Application of Paper-Based Microfluidic Analytical Devices (µPAD) in Forensic and Clinical Toxicology: A Review

The need for providing rapid and, possibly, on-the-spot analytical results in the case of intoxication has prompted researchers to develop rapid, sensitive, and cost-effective methods and analytical devices suitable for use in nonspecialized laboratories and at the point of need (PON). In recent years, the technology of paper-based microfluidic analytical devices (μPADs) has undergone rapid development and now provides a feasible, low-cost alternative to traditional rapid tests for detecting harmful compounds. In fact, μPADs have been developed to detect toxic molecules (arsenic, cyanide, ethanol, and nitrite), drugs, and drugs of abuse (benzodiazepines, cathinones, cocaine, fentanyl, ketamine, MDMA, morphine, synthetic cannabinoids, tetrahydrocannabinol, and xylazine), and also psychoactive substances used for drug-facilitated crimes (flunitrazepam, gamma- hydroxybutyric acid (GHB), ketamine, metamizole, midazolam, and scopolamine). The present report critically evaluates the recent developments in paper-based devices, particularly in detection methods, and how these new analytical tools have been tested in forensic and clinical toxicology, also including future perspectives on their application, such as multisensing paper-based devices, microfluidic paper-based separation, and wearable paper-based sensors

Pre-amyloid oligomers budding:a metastatic mechanism of proteotoxicity

The pathological hallmark of misfolded protein diseases and aging is the accumulation of proteotoxic aggregates. However, the mechanisms of proteotoxicity and the dynamic changes in fiber formation and dissemination remain unclear, preventing a cure. Here we adopted a reductionist approach and used atomic force microscopy to define the temporal and spatial changes of amyloid aggregates, their modes of dissemination and the biochemical changes that may influence their growth. We show that pre-amyloid oligomers (PAO) mature to form linear and circular protofibrils, and amyloid fibers, and those can break reforming PAO that can migrate invading neighbor structures. Simulating the effect of immunotherapy modifies the dynamics of PAO formation. Anti-fibers as well as anti-PAO antibodies fragment the amyloid fibers, however the fragmentation using anti-fibers antibodies favored the migration of PAO. In conclusion, we provide evidence for the mechanisms of misfolded protein maturation and propagation and the effects of interventions on the resolution and dissemination of amyloid pathology

Recent advances in the applications of CE to forensic sciences (2001-2004)

The present article reviews the applications of CE in forensic science covering the periodfrom 2001 until the first part of 2005. The overview includes the most relevant examples of analytical applications of capillary electrophoretic and electrokinetic techniques in the following fields: (i) Forensic drugs and poisons, (ii) explosive analysis and gunshot residues, (iii) small ions of forensic interest, (iv) forensic DNA and RNA analysis, (v) proteins of forensic interest, and (vi) ink analysis

Recent advances in the applications of CE to forensic sciences (2005-2007)

The present article reviews the applications of CE in forensic science covering the period from 2005 until the first part of 2007. The overview includes the most relevant examples of analytical applications of capillary electrophoretic and electrokinetic techniques in the following fields: (i) forensic drugs, toxicants and dyes, (ii) small ions of forensic interest (iii) explosives, (iv) forensic DNA, and (v) other biopolymers of forensic interest

Biomarkers for the identification of alcohol use/abuse: a critical review.

Alcohol abuse represents a highly relevant medical, social, and economic problem all over the world. The diagnosis of conditions of alcohol use or abuse is complex, requiring different and integrated methodologies; among them the use of biomarkers is a very helpful and objective tool. This review article discusses the currently available biomarkers of alcohol abuse, showing their positive and negative characteristics in terms of detection window, diagnostic sensitivity, diagnostic specificity, and analytical feasibility. Particular attention is dedicated to the most used biomarkers, represented by liver enzymes (AST, ALT, and GGT), MCV, CDT, EtG and EtS, FAEE, and PEth. A critical analysis of the different biomarkers showed wide variability in terms of detection window, sensitivity, and specificity. On this basis, the choice of any indicator should depend on the aim and context for which the diagnosis of alcohol abuse is required (e.g., clinical, fitness for driver's license, fitness to work, child custody). Moreover, this study showed that the diagnosis of alcohol abuse cannot be based only on the use of biomarkers, but it must also consider the integration of anamnestic, clinical, instrumental, and laboratory data

Carbohydrate Deficient Transferrin, a reliable marker of chronic alcohol abuse in both forensic and clinical settings - a review.

The paper reports an updated review of pre-analytical, analytical, interpretative aspects of carbohydrate deficient transferri

Ischemic stroke due to sporadic and genetic pulmonary arteriovenous malformations: case report

Pulmonary arteriovenous malformations (PAVMs) encompass congenital and genetic vascular anomalies characterized by complex interlacing of arteries and veins connected by fistulas, which allow rapid and continuous extracardiac right-to-left shunting (RLS). Presenting neurologic manifestations of PAVM include brain abscess and stroke, as the consequence of paradoxical embolism. Although rare, PAVM represents an overlooked cause of cryptogenic ischemic stroke in young adults, being misdiagnosed as patent foramen ovale and a preventable trigger of silent cerebral ischemic changes. In the emergency clinical setting, the recommended ischemic stroke workup in patients with RLS should include the influence of postural changes and the effect of Valsalva maneuver on the entity of the RLS on contrast-enhanced transcranial color Doppler ultrasound and the delay in the right inferior pulmonary vein and left heart opacification on contrast-enhanced transthoracic echocardiography. This is in addition to the evaluation of chest X-rays or thoracic computed tomography. We here describe two patients with ischemic stroke due to sporadic and genetic PAVM-associated paradoxical embolism

Recent advances in the application of CE to forensic sciences, an update over years 2009-2011

The present article reviews and comments the applications of capillary electrophoresis in the different areas of forensic sciences covering the time from the second half of 2009 until the first part of 2011, being the latest update of previous reviews covering the years from 2001 to 2009. Numerous articles reporting applications of capillary electrophoresis to analytical problems of potential interest for the forensic researchers and scientists can be found in the most qualified journals of analytical chemistry, analytical biochemistry, pharmacology, toxicology, laboratory medicine, human genetics, etc. However, the present review has been focused on discussing only the most relevant examples of analytical applications of capillary electrophoretic and electrokinetic techniques published in the following fields: (i) illicit and abused drugs, (ii) ions and small molecules of forensic interest, (iii) proteins and peptides of forensic interest, (iv) dyes and inks, (v) forensic DNA. The present review collects and comments on 60 references

Current role of capillary electrophoretic/electrokinetic techniques in forensic toxicology.

The current application of capillary electrophoresisin forensic toxicology has been critically reviewedwith special focus on the areas where this technique hasshown real advantages over chromatographic methods. Forexample, capillary electrophoresis has been most successfullyapplied to the chiral analysis of some drugs of forensicinterest, including amphetamines and their congeners.Another typical application field of capillary electrophoresisis represented by protein analysis. Recently, specialinterest has been paid to carbohydrate deficient transferrin(CDT), the most important biological marker of chronicalcohol abuse. Other specific applications of capillaryelectrophoresis of potential forensic toxicological concernare also discussed. The review includes 62 references