New challenges and innovation in forensic toxicology: focus on the "New Psychoactive Substances".

In the recent years, new molecules have appeared in the illicit market, claimed to contain "non-illegal" compounds, although exhibiting important psychoactive effects; this heterogeneous and rapidly evolving class of compounds are commonly known as "New Psychoactive Substances" or, less properly, "Smart Drugs" and are easily distributed through the e-commerce or in the so-called "Smart Shops". They include, among other, synthetic cannabinoids, cathinones and tryptamine analogs of psylocin. Whereas cases of intoxication and death have been reported, the phenomenon appears to be largely underestimated and is a matter of concern for Public Health. One of the major points of concern depends on the substantial ineffectiveness of the current methods of toxicological screening of biological samples to identify the new compounds entering the market. These limitations emphasize an urgent need to increase the screening capabilities of the toxicology laboratories, and to develop rapid, versatile yet specific assays able to identify new molecules. The most recent advances in mass spectrometry technology, introducing instruments capable of detecting hundreds of compounds at nanomolar concentrations, are expected to give a fundamental contribution to broaden the diagnostic spectrum of the toxicological screening to include not only all these continuously changing molecules but also their metabolites. In the present paper a critical overview of the opportunities, strengths and limitations of some of the newest analytical approaches is provided, with a particular attention to liquid phase separation techniques coupled to high accuracy, high resolution mass spectrometr

Analysis of illicit drugs seized in the Province of Florence from 2006 to 2016

Comprehension of illicit drug market's features at local level is useful to plan and to correctly set-up specific informative and contrast activities. In this paper we report trends, purities and consumption estimations of illicit substances available on the Florentine territory from 2006 to 2016. These data were obtained by the analysis of 10,451 samples seized by the Law Enforcement Agencies in case of personal use offence. Analytical procedures consisted in targeted and untargeted analyses by gas chromatography-flame ionization detector, gas chromatography\u2013mass spectrometry and liquid chromatography\u2013tandem mass spectrometry. The most detected substances were: cannabis (78.0%; resin: 51.7%; herb: 26.3%), cocaine (10.4%), opiates (6.6%; heroin: 6.5%; morphine: 0.1%), ketamine (1.4%), amphetamines (1.3%; 3,4-methylenedioxymethamphetamine \u2013 MDMA \u2013: 0.7%; methamphetamine: 0.6%; amphetamine: <0.1%) and methadone (1.3%). Cocaine, heroin and methamphetamine purities were higher than their mean values estimated for the Italian and European market, while THC content in cannabis seizures was unexpectedly below the European mean values. Starting from 2015, a total of 5 new psychoactive substances (NPS) were detected in seized material, mainly composed of white powders (pentedrone, 3-methylmethcathinone, 4-fluoroamphetamine, methoxethamine and AB-FUBINACA). Most of the seizures (75.5%) were from young male adults (14\u201334 years old). These data contribute to highlight new trends in the illicit drug market in the Tuscany area, but also to verify the persistence of old habits of drug consumption, confirming the need for more effective counteraction and prevention plans, especially among young people, where the diffusion of the legal highs is worrisome, also in consideration of the young age and the unconsciousness of the possible health effects

Rapid optimized separation of bromide in serum samples with capillary zone electrophoresis by using glycerol as additive to the background electrolyte

After decades of neglect, bromide has recently been re-introduced in therapy as an effective anti-epileptic drug. The present paper describes the methodological optimization and validation of a method based on capillary zone electrophoresis for the rapid determination of bromide in serum using a high-viscosity buffer and a short capillary (10 cm). The optimized running buffer was composed of 90 mM sodium tetraborate, 10 mM sodium chloride, pH 9.24 and 25% glycerol. The separation was carried out at 25 kV at a temperature of 20 \ub0C. Detection was by direct UV absorption at 200 nm wavelength. The limit of detection (signal-to-noise ratio = 5) in serum was 0.017 mM. The precision of the method was verified in blank serum samples spiked with bromide, obtaining intra-day and day-to-day tests, relative standard deviation values 640.2% in terms of migration times and values <2% in terms of peaks areas, respectively

Readiness for enhanced self-health management among people with diabetes mellitus Disposición para el control aumentado del régimen terapéutico entre personas con diabetes mellitus Disposição para controle aumentado do regime terapêutico entre pessoas com diabetes mellitus

OBJECTIVE: To identify the nursing diagnosis, readiness for enhanced self-health management, among people with type 2 diabetes who are adherent to pharmacological treatment. METHODS: The sample consisted of 579 subjects from 12 primary care services who received home visits. To determine adherence to the pharmacological treatment, the pill count test was conducted. Those classified as adherent were given a checklist with the defining characteristics of the nursing diagnosis, readiness for enhanced self-health management. RESULTS: Subjects with type 2 diabetes who presented with the nursing diagnosis were not alcoholics (p = 0.003), did not miss their diabetes consultations (p = 0.000), and had no difficulties / inappropriate behaviors with regard to taking their oral antidiabetic agents (p = 0.000). CONCLUSION: The identification of human responses to the clinical treatment of type 2 diabetes should be continuous, so that nurses can understand the factors involved in the readiness to enhance therapeutic control.<br>OBJETIVO: identificar el diagnóstico de enfermería disposición para el control aumentado del régimen terapéutico entre personas con diabetes tipo 2 adheridas al tratamiento farmacológico. MÉTODOS: La muestra estuvo constituida por 579 sujetos de 12 servicios de atención primaria que recibieron visitas domiciliarias. Para determinar la adhesión al tratamiento farmacológico fue realizado el test del recuento de comprimidos. En aquellos clasificados como adherentes se aplicó un check list con las características definidoras del diagnóstico de enfermería disposición para el control aumentado del régimen terapéutico. RESULTADOS: Los sujetos con DM 2 que presentaron el diagnóstico de enfermería estudiado no eran etílicos (p=0,003), no faltaban a las consultas para DM 2 (p=0,000) y no tenían dificultades/comportamientos inadecuados en la toma de los antidiabéticos orales (p=0,000). CONCLUSIÓN: La identificación de respuestas humanas frente al tratamiento clínico de los sujetos con diabetes tipo 2 debe ser continua para que el enfermero pueda conocer los factores involucrados en una disposición aumentada para el control terapéutico.<br>OBJETIVO: identificar o diagnóstico de enfermagem disposição para controle aumentado do regime terapêutico entre pessoas com diabetes tipo 2 aderentes ao tratamento farmacológico. MÉTODOS: A amostra foi constituída de 579 sujeitos de 12 serviços de atenção primária que receberam visitas domiciliares. Para determinar a adesão ao tratamento farmacológico foi realizado o teste da contagem de comprimidos. Naqueles classificados como aderentes foi aplicado um check list com as características definidoras do diagnóstico de enfermagem disposição para controle aumentado do regime terapêutico. RESULTADOS: Os sujeitos com DM 2 que apresentaram o diagnóstico de enfermagem estudado não eram etilistas (p=0,003), não faltavam as consultas para DM 2 (p=0,000) e não tinham dificuldades/comportamentos inadequados na tomada dos antidiabéticos orais (p=0,000). CONCLUSÃO: A identificação de respostas humanas frente ao tratamento clínico dos sujeitos com diabetes tipo 2 deve ser contínua para que o enfermeiro possa conhecer os fatores envolvidos numa disposição aumentada para o controle terapêutico

Emerging importance of oxidative stress in regulating striated muscle elasticity

The contractile function of striated muscle cells is altered by oxidative/nitrosative stress, which can be observed under physiological conditions but also in diseases like heart failure or muscular dystrophy. Oxidative stress causes oxidative modifications of myofilament proteins and can impair myocyte contractility. Recent evidence also suggests an important effect of oxidative stress on muscle elasticity and passive stiffness via modifications of the giant protein titin. In this review we provide a short overview of known oxidative modifications in thin and thick filament proteins and then discuss in more detail those oxidative stress-related modifications altering titin stiffness directly or indirectly. Direct modifications of titin include reversible disulfide bonding within the cardiac-specific N2-Bus domain, which increases titin stiffness, and reversible S-glutathionylation of cryptic cysteines in immunoglobulin-like domains, which only takes place after the domains have unfolded and which reduces titin stiffness in cardiac and skeletal muscle. Indirect effects of oxidative stress on titin can occur via reversible modifications of protein kinase signalling pathways (especially the NO-cGMP-PKG axis), which alter the phosphorylation level of certain disordered titin domains and thereby modulate titin stiffness. Oxidative stress also activates proteases such as matrix-metalloproteinase-2 and (indirectly via increasing the intracellular calcium level) calpain-1, both of which cleave titin to irreversibly reduce titin-based stiffness. Although some of these mechanisms require confirmation in the in vivo setting, there is evidence that oxidative stress-related modifications of titin are relevant in the context of biomarker design and represent potential targets for therapeutic intervention in some forms of muscle and heart disease