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Objective: We aimed to investigate substance use and its association with eating attitudes and behaviors among male Palestinian refugees. Methods: In a cross-sectional study, male Palestinian refugees(N = 566) were recruited to fill out self-administrated questionnaire on eating attitudes and behaviors (EAT-26) and to give urine samples to test current illicit drug use. Results: The response rate was 47.7%. Substance use was highly prevalent among participants (28.9%). The percentage of participants with eating disorders (ED) among substance users was as follows: Any illicit drug (30.8%), benzodiazepine (32.6%), methamphetamines(40.7%), amphetamine (39.3%), tetrahydrocannabinol (25.8%), barbiturates (20%),and alcohol (12.50%). Obese participants were at higher risk of having ED(OR = 2.344, p <.05) than underweight participants. Binge eaters were more likely to be tetrahydrocannabinol users (OR = 2.745, p <.05). Increased riskof self-induced vomiting behavior was associated with binge behavior (OR = 5.97, p <.05, laxative use (OR = 26.38, p <.01), barbiturates use (OR = 59.36, p <.05), waterpipe smoking (OR = 8.62, p <.05), vape smoking (OR = 10.37, p <.05), and inversely associated with age (OR = 0.832, p <.001). Conclusion: Findings from this study demonstrated a substantially increased frequency of substance use among Palestinian refugees with ED and unhealthy weight control behaviors. This study highlighted new challenge for the health system to deal with new emerging health conditions among male refugees. [ABSTRACT FROM AUTHOR]

Cyanine derivatives are organic dyes widely used for optical imaging. However, their potential in longitudinal optoacoustic imaging and photothermal therapy remains limited due to challenges such as poor chemical stability, poor photostability, and low photothermal conversion. In this study, we present a new structural modification for cyanine dyes by introducing a strongly electron-withdrawing group (barbiturate), resulting in a new series of barbiturate-cyanine dyes (BC810, BC885, and BC1010) with suppressed fluorescence and enhanced stability. Furthermore, the introduction of BC1010 into block copolymers (PEG 114 -b-PCL 60) induces aggregation-caused quenching, further boosting the photothermal performance. The photophysical properties of nanoparticles (BC1010-NPs) include their remarkably broad absorption range from 900 to 1200 nm for optoacoustic imaging, allowing imaging applications in NIR-I and NIR-II windows. The combined effect of these strategies, including improved photostability, enhanced nonradiative relaxation, and aggregation-caused quenching, enables the detection of optoacoustic signals with high sensitivity and effective photothermal treatment of in vivo tumor models when BC1010-NPs are administered before irradiation with a 1064 nm laser. This research introduces a barbiturate-functionalized cyanine derivative with optimal properties for efficient optoacoustics-guided theranostic applications. This new compound holds significant potential for biomedical use, facilitating advancements in optoacoustic-guided diagnostic and therapeutic approaches. Barbiturate functionalized cyanine (BC1010) was developed and nanoformulated for efficient NIR-II OptA imaging of deep tumors and photothermal therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

A highly stereoselective synthesis of fused heterocycles with multiple stereocenters via an internal redox reaction/inverse electron-demand hetero-Diels–Alder (IEDHDA) reaction sequence is described. The present reaction sequence has three interesting features: (1) complete control of two potentially competitive processes, i.e., hetero-Diels–Alder reaction and [1,5]-hydride shift; (2) one-shot construction of the complicated 6/7/6-fused heterocyclic structure having multiple stereocenters; and (3) high control of its stereoselectivity. When alkenylidene barbiturates with an allyl benzyl ether moiety were treated with a catalytic amount of Sc(OTf)3 and 2,2′-bipyridine, the internal redox reaction/IEDHDA reaction proceeded successively to afford 6/7/6-fused heterocycles in good chemical yields with good to excellent diastereoselectivities. [ABSTRACT FROM AUTHOR]

This case report presents the clinical scenario of a 22 years old female patient with decade long history of seizure disorder and is on chronic anti-seizure management therapy. The patient's initial symptoms manifested as lesions over the oral cavity, over the period of time the lesions progressed to scalp, chest and buttocks. Pemphigus is a rare heterogeneous group of autoimmune disease that affects the skin and the mucous membrane. A combination of inappropriate activation of host B lymphocytes producing intracellular ImmunoglobulinG antibodies and biochemical interactions results in the drug-induced pemphigus. Acantholypsia is the term for the process by which these auto antibodies target the desmogleins and split the cells in the epidermis. This case emphasizes the requisite for further research on understanding the effect of anti-seizure therapy. [ABSTRACT FROM AUTHOR]

Barbiturates are a class of sedative and hypnotic drugs. These are commonly used as antiepileptics and anesthetic agents now. Current usage of sedatives in India is about 1.08%, and the abuse is about 0.11%. Barbiturate overdose or poisonings can lead to severe central nervous system depression, potentially life-threatening respiratory depression, and may lead to respiratory arrest. Treatment in the majority of cases of barbiturate poisoning is artificial ventilation and other supportive therapies. Extracorporeal treatments (ECTRs) are required in only 0.1% of cases of poisoning. There is a lack of prospective intervention studies for obvious ethical reasons; however, the ECTR in poisoning (EXTRIP) workgroup recommends the use of ECTRs in severe barbiturate overdose/poisoning. [ABSTRACT FROM AUTHOR]

This article discusses a study on the chemoselective reduction of barbiturates using photochemically excited flavin catalysts. The researchers explored the use of samarium(II) iodide and reduced flavins as reductants for barbiturates with multiple carbonyl groups. They found that flavin-mediated reduction led to the formation of alicyclic hemiaminals, providing a new method for reductive cyclizations. The study also compared flavin catalysis to the well-established SmI2 reductant and found that flavin catalysis proceeds differently, making it useful for various transformations that require reductive activation of carbonyl functional groups. [Extracted from the article]

In the present study, the aimed enamines 3 a–j were synthesized with yield ranging between 65 and 81 % by the reaction of 5‐((dimethylamino)methylene)‐1,3‐dimethylpyrimidine‐2,4,6(1H,3H,5H) ‐trione (2) with different amines at room temperature (25 °C). The structures of all synthesized compounds were characterized using different spectroscopic techniques. Molecular docking studies of the new compounds 3 a–j were carried out with human estrogen receptor (hER) enzyme to evaluate their activities as an effective drug molecules. It was investigated that the compounds 3 b, 3 e, 3 f and 3 j revealed the best binding affinities. All new compounds were evaluated towards antifungal activities, which conceded that the compound 3 e displayed a remarkable antifungal activity compared to the Fluconazole and Nystatin, and its Minimum Inhibitory Concentration (MIC) found to be 0.011 mM, while for Fluconazole the MIC value exhibited at 0.046 mM. Additionally, the toxicity for the new compounds found to be better than tamoxifen on MCF‐7 cells and among these molecules, the compound 3 e displayed the lowest IC50 value. [ABSTRACT FROM AUTHOR]

A novel and interesting controllable spirocyclization of unsaturated barbiturates with enamino esters for the assembly of cyclopentenyl and pyrrolinyl spirobarbiturates has been developed under ball-milling conditions. The present protocol features high chemoselectivity and efficiency, excellent functional group tolerance and mild reaction conditions. [ABSTRACT FROM AUTHOR]

Adolescence is a critical developmental stage for the initiation of substance use worldwide, which is one of the main risk-taking behaviors that may impact adolescents' physical and mental well-being. The aims of this study were to (1) assess the prevalence of the co-use of tranquilizers, sedatives, and sleeping pills with alcohol (TSSp&AC) by gender in the Spanish adolescent population in 2018 and (2) identify the variables associated with TSSp&AC. An observational cross-sectional study following STROBE guidelines was conducted. We analyzed data from 38,010 adolescents aged 14 to 18 years old (18,579 males and 19,431 females) who participated in ESTUDES (Survey on Drug Use in Secondary Education in Spain) 2018. Female adolescents reported a higher prevalence of TSSp&AC than males (p < 0.001). The factors associated with female co-use were being 16–18 years of age (OR 1.65); the consumption of tobacco (OR 1.73), cocaine (OR 1.84), other illicit psychoactive drugs (OR 1.89); and novel illicit psychoactive drugs (OR 1.74); no perceived health risk from the consumption of TSSps (OR 2.45); and the perceived availability of TSSps (OR 2.23) and alcohol (OR 2.09). There are several factors associated with TSSp&AC in Spanish female adolescents with potential implications for healthcare providers. [ABSTRACT FROM AUTHOR]

The barbiturate drug pentobarbital is commonly used by veterinarians for the euthanasia of domestic animals. During the veterinary forensic autopsy, it is sometimes necessary to determine whether the animal was chemically euthanized with pentobarbital. The use of a human immunochromatographic test for barbiturate screening utilizing dog or cat urine has been previously validated; however, the use of alternative matrices for this purpose is yet to be explored when urine is not available. Postmortem heart, liver, spleen, skeletal muscle, blood and/or urine samples from 20 dogs and 26 cats with a reported chemical euthanasia status were processed using two different methods, bead homogenization and sonication, and screened for barbiturates using a human immunochromatographic test. There was 100% agreement of the immunochromatographic test results using the sonication method with the reported euthanasia status of both dogs and cats. Using the bead homogenization method, agreement with the reported euthanasia status was 93.3% and 96.7% for dogs and cats, respectively, due to invalid test results from four dog and two cat samples. A subset of liver samples (10 canine and 10 feline) was analyzed via gas chromatography–mass spectrometry, and there was 100% agreement between the immunochromatographic test results and gas chromatography–mass spectrometry results for both cats and dogs. Overall, our results support the use of a variety of alternative matrices for barbiturate screening in cats and dogs. [ABSTRACT FROM AUTHOR]

Electroconvulsive Therapy (ECT) is an effective treatment for mood disorders, particularly treatment-resistant depression, and several psychiatric illnesses. Anesthetic management of patients undergoing ECT requires an understanding of ECT, the physiologic changes induced by electrical stimulus, the anesthetic agents used, and the potential complications associated with the procedure. Numerous medical and surgical conditions can impact procedural approach and anesthetic management. ECT is challenging due to its typically off-site location, fast-paced general anesthesia with bag-mask ventilation, selection of anesthetic agents that minimally affect the seizure, patient's comorbidities, and unique physiologic responses. This comprehensive review aims to update anesthetists on the periprocedural management of patients undergoing ECT. [ABSTRACT FROM AUTHOR]

This study developed a facile, highly sensitive technique for extracting and quantifying barbiturates in serum samples. This method combined ultrasound and surfactant‐assisted dispersive liquid–liquid microextraction with poly(ethylene oxide)‐mediated stacking in capillary electrophoresis. Factors influencing the extraction and stacking performance, such as the type and volume of extraction solvents, the type and concentration of surfactant, extraction time, salt additives, sample matrix, solution pH, and composition of the background electrolyte, were carefully studied and optimized to achieve the optimal detection sensitivity. Under the optimized extraction (injecting 140 μL C2H4Cl2 into 1 mL of sample with pH 4 (5 mM sodium phosphate containing 0.05 mM Tween 20 and sonication for 1 min) and separation conditions (150 mM tris(hydroxymethyl)aminomethane‐borate with pH 8.5 containing 0.5% (m/v) poly(ethylene oxide)), the limits of detection (signal‐to‐noise ratio = 3) of five barbiturates ranged from 0.20 to 0.33 ng/mL, and the calculated sensitivity improvement ranged from 868‐ to 1700‐fold. The experimental results revealed excellent linearity (R2 > 0.99), with relative standard deviations of 2.1%–3.4% for the migration time and 4.3%–5.7% for the peak area. The recoveries of the spiked serum samples were 97.1% –110.3%. Our proposed approach offers a rapid and practical method for quantifying barbiturates in biological fluids. [ABSTRACT FROM AUTHOR]

Alcohol use disorders (AUDs) are prevalent in intensive care units (ICUs). Alcohol abuse and/or dependence, leading to alcohol withdrawal syndrome (AWS), is as high as 10% or more. There seem to be wide variations in management strategies used to manage these patients, prompting an evaluation of the knowledge gap as well as finding the barriers. Noting lack of such literature in the Indian setting, a survey is undertaken to evaluate practice patterns surrounding the identification and management of alcohol dependence/abuse and AWS in the Indian critical care scenario. The main respondents of the survey are independent practitioners with anesthesia as their base specialty and overwhelmingly practice in multidisciplinary ICUs. They estimated AUD prevalence to be under 10%. The reason most expressed for lack of AUD documentation is fear of insurance rejection. Very few used risk assessment tool in evaluation of AUDs and AWS. Awareness of ICD 10/DSM-V components of AWS diagnosis was negligible. Chlordiazepoxide and lorazepam were used either in a fixed- or symptom-based therapy. Compared to available literature, haloperidol use is excessive, while barbiturates rarely. The wide variation is seen with the dose and frequency of thiamine in AWS without neurological complications. The impact on mortality and morbidity is poorly understood. In conclusion, the survey reported a lower prevalence compared to international literature. Insurance rejection is one of the main factors in limiting adequate history taking or documenting AUDs. Alcohol withdrawal syndrome risk assessment, monitoring, and management is variable and suboptimal. Variability in all aspects of AUDs is attributable to the knowledge gap. Further studies are needed to bridge the research gap. [ABSTRACT FROM AUTHOR]

Pyrimidine annulated five‐membered heterocyclic scaffolds containing oxygen as furopyrimidine, particularly furo[2,3‐d]pyrimidine derivatives are an important class of heterocyclic compounds in pharmaceutical discovery research. Furo[2,3‐d]pyrimidines are generally synthesized either from a pyrimidine derivative by constructing a furan ring on the parent pyrimidine ring or from a suitably functionalized furan ring by generating the pyrimidine ring on the parent furan ring. Moreover, there is a wide range of multicomponent reactions that include barbituric acids as starting material for the synthesis of these compounds. Also, the reaction of barbituric acids with alkenes, alkynes, aldehydes, ketones, ninhydrin, and chloroacetylchloride, and Cloke–Wilson rearrangement of spirocyclopropyl barbiturates afforded furo[2,3‐d]pyrimidine derivatives. This review is an attempt to compile the literature of various synthetic procedures toward barbituric acids‐based furo[2,3‐d]pyrimidine and spirofuro[2,3‐d]pyrimidines. [ABSTRACT FROM AUTHOR]

BackgroundAntimicrobial resistance (AMR) in Neisseria gonorrhoeae is an urgent global health threat. Zoliflodacin is a novel antibiotic undergoing clinical trials for the treatment of gonorrhoea. While there are limited data regarding zoliflodacin resistance in N. gonorrhoeae, three amino acid mutations have been associated with increased MICs of zoliflodacin.ObjectivesTo determine the prevalence of three amino acid mutations associated with zoliflodacin resistance within a large, public database of nearly 13 000 N. gonorrhoeae genomes.MethodsPathogenWatch is an online genomic epidemiology platform with a public database of N. gonorrhoeae genomes. That database was used to extract gyrB sequence data and a Basic Local Alignment Search Tool (BLAST) search was performed to identify any of the three amino acid mutations in GyrB that are associated with increased zoliflodacin MICs: D429N, K450N or K450T. As a control for the search methodology, all GyrA sequences were also extracted and S91F mutations were identified and compared with the PathogenWatch database.ResultsIn total, 12 493 N. gonorrhoeae genomes from the PathogenWatch database were included. Among those genomes, none was identified that harboured any of the three mutations associated with increased zoliflodacin MICs. One genome was identified to have a mutation at position 429 in GyrB (D429V).ConclusionsThe findings suggest that the prevalence of the three mutations associated with zoliflodacin resistance in N. gonorrhoeae is very low. However, further research into the mechanisms of zoliflodacin resistance in N. gonorrhoeae is needed. Genomic epidemiology platforms like PathogenWatch can be used to enhance the global surveillance of AMR.

Resumen: Introducción: El aumento de la presión intracraneal se ha asociado a un pronóstico neurológico desfavorable y a un incremento en la mortalidad en pacientes con traumatismo craneoencefálico grave. Tradicionalmente, las terapias para disminuir la presión intracraneal se administran utilizando un enfoque progresivo, reservando el uso de opciones más agresivas para los casos sin respuesta a intervenciones de primer nivel, o de hipertensión intracraneal refractaria. Desarrollo: El valor terapéutico de las intervenciones de rescate para la hipertensión intracraneal, así como el momento adecuado para su uso ha sido debatido constantemente en la literatura. En esta revisión, discutiremos las principales opciones de tratamiento para la hipertensión intracraneal refractaria posterior a un traumatismo craneoencefálico grave en adultos. Tenemos la intención de llevar a cabo una revisión en profundidad de los ensayos controlados aleatorios más representativos sobre las diferentes intervenciones terapéuticas de rescate, incluyendo la craniectomía descompresiva, hipotermia terapéutica y barbitúricos. Además, discutiremos las perspectivas futuras de estas opciones de tratamiento. Conclusiones: La evidencia parece mostrar que se puede reducir la mortalidad al utilizar estas intervenciones de rescate como terapia de último nivel, sin embargo, este beneficio viene acompañado de una discapacidad severa. La decisión de realizar o no estas intervenciones debe ser individualizada y centrada en el paciente. El desarrollo e integración de diferentes variables fisiológicas a través de monitorización multimodal es de suma importancia para poder proporcionar información pronóstica más sólida a los pacientes que enfrentan este tipo de decisiones. Abstract: Introduction: Increased intracranial pressure has been associated with poor neurological outcomes and increased mortality in patients with severe traumatic brain injury. Traditionally, intracranial pressure-lowering therapies are administered using an escalating approach, with more aggressive options reserved for patients showing no response to first-tier interventions, or with refractory intracranial hypertension. Development: The therapeutic value and the appropriate timing for the use of rescue treatments for intracranial hypertension have been a subject of constant debate in literature. In this review, we discuss the main management options for refractory intracranial hypertension after severe traumatic brain injury in adults. We intend to conduct an in-depth revision of the most representative randomised controlled trials on the different rescue treatments, including decompressive craniectomy, therapeutic hypothermia, and barbiturates. We also discuss future perspectives for these management options. Conclusions: The available evidence appears to show that mortality can be reduced when rescue interventions are used as last-tier therapy; however, this benefit comes at the cost of severe disability. The decision of whether to perform these interventions should always be patient-centred and made on an individual basis. The development and integration of different physiological variables through multimodality monitoring is of the utmost importance to provide more robust prognostic information to patients facing these challenging decisions.

Gamma-aminobutyric acid (GABA), a nonpeptide amino acid transmitter, is a major component of modern neuropharmacology and one of the most crucial target sites for general anesthetics and therapeutic drugs. GABA type A receptors (GABA A Rs) are the most abundant inhibitory neurotransmitter receptors in the central nervous system. They are part of the rapid-acting, ligand-gated ion channel (LGIC) receptor category, a pentameric Cys-loop superfamily member that mediates inhibitory neurotransmission in the mature brain. GABA A Rs mainly consist of two α subunits, two β subunits, and one additional subunit from either γ or δ arranged around a central chloride (Cl -) selective channel. Multiple GABA A R subunit subtypes and splice variants have been identified. Each variant of GABA A R exhibits distinct biophysical and pharmacologic properties. Several compounds allosterically modulate the GABA A R positively or negatively. The widely used positive GABA A R modulators include benzodiazepines (anxiolytic and anticonvulsant), general anesthetics (volatile agents like isoflurane, and intravenous agents like barbiturates, etomidate, and propofol), long-chain alcohols, some anticonvulsants, and neuroactive steroids. The binding sites for each drug are distinctly different. The anesthetic drugs enhance receptor-mediated synaptic transmission and thus interrupt the thalamocortical transmission, which controls the sleep–wake patterns. Abnormality in the GABA A R function has been implicated in several neurological conditions, such as sleep disorders, seizures, depression, cognitive function, neurological recovery after injury, and neuroplasticity. Understanding the GABA A R lays the foundation for the development of highly specific drugs in the treatment of neurological disorders and general anesthesia. [ABSTRACT FROM AUTHOR]

The covalent modification of the metallic phase of MoS2 with a Hamilton‐type ligand is presented, transforming MoS2 to a recognition platform which is able to embrace barbiturate moieties via hydrogen bonding. The successful hydrogen bonding formation is easily monitored by simple electrochemical assessments, if a ferrocene‐labeled barbiturate analogue is utilized as a proof of concept. Full spectroscopic, thermal, and electron microscopy imaging characterization is provided for the newly formed recognition system, along with valuable insights concerning the electrochemical sensing. The given methodology expands beyond the sensing applications, confidently entering the territory of supramolecular interactions on the surface of 2D transition metal dichalcogenides. The well‐designed host‐guest chemistry presented herein, constitutes a guide and an inspiration for hosting customized‐structured functional building blocks on MoS2 and its relatives via hydrogen bonding, opening up new opportunities regarding potential applications. [ABSTRACT FROM AUTHOR]

In critically ill patients requiring intensive care, increased oxidative stress plays an important role in pathogenesis. Sedatives are widely used for sedation in many of these patients. Some sedatives are known antioxidants. However, no studies have evaluated the direct scavenging activity of various sedative agents on different free radicals. This study aimed to determine whether common sedatives (propofol, thiopental, and dexmedetomidine (DEX)) have direct free radical scavenging activity against various free radicals using in vitro electron spin resonance. Superoxide, hydroxyl radical, singlet oxygen, and nitric oxide (NO) direct scavenging activities were measured. All sedatives scavenged different types of free radicals. DEX, a new sedative, also scavenged hydroxyl radicals. Thiopental scavenged all types of free radicals, including NO, whereas propofol did not scavenge superoxide radicals. In this retrospective analysis, we observed changes in oxidative antioxidant markers following the administration of thiopental in patients with severe head trauma. We identified the direct radical-scavenging activity of various sedatives used in clinical settings. Furthermore, we reported a representative case of traumatic brain injury wherein thiopental administration dramatically affected oxidative-stress-related biomarkers. This study suggests that, in the future, sedatives containing thiopental may be redeveloped as an antioxidant therapy through further clinical research. [ABSTRACT FROM AUTHOR]

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Throughout human history, numerous therapeutic substances have been used for their hypnotic and sedative effects, but many of these have limited efficacy. More recently, in the late 19th century, agents such as paraldehyde, chloral hydrate and bromines were used, until the sedative and hypnotic properties of barbiturates were discovered in the early 20th century. Barbiturates act on the central nervous system through nonspecific depression, manifesting at the level of the cerebral cortex, the limbic system, the hypothalamus and the thalamus. Even at low doses the ascending activating reticular system is depressed. Barbituric and thiobarbituric acid derivatives have become increasingly studied by medical researchers, because they possess a wide range of biological activities, such as the ability to act as enzyme inhibitors, being antibacterial, anticancer, immunomodulatory, antifungal and antioxidant agents. [ABSTRACT FROM AUTHOR]

Introduction: Drug-target interaction prediction is one important step in drug research and development. Experimental methods are time consuming and laborious. Methods: In this study, we developed a novel DTI prediction method called EnGDD by combining initial feature acquisition, dimensional reduction, and DTI classification based on Gradient boosting neural network, Deep neural network, and Deep Forest. Results: EnGDD was compared with seven stat-of-the-art DTI prediction methods (BLM-NII, NRLMF, WNNGIP, NEDTP, DTi2Vec, RoFDT, and MolTrans) on the nuclear receptor, GPCR, ion channel, and enzyme datasets under cross validations on drugs, targets, and drug-target pairs, respectively. EnGDD computed the best recall, accuracy, F1-score, AUC, and AUPR under the majority of conditions, demonstrating its powerful DTI identification performance. EnGDD predicted that D00182 and hsa2099, D07871 and hsa1813, DB00599 and hsa2562, D00002 and hsa10935 have a higher interaction probabilities among unknown drug-target pairs and may be potential DTIs on the four datasets, respectively. In particular, D00002 (Nadide) was identified to interact with hsa10935 (Mitochondrial peroxiredoxin3) whose up-regulation might be used to treat neurodegenerative diseases. Finally, EnGDD was used to find possible drug targets for Parkinson's disease and Alzheimer's disease after confirming its DTI identification performance. The results show that D01277, D04641, and D08969 may be applied to the treatment of Parkinson's disease through targeting hsa1813 (dopamine receptor D2) and D02173, D02558, and D03822 may be the clues of treatment for patients with Alzheimer's disease through targeting hsa5743 (prostaglandinendoperoxide synthase 2). The above prediction results need further biomedical validation. Discussion: We anticipate that our proposed EnGDD model can help discover potential therapeutic clues for various diseases including neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

A case of fatal poisoning involving multiple psychotropic drugs is presented. Quantitative toxicological analysis showed femoral blood concentrations of pentobarbital, phenobarbital, duloxetine, acetaminophen and tramadol were 10.39, 22.57, 0.22, 0.61 and 0.22 µg/ml, respectively. We concluded that the death was due to the additive effects of two barbiturates. As both pentobarbital and phenobarbital act on gamma-aminobutyric acid (GABA) receptors, central nervous system activity was suppressed, causing respiratory depression. Additive pharmacological effects should be considered in cases of massive ingestion of multiple drugs. [ABSTRACT FROM AUTHOR]

Two groups of facts have been established in previous drug development studies of the non-benzodiazepine anxiolytic fabomotizole. First, fabomotizole prevents stress-induced decrease in binding ability of the GABAA receptor's benzodiazepine site. Second, fabomotizole is a Sigma1R chaperone agonist, and exposure to Sigma1R antagonists blocks its anxiolytic effect. To prove our main hypothesis of Sigma1R involvement in GABAA receptor-dependent pharmacological effects, we performed a series of experiments on BALB/c and ICR mice using Sigma1R ligands to study anxiolytic effects of benzodiazepine tranquilizers diazepam (1 mg/kg i.p.) and phenazepam (0.1 mg/kg i.p.) in the elevated plus maze test, the anticonvulsant effects of diazepam (1 mg/kg i.p.) in the pentylenetetrazole-induced seizure model, and the hypnotic effects of pentobarbital (50 mg/kg i.p.). Sigma1R antagonists BD-1047 (1, 10, and 20 mg/kg i.p.), NE-100 (1 and 3 mg/kg i.p.), and Sigma1R agonist PRE-084 (1, 5, and 20 mg/kg i.p.) were used in the experiments. Sigma1R antagonists have been found to attenuate while Sigma1R agonists can enhance GABAARs-dependent pharmacological effects. [ABSTRACT FROM AUTHOR]

Herein, a straightforward synthesis approach for the formation of anisotropic microswimmers is proposed as an alternative to a top–down fabrication for asymmetric artificial swimmers. Melamine barbiturate (MBA)–self‐assembled supramolecular crystals are utilized as an asymmetric matrix for selective chemical platinum deposition. Surface functional groups of prevalent crystallographic planes for platinum sorption are presented by acidic sites of the assembly. The formed platinum catalytic layer is separated from the bulk MBA and investigated using X‐Ray photoelectron spectroscopy and scanning electron microscope energy‐dispersive X‐Ray spectroscopy analysis. Both methods confirm platinum adsorption and reduction of platinum ions during the deposition process. The MBA asymmetric swimmers show directional motion in a fuel environment, proved by the mean‐squared displacement study. Previously reported pH‐dependency and encapsulation capacity of MBA opens wide opportunities for functional materials formation. [ABSTRACT FROM AUTHOR]

The kinetics of tautomerization reactions of thiobarbituric acid were thoroughly investigated at the B3LYP/6‐311+G(3df,2p) level of theory and elevated temperatures from 260 to 1000 K. The kinetic parameters were determined by employing canonical variational transition state theory (CVT). The quantum tunneling effect was included by centrifugal‐dominant small‐curvature semiclassical adiabatic ground‐state approximation method. Intrinsic reaction coordinate (IRC) analysis was performed to certify a unique connection from an obtained transition state configuration to optimized structures of reactant and products. The reaction forces and reaction force constants were computed across the IRC of each reaction. Then, using extremums of reaction forces, each reaction was partitioned into three stages containing reactant, transition state, and product stages. The extent of reactions was followed along with three reaction stages. The dependence of kinetic parameters and curvature of Arrhenius plots on temperature were investigated and discussed in the framework of CVT. To further unveil the mechanism of the reactions, the quantum theory of atoms in molecules was employed. To do this aim, QTAIM descriptors on the bond critical point (BCP) of involved bonds including the density of electrons, Laplacian of the density of electrons, Lagrangian kinetic energy, potential energy, and energy density were computed and surveyed along with reaction extent through IRC. [ABSTRACT FROM AUTHOR]

Abstract Background Depression is a common disorder that affects patients' quality of life and incurs health system costs. Due to the resistance to treat depression, better understanding of neurophysiology was considered; one of the implications is the glutamatergic system. This study aims to systematically review clinical trials investigating the antidepressant effects of kainate receptor antagonists. Methods The study protocol was registered in PROSPERO (CRD42021213912). Scopus, ISI, Embase, PubMed, Cochrane Library, Google Scholar, and two trial registries were searched for randomized controlled trials on the effectiveness of topiramate, phenobarbital, and other ten barbiturates in depression. The difference with control groups in terms of changing depressive symptoms was the primary outcome. Results Nine trials were identified, in which 784 patients were studied. The efficacy of thiopental was comparable to that of imipramine, with fewer side effects. When administered with electroconvulsive therapy, it had fewer to similar effects and fewer side effects than ketamine. Both monotherapy and adjunctive therapy with topiramate were effective and tolerable in treating depressed patients. Phenobarbital had therapeutic effects compared to imipramine and amitriptyline with fewer side effects. Conclusion Regarding the glutamatergic hypothesis of depression and obtained promising results, further studies of kainate receptor antagonists in high‐quality trials are recommended. Given the high prevalence of depression in epileptic patients, more problems with its treatment, and the fact that the studied agents were anticonvulsants, it is recommended that future studies prioritize depressed‐epileptic patients.

The incidence of head and neck squamous cell carcinoma (HNSCC) is increasing and the conventional treatments for this form of cancer can be tough. Despite the success of existing immunotherapies in some HNSCC patients, many do not respond to this type of treatment. Thus, the development of novel anti-cancer therapies should be prioritized. In the current study, the anticancer activity of a panel of novel compounds, herein termed marine product mimics (MPMs), against HNSCC cell lines is explored. The previously reported compound MPM-1, which is structurally related to the novel MPMs, was shown to have promising effects on the HNSCC cell line HSC-3. The results from the current study indicate that the novel MPMs are more potent than MPM-1 but cause a similar type of cell death. The results indicated that the MPMs must cross through the cell membrane to exert their action and that they are lysosomotropic. Further experiments showed that some of the MPMs could induce phosphorylation of eukaryotic initiation factor 2α (eIF2α) in HSC-3 and UT-SCC-24A cells, which indicates that they can activate the integrated stress response that is strongly associated with immunogenic cell death. Cell surface expression of calreticulin and release of HMGB1 and ATP, which are all hallmarks of immunogenic cell death, was also demonstrated in HSC-3 and UT-SCC-24A cells treated with MPMs. This suggests that the MPMs are interesting candidates for future HNSCC cancer therapies. [ABSTRACT FROM AUTHOR]

A highly efficient, fast, catalyst‐free, and atom economical method was developed for the synthesis of 5‐benzylidenebarbiturates. Thus, reacting barbituric acid and aldehydes in water as a green solvent under electrochemical conditions afforded the synthesis of the target compounds in six minutes and in highly pure forms. The effects of solvent, reaction time, temperature, electrolyte, and electrode material were studied to optimize the reaction conditions. The scope of the reaction was broadened by the synthesis of 5‐(arylidene)barbiturate derivatives 3 a–3 q using different aldehydes. Calculation of the green chemistry metrics proved the efficiency of the reaction in terms of E‐factor, mass intensity, mass productivity, and reaction mass efficiency. Compound 3 g [5‐(4‐(dimethylamino)benzylidene) barbiturate] was used for the colorimetric detection of cyanide ion over dynamic linear range 1–25 μM with limit of detection (LOD) of 0.86 μM. [ABSTRACT FROM AUTHOR]

Zulresso (brexanolone) is an aqueous formulation of the neurosteroid, allopregnanolone, and the only FDA-approved medication for the treatment of postpartum depression (PPD). While brexanolone is effective for the treatment of PPD, lengthy infusion time and high cost can be prohibitive. Failure of GABAA receptors to adapt to fluctuating neurosteroid levels is considered to predispose women to mood disorders in the postpartum period. Brexanolone is thought to act via stimulation of d subunit-containing GABAA receptors, which are extrasynaptic and localized to particular brain regions. Neurosteroid stimulation of d subunit-containing GABAA receptors leads to sustained inhibition (hyperpolarization) of GABAergic neurons, which makes d subunit-containing GABAA receptors a potentially important pharmacologic target. Barbiturates and pyrazolopyridines are potent stimulators of d subunit-containing GABAA receptors and therefore potentially cost-effective treatments for PPD. Barbiturates are often not prescribed, owing to risk of dependence and respiratory depression. The pyrazolopyridines were tested several decades ago for anxiety and depression but never developed commercially. Herein we use the FDA-approved dosing schedule of brexanolone and GABAA receptor binding data from various animal models to examine the safety, efficacy, and potential clinical utility of barbiturates and pyrazolopyridines for the treatment of PPD. We suggest consideration of repurposing barbiturates and pyrazolopyridines as safe and readily available treatment alternatives for PPD. [ABSTRACT FROM AUTHOR]

The goal of the Sexually Transmitted Infection Clinical Trial Group's Antimicrobial Resistance (AMR) in Neisseria gonorrhoeae (NG) meeting was to assemble experts from academia, government, nonprofit and industry to discuss the current state of research, gaps and challenges in research and technology and priorities and new directions to address the continued emergence of multidrug-resistant NG infections. Topics discussed at the meeting, which will be the focus of this article, include AMR NG global surveillance initiatives, the use of whole genome sequencing and bioinformatics to understand mutations associated with AMR, mechanisms of AMR, and novel antibiotics, vaccines and other methods to treat AMR NG. Key points highlighted during the meeting include: (i) US and International surveillance programs to understand AMR in NG; (ii) the US National Strategy for combating antimicrobial-resistant bacteria; (iii) surveillance needs, challenges, and novel technologies; (iv) plasmid-mediated and chromosomally mediated mechanisms of AMR in NG; (v) novel therapeutic (eg, sialic acid analogs, factor H [FH]/Fc fusion molecule, monoclonal antibodies, topoisomerase inhibitors, fluoroketolides, LpxC inhibitors) and preventative (eg, peptide mimic) strategies to combat infection. The way forward will require renewed political will, new funding initiatives, and collaborations across academic and commercial research and public health programs.

Zulresso (brexanolone) is an aqueous formulation of the neurosteroid, allopregnanolone, and the only FDA-approved medication for the treatment of postpartum depression (PPD). While brexanolone is effective for the treatment of PPD, lengthy infusion time and high cost can be prohibitive. Failure of GABAA receptors to adapt to fluctuating neurosteroid levels is considered to predispose women to mood disorders in the postpartum period. Brexanolone is thought to act via stimulation of δ subunit-containing GABAA receptors, which are extrasynaptic and localized to particular brain regions. Neurosteroid stimulation of δ subunit-containing GABAA receptors leads to sustained inhibition (hyperpolarization) of GABAergic neurons, which makes δ subunit-containing GABAA receptors a potentially important pharmacologic target. Barbiturates and pyrazolopyridines are potent stimulators of δ subunit-containing GABAA receptors and therefore potentially cost-effective treatments for PPD. Barbiturates are often not prescribed, owing to risk of dependence and respiratory depression. The pyrazolopyridines were tested several decades ago for anxiety and depression but never developed commercially. Herein we use the FDA-approved dosing schedule of brexanolone and GABAA receptor binding data from various animal models to examine the safety, efficacy, and potential clinical utility of barbiturates and pyrazolopyridines for the treatment of PPD. We suggest consideration of repurposing barbiturates and pyrazolopyridines as safe and readily available treatment alternatives for PPD.

The titled molecular salt dimethyl ammonium 5-(2,4-dinitrophenyl)-1,3-dimethyl barbiturate has been prepared from the ethanolic solution of 1-chloro-2,4-dinitrobenzene, 1,3-dimethylbarbituric acid and dimethyl amine. FT-IR, ¹H-NMR, 13C-NMR, and single crystal diffraction results support the proposed structure of the compound. The crystal structure of the titled complex [monoclinic, space group p21/n, a=11.5729 (15)Å, b=8.6857(11) Å, c=16.701(2) Å, Z=4] are analyzed by single-crystal X-ray diffraction. In this crystal, intermolecular N-H...O and C-H...O hydrogen bonds forming a three dimensional network and small red spot in Hirshfeld surfaces indicates the presence of C-H...π interactions. [ABSTRACT FROM AUTHOR]

Background: A limited number of studies have analyzed prescribing among Medicare‐enrolled adults at risk for opioid overdoses. The objectives of this study were to evaluate prescribing for naloxone and central nervous system (CNS) active medications and to determine the relationships of patient characteristics with exposure to these medications. Methods: This was a retrospective cross‐sectional analysis of a Medicare‐enrolled medication therapy management eligible cohort. Patients were stratified into two cohorts, individuals with a mean daily morphine milligram equivalent (MME) dose <50 and individuals with MME ≥50. Medications assessed included benzodiazepines, skeletal muscle relaxants (SMR), hypnotics, gabapentanoids, selective‐serotonin reuptake inhibitors (SSRI), serotonin–norepinephrine reuptake inhibitors (SNRI), tricyclic antidepressants (TCA), antipsychotics, barbiturates, other antiepileptics, hydroxyzine, and naloxone. Chi‐square with odds ratios and logistic regressions determined the relationships of medications and patient characteristics with mean daily MME ≥50. Relationship between medications and opioid dose was adjusted for age and sex. Results: There were 3452 patients with a daily MME <50 and 1116 with a daily MME ≥50. After adjusting for age and sex, patients with a daily MME ≥50 were more likely to be prescribed hypnotics (OR: 1.41, 95% CI 1.17–1.70), SNRIs (OR: 1.39, 95% CI 1.17–1.64), and naloxone (OR: 3.21, 95% CI 2.49–4.12) (p < 0.001). Nine percent of eligible patients received naloxone. Age groups of persons <85 years of age had 1.58–4.04 (p ≤ 0.004) times the odds of being prescribed a mean daily MME ≥50. Conclusion: Nearly one‐fourth of patients were prescribed a mean daily opioid therapy of MME ≥50. These patients were more likely to be prescribed hypnotics, SNRIs, and naloxone. Patients receiving chronic high‐dose opioid therapy were more likely to be in age groups of persons <85 years. Naloxone may be underprescribed among eligible adults. Targeted medication services may ensure optimal prescribing among Medicare patients with chronic opioid therapies. [ABSTRACT FROM AUTHOR]

Introduction: Management of a withdrawal syndrome following cessation of regular gamma‐hydroxybutyrate (GHB) use, and its precursors, can represent a clinical challenge due to rapid onset delirium and/or seizures. Severe GHB withdrawal can be characterised by persistent or worsening features despite increasing benzodiazepine doses and regular baclofen. Barbiturates, such as phenobarbital, are an appealing option in this context due to their unique GABA‐A receptor action. Case Series: This series describes the use of phenobarbital in 13 cases, 12 patients, across two hospitals in Sydney, Australia, with persistent or progressive GHB withdrawal despite benzodiazepine‐based management. A median cumulative dose of oral diazepam prior to commencing phenobarbital was 120 mg (range 80–255 mg). The median time from the last GHB use to the first dose of phenobarbital was 24 h (range 7–57 h). Eight cases received phenobarbital orally on a general ward and 5 intravenously in intensive care units. An improvement in GHB withdrawal symptoms was observed after phenobarbital in all cases and there were no adverse events related to phenobarbital. Discussion and Conclusion: This case series suggests that phenobarbital for the management of benzodiazepine‐resistant GHB withdrawal can be safe, even in general inpatient settings, and may avert the progression of delirium. Most data on the management of GHB withdrawal comes from case reports or series, such as this one. This highlights the need for prospective trials to establish an evidence base for therapeutic approaches, including validated measures of withdrawal severity and more information relating to the safe and effective dosing of phenobarbital. [ABSTRACT FROM AUTHOR]

Background: Depression is a common disorder that affects patients' quality of life and incurs health system costs. Due to the resistance to treat depression, better understanding of neurophysiology was considered; one of the implications is the glutamatergic system. This study aims to systematically review clinical trials investigating the antidepressant effects of kainate receptor antagonists. Methods: The study protocol was registered in PROSPERO (CRD42021213912). Scopus, ISI, Embase, PubMed, Cochrane Library, Google Scholar, and two trial registries were searched for randomized controlled trials on the effectiveness of topiramate, phenobarbital, and other ten barbiturates in depression. The difference with control groups in terms of changing depressive symptoms was the primary outcome. Results: Nine trials were identified, in which 784 patients were studied. The efficacy of thiopental was comparable to that of imipramine, with fewer side effects. When administered with electroconvulsive therapy, it had fewer to similar effects and fewer side effects than ketamine. Both monotherapy and adjunctive therapy with topiramate were effective and tolerable in treating depressed patients. Phenobarbital had therapeutic effects compared to imipramine and amitriptyline with fewer side effects. Conclusion: Regarding the glutamatergic hypothesis of depression and obtained promising results, further studies of kainate receptor antagonists in high‐quality trials are recommended. Given the high prevalence of depression in epileptic patients, more problems with its treatment, and the fact that the studied agents were anticonvulsants, it is recommended that future studies prioritize depressed‐epileptic patients. [ABSTRACT FROM AUTHOR]

Background: Etomidate, barbiturates, alfaxalone, and propofol are anesthetics that allosterically modulate γ-aminobutyric acid type A (GABAA) receptors via distinct sets of molecular binding sites. Two-state concerted coagonist models account for anesthetic effects and predict supra-additive interactions between drug pairs acting at distinct sites. Some behavioral and molecular studies support these predictions, while other findings suggest potentially complex anesthetic interactions. We therefore evaluated interactions among four anesthetics in both animals and GABAA receptors.Methods: The authors used video assessment of photomotor responses in zebrafish larvae and isobolography to evaluate hypnotic drug pair interactions. Voltage clamp electrophysiology and allosteric shift analysis evaluated coagonist interactions in α1β3γ2L receptors activated by γ-aminobutyric acid (GABA) versus anesthetics [log(d, AN):log(d, GABA) ratio]. Anesthetic interactions at concentrations relevant to zebrafish were assessed in receptors activated with low GABA.Results: In zebrafish larvae, etomidate interacted additively with both propofol and the barbiturate R-5-allyl-1-methyl m-trifluoromethyl mephobarbital (R-mTFD-MPAB; mean ± SD α = 1.0 ± 0.07 and 0.96 ± 0.11 respectively, where 1.0 indicates additivity), while the four other drug pairs displayed synergy (mean α range 0.76 to 0.89). Electrophysiologic allosteric shifts revealed that both propofol and R-mTFD-MPAB modulated etomidate-activated receptors much less than GABA-activated receptors [log(d, AN):log(d, GABA) ratios = 0.09 ± 0.021 and 0.38 ± 0.024, respectively], while alfaxalone comparably modulated receptors activated by GABA or etomidate [log(d) ratio = 0.87 ± 0.056]. With low GABA activation, etomidate combined with alfaxalone was supra-additive (n = 6; P = 0.023 by paired t test), but etomidate plus R-mTFD-MPAB or propofol was not.Conclusions: In both zebrafish and GABAA receptors, anesthetic drug pairs interacted variably, ranging from additivity to synergy. Pairs including etomidate displayed corresponding interactions in animals and receptors. Some of these results challenge simple two-state coagonist models and support alternatives where different anesthetics may stabilize distinct receptor conformations, altering the effects of other drugs.Editor’s Perspective: [ABSTRACT FROM AUTHOR]

Urea and barbiturates are bioactive compounds with diverse applications, ranging from pharmaceuticals to industrial processes. In reference to their biological relevance, it is essential to detect and quantify urea and barbiturates with high selectivity and sensitivity. The development of synthetic receptors for their recognition is a topic of research in supramolecular chemistry. This review highlights the progress in the development of synthetic receptors in last four decades for the selective recognition of urea and barbiturates. [Display omitted] • Synthetic receptors for urea recognition. • Synthetic receptors for barbiturates. • Macrocyclic and acyclic receptors. • Comprehensive review work on urea and barbiturate recognitions. Urea and barbiturates are bioactive compounds with diverse applications, ranging from pharmaceuticals to industrial processes. Urea functionality and barbiturates are present in various bioactive substances, including several clinically approved drugs. For analytic, diagnostic, and therapeutic applications, it is essential to detect and quantify urea and barbiturates with high selectivity and sensitivity. The development of the synthetic receptors for urea and barbiturates recognition involves the incorporation of specific functional groups and structural motifs to create binding sites that can interact selectively with urea and barbiturates. Consequently, a myriad of receptors for selective recognition and sensing of urea and barbiturates have been reported to date. The binding affinity, selectivity as well as supramolecular host–guest interactions of these receptors were studied by various methods, including UV–vis, fluorescence, 1H NMR titration, and single crystal X-ray diffraction analysis. These receptors offer valuable tools for detecting and quantifying urea and barbiturates in complex biological and environmental samples, leading to advancements in various fields and facilitating the development of novel diagnostic and therapeutic strategies. This review highlights the progress in the development of synthetic receptors for the selective recognition of urea and barbiturates. [ABSTRACT FROM AUTHOR]

Pentobarbital is a Schedule II/III short-acting barbiturate with limited medical use in humans. Veterinary professionals use pentobarbital to euthanize dogs, cats, and other companion animals. Pentobarbital is also utilized in capital punishment and small amounts are illegally shipped or diverted to assist in suicides. However, five kilograms of pentobarbital smuggled in from Mexico was recently seized by an organized crime drug enforcement task force (along with fentanyl, heroin, and cocaine), which may suggest a shift in illicit supply. We investigated potential indicators of illicit pentobarbital use or availability in the US to help determine whether this drug is becoming an emerging public health concern. The National Drug Early Warning System requested information on pentobarbital from its sentinel surveillance sites and collaborators and conducted a search of current literature. In early 2024, multiple batches of counterfeit pills (e.g., pressed as "M30s" to represent oxycodone) confiscated near the Southwest border tested positive for pentobarbital plus combinations of fentanyl, fentanyl analogs, and xylazine. Other indicators suggest pentobarbital is being smuggled in powder form and possibly sold as another drug such as heroin. One national drug analysis program detected pentobarbital in 217 drug submissions from 2020 to 2023, and there were at least 12 fatal exposures linked to use from 2020 to 2022. Continued monitoring of illicit use and availability is needed as pentobarbital may continue to appear on the illicit market. Unknown exposure can occur if the drug is mixed into counterfeit pills or sold in powder form represented to be another drug. • Little is known regarding availability or use of illicit pentobarbital in the US. • Pentobarbital in powder form can be sold as or mistaken for heroin or fentanyl. • Pentobarbital is now being detected in counterfeit pills also containing fentanyl. • Fatal exposures appear to be rare but toxicology and self-report data are lacking. • Monitoring is needed as pentobarbital may continue to appear on the illicit market. [ABSTRACT FROM AUTHOR]

• Enhanced Sensitivity: achieved low LODs and interference-free electropherograms. • Clinical Applicability: successfully analyzed human serum samples. • Innovative Methodology: integrated UA-DLLME and LVSS for analysis of two pairs of barbiturate enantiomer drugs. • Sensitivity Boost: attained a 6200–6400-fold sensitivity enhancement. • Efficient Analysis: provided a simple, high-efficiency method for biosample analysis. A rapid, straightforward, and sensitive approach to quantifying enantiomeric barbiturates in serum was developed by integrating ultrasound-assisted dispersive liquid–liquid microextraction (UA-DLLME) with large-volume sample stacking (LVSS) in capillary electrophoresis (CE). UA-DLLME was employed for sample preparation, and on-column preconcentration by using LVSS with polarity switching was implemented to enhance sensitivity. We thoroughly investigated and optimized various parameters influencing extraction and stacking to achieve optimal detection performance with the highest enrichment efficiencies. Under optimal extraction conditions (injection of a mixed solution containing 40 μL of CHCl 3 and 200 μL of tetrahydrofuran into 1 mL of a sample solution at pH 10.0), LVSS was performed using 600 mM Tris-boric acid (pH 9.5) containing 35 mM hydroxypropyl-β-cyclodextrin and sodium taurodeoxycholate hydrate. A voltage of 20 kV was applied and a preinjection water plug was loaded at a height of 25 cm for 10 s. Subsequently, the sample solution was injected at a height of 25 cm for 480 s, after which a voltage of −20 kV was applied and the sample stacking was initiated. The stacking process was completed when 95 % of the separation current was attained. Under optimized conditions, the contraction folds of the four barbiturate analytes (R, S -Secobarbital, R, S -pentobarbital) were improved by approximately 6400-fold, achieving detection limits of 0.1 ng/mL. The limits of quantification for all analyte enantiomers were 0.5–50 ng/mL, demonstrating good linearity (r > 0.997). Migration times exhibited a relative standard deviation of less than 1.7 %, whereas peak areas for the four analytes exhibited a deviation of 8.7 %. Finally, the established method was effectively applied to the analysis of human serum samples. [ABSTRACT FROM AUTHOR]