Bar Adsorptive Microextraction Approach for Trace Determination of Local Anesthetics in Urine Matrices.

The present work reports the development, optimization, and validation, of a methodology to determine lidocaine, procaine, tetracaine, and benzocaine in urine matrices. Two extractive preconcentration techniques, solid-phase microextraction (SPME) LC Tips and bar adsorptive microextraction (BAμE), were studied and applied to the four target anesthetics, followed by gas chromatography-mass spectrometry (GC-MS) analysis. Several parameters that could affect microextraction and back-extraction were optimized using two different designs of experiments (Box-Behnken and full-factorial) to maximize extraction efficiency from aqueous media.

Chemical Analysis of Gunpowder and Gunshot Residues.

The identification of firearms is of paramount importance for investigating crimes involving firearms, as it establishes the link between a particular firearm and firearm-related elements found at a crime scene, such as projectiles and cartridge cases. This identification relies on the visual comparison of such elements against reference samples from suspect firearms or those existing in databases. Whenever this approach is not possible, the chemical analysis of the gunpowder and gunshot residue can provide additional information that may assist in establishing a link between samples retrieved at a crime scene and those from a suspect or in the identification of the corresponding model and manufacturer of the ammunition used.

Determination of phytocannabinoids in cannabis samples by ultrasound-assisted solid-liquid extraction and high-performance liquid chromatography with diode array detector analysis.

The characterisation of cannabis plants, especially the determination of specific phytocannabinoids, has gained enormous importance in the last decade, mainly due to the recent changes in cannabis control in several countries or states. This is particularly relevant for the forensic, medical or recreative industry to have a rapid, inexpensive, and reliable methodology to identify and quantify phytocannabinoids. Furthermore, spiking cannabis products with Δ-tetrahydrocannabinol (THC) is a contemporary trend that demands improving or replacing current methods to include this cannabinoid.

GC-MS Silylation Derivative Method to Characterise Black BIC Ballpoint 2-Phenoxyethanol Ratio Evaporation Profile-A Contribution to Ink Ageing Estimation.

One of the major challenges in forensic document analysis is estimating the age of ink deposition on a manually written document. The present work aims to develop and optimise a methodology, based on the evaporation of 2-phenoxyethanol (PE) over time, that can contribute to ink age estimation. A black BIC Crystal Ballpoint Pen was purchased in a commercial area, and ink deposition began in September 2016 over 1095 days.

An Umbrella Review of the Evidence of Sex Determination Procedures in Forensic Dentistry.

Sex determination in forensic dentistry is a major step towards postmortem profiling. The most widely recognized method is DNA, yet its application in the dental field of forensic sciences is still impractical. Depending on the conditions of the remains, teeth are often the only surviving organ.

Novel Psychoactive Substances: The Razor's Edge between Therapeutical Potential and Psychoactive Recreational Misuse.

Background: Novel psychoactive substances (NPS) are compounds of natural and synthetic origin, similar to traditional drugs of abuse. NPS are involved in a contemporary trend whose origin lies in a thinner balance between legitimate therapeutic drug research and legislative control. The contemporary NPS trend resulted from the replacement of MDMA by synthetic cathinones in 'ecstasy' during the 2000s.

Inflammatory factors, genetic variants, and predisposition for preterm birth.

Preterm birth is a major clinical and public health challenge, with a prevalence of 11% worldwide. It is the leading cause of death in children younger than 5 years old and represents 70% of neonatal deaths and 75% of neonatal morbidity. Despite the clinical and public health significance, this condition's etiology is still unclear, and most of the cases are spontaneous.

Validation of the Third Molar Maturation Index (I) to assess the legal adult age in the Portuguese population.

Age estimation is a major step in forensic and legal procedures. Its relevance has been increasing due to growing society issues, such as identification of missing people, crimes against minors or lack of valid identification papers from locals or foreigners. Evaluation of the cut-off value of the Third Molar Maturation Index (I) = 0.

hiPSC-Based Model of Prenatal Exposure to Cannabinoids: Effect on Neuronal Differentiation.

Phytocannabinoids are psychotropic substances ofcannabis with the ability to bind endocannabinoid (eCB) receptors that regulate synaptic activity in the central nervous system (CNS). Synthetic cannabinoids (SCs) are synthetic analogs of Δ-tetrahydrocannabinol (Δ-THC), the psychotropic compound of cannabis, acting as agonists of eCB receptor CB. SC is an easily available and popular alternative to cannabis, and their molecular structure is always changing, increasing the hazard for the general population.

Neuroprotection or Neurotoxicity of Illicit Drugs on Parkinson's Disease.

Parkinson's Disease (PD) is currently the most rapid growing neurodegenerative disease and over the past generation, its global burden has more than doubled. The onset of PD can arise due to environmental, sporadic or genetic factors. Nevertheless, most PD cases have an unknown etiology.

Extraction Procedures for Hair Forensic Toxicological Analysis: A Mini-Review.

In forensic toxicology, drugs of abuse are routinely analyzed due to legal statute in medical or legal investigation, such as death cases, poisoning cases, and drug misuse, determining potential exposure to controlled substances. Despite the widespread use of blood and urine as matrices for forensic toxicological analysis, the use of hair samples has grown as the limitations associated with this matrix are overcome and new areas of application emerge. Hair provides several advantages over urine and blood, such as the easiness of sample collection and the ability to provide a retrospective analysis of drug consumption.

The synthetic cannabinoid JWH-018 modulates Saccharomyces cerevisiae energetic metabolism.

Synthetic cannabinoids are a group of novel psychoactive substances with similar properties to Δ9-THC. Among the vast number of synthetic cannabinoids, designed to be tested in clinical trials, JWH-018 was the first novel psychoactive substance found in the recreational drug marketplace. The consumption of JWH-018 shows typical effects of CB1 agonists including sedation, cognitive dysfunction, tachycardia, postural hypotension, dry mouth, ataxia and psychotropic effects, but appeared to be more potent than Δ9-THC.

Development of a high throughput methodology to screen cathinones' toxicological impact.

Current trend of novel psychoactive substances (NPS) among teenagers is posing new clinical, scientific and forensic societal questions. Synthetic cathinones are among the most consumed groups of NPS appearing on the street market and internet on a regular basis. The properties of these substances change regularly, due to structural modification to circumvent legislation.

Glycation potentiates α-synuclein-associated neurodegeneration in synucleinopathies.

α-Synuclein misfolding and aggregation is a hallmark in Parkinson's disease and in several other neurodegenerative diseases known as synucleinopathies. The toxic properties of α-synuclein are conserved from yeast to man, but the precise underpinnings of the cellular pathologies associated are still elusive, complicating the development of effective therapeutic strategies. Combining molecular genetics with target-based approaches, we established that glycation, an unavoidable age-associated post-translational modification, enhanced α-synuclein toxicity in vitro and in vivo, in Drosophila and in mice.

Effect of β-Cyclodextrin on the Multistate Species Distribution of 3-Methoxy-4',7-dihydroxyflavylium. Discrimination of the Two Hemiketal Enantiomers.

The effect of β-cyclodextrin on the mole fraction distribution of the multistate species of the anthocyanin model compound, 3-methoxy-4',7-dihydroxyflavylium, was studied by NMR, stopped flow, circular dichroism, and UV-visible absorption spectroscopy. The formation of inclusion complexes with hemiketal and trans-chalcone, possessing transition dipole moments in a parallel orientation to the cyclodextrin n-fold axis, was unequivocally proved by means of the positive-induced circular dichroism signal. The discrimination of the two hemiketal enantiomers was achieved by the splitting of H NMR peaks in the presence β-cyclodextrin.

Toxicological impact of JWH-018 and its phase I metabolite N-(3-hydroxypentyl) on human cell lines.

The emergence and abuse of synthetic cannabinoids has been increasing as an alternative to cannabis, mainly among youth. As their appearance on the drug market has been recent, the pharmacological and toxicological profiles of these psychoactive substances are poorly understood. Current studies suggest that they have stronger effects compared to their natural alternatives and their metabolites retain affinity towards CB1 receptors in CNS.

Evolution of the human immunodeficiency virus type 2 envelope in the first years of infection is associated with the dynamics of the neutralizing antibody response.

Background: Differently from HIV-1, HIV-2 disease progression usually takes decades without antiretroviral therapy and the majority of HIV-2 infected individuals survive as elite controllers with normal CD4⁺ T cell counts and low or undetectable plasma viral load. Neutralizing antibodies (Nabs) are thought to play a central role in HIV-2 evolution and pathogenesis. However, the dynamic of the Nab response and resulting HIV-2 escape during acute infection and their impact in HIV-2 evolution and disease progression remain largely unknown.

Transthyretin proteins regulate angiogenesis by conferring different molecular identities to endothelial cells.

Familial amyloidotic polyneuropathy (FAP) has a high prevalence in Portugal, and the most common form of hereditary amyloidosis is caused by an amyloidogenic variant of transthyretin (TTR) with a substitution of methionine for valine at position 30 (V30M). Until now, the available efficient therapy is liver transplantation, when performed in an early phase of the onset of the disease symptoms. However, transplanted FAP patients have a significantly higher incidence of early hepatic artery thrombosis compared with non-FAP transplanted patients.

Circular dichroism of anthocyanidin 3-glucoside self-aggregates.

Self-association constants for the flavylium cations of the six most common anthocyanidin 3-glucosides were determined by circular dichroism (CD) and UV-Vis spectroscopy. Along with previous (1)H NMR results, all measurements were consistent with a monomer-dimer model. The CD spectra of the anthocyanidin 3-glucosides were similar to the analogues 3,5-diglucosides.

An ancestral HIV-2/simian immunodeficiency virus peptide with potent HIV-1 and HIV-2 fusion inhibitor activity.

Objectives: To produce new fusion inhibitor peptides for HIV-1 and HIV-2 based on ancestral envelope sequences.

Methods: HIV-2/simian immunodeficiency virus (SIV) ancestral transmembrane protein sequences were reconstructed and ancestral peptides were derived from the helical region 2 (HR2). The activity of one ancestral peptide (named P3) was examined against a panel of HIV-1 and HIV-2 primary isolates in TZM-bl cells and peripheral blood mononuclear cells and compared to T-20.

Insights into the molecular mechanism of protein native-like aggregation upon glycation.

Several human neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Familial Amyloidotic Polyneuropathy, have long been associated with, structural and functional changes in disease related proteins leading to aggregation into amyloid fibrils. Such changes can be triggered by post-translational modifications. Methylglyoxal modifications have been shown to induce the formation of small and stable native-like aggregates in the case of the amyloidogenic proteins insulin and α-synuclein.

Resistance to antibody neutralization in HIV-2 infection occurs in late stage disease and is associated with X4 tropism.

Objectives: To characterize the nature and dynamics of the neutralizing antibody (NAb) response and escape in chronically HIV-2 infected patients.

Methods: Twenty-eight chronically infected adults were studied over a period of 1-4 years. The neutralizing activity of plasma immunoglobulin G (IgG) antibodies against autologous and heterologous primary isolates was analyzed using a standard assay in TZM-bl cells.