ABSTRACT
The formation of red discolorations ('blood stains') on the Turin Shroud (TS), a Christian relic believed to be the burial cloth of Jesus of Nazareth, is controversially discussed. We performed experiments to identify possible explanations for the formation of the stains on the hands and forearms of the Turin Shroud Man (TSM). In preliminary non-standardised experiments, after applying blood to the dorsal and palmar side of the probands' wrists, they moved their arms around at their own discretion to provoke blood flows as similar as possible to those on the TS. A blood stain pattern similar to that on the left wrist could be provoked by slowly turning the wrist to the ulnar side. In contrast, a branched pattern of multiple streaks, as depicted on the forearms, was difficult to reproduce. In a standardised test setup, the probands moved their dry, dirtied, or oiled arms jerkily in a predetermined sequence of movements. More body hair only slightly facilitated the formation of a branched pattern. On oiled skin, however, the formation of branches was significantly facilitated. This may support the hypothesis that the blood stains on the forearms were formed by moving the body between the unnailing and the burial. The formation of a branched pattern seems feasible if the arms were moved jerkily and were possibly exposed to water and oils postmortem (e.g. transporting the washed and oiled body). Nevertheless, the well-defined blood stains with multiple branchings are difficult to explain. Additionally, the blood stains on the forearms may have originated from deep scourging wounds, where dried blood was again mobilised by water (and oil). We are aware that no reliable conclusions about the formation of the 'blood stains' on the TS can be drawn from our findings. However, they may contribute to the discussion on this topic.
Subject(s)
Blood Stains , Hand , Humans , Male , Nails , Forearm/blood supplyABSTRACT
Synthetic cannabinoids become increasingly popular as a supposedly safe and legal alternative to cannabis. In order to circumvent the German New Psychoactive Substances Law, producers of so-called herbal mixtures rapidly design new substances with structural alterations that are not covered by the law. Acting as full agonists not only at the cannabinoid receptors 1 and 2, synthetic cannabinoids might have not only desired mental but also serious physical adverse effects. However, knowledge of adverse effects of specific substances is sparse and incomplete. This also accounts for 5F-Cumyl-PEGACLONE, a synthetic cannabinoid, which has been detected regularly in Germany in recent years. By using an animal model, the isolated perfused Langendorff heart, the study at hand aimed on finding out more about possible cardiovascular adverse effects of 5F-Cumyl-PEGACLONE. Hearts of male Wistar rats, which were excised postmortem, were exposed to two different concentrations of 5F-Cumyl-PEGACLONE: 13 hearts were exposed to 50 ng/ml and 12 hearts were exposed to 100 ng/ml. Thirteen control hearts were merely exposed to an additional amount of buffer solution. Functional parameters heart rate, minimal and maximum left ventricular pressure and coronary flow were documented at pre-defined time points during and after the administration of 5F-Cumyl-PEGACLONE/additional buffer solution. Electrocardiograms (ECGs) were documented throughout the experiments and evaluated afterwards. Kruskal-Wallis analysis was performed for each functional parameter as well as for the duration of the QRS complexes and the duration of RR intervals as derived from the ECGs. Furthermore, a multivariate analysis, comprising all functional and ECG parameters, was performed. Kruskal-Wallis analysis revealed only single significant p-values for QRS duration and minimum left ventricular pressure that did not pass a Bonferroni test. The results of the multivariate approach were also comparably homogeneous, but still the model correctly recognized hearts exposed to 100 ng/ml of 5F-Cumyl-PEGACLONE more often than hearts exposed to the low concentration of 5F-Cumyl-PEGACLONE or additional buffer solution. Evaluation of the ECGs presented single cases of ST depression and QT prolongation. Though certainly not unambiguous, these findings support the assumption that 5F-Cumyl-PEGACLONE can cause severe, if not lethal, cardiac adverse effects like arrhythmias or myocardial infarctions especially if it is consumed in combination with other drugs like alcohol or if the consumer suffers from pre-existing heart diseases.
Subject(s)
Cannabinoids , Cannabis , Hallucinogens , Male , Rats , Animals , Rats, Wistar , Cannabinoids/analysisABSTRACT
The Turin Shroud (TS) is a Christian relic interpreted to be the burial cloth of Jesus of Nazareth. It exhibits red discolorations that have been interpreted as blood stains and that are the subjects of a highly controversial discussion. We conducted experiments to identify theoretically possible explanations for the stains attributed to the crown of thorns, the lance wound and the belt of blood. In the experiments with a focus on the stains attributed to the crown of thorns, a very similar stain pattern as on the TS could be provoked by simulating the following sequence of events: blood from antemortem scalp wounds is covering hair and face; blood is coagulating and/or drying; blood components are mobilised by postmortem washing and oiling. A stain pattern very similar to the belt of blood on the TS was successfully provoked by simulating the following sequence of events: The body is lying in a supine position, blood or bloodied water flowing from a wound at the right lateral chest wall; the body is rotated to the left side; the Shroud is tucked under the back; the body is rotated back to a supine position and laid onto the Shroud. The so-called serum ring surrounding the stain attributed to the lance wound could be reproduced by sequential application of serum and whole blood samples or of pleural effusion and whole blood samples onto cotton cloth. It is obvious that any attempt to interpret the assumed blood stain pattern on the TS has serious limitations. Nevertheless, it seems remarkable that we were able to reproduce findings that appear to be very similar to stains on the TS.
Subject(s)
Blood Stains , Humans , Coloring Agents , Christianity , Autopsy , ClothingABSTRACT
BACKGROUND: Workplace violence is widespread, but studies on workplace violence against health professions in outpatient settings are sparse. We aimed to examine, for the first time, the prevalence of workplace violence against medical assistants as well as potential sociodemographic, occupational and health-related correlates of the exposure to workplace violence. METHODS: We used data from a survey (03-05/2021) among medical assistants in Germany (n = 424). We assessed the 12-month prevalence (yes/no) of verbal violence, physical violence, and sexual harassment as well as the types of perpetrators of workplace violence. Further, information was gathered on sociodemographic (e.g., age, educational level), occupational (e.g., years in job), and mental health-related factors (i.e., anxiety, depression). The 12-month prevalences of the different types of workplace violence were merged into a single variable ("any workplace violence" vs. none) for association analysis. We ran multivariable Poisson regression models to examine potential associations between sociodemographic and occupational correlates (i.e., independent variables) with any workplace violence as dependent variable and in addition between any workplace violence (independent variable) and dichotomized mental health as dependent variable. RESULTS: Overall, 59.4% of the medical assistants reported verbal violence, 5.9% reported physical violence, 3.8% reported sexual harassment, and 60.1% reported any workplace violence in the previous 12 months. Patients were reported to be the main perpetrators, followed by patients' relatives. Younger age, being single, and working in a medical care center were sociodemographic and occupational correlates of workplace violence (PRs ≥ 1.27). Workplace violence was significantly associated with mental health variables (PRs ≥ 1.72). CONCLUSION: Medical assistants experience workplace violence, in particular verbal violence. To devise preventive measures, prospective studies are needed to confirm the potential risk groups for workplace violence and the potential mental health sequels of workplace violence observed in our study.
Subject(s)
Workplace Violence , Humans , Cross-Sectional Studies , Prevalence , Surveys and Questionnaires , Physical Abuse , Workplace/psychologyABSTRACT
Age-at-death estimation is of great relevance for the identification of unknown deceased individuals. In skeletonised corpses, teeth and bones are theoretically available for age estimation, but in many cases, only single bones or even only bone fragments are available for examination. In these cases, conventional morphological methods may not be applicable, and the application of molecular methods may be considered. Protein-based molecular methods based on the D-aspartic acid (D-Asp) or pentosidine (Pen) content have already been successfully applied to bone samples. However, the impact of the analysed type of bone has not yet been systematically investigated, and it is still unclear whether data from samples of one skeletal region (e.g. skull) can also be used for age estimation for samples of other regions (e.g. femur). To address this question, D-Asp and Pen were analysed in bone samples from three skeletal regions (skull, clavicle, and rib), each from the same individual. Differences between the bone types were tested by t-test, and correlation coefficients (ρ) were calculated according to Spearman. In all types of bone, an age-dependent accumulation of D-Asp and Pen was observed. However, both parameters (D-Asp and Pen) exhibited significant differences between bone samples from different anatomical regions. These differences can be explained by differences in structure and metabolism in the examined bone types and have to be addressed in age estimation based on D-Asp and Pen. In future studies, bone type-specific training and test data have to be collected, and bone type-specific models have to be established.
Subject(s)
D-Aspartic Acid , Fractures, Bone , Humans , D-Aspartic Acid/analysis , Proteins , Skull , CadaverABSTRACT
If the patient is unable to appear in court due to illness, a certificate of incapacity to stand trial or travel (civil resp. criminal law) must be submitted. METHODS: Over a period of 2;2 years, 34 certificates submitted in the context of criminal or civil proceedings at 4 different district and regional courts were analyzed anonymously. RESULTS: Major deficiencies in the content of the certificates were revealed. As a rule, certificates were submitted without justification for the stated inability to stand trial, or certificates of incapacity for work were submitted instead. The role of the physician as an expert witness, which should enable the court to make an independent decision, was exercised only very occasionally. DISCUSSION: The deficiencies shown are probably due to uncertainties in the issuance of the certificates. It is important that the certificate contains a diagnosis, the underlying diagnostics, the type and probable duration of the assumed incapacity and a generally understandable, sufficient justification for this.
Subject(s)
Expert Testimony , HumansABSTRACT
Temperature-based methods are widely accepted as the gold standard for death time estimation. In the absence of any other information, the nomogram method generally assumes that a person died with a core body temperature of approximately 37.2 °C. Nevertheless, several external and internal factors may alter the body temperature during agony. A retrospective medical record analysis was carried out on in-hospital death cases from two consecutive years of surgical intensive care units to determine the effects of factors influencing the core body temperature at the point of death. Data from 103 case files were included in the statistical data evaluation. The body temperature fluctuated between and within individuals over time. No clear correlation to certain death groups was observed. Even primary cardiac deaths showed broad intervals of temperatures at the point of death. Men seem to die with higher body temperatures than women. The presented data highlight potential biases for death time estimations when generally assuming a core body temperature of 37.2 °C. In conclusion, the estimation of the time of death should include various methods, including a non-temperature-dependent method. Any uncertainties regarding the body temperature at point of death need to be resolved (e.g. by identifying fever constellations) and elucidated if elimination is not possible.
Subject(s)
Body Temperature , Fever , Female , Hospital Mortality , Hospitals , Humans , Male , Retrospective StudiesABSTRACT
BACKGROUND: Sexual and domestic violence against women and young girls are widespread and can lead to significant psychological, psychosocial and health consequences for the victims. "Confidential Securing of Evidence" ("vertrauliche Spurensicherung", VSS) offers victims the opportunity to have the consequences of the violent acts they have suffered documented without primary police involvement, thus gaining time for decision-making. However, VSS and, in general, the care for victims of violence pose special challenges to physicians. In North Rhine-Westphalia, the documentation app iGOBSIS was developed in a project to support physicians in the care for victims of violence, especially in the VSS. OBJECTIVES: The aim of the work was to clarify how physicians in North Rhine-Westphalia evaluate the functionality of violence victim care and VSS. Specifically, main deficits were to be identified, and suggestions and recommendations for optimizing care and VSS be explored. MATERIALS AND METHODS: Interviews with 39 physicians were conducted in focus groups and analyzed using qualitative content analysis. RESULTS: Medical care for victims of violence and VSS are mainly complicated by stress and time constraints and lack of professional qualification. There is a need for more public relations and educational work, better professional qualification, consistent documentation and secure funding. CONCLUSIONS: Readily available forensic medical support for documentation that will hold up in court, secure funding, networking and public relations are important elements to ensure good medical care for victims of violence and a functional VSS.
Subject(s)
Domestic Violence , Physicians , Documentation , Female , Germany , Humans , Qualitative ResearchABSTRACT
The diagnosis of death due to violent asphyxiation may be challenging if external injuries are missing, and a typical acute emphysema (AE) "disappears" in pre-existing chronic emphysema (CE). Eighty-four autopsy cases were systematically investigated to identify a (histo-) morphological or immunohistochemical marker combination that enables the diagnosis of violent asphyxiation in cases with a pre-existing CE ("AE in CE"). The cases comprised four diagnostic groups, namely "AE", "CE", "acute and chronic emphysema (AE + CE)", and "no emphysema (NE)". Samples from all pulmonary lobes were investigated by conventional histological methods as well as with the immunohistochemical markers Aquaporin 5 (AQP-5) and Surfactant protein A1 (SP-A). Particular attention was paid to alveolar septum ends ("dead-ends") suspected as rupture spots, which were additionally analyzed by transmission electron microscopy. The findings in the four diagnostic groups were compared using multivariate analysis and 1-way ANOVA analysis. All morphological findings were found in all four groups. Based on histological and macroscopic findings, a multivariate analysis was able to predict the correct diagnosis "AE + CE" with a probability of 50%, and the diagnoses "AE" and "CE" with a probability of 86% each. Three types of "dead-ends" could be differentiated. One type ("fringed ends") was observed significantly more frequently in AE. The immunohistochemical markers AQP-5 and SP-A did not show significant differences among the examined groups. Though a reliable identification of AE in CE could not be achieved using the examined parameters, our findings suggest that considering many different findings from the macroscopical, histomorphological, and molecular level by multivariate analysis is an approach that should be followed.
Subject(s)
Emphysema , Pulmonary Emphysema , Asphyxia/pathology , Autopsy , Emphysema/metabolism , Emphysema/pathology , Humans , Lung/pathology , Pulmonary Emphysema/diagnosis , Pulmonary Emphysema/pathologyABSTRACT
Genetic analyses such as STR-typing are routinely used for identification purposes in forensic casework. Although genotyping techniques only require a minimum amount of DNA to provide a genetic profile, DNA quality differs not only between but also within tissues during ongoing decomposition. Initiated by a recent case where, due to the constitution of the body, preferred tissue was not available or only resulted in a partial and not usable DNA profile, the analysis of intervertebral discs as a source of DNA was considered. As the analysis of this tissue resulted in a high quality DNA profile a further study was performed in which thirty intervertebral discs dissected from bodies in different stages of decay were analyzed. All samples yielded good quality DNA in quantities suitable for STR-based amplification with no or only low degradation indices, resulting in complete genetic profiles. These results demonstrate the robustness of human intervertebral disc tissue as a source of DNA for molecular identification purposes.
Subject(s)
DNA Fingerprinting , Intervertebral Disc , DNA , DNA Degradation, Necrotic , Humans , Microsatellite RepeatsABSTRACT
Specifying a singular specific cause of death or an appropriate causal chain in the death certificate can be challenging, especially in cases of elderly, multimorbid deceased persons.The German cause of death statistics suggest that mental illnesses, including dementia, are beneath the most frequent causes of death. But when looking at death certificates in the context of dementia considerable information gaps and a lack of plausibility in the causal chain can be observed quite regularly.In this article we give recommendations for the correct designation of the cause of death and underlying diseases in the death certificate. These recommendations are not only to be seen against an academic background. The correct registration of dementia in the causes of death statistics may be a basis for decision making in health politics and is hence in the interest of optimal patient care.
Subject(s)
Cause of Death , Death Certificates , Dementia , Health Policy , Humans , MultimorbidityABSTRACT
It has already been proposed that a combined use of different molecular and morphological markers of aging in multivariate models may result in a greater accuracy of age estimation. However, such an approach can be complex and expensive, and not every combination may be useful. The significance and usefulness of combined analyses of D-aspartic acid in dentine, pentosidine in dentine, DNA methylation in buccal swabs at five genomic regions (PDE4C, RPA2, ELOVL2, DDO, and EDARADD), and third molar mineralization were tested by investigating a sample of 90 oral surgery patients. Machine learning models for age estimation were trained and evaluated, and the contribution of each parameter to multivariate models was tested by assessment of the predictor importance. For models based on D-aspartic acid, pentosidine, and the combination of both, mean absolute errors (MAEs) of 2.93, 3.41, and 2.68 years were calculated, respectively. The additional inclusion of the five DNAm markers did not improve the results. The sole DNAm-based model revealed a MAE of 4.14 years. In individuals under 28 years of age, the combination of the DNAm markers with the third molar mineralization stages reduced the MAE from 3.85 to 2.81 years. Our findings confirm that the combination of parameters in multivariate models may be very useful for age estimation. However, the inclusion of many parameters does not necessarily lead to better results. It is a task for future research to identify the best selection of parameters for the different requirements in forensic practice.
Subject(s)
Age Determination by Teeth/methods , Adolescent , Adult , Aged , Arginine/analogs & derivatives , Arginine/metabolism , Biomarkers/metabolism , Child , CpG Islands/genetics , Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism , D-Aspartate Oxidase/metabolism , D-Aspartic Acid/metabolism , DNA Methylation , Dentin/metabolism , Edar-Associated Death Domain Protein/metabolism , Fatty Acid Elongases/metabolism , Humans , Lysine/analogs & derivatives , Lysine/metabolism , Machine Learning , Middle Aged , Molar, Third/growth & development , Multivariate Analysis , Replication Protein A/metabolism , Tooth Calcification , Young AdultABSTRACT
BACKGROUND: Autopsies regularly aim to clarify the cause of death; however, relatives may directly benefit from autopsy results in the setting of heritable traits ("mortui vivos docent"). CASE PRESENTATION: A case of a sudden unexpected cardiac death of a 5.5-months-old child is presented. Autopsy and thorough postmortem cardiac examinations revealed a massively enlarged heart with endomyocardial fibroelastosis. Postmortem molecular testing (molecular autopsy) revealed an unusual combination of two biparental MYBPC3 gene mutations likely to underlie the cardiac abnormalities. Thus, the molecular autoptic findings also had consequences for the relatives of the deceased child and impact on further family planning. CONCLUSIONS: The presented case highlights the need for clinical autopsies including cardiac examinations and postmortem molecular testing; it also paves the way for further cascade screening of family members for cardiac disease, if a distinct genetic disorder is suspected.
Subject(s)
Carrier Proteins/genetics , Death, Sudden, Cardiac/etiology , Endocardial Fibroelastosis/genetics , Mutation , Autopsy , Cardiomegaly/genetics , Cardiomegaly/pathology , DNA Mutational Analysis , Death, Sudden, Cardiac/pathology , Endocardial Fibroelastosis/pathology , Fatal Outcome , Genetic Predisposition to Disease , Heredity , Heterozygote , Humans , Infant , Male , Myocardium/pathology , Pedigree , PhenotypeABSTRACT
Age at death estimation in cases of human skeletal finds is an important task in forensic medicine as well as in anthropology. In forensic medicine, methods based on "molecular clocks" in dental tissues and bone play an increasing role. The question, whether these methods are applicable also in cases with post-depositional intervals far beyond the forensically relevant period, was investigated for two "protein clocks", the accumulation of D-aspartic acid (D-Asp) and the accumulation of pentosidine (Pen) in dentine. Eight teeth of skeletons from different burial sites in Austria and with post-depositional intervals between c. 1216 and c. 8775 years were analysed. The results of age at death estimation based on D-Asp and Pen in dentine were compared to that derived from a classical morphological examination. Age at death estimation based on D-Asp resulted consistently in false high values. This finding can be explained by a post-mortem accumulation of D-Asp that may be enhanced by protein degradation. In contrast, the Pen-based age estimates fitted well with the morphological age diagnoses. The described effect of post-mortem protein degradation is negligible in forensically relevant time horizons, but not for post-depositional intervals of thousands of years. That means that the "D-Asp clock" loses its functionality with increasing post-depositional intervals, whereas Pen seems to be very stable. The "Pen-clock" may have the potential to become an interesting supplement to the existing repertoire of methods even in cases with extremely long post-depositional intervals. Further investigations have to test this hypothesis.
Subject(s)
Age Determination by Teeth/methods , Arginine/analogs & derivatives , D-Aspartic Acid/analysis , Dentin/chemistry , Lysine/analogs & derivatives , Arginine/analysis , Austria , Body Remains , Forensic Anthropology , Forensic Medicine , Humans , Lysine/analysis , Time FactorsABSTRACT
Age estimation based on the analysis of DNA methylation patterns has become a focus of forensic research within the past few years. However, there is little data available regarding postmortem DNA methylation analysis yet, and literature mainly encompasses analysis of blood from corpses without any signs of decomposition. It is not entirely clear yet which other types of specimen are suitable for postmortem epigenetic age estimation, and if advanced decomposition may affect methylation patterns of CpG sites. In living persons, buccal swabs are an easily accessible source of DNA for epigenetic age estimation. In this work, the applicability of this approach (buccal swabs as source of DNA) under different postmortem conditions was tested. Methylation levels of PDE4C were investigated in buccal swab samples collected from 73 corpses (0-90 years old; mean: 51.2) in different stages of decomposition. Moreover, buccal swab samples from 142 living individuals (0-89 years old; mean 41.2) were analysed. As expected, methylation levels exhibited a high correlation with age in living individuals (training set: r2 = 0.87, validation set: r2 = 0.85). This was also the case in postmortem samples (r2 = 0.90), independent of the state of decomposition. Only in advanced putrified cases with extremely low DNA amounts, epigenetic age estimation was not possible. In conclusion, buccal swabs are a suitable and easy to collect source for DNA methylation analysis as long as sufficient amounts of DNA are present.
Subject(s)
Aging/genetics , Cyclic Nucleotide Phosphodiesterases, Type 4/genetics , DNA Methylation , Mouth Mucosa/chemistry , Postmortem Changes , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , CpG Islands/genetics , Epigenesis, Genetic , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Real-Time Polymerase Chain Reaction , Young AdultABSTRACT
The temperature-based "Henssge method" is widely applied for death time estimation. For cases with a sudden post-mortem (pm) change in ambient temperature (e.g., by bringing the deceased into a cooling chamber), a mathematical approach has already been proposed [1] that enables estimation of the time of death by back-calculation of body temperature. This approach was evaluated under clinically controlled conditions. Twenty-five individuals who died in a neurosurgical intensive care unit were brought to cooling storage after approximately 3 h pm. Body temperature was repeatedly measured on the ward and in cooling storage over a period of 9 h pm. Back-calculation of body temperature was carried out on the basis of the proposed mathematical approach for cases with pm changes in ambient temperature; the results were compared to the known body temperatures. In many cases, the back-calculated and true body temperatures differed widely. Bodies regularly cooled down slower after being brought into cooling storage than the back-calculations indicated. The sudden change in ambient temperature could only be addressed roughly by the proposed method of back-calculation. In conclusion, the evaluated approach for addressing pm changes in ambient temperature should only be applied with great caution.
Subject(s)
Cold Temperature , Models, Biological , Postmortem Changes , Specimen Handling , Body Temperature , Humans , Time FactorsABSTRACT
There is a growing perception that DNA methylation may be influenced by exogenous and endogenous parameters. Knowledge of these factors is of great relevance for the interpretation of DNA-methylation data for the estimation of chronological age in forensic casework. We performed a literature review to identify parameters, which might be of relevance for the prediction of chronological age based on DNA methylation. The quality of age predictions might particularly be influenced by lifetime adversities (chronic stress, trauma/post-traumatic stress disorder (PTSD), violence, low socioeconomic status/education), cancer, obesity and related diseases, infectious diseases (especially HIV and Cytomegalovirus (CMV) infections), sex, ethnicity and exposure to toxins (alcohol, smoking, air pollution, pesticides). Such factors may alter the DNA methylation pattern and may explain the partly high deviations between epigenetic age and chronological age in single cases (despite of low mean absolute deviations) that can also be observed with "epigenetic clocks" comprising a high number of CpG sites. So far, only few publications dealing with forensic age estimation address these confounding factors. Future research should focus on the identification of further relevant confounding factors and the development of models that are "robust" against the influence of such biological factors by systematic investigations under targeted inclusion of diverse and defined cohorts.
Subject(s)
Aging/genetics , CpG Islands , DNA Methylation , Epigenomics/methods , Forensic Genetics/methods , Female , Humans , MaleABSTRACT
BACKGROUND: Age-associated DNA methylation changes provide a promising biomarker for the aging process. While genome-wide DNA methylation profiles enable robust age-predictors by integration of many age-associated CG dinucleotides (CpGs), there are various alternative approaches for targeted measurements at specific CpGs that better support standardized and cost-effective high-throughput analysis. RESULTS: In this study, we utilized 4647 Illumina BeadChip profiles of blood to select CpG sites that facilitate reliable age-predictions based on pyrosequencing. We demonstrate that the precision of DNA methylation measurements can be further increased with droplet digital PCR (ddPCR). In comparison, bisulfite barcoded amplicon sequencing (BBA-seq) gave slightly lower correlation between chronological age and DNA methylation at individual CpGs, while the age-predictions were overall relatively accurate. Furthermore, BBA-seq data revealed that the correlation of methylation levels with age at neighboring CpG sites follows a bell-shaped curve, often associated with a CTCF binding site. We demonstrate that within individual BBA-seq reads the DNA methylation at neighboring CpGs is not coherently modified, but reveals a stochastic pattern. Based on this, we have developed a new approach for epigenetic age predictions based on the binary sequel of methylated and non-methylated sites in individual reads, which reflects heterogeneity in epigenetic aging within a sample. CONCLUSION: Targeted DNA methylation analysis at few age-associated CpGs by pyrosequencing, BBA-seq, and particularly ddPCR enables high precision of epigenetic age-predictions. Furthermore, we demonstrate that the stochastic evolution of age-associated DNA methylation patterns in BBA-seq data enables epigenetic clocks for individual DNA strands.
Subject(s)
Aging/genetics , DNA Methylation , Epigenesis, Genetic/physiology , Epigenomics/methods , High-Throughput Nucleotide Sequencing , Blood/metabolism , Genetic Markers , HumansABSTRACT
Alcohol is the most widely used recreational drug in Western countries. It affects the psychophysical performance in different ways, e.g. by reducing cognitive functions, causing coordination disturbances or impairing vision. Visual impairments both concern oculomotor and visual sensory functions, such as decreased mesopic vision, decreased field of vision and an increase of saccadic eye movements. During cycling trials with alcoholised test persons, repeated measurements of (1.) the time needed to read a 50-word text, (2.) the time to perform a swing test by tenfold touching the moving fingertip of the examiner, and (3.) the amplitude of fusion were carried out. The results of these tests were further evaluated to test the hypothesis that impaired vision is significantly correlated to reduced cycling performances of alcoholised persons. In a second step, it was examined which test is most useful to identify alcohol intoxicated cyclists. The ophthalmologic examination results of the groups of best and worst cycling-performing test persons at blood alcohol levels between 0.10% and 0.15% were set into relation to the documented allocated demerits. Additionally, the individual results of these persons were compared to the state of soberness. The time needed to read a 50-word text significantly correlated with the cycling performance. As this is an easy and objective test, it might contribute to a synoptic evaluation of the psychophysical performance of a drunken cyclist.
Subject(s)
Alcohol Drinking/adverse effects , Alcohol Drinking/physiopathology , Adolescent , Adult , Alcohol Drinking/psychology , Bicycling , Cognition , Female , Humans , Male , Middle Aged , Saccades , Vision, Ocular , Young AdultABSTRACT
Palmar plantar erythrodysesthesia (hand-foot syndrome, HFS) is a common adverse event of treatment with cytostatic chemotherapeutics such as capecitabine. Histopathological findings are nonspecific and may even include generalized epidermal necrolysis. A total of 50 patients were examined before and after the intake of capecitabine to assess if HFS may result in relevant changes of the palmar epidermal ridge configurations with possible consequences for the patients who want to travel abroad. In total, 14 of the 50 patients developed HFS (28%) with HFS grades 1-3 observed. HFS grade 4 was not observed. HFS of grade 2 and 3 was associated with a temporary macroscopic loss of the epidermal ridges. No dactyloscopic changes that might have led to a false identification were seen in those cases. Patients with a risk of HFS development who want to travel abroad should carry a medical pass of the chemotherapeutic treatment to prevent them from difficulties in identification controls.