Injury pattern and the biomechanical assessment of skull fracture risk in blows with a rubber mallet.

Acts of violence often result in blunt force trauma. On behalf of the court, forensic experts not only have to assess injuries in terms of morphology or severity, but they also have to give statements regarding the risk of potential fatal injuries. We describe a case of domestic violence where a man hit the head of his wife using a rubber mallet. His wife sustained extensive and multiple parietal scalp lacerations and avulsions with exposure of the cranial bone. A CCT revealed neither skull fractures nor intracranial injuries. Biomechanical measurements were performed using a bowling ball and an animal head representing head surrogates. In comparison to steel hammer impacts we hypothesized longer contact durations and lower maximum contact forces in blows with a rubber mallet. However, contact durations in the magnitude of 3ms do not confirm our hypothesis. The contact forces calculated based on mallet and animal head accelerations were between 2.97kN and 4.68kN. These force values are rather below the parietal fracture thresholds, explaining the absence of parietal skull fractures in the case presented. Moreover, the relatively low Young's modulus comes along with a deformation of the rubber mallet and a decrease in contact pressure. In summary, contact times could be reliably estimated, while contact forces remained largely uncertain.

Establishment of two forensic medicine OSCE stations on the subject of external post-mortem examination.

An improvement in quality of medical external post-mortem examinations among others can be achieved by more intensive training of medical students. Modern learning and teaching methods such as e-learning modules and SkillsLab stations should be used for this. The introduction of corresponding methods of assessment such as the OSCE procedure is necessary to test the success of learning. In Halle (Germany), two OSCE stations on the subject of external post-mortem examinations were introduced in 2016. The 'practical external post-mortem examination' station test skills and abilities students have learned during practical external post-mortem examination in small group classes on a simulation doll. At the 'death certificate' station, an original death certificate must be filled in, testing the knowledge, skills and abilities learned in the SkillsLab station and during e-learning. A total of 148 students took part in the test. At both stations, at least two thirds of the students (69.5 and 81.7%) were able to show good or very good test results. In addition to the strengths, a detailed evaluation of the test results showed that there were still deficits in terms of the corresponding courses (e.g. inspection of the neck region in the small group classes), which will have to be remedied in the future. When analysing the test concept and the test implementation, objectivity was nearly perfect. There was a satisfactory internal consistency and stability over 8 months. Ultimately, in addition to several strengths (such as good understanding and transparency of the checklists) the evaluation of the examiners also showed further potential areas for improvement (e.g. harmonisation of the degree of difficulty for the individual rotations) when designing the OSCE stations. Overall, it was possible to determine that the OSCE testing format is a suitable tool to test external post-mortem examination skills and that conclusions about improvements in teaching can also be drawn from this.

In vivo diffusion-weighted MRI using perfluorinated gases: ADC comparison between healthy and elastase-treated rat lungs.

PURPOSE: MRI with perfluorinated gases has been shown as an alternative to hyperpolarized gases to image both microstructure and gas diffusivity in the lung. The aim of this study was to measure diffusion restriction of C2 F6 in rat lungs and to compare the different levels of restriction between healthy and emphysematous tissue. METHODS: For this purpose, two groups of rats-healthy and mono-lobar elastase-induced animals-were measured. While being ventilated with a mixture of C2 F6 and oxygen four diffusion weighted 19F-images where acquired for each animal and corresponding ADC-maps were calculated. RESULTS: No significant apparent diffusion coefficient (ADC) differences were found between healthy lungs; however, the elastase treated lungs showed a significant increase in ADC. CONCLUSION: These results demonstrate that ADC measurements with C2 F6 are sensitive to the microstructure of rat lungs showing that the diffusion of this gas is limited to different levels in healthy and in emphysematous tissue.

Evaluation of body fat composition after linagliptin treatment in a rat model of diet-induced obesity: a magnetic resonance spectroscopy study in comparison with sibutramine.

The effects of linagliptin on fat content in diet-induced obese rats were compared with those of the appetite suppressant sibutramine. Female Wistar rats fed a high-fat diet (HFD) for 3 months received vehicle, linagliptin (10 mg/kg) or sibutramine (5 mg/kg) treatment orally, once daily for 6 additional weeks, while continuing the HFD. Magnetic resonance spectroscopy analysis of fat content was performed at baseline and at the end of the 6-week treatment period. Linagliptin treatment profoundly reduced hepatic fat compared with vehicle, with an effect comparable to that of sibutramine. The vehicle-corrected mean change (95% CI) from baseline in hepatic fat and intramyocellular lipid was -59.0% (-104.3%, -13.6%; p = 0.015) and -62.1% (-131.6%, 7.4%; p = 0.073), respectively, for linagliptin compared with -54.3% (-101.5%, -7.1%; p = 0.027) and -72.4% (-142.4%, -2.4%; p = 0.044), respectively, for sibutramine.

Inhibition of acetyl-CoA carboxylase 2 enhances skeletal muscle fatty acid oxidation and improves whole-body glucose homeostasis in db/db mice.

AIMS/HYPOTHESIS: Excessive ectopic lipid deposition contributes to impaired insulin action in peripheral tissues and is considered an important link between obesity and type 2 diabetes mellitus. Acetyl-CoA carboxylase 2 (ACC2) is a key regulatory enzyme controlling skeletal muscle mitochondrial fatty acid oxidation; inhibition of ACC2 results in enhanced oxidation of lipids. Several mouse models lacking functional ACC2 have been reported in the literature. However, the phenotypes of the different models are inconclusive with respect to glucose homeostasis and protection from diet-induced obesity. METHODS: Here, we studied the effects of pharmacological inhibition of ACC2 using as a selective inhibitor the S enantiomer of compound 9c ([S]-9c). Selectivity was confirmed in biochemical assays using purified human ACC1 and ACC2. RESULTS: (S)-9c significantly increased fatty acid oxidation in isolated extensor digitorum longus muscle from different mouse models (EC(50) 226 nmol/l). Accordingly, short-term treatment of mice with (S)-9c decreased malonyl-CoA levels in skeletal muscle and concomitantly reduced intramyocellular lipid levels. Treatment of db/db mice for 70 days with (S)-9c (10 and 30 mg/kg, by oral gavage) resulted in improved oral glucose tolerance (AUC -36%, p < 0.05), enhanced skeletal muscle 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) uptake, as well as lowered prandial glucose (-31%, p < 0.01) and HbA(1c) (-0.7%, p < 0.05). Body weight, liver triacylglycerol, plasma insulin and pancreatic insulin content were unaffected by the treatment. CONCLUSIONS/INTERPRETATION: In conclusion, the ACC2-selective inhibitor (S)-9c revealed glucose-lowering effects in a mouse model of diabetes mellitus.

Apparent diffusion coefficient of hyperpolarized (3)He with minimal influence of the residual gas in small animals.

The apparent diffusion coefficient (ADC) of hyperpolarized (HP) gases is a parameter that reflects changes in lung microstructure. However, ADC is dependent on many physiological and experimental variables that need to be controlled or specified in order to ensure the reliability and reproducibility of this parameter. A single breath-hold experiment is desirable in order to reduce the amount of consumed HP gas. The application of a positive end-expiratory pressure (PEEP) causes an increase in the residual gas volume. Depending on the applied PEEP, the ratio between the incoming and residual gas volumes will change and the ADC will vary, as long as both gases do not have the same diffusion coefficient. The most standard method for human applications uses air for breathing and a bolus of pure HP (3)He for MRI data acquisition. By applying this method in rats, we have demonstrated that ADC values are strongly dependent on the applied PEEP, and therefore on the residual gas volume in the lung. This outcome will play an important role in studies concerning certain diseases, such as emphysema, which is characterized by an increase in the residual volume. Ventilation with an oxygen-helium mixture (VOHeM) is a proposed single breath-hold method that uses two different gas mixtures (O(2)-(4)He for ventilation and HP (3)He-N(2) for imaging). The concentration of each gas in its respective mixture was calculated in order to obtain the same diffusion coefficient in both mixtures. ADCs obtained from VOHeM are independent of PEEP, thus minimizing the effect of the different residual volumes.

[Assessment of fitness for police custody: the physicians' responsibility and legal liability]. / Gewahrsamstauglichkeitsuntersuchung - Ärztliche Pflicht und rechtliche Verantwortung.

In contrast to several other European countries, German law provides only insufficient regulations on who is responsible for the medical assessment of persons in police custody. The police frequently report that doctors refuse to assess fitness for custody. Under consideration of the current legal background, we will discuss whether and, if so, which physicians can be obligated to carry out these assessments. We also examine a physician's possible exposure to criminal and civil liability if he or she refuses to assess fitness for custody or fails to render a correct assessment.

[Legal consequences in cases of deaths in police custody]. / Strafprozessuale Folgen bei Todesfällen im Polizeigewahrsam.

From 1993 to 2003, 128 people died in police custody in Germany. The autopsy records allowed a more detailed analysis in 60 of these cases. The most frequent cause of death was cerebro-cranial trauma followed by alcohol, drug and medication poisoning. 24 (40%) of those 60 cases led to preliminary proceedings against responsible personnel such as doctors, police officers, paramedics and a hospital nurse. Prosecution later dropped proceedings in 75% of these cases in accordance with Section 170 Subsection 2 of the German Code of Criminal Procedure since there was no criminal conduct. In 2 of the cases, charges were dropped on condition. Only one of these 24 cases led to a conviction by an order of summary punishment. This case study discusses the legal assessment in the light of the high burden of proof required in a criminal case in Germany.

Marfan syndrome: clinical consequences resulting from a medicolegal autopsy of a case of sudden death due to aortic rupture.

To investigate the sudden death of a 31-year-old man, a medicolegal autopsy was performed. Major findings were a dilated aortic root with a longitudinal rupture of the intima and dissection of aorta and right coronary artery and consequent tamponade of the pericardial sac. Moreover, arachnodactyly and other skeletal deformities in combination with the histological finding of a pseudocystic medionecrosis of the aortic wall were noted. By sequencing of the FBN1 gene, a mutation (1622G>A) leading to the diagnosis of Marfan syndrome was found. Genetic counseling was recommended to the relatives who reported that the father of the deceased had died at the same age from aortic rupture. While fortunately the child of the deceased lacked this mutation, it was found in his younger sister. The results of the autopsy thus enabled early diagnosis and beginning of treatment in the sister and thus a considerable statistical increase in lifespan. With this report, we want to show that medicolegal autopsies can also have medical consequences for relatives. We argue that in all sudden and unexpected deaths in young persons up to 35 years an autopsy should be performed, not only to detect unnatural causes of death but also to identify heritable diseases and thus aid the relatives.

Targeted release of oncolytic measles virus by blood outgrowth endothelial cells in situ inhibits orthotopic gliomas.

Malignant gliomas remain largely incurable despite intensive efforts to develop novel therapies. Replicating oncolytic viruses have shown great promise, among them attenuated measles viruses of the Edmonston B strain (MV-Edm). However, host immune response and the infiltrative nature of gliomas limit their efficacy. We show that human blood outgrowth endothelial cells (BOECs), readily expandable from peripheral blood, are easily infected by MV-Edm and allow replication of MV-Edm while surviving long enough after infection to serve as vehicles for MV-Edm (BOEC/MV-Edm). After intravenous and peritumoral injection, BOEC/MV-Edm deliver the viruses selectively to irradiated orthotopic U87 gliomas in mice. At the tumor, MV-Edm produced by the BOECs infect glioma cells. Subsequent spread from tumor cell to tumor cell leads to focal infection and cytopathic effects that decrease tumor size and, in the case of peritumoral injection, prolong survival of mice. Since MV-Edm within BOECs are not readily neutralized and because BOEC/MV-Edm search and destroy glioma cells, BOEC/MV-Edm constitute a promising novel approach for glioma therapy.

DNA polymorphisms in the tyrosine hydroxylase and GNB3 genes: association with unexpected death from acute myocardial infarction and increased heart weight.

Sudden and unexpected death from myocardial infarction (MI) is one of the most commonly observed findings in forensic medicine. To investigate the biochemical and genetic background of this disease we investigated the genotypes for two polymorphisms associated with hypertension: TH01, a tetrameric microsatellite in the tyrosine hydroxylase gene and the single nucleotide polymorphism C825T in the GNB3 gene in 116 sudden deaths from MI (78 males, 38 females) and in a control group of 137 deaths from natural causes other than MI (52 males, 85 females). For TH01 no correlation with the prevalence of MI was found. For C825T, results were different. While for the male individuals allelic frequencies and genotype distributions were similar in both groups, T-homozygosity was significantly more common in female fatalities from MI than in the female control group (24% versus 7%; Relative Risk 2.29). Nevertheless, neither for TH01 nor for C825T an association with heart weight was found. Thus our results demonstrate that the C825T polymorphism may play a role in the development of myocardial infarctions, at least in females. They also demonstrate that the genetic component in complex diseases like MI may depend on the gender of the patients. As the influence of this polymorphism on arterial blood pressure appears to be relatively small, and G-proteins are involved in numerous intracellular signal cascades it can be speculated that T-homozygosity at this locus might influence the incidence or mortality of cardiovascular disease via hitherto unknown mechanisms.

Brain tissue biomechanics in cortical contusion injury: a finite element analysis.

The controlled cortical impact model has been used extensively to study focal traumatic brain injury. Although the impact variables can be well defined, little is known about the biomechanical trauma as delivered to different brain regions. This knowledge however could be valuable for interpretation of experiment (immunohistochemistry etc.), especially regarding the comparison of the regional biomechanical severity level to the regional magnitude of the trauma sequel under investigation. We used finite element (FE) analysis, based on high resolution T2-weighted MRI images of rat brain, to simulate displacement, mean stress, and shear stress of brain during impact. Young's Modulus E, to describe tissue elasticity, was assigned to each FE in three scenarios: in a constant fashion (E = 50 kPa), or according to the MRI intensity in a linear (E = [10, 100] kPa) and inverse-linear fashion (E = [100, 10] kPa). Simulated tissue displacement did not vary between the 3 scenarios, however mean stress and shear stress were largely different. The linear scenario showed the most likely distribution of stresses. In summary, FE analysis seems to be a suitable tool for biomechanical simulation, however, to be closest to reality tissue elasticity needs to be determined with a more specific approach, e.g. by means of MRI elastography.

Sudden cardiac death in hereditary hemochromatosis: an underestimated cause of death?

Hereditary hemochromatosis (HH) is a frequent autosomal recessive disease which causes iron-overload of various organs. Of all northern European affected individuals, 90-95% show 1 of 3 known point mutations in the HFE gene. Symptoms and organs involved can vary considerably: Only a small fraction of the 200,000-400,000 persons affected in Germany develop the classical picture of liver cirrhosis and/or pancreatic fibrosis. Nevertheless, the life expectancy of persons with moderate or even subclinical symptoms is reduced, in many cases due to myocardial damage leading to cardiomyopathy with greatly increased risk of sudden cardiac death. Although the high prevalence of HH suggests that sudden cardiac death due to cardiac HH is a relatively common cause of death, the forensic literature lacks such reports. We present the case of sudden cardiac death in a young man with histological findings of massive cardial hemochromatosis which is characterized by the fact that none of the three known mutations for HH were found. This case demonstrates that genetic screening alone might not be sufficient to identify all persons at risk to developing HH.

Long-time in-vivo metabolic monitoring following experimental brain contusion using proton magnetic resonance spectroscopy.

In a Sham-controlled study we applied proton magnetic resonance spectroscopy (1H-MRS) at 4.7 T to a model of experimental traumatic brain contusion. The time course of cerebral metabolite changes was monitored in serial investigation in 14 Sprague Dawley rats up to 4 weeks after trauma. 6 animals served as controls. 1H-MRS spectra were acquired from a voxel covering the hippocampus/basal ganglia ipsi and contralateral to the lesion. Metabolites ratios of the injured hemisphere were compared to those ipsilateral in Sham animals and to those of the contralateral side in the trauma animals. NAA/Cr ratio and Glu/Cr ratio, possible markers of neuronal loss, persistently decreased after trauma to a minimum of -40% and -20% versus controls, respectively. One week after trauma Cho/Cr ratio was strongly increased by 73%. This might indicate a high inflammatory activity at that time. Lac/Cr ratio showed long-lasting and continuing increases up to 2000% versus controls as a sign of permanently shifted posttraumatic energy metabolism. 1H-MRS proved to be a useful non-invasive method for in-vivo monitoring of posttraumatic metabolism also in models of brain contusion. In single cases however, accompanying haemorrhage can potentially prevent useful data acquisition.

Determination of contusion and oedema volume by MRI corresponds to changes of brain water content following controlled cortical impact injury.

The time-course of brain contusion/oedema development as visualised by high-resolution MRI was compared to brain water content following experimental brain contusion. 36 Sprague-Dawley rats underwent Controlled Cortical Impact Injury (CCII), 24 served as controls. In 16 animals serial T2 weighted MRI investigations at 1 h, 4 h, 24 h and 7 d after CCII were performed, in 44 rats hemispheric brain water content was determined at the same time points by wet dry weight method. MRI lesion volume (mm3) and brain water content of injured hemisphere (%) showed for absolute and relative values a strictly parallel course. Significant posttraumatic increases had a maximum at 24 hours. Values on day 7 were below those of 1st h in both methods. The simple non-invasive MRI method quantifies contusion and surrounding penumbra according to elevated tissue water signal. The invasive wet dry weight method quantifies changes of hemispheric brain water content that are likely to take place in contusion core and surrounding penumbra. Therefore, from a theoretical aspect both methods seem comparable. Following experimental brain contusion, the simple MRI method might be an equally sufficient way to describe post-traumatic or post-therapeutic changes of lesion size and brain oedema.

Assessment of shooting distance on the basis of bloodstain analysis and histological examinations.

A 28-year-old man was shot using a pump-gun. The main question to be resolved was whether the biological stain pattern on the suspect's trousers, and in particular the bloodstains, can provide evidence to assess the shooting distance between the suspect and the position of the victim's body. The biological stain pattern (i.e. bloodstains and brain tissue) showed backspatters from the shot entrance wound on the back of the head, while the victim was lying face down and the suspect was standing close behind his head.

New insights into the hemodynamic blood oxygenation level-dependent response through combination of functional magnetic resonance imaging and optical recording in gerbil barrel cortex.

Fast, low-angle shoot functional magnetic resonance imaging (fMRI), based on the blood oxygenation level-dependent (BOLD) effect, was combined with optical recording of intrinsic signals (ORIS) and 2-deoxyglucose labeling in gerbil barrel cortex. We observed over the activated barrel a positive BOLD signal and increased levels of deoxyhemoglobin and total hemoglobin during each period of prolonged (30 sec) D2 vibrissal stimulation. These data show that the hemodynamic basis of this fMRI signal is not necessarily a washout of deoxyhemoglobin, as generally assumed. Instead, they suggest that a positive BOLD signal can also be caused by a local increase of blood volume, even if deoxyhemoglobin levels are persistently elevated. We also show that this alternative interpretation is consistent with theoretical models of the BOLD signal. The changes in BOLD signal and blood volume, which are most tightly correlated with the periodic stimulation, peak at the site of neuronal activation. These results contribute to the understanding of the hemodynamic mechanisms underlying the BOLD signal and also suggest analysis methods, which improve the spatial localization of neuronal activation with both fMRI and ORIS.

Strain diversity in major surface protein 2 expression during tick transmission of Anaplasma marginale.

Specific major surface protein 2 (MSP2) variants are expressed by Anaplasma marginale within the tick salivary gland and, following transmission, are expressed during acute rickettsemia. In previous work, we have shown that a restricted pattern of MSP2 variants is expressed in the salivary glands of Dermacentor andersoni ticks infected with the South Idaho strain of A. marginale. Now we demonstrate that the identical restriction does not apply to two other strains of A. marginale, and that different variants are also expressed when the same strain is transmitted by different Dermacentor spp. This indicates that antigenic diversity among strains is maintained in tick transmission and may be a significant constraint to MSP2 vaccine development.

1H-MR spectroscopic monitoring of posttraumatic metabolism following controlled cortical impact injury: pilot study.

Proton magnetic resonance spectroscopy (1H-MRS) has been increasingly utilised in experimental traumatic brain injury for characterisation of posttraumatic metabolic dysfunction. Following human brain injury pathological findings correlated with outcome measures. Combined with conventional T2-weighted MR imaging MRS is a sensitive tool to evaluate metabolic changes in brain tissue following trauma. Studies have been restricted so far to diffuse axonal injury models and fluid percussion injury. Using a high resolution scanner at 4.7 T, MRI combined with 1H-MRS was applied in a pilot study to the controlled cortical impact injury model of experimental brain contusion (CCII). Eight Sprague-Dawley rats were investigated, of which two served as controls. Four animals were injured 24 h after craniotomy, two investigated at 72 h post craniotomy. MRS/MRI indicated a transient brain oedema development and metabolic changes induced by the craniotomy itself. Following CCII MRI demonstrated that the area of contusion as well as the surrounding brain oedema increased twofold in size within 24 h (p < 0.05). MRS showed an immediate increase of N-acetylaspartate (NAA) and glutamate ipsilateral to the contusion and a drop of NAA on the contralateral side. MRS/MRI investigations in the CCII model demonstrated a potential to further elucidate the pathophysiology following traumatic brain contusion.