). Sixteen patients completed withdrawal, although several had lapses to GBL use during treatment. One patient developed delirium and required transfer to the in-patient detoxification unit. Most patients had persisting insomnia, anxiety and depression for weeks after withdrawal. GBL withdrawal can be managed in ambulatory settings, but needs to be backed up with seamless access to in-patient treatment if required. [ABSTRACT FROM AUTHOR]

γ-Hydroxybutyric acid (GHB) and its metabolic precursors, γ-butyrolactone (GBL) and 1,4-butanediol (1,4-BD), may be among the most favored drugs used to commit drug-facilitated sexual assault (DFSA). In fact, federal legislation was enacted in the form of the Hillory J. Farias and Samantha Reid Date-Rape Drug Prohibition Act of 2000 to control and penalize use and distribution of GHB, GBL, and 1,4 BD. Unfortunately, solid proof of their use in many cases is difficult to obtain because GHB, GBL, and 1,4-BD have strong sedative and memory-impairing effects and are rapidly eliminated after ingestion. To further complicate the matter, GHB is a metabolite of γ-aminobutyric acid (GABA), a naturally occurring neurotransmitter in humans. This review focuses on the chemistry and pharmacology of these drugs and their use in DFSA. An overview of analytical techniques used to identify their presence is provided, as well as guidance on the toxicological interpretation of findings of GHB in biological specimens. [ABSTRACT FROM AUTHOR]

Over the last few years there has been a dramatic increase in the amount of "Fantasy" type drugs seized in New Zealand, with gamma-butyrolactone (GBL) being by far the most prevalent. In 2018, N-methyl-2-pyrrolidone (NMP) was detected in a liquid, along with GBL, for the first time in New Zealand. Since this seizure, the number of seizures containing mixtures of GBL and NMP that have been submitted for analysis by New Zealand authorities have significantly increased, with 82% of submitted samples containing GBL also containing NMP. Analysis of these liquids showed that the majority had GBL and NMP purities of approximately 60-70% and 30-40%, respectively. Subsequent investigations by New Zealand authorities revealed a potential source of these liquids being a diverted legitimate industrial product. The health and psychoactive effects of NMP, along with GBL and NMP mixtures, are unknown. Health statistics in New Zealand have indicated increased harm from GBL use over the last few years. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of the present study was to provide further information about the effects of γ-hydroxybutyrate (GHB) on memory. Initially, the acute effects of gamma-butyrolactone (GBL, 75-200 mg/kg IP), 1,4-butanediol (1,4-BD, 100–300 mg/kg IP), and ethanol (1.0–3.0 g/kg, oral), as well as GHB (100–300 mg/kg IP), were examined in rats responding under a delayed-matching-to-position (DMTP) procedure with delays from 0 to 32 s. Acute administration of all four drugs reduced the number of trials completed and also reduced accuracy during delay trials, but not during trials without a delay. Some tolerance developed to the disruptive effects of GHB following exposure to 300 mg/kg/day for 29 consecutive days. These data indicate that GHB can disrupt working memory and speed of responding, and that tolerance can develop to these effects. Moreover, the acute effects of GHB under the DMTP procedure resemble those of its metabolic precursors, GBL and 1,4-BD, and of the prototypical CNS depressant drug, ethanol. [Copyright &y& Elsevier]

Gamma-hydroxybutyrate (GHB) is used to treat narcolepsy but is also abused. GHB has many actions in common with the GABAB receptor agonist baclofen. To further study the role of GABAB receptors in the effects of GHB. The experiments examined the ability of the GABAB receptor antagonist CGP35348 to attenuate GHB-induced catalepsy in comparison with its ability to attenuate the cataleptic effects of GABAB receptor agonists. In C57BL/6J mice, GHB, the GHB precursor gamma-butyrolactone (GBL), and the GABAB receptor agonists baclofen and SKF97541 all produced catalepsy but differed in potency (i.e., SKF97541>baclofen>GBL>GHB) and in onset of action. The cataleptic effects of drug combinations were assessed at the time of peak effect of each compound, i.e., 60 min after CGP35348 and 60, 30, 30, and 15 min after baclofen, SKF97541, GHB, and GBL, respectively. At 100 mg/kg, CGP35348 shifted the dose–response curves of baclofen and SKF97541 to the right but not those of GHB and GBL; at 320 mg/kg, CGP35348 shifted the curves of all four compounds to the right. The finding that CGP35348 was about threefold less potent to antagonize GHB and GBL than baclofen and SKF97541 is further evidence that the mechanisms mediating the effects of GHB and GABAB agonists are not identical. Differential involvement of GABAB receptor subtypes, or differential interactions with GABAB receptors, may possibly explain why GHB is effective for treating narcolepsy and is abused whereas baclofen is not. [ABSTRACT FROM AUTHOR]

In forensic evidence, γ-hydroxybutyric acid (GHB) has frequently been encountered in one of its salt forms (γ-hydroxybutyrate), but has also been encountered in its free acid form (GHB). Owing to the physical properties, encounters of the free acid have been largely restricted to forensic exhibits comprising aqueous solutions, such as acidic beverages that have been “spiked” or formulated with GHB salts or γ-butyrolactone (GBL). The analysis of GHB free acid presents particular difficulties including the potential for altering the original proportions of GHB free acid, GHB carboxylate, and GBL in the course of analysis, and discrimination between GHB free acid and carboxylate forms. In this work, the formation of GHB free acid in aqueous solutions (water and/or D2O) was studied as a function of solution pH. Proton nuclear magnetic resonance (1HNMR) and Fourier-transform infrared spectrometry (FT-IR) measurements were obtained on freshly prepared mixtures of NaGHB and HCl stock solutions representing a series of points along the GHB titration curve. Both 1HNMR and FT-IR were shown to track the changing proportions of GHB free acid and carboxylate forms as a function of pH, while simultaneously monitoring for the formation of the lactone (GBL). The results were consistent with acid–base conversion behavior for a carboxylic acid. 1HNMR was shown to provide an ideal means for analysis of aqueous-based GHB/GBL forensic exhibits based on simple dilution of the neat liquid exhibit, without altering the original proportions of GHB free acid, carboxylate, and GBL in the samples. [ABSTRACT FROM AUTHOR]

A reference standard for γ-hydroxybutyric acid (GHB) free acid is not commercially available, making its analysis in forensic exhibits more difficult. GHB free acid is typically encountered in aqueous solution and in the presence of the lactone, γ-butyrolactone (GBL), presenting difficulty in Fourier transform infrared (FT-IR) analysis. The strong infrared (IR) absorptivity of the GBL carbonyl band, the shifting of the GBL carbonyl band in aqueous solutions, and the position of the O–H bend for water can mask the main carbonyl band for GHB free acid. Model solutions of β-hydroxybutyric acid (BHB) and GBL were studied in order to further understand the masking of the GHB free acid carbonyl band in FT-IR analysis. The use of second derivative FT-IR spectroscopy was shown to provide resolution of the free acid carbonyl band, and a presumptive test for GHB free acid was developed and applied. An extension of this work included preparing, for use as a standard reference material, small amounts (≤10 mg) of GHB free acid. Preparation was based on the instantaneous reaction of GHB's sodium salt with a stoichiometric amount of hydrochloric acid in aqueous solution, and subsequent isolation of the free acid in neat liquid form. Both FT-IR and proton nuclear magnetic resonance spectra of the neat reference material were obtained and used to verify its identity. The isolation of GHB free acid from actual forensic exhibits is also presented, with identity confirmation using FT-IR. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To describe the clinical features of gamma-hydroxybutyrate (GHB) and gamma-butyrolactone (GBL) toxicity. Methods: Retrospective case-study of 65 GHB and GBL intoxications seen in an urban emergency department. Results: 63% of intoxications occurred in male patients. The median age was 24 years (range 16–41 years). 65% co-ingested alcohol or illicit drugs, mostly MDMA and cocaine. 83% presented with coma. The mean±S.D. time to regain consciousness among comatose patients was 111±61min and was significantly longer in patients who co-abused illicit drugs such as cocaine or MDMA (155±60min). Bradycardia occurred in 38%, hypotension in 6% and hypothermia in 48%. Agitation was observed in 17% of all patients and was significantly more frequent in patients with alcohol co-use (29%). Vomiting occurred in 31% of all patients and tended to be more frequent in patients who co-used alcohol (39%). Management of GHB and GBL overdose was supportive. Four patients needed admission to an intensive care unit for mechanical ventilation (6%). Conclusions: Overdosing of GHB and GBL frequently results in non-reactive coma reflecting the severity of poisoning. Multiple drug use is common and significantly influences the clinical presentation. [Copyright &y& Elsevier]

Rationale: Gamma-hydroxybutyrate (GHB) is becoming an increasingly popular drug of abuse. Metabolic precursors of GHB, gamma-butyrolactone (GBL) and 1,4-butanediol (BDL), are commercially available industrial solvents that may also present potential health risks. Relatively little is known about the neurobehavioral effects of GHB and its precursors. Objective: The aim of the present investigation was to characterize the discriminative stimulus effects of GHB and its precursor, GBL. Methods: Male Sprague--Dawley rats were trained to discriminate GHB [300 mg/kg, IG; n=16] or GBL (150 mg/kg, i.p.; n=8) from vehicle under a fixed ratio 20 (FR 20) schedule of food reinforcement. Stimulus generalization tests were then conducted with several compounds. Results: GHB and GBL produced cross-generalization and BDL was fully substituted for both GHB and GBL. Two benzodiazepines, alprazolam and diazepam, and the 5-HT1A agonist, buspirone, did not substitute for either training drug nor did ethanol or the NMDA antagonists, PCP and ketamine. The GHB antagonist, NCS-382, and the GABAB antagonist, CGP-35348, blocked the discriminative stimulus effects of GHB but not those of GBL. Conclusions: These findings suggest that GHB and its metabolic precursors produce similar subjective effects that differ from those of other sedative-hypnotic drugs. Further investigations into the neurochemical actions underlying the subjective effects of these drugs are warranted. [ABSTRACT FROM AUTHOR]

Studies the stability of gamma-butyrolactone (GBL) and gamma-hydroxybutyric (GHB) acid in alcoholic media. Suggestion that ester formation is dependent on the type of alcohol, the alcohol content of the solution and the pH of the solution; Effect of adding GHB/GBL to hot beverages such as tea or coffee; Absence of ethyl ester of GHB in wine samples which contain GBL as a natural component in very low concentrations.

Gamma-hydroxybutyrate (GHB) is a compound used in the treatment of alcohol withdrawal, narcolepsy, and for induction of anaesthesia. It is also contained in many products illegally marketed as “dietary supplements” and is increasingly being recognised as a potential drug of abuse. We report the case of a 44-year-old man who suffered coma and life-threatening respiratory depression following an accidental overdose of the GHB prodrug, gamma-butyrolactone (GBL), contained in a “health drink”. He made a full recovery following appropriate supportive treatment. GHB toxicity should be included in the differential diagnosis of patients with altered mental state, particularly where there is a history of recreational drug abuse. [ABSTRACT FROM AUTHOR]

The adoption of games in the classroom has been studied from different angles, such as the readiness of teachers to use games or the barriers encountered. However, actual classroom practices with regard to the use of games have not been examined on a larger scale. With this research, we gave teachers a voice to report on their actual practices. We examined the current practices of a large sample of Estonian teachers (N = 1258, which constitutes almost 9% of the total Estonian teacher population) in primary and secondary education in 2017. We found that most of the teachers use games on a regular basis. Mainly, they use the games for motivation and alternation, but they also use them to consolidate and teach new skills. While awareness and motivation are high and experimentation on using games is widespread, practices appear fragmentary and not widely sustained. As a result of this study, we suggest the creation of an evidence base and a better integration of social support structures into teacher education. This is the first large-scale study to look into Estonian teacher's actual practices, and although Estonian teachers have relatively high autonomy and technical skills, we believe that these results and further investigations are applicable in other contexts as well. [ABSTRACT FROM AUTHOR]

In this article the author discusses the paper by J. Bell and R. Collins regarding the administration of detoxification with gamma-butyrolactone (GBL) and gamma-hydroxy butyric acid (GHB) in an out-patient setting. It states that there is limited proof on treatment models for withdrawal delirium and acute intoxication in younger patients. It notes that management of GBL/GHB detoxification in such setting needs a high level of patient compliance.