Acetaldehyde as an underestimated risk factor for cancer development: role of genetics in ethanol metabolism

Chronic ethanol consumption is a strong risk factor for the development of certain types of cancer including those of the upper aerodigestive tract, the liver, the large intestine and the female breast. Multiple mechanisms are involved in alcohol-mediated carcinogenesis. Among those the action of acetaldehyde (AA), the first metabolite of ethanol oxidation is of particular interest. AA is toxic, mutagenic and carcinogenic in animal experiments. AA binds to DNA and forms carcinogenic adducts. Direct evidence of the role of AA in alcohol-associated carcinogenesis derived from genetic linkage studies in alcoholics. Polymorphisms or mutations of genes coding for AA generation or detoxifying enzymes resulting in elevated AA concentrations are associated with increased cancer risk. Approximately 40% of Japanese, Koreans or Chinese carry the AA dehydrogenase 2*2 (ALDH2*2) allele in its heterozygous form. This allele codes for an ALDH2 enzyme with little activity leading to high AA concentrations after the consumption of even small amounts of alcohol. When individuals with this allele consume ethanol chronically, a significant increased risk for upper alimentary tract and colorectal cancer is noted. In Caucasians, alcohol dehydrogenase 1C*1 (ADH1C*1) allele encodes for an ADH isoenzyme which produces 2.5 times more AA than the corresponding allele ADH1C*2. In studies with moderate to high alcohol intake, ADH1C*1 allele frequency and rate of homozygosity was found to be significantly associated with an increased risk for cancer of the upper aerodigestive tract, the liver, the colon and the female breast. These studies underline the important role of acetaldehyde in ethanol-mediated carcinogenesis.

Strangulation signs: initial correlation of MRI, MSCT, and forensic neck findings

PURPOSE: To evaluate multislice spiral computed tomography (MSCT) and magnetic resonance imaging (MRI) findings in hanging and manual strangulation cases and compare them with forensic autopsy results. MATERIALS AND METHODS: Postmortem MSCT and MRI of nine persons who died from hanging or manual strangulation were performed. The neck findings were compared with those discovered during forensic autopsy. In addition, two living patients underwent imaging and clinical examination following severe manual strangulation and near-hanging, respectively. For evaluation, the findings were divided into "primary" (strangulation mark and subcutaneous desiccation (i.e., soft-tissue thinning as a result of tissue fluids being driven out by mechanical compression) in hanging, and subcutaneous and intramuscular hemorrhage in manual strangulation) and "collateral" signs. The Wilcoxon two-tailed test was used for statistical analysis of the lymph node and salivary gland findings. RESULTS: In hanging, the primary and most frequent collateral signs were revealed by imaging. In manual strangulation, the primary findings were accurately depicted, with the exception of one slight hemorrhage. Apart from a vocal cord hemorrhage, all frequent collateral signs could be diagnosed radiologically. Traumatic lymph node hemorrhage (P = 0.031) was found in all of the manual strangulation cases. CONCLUSION: MSCT and MRI revealed strangulation signs concordantly with forensic pathology findings. Imaging offers a great potential for the forensic examination of lesions due to strangulation in both clinical and postmortem settings.

Virtopsy: forensic traumatology of the subcutaneous fatty tissue; multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) as diagnostic tools

Traumatic lesions of the subcutaneous fatty tissue provide important clues for forensic reconstruction. The interpretation of these patterns requires a precise description and recording of the position and extent of each lesion. During conventional autopsy, this evaluation is performed by dissecting the skin and subcutaneous tissues in successive layers. In this way, depending on the force and type of impact (right angle or tangent), several morphologically distinct stages of fatty tissue damage can be differentiated: perilobular hemorrhage (I), contusion (II), or disintegration (III) of the fat lobuli, and disintegration with development of a subcutaneous cavity (IV). In examples of virtopsy cases showing blunt trauma to the skin and fatty tissue, we analyzed whether these lesions can also be recorded and classified using multislice computed tomography (MSCT) and magnetic resonance imaging (MRI). MSCT has proven to be a valuable screening method to detect the lesions, but MRI is necessary in order to properly differentiate and classify the grade of damage. These noninvasive radiological diagnostic tools can be further developed to play an important role in forensic examinations, in particular when it comes to evaluating living trauma victims.

Virtual characters designed for forensic assessment and rehabilitation of sex offenders: standardized and made-to-measure

This paper presents two studies pertaining to the use of virtual characters applied in clinical forensic rehabilitation of sex offenders. The first study is about the validation of the perceived age of virtual characters designed to simulate primary and secondary sexual character of typical adult and child individuals. The second study puts to use these virtual characters in comparing a group of sex offenders and a group of non deviant individuals on their sexual arousal responses as recorded in virtual immersion. Finally, two clinical vignettes illustrating the use of made-to-measure virtual characters to more closely fit sexual preferences are presented in Discussion.

Genome sequence, comparative analysis, and population genetics of the domestic horse

We report a high-quality draft sequence of the genome of the horse (Equus caballus). The genome is relatively repetitive but has little segmental duplication. Chromosomes appear to have undergone few historical rearrangements: 53% of equine chromosomes show conserved synteny to a single human chromosome. Equine chromosome 11 is shown to have an evolutionary new centromere devoid of centromeric satellite DNA, suggesting that centromeric function may arise before satellite repeat accumulation. Linkage disequilibrium, showing the influences of early domestication of large herds of female horses, is intermediate in length between dog and human, and there is long-range haplotype sharing among breeds.

Molecular genetics and functional anomalies in a series of 248 Brugada cases with 11 mutations in the TRPM4 channel.

Brugada syndrome (BrS) is a condition defined by ST-segment alteration in right precordial leads and a risk of sudden death. Because BrS is often associated with right bundle branch block and the TRPM4 gene is involved in conduction blocks, we screened TRPM4 for anomalies in BrS cases. The DNA of 248 BrS cases with no SCN5A mutations were screened for TRPM4 mutations. Among this cohort, 20 patients had 11 TRPM4 mutations. Two mutations were previously associated with cardiac conduction blocks and 9 were new mutations (5 absent from ~14'000 control alleles and 4 statistically more prevalent in this BrS cohort than in control alleles). In addition to Brugada, three patients had a bifascicular block and 2 had a complete right bundle branch block. Functional and biochemical studies of 4 selected mutants revealed that these mutations resulted in either a decreased expression (p.Pro779Arg and p.Lys914X) or an increased expression (p.Thr873Ile and p.Leu1075Pro) of TRPM4 channel. TRPM4 mutations account for about 6% of BrS. Consequences of these mutations are diverse on channel electrophysiological and cellular expression. Because of its effect on the resting membrane potential, reduction or increase of TRPM4 channel function may both reduce the availability of sodium channel and thus lead to BrS.

Pulmonary fat embolism - a prospective study within the forensic autopsy collective of th eRepublic of Iceland

In the last century, studies established the origin of pulmonary fat embolism (PFE) and identified mechanical trauma as main source for PFE. This prospective study focused on determining a possible influence of cardiopulmonary resuscitation (CPR), in the context of an aging population, on the occurrence of PFE. Lung tissue samples from 256 bodies were examined using the twin-edged knife technique without preliminary fixation but after staining with Sudan III. PFE grading was determined according to Falzi and performed at a 10× magnification. For statistical analysis, bodies were grouped by age, gender, and putrefaction and categorized following whether they had experienced trauma, CPR, the combination of both, or no mechanical impact. There was a significant correlation of trauma, CPR, and the combination of both to PFE but no noticeable influence of gender or putrefaction. An age over 70 years promotes a PFE due to resuscitation.