Nonnatural deaths among users of illicit drugs: pathological findings and illicit drug abuse stigmata.

The aim of the study was to provide information on illicit drug abuse stigmata and general pathological findings among an adult narcotic drug-using population aged 20 to 59 years whose death was nonnatural. A total of 1603 medicolegal autopsy reports from 2000 to 2009 concerning cases positive for morphine, heroin, amphetamines, ecstasy, cannabis, LSD (lysergic acid diethylamide), PCP (phencyclidine), and high levels of GHB (γ-hydroxybutyric acid) in addition to methadone and buprenorphine were investigated. Reported findings of hepatitis, portal lymphadenopathy, recent injection marks, drug user's equipment, and numbers of significant pathological conditions were registered and analyzed according to cases positive for opiates, opioids (OPs), and central nervous system (CNS)-stimulating illicit drugs, respectively. Of the selected cases, 1305 were positive for one or more opiate or OP. Cases positive for OPs had significantly more findings of noninfectious pathological conditions. Hepatitis, portal lymphadenopathy, recent injections marks findings of drug user's equipment were all findings found more frequently among the opiate OP-positive individuals. Portal lymphadenopathy was significantly more often found in cases with hepatitis than in cases with other or no infection. In the population positive for CNS stimulants, hepatitis recent injection marks were more frequent findings than in the CNS stimulant-negative group, irrespective of whether they were opiate OP positive or negative.

Lung tissue injury and hemodynamic effects of ventilations synchronized or unsynchronized to continuous chest compressions in a porcine cardiac arrest model.

Aim: Compare lung injury and hemodynamic effects in synchronized ventilations (between two chest compressions) vs. unsynchronized ventilations during cardiopulmonary resuscitation (CPR) in a porcine model of cardiac arrest. Methods: Twenty pigs were randomized to either synchronized or unsynchronized group. Ventricular fibrillation was induced electrically and left for 1.5 minutes. Four minutes of basic chest compression:ventilation (30:2) CPR was followed by eight minutes of either synchronized or unsynchronized ventilations (10/min) during continuous compressions before defibrillation was attempted. Aortic, right atrial and intracerebral pressures, carotid and cerebral blood flow and cardiac output were measured. Airway monitoring included capnography and respiratory function monitor. Macro- and microscopic lung injuries were assessed post-mortem. Results: There were no significant differences between groups in any of the measured hemodynamic variables or inspiration time (0.4 vs. 1.0 s, p = 0.05). The synchronized ventilation group had lower median peak inspiratory airway pressure (57 vs. 94 cm H2O, p < 0.001), lower minute ventilation (3.7 vs. 9.4 l min-1, p < 0.001), lower pH (7.31 vs. 7.53, p < 0.001), higher pCO2 (5.2 vs. 2.5 kPa, p < 0.001) and lower pO2 (31.6 vs. 54.7 kPa, p < 0.001) compared to the unsynchronized group after 12 minutes of CPR. There was significant lung injury after CPR in both synchronized and unsynchronized groups. Conclusion: Synchronized and unsynchronized ventilations resulted in similar hemodynamics and lung injury during continuous mechanical compressions of pigs in cardiac arrest. Animals that received unsynchronized ventilations with one second inspiration time at a rate of ten ventilations per minute were hyperventilated and hyperoxygenated.Institutional protocol number: FOTS, id 6948.

Telomere instability detected in sporadic colon cancers, some showing mutations in a mismatch repair gene.

Human telomeres are essential for genome stability and are composed of long simple tandem repeat arrays (STRs), comprising the consensus TTAGGG repeat interspersed, at the proximal end, with sequence-variant repeats. While the dynamics of telomere attrition through incomplete replication has been studied extensively, the effects on telomeres of error-prone DNA repair processes, known to affect other STRs, are poorly understood. We have compared the TTAGGG and sequence-variant interspersion patterns in the proximal 720 bp of telomeres in colon cancer and normal DNA samples. The frequency of telomere mutations was 5.8% per allele in a randomly collected panel of sporadic colon cancers, showing that telomere mutations occur in vivo. The mutation frequency rose to 18.6% per allele in sporadic tumours that exhibit instability at the polyA tract in the TGFbetaRII gene and to 35% per allele in tumours with somatic mutations in the hMSH2 gene. The majority of the characterized mutations resulted in the loss of one or a few repeats. If the mutation spectrum and frequency described here is reiterated in the rest of the array, there is the potential for extensive telomere destabilization especially in mismatch repair-defective cells. This may in turn lead to a greater requirement for telomere length maintenance earlier in tumourigenesis.

Collaborative EDNAP exercise on the IrisPlex system for DNA-based prediction of human eye colour.

The IrisPlex system is a DNA-based test system for the prediction of human eye colour from biological samples and consists of a single forensically validated multiplex genotyping assay together with a statistical prediction model that is based on genotypes and phenotypes from thousands of individuals. IrisPlex predicts blue and brown human eye colour with, on average, >94% precision accuracy using six of the currently most eye colour informative single nucleotide polymorphisms (HERC2 rs12913832, OCA2 rs1800407, SLC24A4 rs12896399, SLC45A2 (MATP) rs16891982, TYR rs1393350, and IRF4 rs12203592) according to a previous study, while the accuracy in predicting non-blue and non-brown eye colours is considerably lower. In an effort to vigorously assess the IrisPlex system at the international level, testing was performed by 21 laboratories in the context of a collaborative exercise divided into three tasks and organised by the European DNA Profiling (EDNAP) Group of the International Society of Forensic Genetics (ISFG). Task 1 involved the assessment of 10 blood and saliva samples provided on FTA cards by the organising laboratory together with eye colour phenotypes; 99.4% of the genotypes were correctly reported and 99% of the eye colour phenotypes were correctly predicted. Task 2 involved the assessment of 5 DNA samples extracted by the host laboratory from simulated casework samples, artificially degraded, and provided to the participants in varying DNA concentrations. For this task, 98.7% of the genotypes were correctly determined and 96.2% of eye colour phenotypes were correctly inferred. For Tasks 1 and 2 together, 99.2% (1875) of the 1890 genotypes were correctly generated and of the 15 (0.8%) incorrect genotype calls, only 2 (0.1%) resulted in incorrect eye colour phenotypes. The voluntary Task 3 involved participants choosing their own test subjects for IrisPlex genotyping and eye colour phenotype inference, while eye photographs were provided to the organising laboratory and judged; 96% of the eye colour phenotypes were inferred correctly across 100 samples and 19 laboratories. The high success rates in genotyping and eye colour phenotyping clearly demonstrate the reproducibility and the robustness of the IrisPlex assay as well as the accuracy of the IrisPlex model to predict blue and brown eye colour from DNA. Additionally, this study demonstrates the ease with which the IrisPlex system is implementable and applicable across forensic laboratories around the world with varying pre-existing experiences.