Experimental Neurology By Prof Paul Glees Pp xii + 532 (Oxford: Clarendon Press; London: Oxford University Press, 1961) 75s net

The Nervous System

Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children

DNA analysis has seen an incredible development in terms of instrumentation, assays and applications over the last years. Massively parallel sequencing (MPS) and digital PCR are now broadly applied in research and diagnostics, and quantitative PCR is used for more and more practises. All these techniques are based on in vitro DNA polymerization and fluorescence measurements. A major limitation for successful analysis is the various sample-related substances that interfere with the analysis, i.e. PCR inhibitors. PCR inhibition affects library preparation in MPS analysis and skews quantification in qPCR, and some inhibitors have been found to quench the fluorescence of the applied fluorophores. Here, we provide a deeper understanding of mechanisms of specific PCR inhibitors and how these impact specific analytical techniques. This background knowledge is necessary in order to take full advantage of modern DNA analysis techniques, specifically for analysis of samples with low amounts of template and high amounts of background material. The classical solution to handle PCR inhibition is to purify or dilute DNA extracts, which leads to DNA loss. Applying inhibitor-tolerant DNA polymerases, either single enzymes or blends, provides a more straightforward and powerful solution. This review includes mechanisms of specific PCR inhibitors as well as solutions to the inhibition problem in relation to cutting-edge DNA analysis.

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PCR inhibition in qPCR, dPCR and MPS-mechanisms and solutions.

Background: Synthetic cannabinoid receptor agonists (SCRAs) have become the largest group of new psychoactive substances monitored by the European Union Early Warning System. Despite the wide diffusion on the market, data regarding effects, toxicities and mechanisms as well as toxic/lethal doses are still scarce. Methods: A comprehensive literature search for articles published up to January 2019 was performed in multiple electronic databases. Only cases of death in which toxicological analyses revealed the presence of SCRAs in blood or urine and at least an external examination was performed, including those occurred in emergency departments, were included. Results: Of 380 studies identified, 354 were excluded, while 8 additional manuscripts were included through the screening of relevant references cited in the selected articles. A total number of 34 manuscripts (8 case series and 26 case reports) were included. Conclusions: Typical toxic ranges for SCRAs have not been so far identified and the results of toxicological analyses should be interpreted with caution. In death cases involving SCRAs, a thorough post-mortem examination is a prerequisite to assess the role of the substance use in the deceased and to identify a probable mechanism of death. Even after a comprehensive analysis of clinical, circumstantial, toxicological and autoptic data, the cause and manner of death remain unclear in some cases.

Post-Mortem Toxicology: A Systematic Review of Death Cases Involving Synthetic Cannabinoid Receptor Agonists.

Caffeine is the most widely consumed psychoactive compound worldwide. It is mostly found in coffee, tea, energizing drinks and in some drugs. However, it has become really easy to obtain pure caffeine (powder or tablets) on the Internet markets. Mechanisms of action are dose-dependent. Serious toxicities such as seizure and cardiac arrhythmias, seen with caffeine plasma concentrations of 15 mg/L or higher, have caused poisoning or, rarely, death; otherwise concentrations of 3–6 mg/kg are considered safe. Caffeine concentrations of 80–100 mg/L are considered lethal. The aim of this systematic review, performed following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement for the identification and selection of studies, is to review fatal cases in which caffeine has been recognized as the only cause of death in order to identify potential categories at risk. A total of 92 cases have been identified. These events happened more frequently in infants, psychiatric patients, and athletes. Although caffeine intoxication is relatively uncommon, raising awareness about its lethal consequences could be useful for both clinicians and pathologists to identify possible unrecognized cases and prevent related severe health conditions and deaths.

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Caffeine-Related Deaths: Manner of Deaths and Categories at Risk

Caffeine (1,3,7-trimethylxanthine) is a popular mild central nervous system stimulant found in the leaves, seeds and fruits of various plants and in foodstuffs such as coffee, tea, and chocolate, among others. Caffeine is widely used and is not associated with severe side effects when consumed at relatively low doses. Although rarely observed, overdoses can occur. However, only a few fatal caffeine intoxication cases have been reported in the literature. Herein, we report the pathological examination results and information on caffeine concentrations in the blood, urine and main organs in a fatal caffeine intoxication case. Even though high caffeine concentrations were found in the systemic organs, no caffeine-related pathological changes were detected.

Autopsy report for a caffeine intoxication case and review of the current literature

GC-PCI-MS/MS and LC-ESI-MS/MS databases for the detection of 104 psychotropic compounds (synthetic cannabinoids, synthetic cathinones, phenethylamine derivatives).

Development of a preparation method to produce a single sample that can be applied to both LC–MS/MS and GC–MS for the screening of postmortem specimens

Brian Waters

Papers

Autopsy report for a caffeine intoxication case and review of the current literature

GC-PCI-MS/MS and LC-ESI-MS/MS databases for the detection of 104 psychotropic compounds (synthetic cannabinoids, synthetic cathinones, phenethylamine derivatives).

Development of a preparation method to produce a single sample that can be applied to both LC–MS/MS and GC–MS for the screening of postmortem specimens

Methamphetamine and amphetamine concentrations in survivors of body-packer syndrome in Japan.

A report of novel psychoactive substances in forensic autopsy cases and a review of fatal cases in the literature