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The increasing relevance of improved therapeutic monoclonal antibodies (mAbs) to treat neurodegenerative diseases has strengthened the need to reliably measure their brain pharmacokinetic (PK) profiles. The aim of this study was, therefore, to absolutely quantify the therapeutic antibody ocrelizumab (OCR) as a model antibody in mouse brain interstitial fluid (ISF), and to record its PK profile by using cerebral open flow microperfusion (cOFM). Further, to monitor the blood–brain barrier (BBB) integrity using an endogenous antibody with a similar molecular size as OCR. The study was conducted on 13 male mice. Direct and absolute OCR quantification was performed with cOFM in combination with zero flow rate, and subsequent bioanalysis of the obtained cerebral ISF samples. For PK profile recording, cerebral ISF samples were collected bi-hourly, and brain tissue and plasma were collected once at the end of the sampling period. The BBB integrity was monitored during the entire PK profile recording by using endogenous mouse immunoglobulin G1. We directly and absolutely quantified OCR and recorded its brain PK profile over 96 h. The BBB remained intact during the PK profile recording. The resulting data provide the basis for reliable PK assessment of therapeutic antibodies in the brain thus favoring the further development of therapeutic monoclonal antibodies.

Justification In Mexico, the number of unidentified bodies has been steadily rising for years. By now, more than 50,000 bodies are considered unidentified. Forensic laboratories that could perform comparative molecular genetic investigation are often overburdened and examinations can take months. Therefore, pragmatic approaches that can help to identify more unknown bodies must be sought. The increased use of distinctive physical features might be one, and the high rate of tattooed people in Mexico points towards a great potential of tattoos as a tool for identification. The prerequisite for a comparison of antemortem (missing persons) and postmortem (unknown bodies) data is an objective description of the particularities, e.g., of the tattoos. The aim of this study was to establish an objective classification for tattoo motives, taking into consideration local preferences. Methods In the database of the medicolegal services of the Instituto Jaliscience de Ciencias Forenses (IJCF) in Guadalajara, postmortem data of 1000 tattooed bodies from 2019 were evaluated. According to sex and age, the tattooed body localization and the tattoo motives were categorized. Results The 1000 tattooed deceased showed tattoos on 2342 body localizations. The motives were grouped and linked to the following 11 keywords (with decreasing frequency): letters/numbers, human, symbol (other), plant, symbol (religious), animal, object, fantasy/demon/comic, tribal/ornament/geometry, other, unrecognizable. Conclusion Using the proposed classification, tattoo motives can be described objectively and classified in a practical way. If used for antemortem (missing persons) and postmortem (unknown bodies) documentation, motives can be searched and compared efficiently—helping to identify unknown bodies.

Zusammenfassung Einführung Augapfeltätowierungen („eyeball tattoos“, syn. episklerale Tätowierungen) sind ein neuer Trend extremer „body modification“, bei dem mit einer Nadel Tätowierfarbe unter die Bindehaut injiziert wird und zu einer irreversiblen Färbung der Sklera führt. In der medizinischen Fachliteratur werden vermehrt Fallberichte vorgestellt, bei denen teils schwerwiegende Komplikationen aufgetreten sind. Material und Methoden Neben einer aktuellen Literaturreche zum Thema wurde eine Anfrage an 120 zufällig ausgewählte Tattoo-Studios in 6 europäischen Ländern gerichtet, ob sie Eyeball-Tätowierungen anbieten. Die Kommunikation wurde bei den Studios, die diese Frage positiv beantworteten, gezielt vertieft. Ziel war es, einen Eindruck zu Angebot und Nachfrage, der Aufklärung über Risiken, Häufigkeit und Art beobachteter Komplikationen, den Vorerfahrungen und ggf. zur medizinischen Ausbildung der Tätowierenden sowie zum organisatorischen und zum technischen Ablauf der eigentlichen Prozedur der episkleralen Tätowierung im jeweiligen Studio zu gewinnen. Auf Tattoo Conventions und über Foren in sozialen Medien wurden 6 Personen mit max. 7 Jahre alten Eyeball tattoos ausführlich zu ihren Erfahrungen vor, während und nach der Augapfeltätowierung befragt. Resultate Neun Studios teilten mit, Augapfeltätowierungen anzubieten bzw. durch Gasttätowierer organisieren zu können. Die restlichen 49 Studios lehnten diese Prozedur ab. Insgesamt 4 Studios schätzten die Häufigkeit der Prozedur auf 10- bis 20-mal/Jahr; die restlichen Studios gaben an, lediglich sporadische Anfragen zu erhalten. Durch ein Studio wurde der Fall einer schweren Komplikation in Form einer persistierenden anhaltenden Infektion mit initial reduziertem, später gebessertem Visus berichtet. Ein Tätowierer gab an, in ca. jedem 20. Fall Pigmentwanderungen in die periorbitalen Gewebe zu beobachten. Postprozedural wurden bis zu 2 Wochen andauernde Kopfschmerzen, anhaltendes Fremdkörpergefühl und Lichtempfindlichkeit beschrieben. Keine der interviewten Personen mit Eyeball tattoos habe eine bleibende Visusminderung bemerkt, eine beklagte Lichtscheu, eine weitere negative soziale Folgen. Ablehnungserfahrungen seien jedoch seltener als Zuspruch. Schlussfolgerung Episklerale Tätowierungen sind noch selten, nehmen aber stetig zu. Sie werden von Personen durchgeführt, die keine hinreichende medizinische Ausbildung besitzen und eintretende Komplikationen nicht ausreichend einschätzen können. Die im Interview berichtete Seltenheit schwerwiegender Komplikationen kontrastiert mit der Darstellung desaströser Folgen in den sozialen Medien, deren breite Präsenz jedoch auf redundanten Darstellungen einzelner Fälle beruhen kann. Andererseits sind die Angaben der Befürworter zu hinterfragen, weil sie womöglich aus geschäftlichen Überlegungen heraus oder aus Angst vor rechtlichen Konsequenzen Problemfälle unterschlagen oder deren Verläufe beschönigen. Die Diskussion, ob solche risikoreichen irreversiblen Body modifications verboten werden sollten, muss von anderer Stelle geführt werden.

ZusammenfassungTodesfälle in stationärer psychiatrischer Behandlung sind wesentlich seltener als in nichtpsychiatrischen Kliniken. In dieser Arbeit wurden 44 Obduktionsfälle des Instituts für Rechtsmedizin Gießen von Verstorbenen in der stationären Psychiatrie aus einem Zeitraum von 7 Jahren zusammengetragen und ausgewertet. In knapp der Hälfte der Fälle lag eine nichtnatürliche Todesart vor. Affektive Störungen, Schizophrenien und Psychosen waren häufige Grunderkrankungen und Ursache eines Suizids. Im Rahmen der Begutachtung zeigte sich, dass im Einzelfall in den Krankenunterlagen eine lückenlose Dokumentation fehlte. Um Todesfälle im stationären Bereich der Psychiatrie aufzuarbeiten, sind eine vollständig geführte Dokumentation des Aufenthalts des Patienten sowie eine Obduktion mit weiterführenden toxikologischen Untersuchungen unumgänglich.

Bones found by chance can be of great criminal or historical interest. The nature of their appraisal depends on the individual case, the locally effective legislation and the available resources. To assess whether a find is relevant with respect to criminal investigation, the circumstances of the find and the results of the forensic examination carried out by trained personnel must be considered. The aim of this study was to obtain an overview of the circumstances and nature of the finds as well as the results of the subsequent expert opinions by evaluating bone finds from the federal state of Hesse, Germany. For this purpose, over a 10-year period from 2011 to 2020, all bone finds examined at the Institutes of Legal Medicine in Gießen and Frankfurt am Main, Germany, were evaluated retrospectively with regard to the locations and circumstances of the finds, their nature (human or non-human), the postmortem interval, possible traces of violent impact and the results of further examinations. Of the 288 bone finds evaluated, 38.2% were found in forests, meadows and parks. In 50.7%, the finds contained human bones, of which 37.0% had a forensically relevant postmortem interval of 50 years or less. Evidence of trauma was described in 77.4% of the human bone cases: postmortem damage in 78.8%, peri-mortem injury in 9.7% and ante-mortem injury in 11.5%. DNA examinations were performed in 40.4% of the human bone finds. They yielded STR profiles in 81.3%, leading to a definite identification in 35.4%. Among the non-human bones sent in, the most common were bones from pigs (23.4%), deer (18.1%), cattle (16.4%), roe deer (11.7%) and sheep (11.7%). The macroscopic examination is the first step of the forensic-osteological evaluation and sets the course for further examinations or investigations. DNA examinations are of great importance for the reliable identification of human bones. They were responsible for 70.8% of successful identifications.

We report the case of a woman in her thirties who suffered an esophageal rupture while participating in extreme sadomasochistic practices. After herself seeking help in a hospital for complaints alleged to be from a fall, she was initially diagnosed with several broken ribs and a pneumothorax. The cause of the pneumothorax was later discovered to be an esophageal rupture. When confronted with this atypical injury for a fall, the woman admitted to have accidentally swallowed an inflatable gag, which her partner had afterwards inflated. In addition to the esophageal rupture, the patient also had numerous other externally visible injuries of various ages, reportedly also from sadomasochistic acts. Although an in-depth police investigation was conducted and a “slave contract” was found, the woman’s consent to the extreme sexual practices performed by her life partner could not be substantiated conclusively. The man was convicted for intentional infliction of serious as well as dangerous bodily injury and sentenced to a long term in prison.

Zusammenfassung Hintergrund Die Leichenfundortuntersuchung mit rechtsmedizinischer Leichenschau im Vorfeld der Obduktion kann für deren Planung hilfreich sein. Häufigkeit, Umfang und Art der dokumentierten Leichenfundortuntersuchung mit Leichenschau unterliegen interindividuellen und interinstitutionellen Einflüssen. Eine wissenschaftliche Untersuchung rechtsmedizinischer Leichenfundortuntersuchungen und eine systematische Standardisierung gibt es bisher nicht. Material und Methoden Insgesamt 3622 Akten aus dem Archiv des Instituts für Rechtsmedizin der Justus-Liebig-Universität Gießen aus den Jahren 2005–2014 wurden gesichtet. 121 Fälle mit einer Leichenfundortuntersuchung mit Leichenschau durch eine/n Rechtsmediziner/in vor Ort wurden ausgewertet. Ergebnisse Die Leichenfundortuntersuchungen, einschließlich Dokumentation der Befunde, wurden während des 10-jährigen Untersuchungszeitraums unterschiedlich gehandhabt. Es zeigte sich eine Zunahme an Leichenfundortuntersuchungen um rund 380 % vom ersten zum letzten Untersuchungsjahr. Der Anteil an Tötungsdelikten bei den Leichenfundortuntersuchungen betrug 46 %. In 63 % aller Fälle fanden sich Dokumentationslücken, die im Verlauf des Untersuchungszeitraums und mit der häufigeren Anfertigung von Leichenfundortuntersuchungsberichten deutlich abnahmen. Bei der Dokumentation von Verletzungsmustern sank der Anteil an unvollständigen Daten von 89 % auf 11 %, bei den Temperaturmessungen am Leichenfundort von 73 % auf 27 %. Exklusiv am Leichenfundort erhebbare dokumentierte Zusatzinformationen fanden sich im Sinne von Blutspurenverteilungsmustern (48 %) und Hinweisen auf mögliche Tatwerkzeuge (57 %). Schlussfolgerungen Die rechtsmedizinische Leichenfundortuntersuchung mit Leichenschau wurde zunehmend häufiger durchgeführt. Die Untersuchung des Leichnams vor Ort und die Inaugenscheinnahme der Umgebung liefern Informationen, die über die alleinige autoptische Befunderhebung hinausgehen und eine wertvolle Grundlage für die Einordung von Obduktionsbefunden und für rekonstruktive Überlegungen zu Tatgeschehen darstellen. Um die Qualität der Befunderhebungen am Leichenfundort und die Qualität der zugehörigen Dokumentation zu verbessern, ist eine standardisierte Leichenfundortuntersuchung mit Leichenschau und Dokumentation anzustreben.

Zusammenfassung Hintergrund Der Kalmenhof wurde 1888 vom „Verein für die Idiotenanstalt zu Idstein“ gegründet. Während der NS-Zeit wurden in der „Kinderfachabteilung“ hunderte Kinder und Jugendliche von Ärzten und Pflegern getötet. Material und Methoden Nachdem ein historisches Gutachten und Georadaruntersuchungen Hinweise auf Gräber außerhalb einer als Kriegsgräberstätte ausgewiesenen Fläche erbrachte, erfolgten im Sommer 2020 Grabungen. Ergebnisse Außerhalb der Kriegsgräberstätte fanden sich keine Gräber. Innerhalb des Areals wurde eine Mehrfachbestattung von drei Individuen in einer 160 × 65 cm großen Grube entdeckt. Die knöchernen Überreste wurden exhumiert und makroskopisch, radiologisch, toxikologisch und molekulargenetisch untersucht. Zwei Individuen waren männlich, das Sterbealter betrug etwa 2,0 bis 2,25 Jahre und 2,5 Jahre. Das dritte Individuum war eine Jugendliche, die Untersuchungen ihrer sterblichen Überreste erbrachten Hinweise auf wiederholte und längere Zeit bestehende Phasen mit unzureichender Nährstoffversorgung. An keinem der Individuen fanden sich Zeichen einer körperlichen Behinderung, prä- oder perimortale Verletzungen. Die toxikologischen Untersuchungen verliefen für alle Individuen negativ. Für die beiden kindlichen Skelette konnte ein vollständiges STR-Profil erstellt werden, an dem jugendlichen Skelett gelang lediglich eine Geschlechtsbestimmung. Diskussion Die Ergebnisse stützen historische Angaben, wonach Gräber mehrfach belegt wurden. Demgegenüber war eine Unterteilung des Friedhofes nach dem Sterbealter nicht nachvollziehbar, ebenso wenig, dass sich auf angrenzenden Grundstücken Gräber befinden. Durch die gewonnenen Erkenntnisse wurde ein konkreter Identitätsverdacht für die drei Individuen erarbeitet. Die knöchernen Überreste wurden am Volkstrauertag 2020 im Rahmen einer Gedenkveranstaltung wieder beigesetzt.

Peer reviewed: True, Immune mediated inflammatory diseases (IMIDs) are a heterogeneous group of debilitating, multifactorial and unrelated conditions featured by a dysregulated immune response leading to destructive chronic inflammation. The immune dysregulation can affect various organ systems: gut (e.g., inflammatory bowel disease), joints (e.g., rheumatoid arthritis), skin (e.g., psoriasis, atopic dermatitis), resulting in significant morbidity, reduced quality of life, increased risk for comorbidities, and premature death. As there are no reliable disease progression and therapy response biomarkers currently available, it is very hard to predict how the disease will develop and which treatments will be effective in a given patient. In addition, a considerable proportion of patients do not respond sufficiently to the treatment. ImmUniverse is a large collaborative consortium of 27 partners funded by the Innovative Medicine Initiative (IMI), which is sponsored by the European Union (Horizon 2020) and in-kind contributions of participating pharmaceutical companies within the European Federation of Pharmaceutical Industries and Associations (EFPIA). ImmUniverse aims to advance our understanding of the molecular mechanisms underlying two immune-mediated diseases, ulcerative colitis (UC) and atopic dermatitis (AD), by pursuing an integrative multi-omics approach. As a consequence of the heterogeneity among IMIDs patients, a comprehensive, evidence-based identification of novel biomarkers is necessary to enable appropriate patient stratification that would account for the inter-individual differences in disease severity, drug efficacy, side effects or prognosis. This would guide clinicians in the management of patients and represent a major step towards personalized medicine. ImmUniverse will combine the existing and novel advanced technologies, including multi-omics, to characterize both the tissue microenvironment and blood. This comprehensive, systems biology-oriented approach will allow for identification and validation of tissue and circulating biomarker signatures as well as mechanistic principles, which will provide information about disease severity and future disease progression. This truly makes the ImmUniverse Consortium an unparalleled approach.

Topically applied drug products have experienced an extraordinary price increase in the United States, mostly due to a lack of generic products. Generic drug development is hindered by high costs and risks associated with clinical endpoint studies required to show bioequivalence (BE) of prospective generic products relative to their reference products. There is a continued need for cost- and time-efficient alternatives to clinical endpoint studies to determine BE of topically applied dermal drug products. Cutaneous PK-based BE studies present such an alternative and dOFM (dermal open flow microperfusion) has already been successfully used in several verifications studies to show an accurate and sensitive assessment of the rate and extent at which drugs become available in the skin. dOFM technology is discussed as well as the dOFM setup of clinical pilot and main studies to achieve BE assessment with a minimum number of participants and an outlook is given on the use of dOFM technology for other drug products.

Background: Pharmacokinetic (PK) assessment of drugs in brain is especially challenging, as the blood-brain-barrier (BBB) impedes the access of substances to the brain. However, rising incidence of monoclonal antibodies as treatment option for diseases of the central nervous system makes continuous measurement of their brain PK profile with verifiably intact BBB increasingly relevant. Such measurements can be performed with continuous brain interstitial fluid (ISF) sampling techniques like e.g., cerebral open flow microperfusion (cOFM). Although cOFM has already provided antibody concentrations in brain ISF in a time-resolved manner, accurate time-resolved quantification of antibody in brain to record the PK profile requires continuous sampling over an extended period of time and knowledge on the BBB integrity for the respective study drug during the entire sampling period. We thus aimed to absolutely quantify the therapeutic antibody ocrelizumab (OCR) in mouse brain ISF over 96 hours, and to record its PK profile. OCR, with a target on human CD20+ B-cells, was selected as study drug. We also aimed to monitor the BBB integrity during the entire study duration using an endogenous antibody as tracer with similar molecular size as OCR. Methods: Direct and absolute OCR quantification was performed using cOFM combined with the quantification protocol Zero Flow Rate, and data were corrected with the cOFM probe´s in vivo relative recovery. For PK profile recording the cOFM samples were collected bi-hourly, and brain tissue and plasma at the end of the sampling period. BBB monitoring was performed simultaneously during the entire PK profile recording using the endogenous mIgG1. This study was performed in male C57Bl/6 mice. Results: We directly, absolutely quantified OCR, and reliably recorded its brain PK profile over 96 hours. BBB integrity was sustained during the entire study. Conclusions: Results demonstrated that cOFM is able to accurately, absolutely quantify OCR in brain ISF and to record its brain PK profile over a prolonged duration with verifiably intact BBB. Our data provide the basis for reliable PK assessment of therapeutic antibodies in brain, which is likely to promote the development of therapeutic monoclonal antibodies to treat neurological diseases.

The lancet / Regional health. Europe 15, 100330 (2022). doi:10.1016/j.lanepe.2022.100330, Published by Elsevier, [Amsterdam]

Postmortem detection of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) after the exhumation of a corpse can become important, e.g. in the case of subsequent medical malpractice allegations. To date, data on possible detection periods [e.g. by reverse transcription polymerase chain reaction (RT-PCR)] or on the potential infectivity of the virus after an exhumation are rare. In the present study, these parameters were examined in two cases with a time span of approximately 4 months between day of death and exhumation. Using SARS-CoV-2 RT-PCR on swabs of both lungs and the oropharynx detection was possible with cycle threshold (Ct) values of about 30 despite signs of beginning decay. RT-PCR testing of perioral and perinasal swabs and swabs collected from the inside of the body bag, taken to estimate the risk of infection of those involved in the exhumation, was negative. Cell culture-based infectivity testing was negative for both, lung and oropharyngeal swabs. In one case, RT-PCR testing at the day of death of an oropharyngeal swab showed almost identical Ct values as postmortem testing of an oropharyngeal swab, impressively demonstrating the stability of viral RNA in the intact corpse. However, favorable climatic conditions in the grave have to be taken into account, as it was wintertime with constant low temperatures. Nevertheless, it was possible to demonstrate successful postmortem detection of SARS-CoV-2 infection following exhumation even after months in an earth grave.

Hintergrund: In Frankfurt am Main (~750.000 Einwohner) wird die erste Leichenschau im Auftrag der Polizei tagsüber durch einen dafür eingerichteten rechtsmedizinischen Dienst vorgenommen. Nachts und am Wochenende führen diese Tätigkeit Ärzte des ärztlichen Bereitschaftsdienstes (ÄBD) der kassenärztlichen Vereinigung durch. Material und Methoden: Für das Jahr 2019 wurden die im Rahmen dieser ersten Leichenschauen ausgestellten Leichenschauscheine hinsichtlich der attestierten Todesart ausgewertet und die Ergebnisse mit denen einer ggf. im Nachgang durchgeführten Sektion, inklusive Zusatzuntersuchungen, verglichen. Von den Ärzten des ÄBD konnten 461 Leichenschauen in die Auswertung eingeschlossen werden, davon erfolgte in 76 Fällen eine Obduktion. Im Nachgang der 364 rechtsmedizinischen Leichenschauen wurden 78 Obduktionen durchgeführt. Ergebnisse: Veränderungen in der Todesart nach Sektion ergaben sich für die Leichenschauen des ÄBD in 57, bei den rechtsmedizinischen Leichenschauen in 49 Fällen, wobei insbesondere eine bei Leichenschau attestierte ungeklärte Todesart in einen natürlichen Tod spezifiziert werden konnte. Nach der Obduktion fanden sich bei den rechtsmedizinischen Leichenschauen 8 Fälle, bei denen des ÄBD 19 Fälle eines nichtnatürlichen (statt weiterhin ungeklärten) Todes. Bei den rechtsmedizinisch beschauten Fällen änderte sich zudem nach der Sektion in einem Fall die Todesart von natürlich zu nichtnatürlich, bei denen des ÄBD kam es in einem Fall zu einer Änderung von nichtnatürlich zu natürlich. Diskussion: Die Veränderung bzw. Spezifizierung der Todesart nach der Sektion beider Kollektive verdeutlicht, wie wichtig eine Steigerung der Sektionsrate wäre, und dass auch bei professioneller Durchführung der Leichenschau das Erkennen der Todesart Probleme bereitet. Background: In Frankfurt am Main (~750,000 inhabitants) first postmortem external examinations are carried out by two institutions at the request of the police. During daytime the medical team of the Institute of Forensic Medicine performs first postmortem external examinations, whereas during nights and weekends, the examinations are carried out by physicians of the medical emergency service (ÄBD). Material and methods: For the year 2019 both examiner groups were evaluated with respect to the certification of the manner of death during the first postmortem external examination. Evaluation results were then compared with those of a subsequent autopsy. For the ÄBD group 461 examinations resulting in 76 autopsies were included in this study, whereas for the forensic medicine group 364 examinations were included, which resulted in 78 autopsies. Results: In 57 cases of the ÄBD the manner of death had to be changed based on the autopsy findings (49 cases in the forensic medicine group). This fraction of cases mainly consisted of a change from an undetermined to a natural manner of death. In 19 cases of the ÄBD and 8 cases of the forensic medicine group the manner of death was changed from undetermined to unnatural death. In one case of the forensic medicine group the manner of death had to be changed from natural to unnatural, 1 case from the ÄBD changed from unnatural to natural. Discussion: The necessity for changing manners of death after performing a medicolegal autopsy in a relatively high percentage of examinations in both subgroups stresses the need for an increase of the autopsy rate. Furthermore, the data showed that even with a professionalized approach using forensic experts for first postmortem external examinations, special case constellations pose great challenges on the medical examiner.

Zusammenfassung Einleitung Funde von Knochen(fragmenten) können von Interesse für Strafverfolgungs- oder Denkmalbehörden sein. Die forensisch-osteologische Begutachtung kann zur Einordnung der Bedeutung des Fundes beitragen. Ziel der Studie war, durch eine Auswertung von am Institut für Rechtsmedizin Gießen begutachteten Knochenfunden einen Überblick über Umstände und Art der Funde sowie Umfang und Ergebnisse der Begutachtungen zu erhalten. Material und Methoden Für den Zeitraum von 2005 bis 2019 wurden im Institut archivierte osteologische Gutachten analysiert und Daten zu Fundort, -umständen, Humanspezifität, postmortalem Intervall, Spuren von Gewalteinwirkungen und die Ergebnisse weiterführender Untersuchungen ausgewertet. Ergebnisse Von 172 begutachteten Knochenfunden wurden 40 % in Wald- und Wiesengebieten aufgefunden. In 58 % enthielten die Funde menschliche Knochen, davon wurde in 32 % eine forensisch relevante Liegezeit nicht ausgeschlossen. Zeichen perimortaler Gewalteinwirkung fanden sich in 6 % menschlicher Knochenfunde. Ergänzende DNA-Untersuchungen wurden in 20 % aller Funde durchgeführt; davon verlief in 62 % die Typisierung humaner STR erfolgreich, und in 41 % gelang die Zuordnung zu einem antemortalen Profil. Bei den zur Begutachtung übersandten nichtmenschlichen Knochen handelte es sich am häufigsten um Knochen von Hirsch bzw. Reh (32 %), Schwein (29 %) und Rind (14 %). Diskussion Die Begutachtung von Knochenfunden soll Behörden ermöglichen, die (straf-)rechtliche Relevanz eines Fundes einzuordnen. Die makroskopische Untersuchung ist dafür von großer Bedeutung. Für die Identifizierung menschlicher Knochen besitzen DNA-Vergleichsuntersuchungen einen großen Stellenwert. Sie waren für 81 % der erfolgreichen Identifizierungen der Fälle mit menschlichen Knochen verantwortlich.

ZusammenfassungBei der Identifizierung einer unbekannten, stark verwesten Leiche oder eines Skelettes ohne Hinweise auf die Identität durch die Auffindesituation spielt die Erstellung des sog. biologischen Profils eine entscheidende Rolle. Vorgestellt wird ein Leichenfund in einem mehr oder weniger frei zugänglichen Kellerabteil eines Mehrfamilienhauses. Der Leichnam war weitgehend skelettiert, das Skelett jedoch durch mumifizierte Weichteilreste noch nahezu vollständig zusammengehalten. Bei den Hinweisen auf die Identität ergaben sich insbesondere in der Altersschätzung scheinbare Widersprüche, die jedoch zufällig eine relativ genau zutreffende Schätzung lieferten. Die Überreste konnten mittels forensischer DNA-Analyse einer seit 4 Jahren vermissten 49-Jährigen zugeordnet werden. Als Todesursache wurde ein Kältetod diskutiert.Der Fall wies eine außergewöhnliche Auffindesituation auf, die an Bilder von „Skelettfunden“ in Kriminalverfilmungen erinnerte. Derartige Befunde dürften jedoch in der Realität wohl nur sehr selten vorkommen. Darüber hinaus werden die Wichtigkeit und die Probleme der forensisch-osteologischen Untersuchungen bei der Identifizierung eines stark verwesten, unbekannten Leichnams demonstriert.

Skin equivalents and skin explants are widely used for dermal penetration studies in the pharmacological development of drugs. Environmental parameters, such as the incubation and culture conditions affect cellular responses and thus the relevance of the experimental outcome. However, available systems such as the Franz diffusion chamber, only measure in the receiving culture medium, rather than assessing the actual conditions for cells in the tissue. We developed a sampling design that combines open flow microperfusion (OFM) sampling technology for continuous concentration measurements directly in the tissue with microfluidic biosensors for online monitoring of culture parameters. We tested our design with real-time measurements of oxygen, glucose, lactate, and pH in full-thickness skin equivalent and skin explants. Furthermore, we compared dermal penetration for acyclovir, lidocaine, and diclofenac in skin equivalents and skin explants. We observed differences in oxygen, glucose, and drug concentrations in skin equivalents compared to the respective culture medium and to skin explants.

Background Burn wound progression is a significant problem as burns initially thought to be superficial can actually become full thickness over time. Cooling is an efficient method to reduce burn wound conversion. However, if the cooling agent is below room temperature, depending on the wound size the patient is at risk of hypothermia. Additionally, tissue perfusion is reduced leading to an aggravation of burn wound progression. We investigated if wound dressings based on non-pre-cooled bacterial nanocellulose (BNC) with a high water content cool a burn just by evaporation and reduce the intradermal damages in the skin. Material and methods In a human ex-vivo model, skin explants underwent contact burns using a 100 °C hot steel block. The burned areas were divided into two groups of which one was cooled with a BNC-based wound dressing. Intradermal temperature probes measured temperature in cooled and uncooled burn sites over 24 h. For histological assessments of the burned areas biopsies were taken at different time points. High mobility group box-1 (HMBG1) staining served as marker for cell vitality and necrosis in the different skin layers. Results Intradermal temperature measurement showed that application of the BNC-based wound dressing reduced temperature significantly in burned skin. This cooling effect resulted in a maximum temperature difference of 6.4 ± 1.9 °C and a significant mean reduction of the area under the curve in the first hour after burn of 62% (p Conclusion Based on our results, BNC-based wound dressings cool a burn. Intradermal temperature as well as thermal damage of the tissue was reduced. The tested BNC-based wound dressing can be used without pre-cooling to cool a burn as well as to reduce the burn BNC-based wound progression through its evaporation cooling effect.

Background Bacterial nanocellulose (BNC) is considered a promising carrier for various substances and novel approaches using BNC in combination with antiseptics are well documented. However, the difference in the molecular weight of these molecules influences their uptake by and release from BNC. Analysing the diffusion of standard molecules with different weight, e.g. dextrans, offers the possibility to investigate the mobility of various molecules. We aimed to test the use of BNC regarding uptake and release of different standard molecules as well as two commercially available antiseptics for possible applications in future wound dressings. Material and methods Diffusion profiles, uptake and release of three FITC-dextran molecules differing in weight as well as octenidine (Octenisept®) and povidone-iodine (Betaisodona®)-based antiseptics were tested with BNC-based wound dressings. Furthermore, the antiseptic efficacy of BNC in combination with antiseptics against Staphylococcus aureus was tested. Results Uptake and release capacity for FITC-dextran molecules showed a molecular weight-dependent mobility from BNC into an agarose gel. The loading capacity of BNC was also inversely proportional to the molecular weight of the antiseptics. The release test for octenidine showed a sustained and prolonged delivery into a solid matrix, whereas povidone-iodine was released faster. Both antiseptic solutions combined with BNC showed a good dose-dependent efficacy against S. aureus. Conclusion Results obtained from the mobility of FITC-dextran molecules in the BNC matrix could open possible applications for the combination of BNC with other molecules for medical applications. Combination of both tested antiseptics with BNC showed to be an efficient approach to control bacterial infections.

This paper describes a new approach to the early-stage optimization of topical products and selection of lead formulation candidates. It demonstrates the application of open flow microperfusion in vitro in conjunction with the Franz diffusion cell to compare time-resolved, 24-hour profiles of diclofenac passive diffusion through all skin layers (including the skin barrier, dermis, and subcutis) resulting from nine topical formulations of different composition. The technique was successfully validated for in vitro sampling of diclofenac in interstitial fluid. A multi-compartmental model integrating the two datasets was analyzed and revealed that the passive diffusion of diclofenac through the dermis and subcutis does not correlate with its diffusion through the skin barrier and cannot be predicted using Franz diffusion cell data alone. The combined application of the two techniques provides a new, convenient tool for product development and selection enabling the comparison of topical formulation candidates and their impact on drug delivery through all skin layers. This approach can also generate the experimental data required to improve the robustness of mechanistic PBPK models, and when combined with clinical sampling via open flow microperfusion - for the development of better in vivo-in vitro correlative models.

In Mexico, the number of unidentified bodies has been steadily rising for years. By now, more than 50,000 bodies are considered unidentified. Forensic laboratories that could perform comparative molecular genetic investigation are often overburdened and examinations can take months. Therefore, pragmatic approaches that can help to identify more unknown bodies must be sought. The increased use of distinctive physical features might be one, and the high rate of tattooed people in Mexico points towards a great potential of tattoos as a tool for identification. The prerequisite for a comparison of antemortem (missing persons) and postmortem (unknown bodies) data is an objective description of the particularities, e.g., of the tattoos. The aim of this study was to establish an objective classification for tattoo motives, taking into consideration local preferences.In the database of the medicolegal services of the Instituto Jaliscience de Ciencias Forenses (IJCF) in Guadalajara, postmortem data of 1000 tattooed bodies from 2019 were evaluated. According to sex and age, the tattooed body localization and the tattoo motives were categorized.The 1000 tattooed deceased showed tattoos on 2342 body localizations. The motives were grouped and linked to the following 11 keywords (with decreasing frequency): letters/numbers, human, symbol (other), plant, symbol (religious), animal, object, fantasy/demon/comic, tribal/ornament/geometry, other, unrecognizable.Using the proposed classification, tattoo motives can be described objectively and classified in a practical way. If used for antemortem (missing persons) and postmortem (unknown bodies) documentation, motives can be searched and compared efficiently-helping to identify unknown bodies.

Purpose To investigate the most peripheral corneal nerve plexus using high-resolution micro-optical coherence tomography (µOCT) imaging and to assess µOCT's clinical potential as a screening tool for corneal and systemic diseases. Methods An experimental high-resolution (1.5 × 1.5 × 1 µm) µOCT setup was applied for three-dimensional imaging of the subbasal nerve plexus in nonhuman primates (NHPs) and swine within 3 hours postmortem. Morphologic features of subbasal nerves in µOCT were compared to β3 tubulin-stained fluorescence confocal microscopy (FCM). Parameters such as nerve density, nerve distribution, and imaging repeatability were evaluated, using semiautomatic image analysis in form of a custom corneal surface segmentation algorithm and NeuronJ. Results Swine and NHP corneas showed the species-specific nerve morphology in both imaging modalities. Most fibers showed a linear course, forming a highly parallel pattern, converging in a vortex with overall nerve densities varying between 9.51 and 24.24 mm/mm2. The repeatability of nerve density quantification of the µOCT scans as approximately 88% in multiple image recordings of the same cornea. Conclusions Compared to the current gold standard of FCM, µOCT's larger field of view of currently 1 × 1 mm increases the conclusiveness of density measurements, which, coupled with µOCT's feature of not requiring direct contact, shows promise for future clinical application. The nerve density quantification may be relevant for screening for systemic disease (e.g., peripheral neuropathy). Translational Relevance Technological advances in OCT technology may enable a quick assessment of corneal nerve density, which could be valuable evaluating ophthalmic and systemic peripheral innervation.

Decarbonization of industry is a key challenge to achieve the Paris climate goals. Digitalization of the industry is a cornerstone of this journey. In this paper we present our modelling work towards the creation of a Digital Energy Twin of the energy supply system of a printed boarding circuit manufacturing by means of a classical use case, system design optimization. The simulation approach allowed us to fairly compare the improvements done in the energy supply system by evaluating those under the same operating conditions. Integration of waste chiller’s waste heat can cover most of the low temperature grid heat demand while the additional generation of chilled water reduces the amount of water pump from and back to the river.

In burn injuries, risk factors and limitations to treatment success are difficult to assess clinically. However, local cellular responses are characterized by specific gene-expression patterns. MicroRNAs (miRNAs) are single-stranded, non-coding RNAs that regulate mRNA expression on a posttranscriptional level. Secreted through exosome-like vesicles (ELV), miRNAs are intracellular signalers and epigenetic regulators. To date, their role in the regulation of the early burn response remains unclear. Here, we identified 43 miRNAs as potential regulators of the early burn response through the bioinformatics analysis of an existing dataset. We used an established human ex vivo skin model of a deep partial-thickness burn to characterize ELVs and miRNAs in dermal interstitial fluid (dISF). Moreover, we identified miR-497-5p as stably downregulated in tissue and dISF in the early phase after a burn injury. MiR-218-5p and miR-212-3p were downregulated in dISF, but not in tissue. Target genes of the miRNAs were mainly upregulated in tissue post-burn. The altered levels of miRNAs in dISF of thermally injured skin mark them as new biomarker candidates for burn injuries. To our knowledge, this is the first study to report miRNAs altered in the dISF in the early phase of deep partial-thickness burns.

Background and objectives A recent generation of 5,500 nm wavelength carbon monoxide (CO) lasers could serve as a novel tool for applications in medicine and surgery. At this wavelength, the optical penetration depth is about three times higher than that of the 10,600 nm wavelength carbon dioxide (CO2 ) laser. As the amount of ablation and coagulation is strongly influenced by the wavelength, we anticipated that CO lasers would provide extended coagulation zones, which could be beneficial for several medical applications, such as tissue tightening effects after laser skin resurfacing. Until now, the 1,940 nm wavelength thulium fiber (Tm:fiber) laser is primarily known as a non-ablative laser with an optical penetration depth that is eight times higher than that of the CO2 laser. The advantage of lasers with shorter wavelengths is the ability to create smaller spot sizes, which has a determining influence on the ablation outcome. In this study, the ablation and coagulation characteristics of a novel CO laser and a high power Tm:fiber laser were investigated to evaluate their potential application for fractional ablation of the skin. Study design/materials and methods Laser-tissue exposures were performed using a novel CO laser, a modified, pulse-width-modulated CO2 laser, and a Tm:fiber laser. We used discarded ex vivo human skin obtained from abdominoplasty as tissue samples. Similar exposure parameters, such as spot size (108-120 μm), pulse duration (2 milliseconds), and pulse energy (~10-200 mJ) were adjusted for the different laser systems with comparable temporal pulse structures. Laser effects were quantified by histology. Results At radiant exposures 10-fold higher than the ablation threshold, the CO laser ablation depth was almost two times deeper than that of the CO2 laser. At 40-fold of the ablation threshold, the CO laser ablation was 47% deeper. The ablation craters produced by the CO laser exhibited about two times larger coagulation zones when compared with the CO2 laser. In contrast, the Tm:fiber laser exhibited superficial ablation craters with massive thermal damage. Conclusions The tissue ablation using the Tm:fiber laser was very superficial in contrast to the CO laser and the CO2 laser. However, higher etch depths should be obtainable when the radiant exposure is increased by using higher pulse energies and/or smaller spot sizes. At radiant exposures normalized to the ablation threshold, the CO laser was capable of generating deeper ablation craters with extended coagulation zones compared with the CO2 laser, which is possibly desirable depending on the clinical goal. The effect of deep ablation combined with additional thermal damage on dermal remodeling needs to be further confirmed with in vivo studies. Lasers Surg. Med. © 2020 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Continuous subcutaneous insulin infusion (CSII) is a widely used treatment for diabetes patients. Insulin infusion sets (CSII-catheters) are continuously optimized regarding size, handling and safety, but recurring dysfunction (kinking or occlusion), due to different user situations, behavior or chain of events, demand new ways to improve the functionality and safety in patients experiencing these issues. A novel CSII-catheter design (Lantern) features additional lateral perforations, which guarantee functionality even in case of kinking or occlusion. This study aimed to compare functionality, insulin distribution, and failure rate of Lantern and standard catheters using excised human adipose tissue samples. Novel Lantern CSII-catheters (open and artificially occluded) and commercially available standard CSII-catheters were inserted into adipose tissue samples. A mixture of insulin and contrast agent was infused as single bolus (7 IU) with an insulin infusion pump at highest flow rate (1 IU/s). Microtomography images and surface-to-volume ratios were used to assess insulin distribution and depot volume indicating the functionality of CSII-catheters. Failure rate was measured by flow-stop alerts of the pump. We found no difference in the volume of insulin depots compared with the nominal volume of 70 μL. Surface-to-volume ratios showed no significant difference among CSII-catheters. None of the catheters triggered any flow-stop alarm. The novel Lantern CSII-catheter design achieved similar insulin distribution as commercially available CSII-catheters. Moreover, functionality of Lantern CSII-catheters was guaranteed during occlusion, which is an improvement compared with standard CSII-catheters. We conclude that the novel CSII-catheter design has the potential to provide a valuable contribution to patient well-being and safety.

Background/objectives Standard optical coherence tomography angiography (OCTA) has been limited to imaging blood vessels actively undergoing perfusion, providing a temporary picture of surface microvasculature. Capillary perfusion in the skin is dynamic and changes in response to the surrounding tissue's respiratory, nutritional, and thermoregulatory needs. Hence, OCTA often represents a given perfusion state without depicting the actual extent of the vascular network. Here we present a method for obtaining a more accurate anatomic representation of the surface capillary network in human skin using OCTA, along with proposing a new parameter, the Relative Capillary Capacity (RCC), a quantifiable proxy for assessing capillary dilation potential and permeability. Methods OCTA images were captured at baseline and after compression of the skin. Baseline images display ambient capillary perfusion, while images taken upon capillary refill display the network of existing capillaries at full capacity. An optimization-based automated vessel segmentation method was used to automatically analyze and compare OCTA image sequences obtained from two volunteers. RCC was then compared with visual impressions of capillary viability. Results Our OCTA imaging sequence provides a method for mapping cutaneous capillary networks independent of ambient perfusion. Differences between baseline and refill images clearly demonstrate the shortcomings of standard OCTA imaging and produce the RCC biometric as a quantifiable proxy for assessing capillary dilation potential and permeability. Conclusion Future dermatological OCTA diagnostic studies should implement the Capillary Refill Methods over standard imaging techniques and further explore the relevance of RCC to differential diagnosis and dermatopathology. Lasers Surg. Med. © The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals, Inc.

Arztinnen und Arzte werden im Rahmen ihrer Berufsausubung zunehmend mit rechtlichen Fragen konfrontiert. Aufgrund einer Starkung der Patientenrechte durch die Vorschriften zum Behandlungsvertrag (§§ 630a ff. BGB), aber auch einer umfangreichen Rechtsprechung, Gesetzen oder Leitlinien ist eine starke Reglementierung der Medizin zu beobachten. Die arztliche Approbationsordnung erwahnt Rechtsfragen der arztlichen Berufsausubung als Unterrichtsgegenstand. Eine verbindliche Regelung uber den Umfang und Inhalt medizinrechtlichen Unterrichts existiert nicht. Der Nationale Lernzielkatalog fur Mediziner (NLKM) greift diese Problematik auf und beschreibt Lernziele, welche die ethischen und rechtlichen Kenntnisse, Fahigkeiten und Fertigkeiten definieren, die Medizinstudierenden im Verlauf ihres Studiums vermittelt werden sollen. Der NKLM entfaltet jedoch gegenuber den medizinischen Fakultaten keine Bindungswirkung. Erstmals wurden Studierende im praktischen Jahr (PJ) an 18 medizinischen Fakultaten mittels eines standardisierten Fragebogens nach ihrer Einschatzung der Bedeutung des Medizinrechts insgesamt und auch zu medizinrechtlichen Einzelthemen befragt. Von den befragten Studierenden sah die ganz grose Mehrheit die Vermittlung von Rechtskenntnissen als sehr wichtig bzw. als auserordentlich wichtig an. Uberwiegend wurde die Etablierung einer eigenstandigen Lehrveranstaltung zum Medizinrecht mit einer Verankerung in der arztlichen Approbationsordnung fur sinnvoll erachtet. Die Relevanz einzelner Themen wurde unterschiedlich beurteilt. So wurden u. a. die Themen Aufklarung und Einwilligung, Rechtsfragen bei Verdacht auf Kindesmisshandlung, Verhalten bei einem Behandlungsfehlervorwurf, arztliche Schweigepflicht und Dokumentationspflichten des Arztes als relevant eingestuft. Als weniger wichtig werden z. B. gesehen: Rechtsfragen der Komplementarmedizin, der Reproduktionsmedizin, ethisch-religios-weltanschauliche Konflikte, einschlieslich Sterbehilfe, oder die Rolle von Ethikkommissionen. Die Studierenden zeigen sich gegenuber Fragen des Medizinrechts grundsatzlich offen und sehen die Relevanz zahlreicher konkreter Rechtsfragen. Dies sollte bei der weiteren Diskussion zum NKLM, aber auch von den medizinischen Fakultaten und den in der Lehre Tatigen starker berucksichtigt werden. Sinnvoll erscheint die Bereitstellung eines Lehrbeauftragten fur Medizinrecht.

The agenesis of one or both upper thyroid horns (UTH) cannot be considered rare with an incidence ranging between 0.8–9.4%. Studies so far have mostly described frequencies, yet surveys on its morphology and traumatology are missing. It is unknown to what extent this anatomical variant impacts the overall symmetry of the larynx. For the trauma reconstruction after cervical trauma this knowledge is required as an asymmetric larynx can show a different fracture pattern. In this investigation, larynxes with unilateral (n = 21)/bilateral (n = 5) agenesis of the upper thyroid horn(s) and a control group with regular larynxes (n = 23) were juxtaposed. Various measurements were taken after μ-CT scanning. In total 10 distances/angles for the thyroid cartilage and 8 for the cricoid cartilage were compared. Using intra-individual and matched pair comparisons the symmetry was assessed. The results of this investigation showed significant differences in the intra-individual and pairwise comparison for the opening angle and the length of the thyroid alae although the lateral inclination of the thyroid alae showed no significant difference. Combining these three parameters into one symmetry score, the comparison was not significant. This research demonstrates that neither unilateral nor bilateral agenesis of the UTH is related to a structural disbalance of the larynx. Thus, different fracture patterns or vulnerabilities are not to be expected.

Der Schadel stellt haufig das Ziel interpersoneller Gewalt dar und weist infolge von schweren (todlichen) Unfallen nicht selten Verletzungen auf. Bestimmte Frakturmuster des Gehirnschadels lassen sich unter rekonstruktiven Gesichtspunkten interpretieren. Publikationen hierzu thematisieren diesbezuglich jedoch eher Frakturen des Schadeldachs als jene der Schadelbasis. Ein aktueller Sektionsfall, bei dem es durch ein disloziertes Mandibulakopfchen zu einer Lochfraktur der Schadelbasis gekommen war, gab Anlass zu einer retrospektiven Auswertung von Obduktionsfallen aus den Instituten fur Rechtsmedizin in Frankfurt am Main, Giesen und Homburg (Saar) in einem Zehnjahreszeitraum. Daruber hinaus erfolgte eine Literaturrecherche uber die Metadatenbank PubMed. Im Auswertungszeitraum von 2009 bis 2018 wurden in den genannten rechtsmedizinischen Instituten 10.733 gerichtliche Obduktionen durchgefuhrt. Es fanden sich lediglich 2 Falle von Lochfrakturen der Schadelbasis, bei denen jeweils das intakte Unterkieferkopfchen im Sinne einer zentralen Kiefergelenkluxation in die mittlere Schadelgrube eingedrungen war. Bei beiden Verstorbenen war ein Sturzgeschehen ursachlich, die Lochfraktur, fur sich betrachtet, jedoch nicht todesursachlich. Die Literaturrecherche erbrachte mehrere klinische Fallberichte, systematisch aufgearbeitete Fallserien und Ubersichtsarbeiten sowie eine rechtsmedizinische Kasuistik. Als Hauptursache der superioren bzw. zentralen Kiefergelenkluxationen werden Verkehrsunfalle angesehen. Die in der klinischen Fachliteratur beschriebenen, mit dieser Fraktur einhergehenden typischen Symptome (Malokklusion mit einem unilateral offenen und kontralateralen Kreuzbiss, fixierte Mandibulastellung) konnen postmortal durch Rigor mortis und Dunsung der Gesichtsweichteile uberlagert werden und fallen somit bei der auseren Leichenschau ggf. nicht auf. Bei dieser besonderen Lochfraktur der Schadelbasis handelt es sich um eine auserst seltene Verletzung, die – analog zur Schadelbasisringfraktur – als Sonderform einer Biegungsfraktur der Schadelbasis betrachtet werden kann. Ihr Auftreten lasst rekonstruktive Aussagen zum Unfall- bzw. Tatgeschehen zu. Als Verletzungsmechanismus ist die Fortleitung einer von vorn unten auf das Kinn einwirkenden stumpfen Gewalteinwirkung anzusehen.

When people judge the duration of stimuli, judgments are influenced by the physical size of these stimuli. Specifically, people tend to judge the duration of large stimuli longer than the duration of small stimuli. However, some authors (Bottini & Casasanto, 2010; Ma, Yang, & Zhang, 2012) have reported that even implicit size can affect duration estimates. The present study extends the results of these studies. Specifically, we examined whether the imagined size of objects would also influence duration estimates. In each trial, participants reproduced the duration of an animal word. During the presentation of the word, they were asked to imagine the word's referent. The animals employed in all experiments varied in size. In Experiment 1, participants were instructed to imagine the animals in a fixed context. Reproduced duration increased not only with the numbers of letters of the animal word (i.e., physical size) but also with the size of the word's referent (i.e., implicit size of the animal). Experiments 2 and 3 examined whether the effect of size would increase when the size of the animals was made more salient. The results of all experiments showed that reproduced duration increases with implicit stimulus size. In addition, Experiments 2 and 3 provide some evidence that the imagined size effect becomes more pronounced when the participant's attention is drawn to the size differences among the imagined animals. It is argued that the implicit size effect is mediated by mental imagery that operates on pre-existing space-time associations. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Background Trisomy 21 is the most common human chromosomal abnormality. Its manifestation includes intellectual impairment and more or less typical anatomical malformations and functional deficiencies that can cause sudden or unexpected deaths. Typical medicolegal questions at autopsy are related to medical malpractice, improper care, neglect, or abuse, and, depending on the cause of death, whether the death might have been avoidable. The aim of this study was to examine whether the causes of death in individuals with trisomy 21 were linked to the known health risks for this condition and to consider how these deaths might have been prevented. Material and methods A retrospective study was performed at the Institutes for Legal Medicine in Giessen and Frankfurt am Main, Hesse, Germany. All records for forensic autopsy cases within a 20-year period from 1998 to 2017 were reviewed for the diagnosis trisomy 21”, respectively, “Down’s syndrome”. Results Twenty-three cases complied with the inclusion criteria trisomy 21 and autopsy. The age of the deceased ranged from 23 days to 61 years. Infectious diseases, mainly respiratory, were the leading cause of death, followed by accidental deaths. Conclusion The medicolegal relevance of the known health risks in Down’s syndrome could be illustrated by the autopsy findings and the results of the additional examinations. The known high susceptibility to infections, with an increased risk of a rapid course and lethal outcome, in individuals with Down’s syndrome could be confirmed in our study. A sound knowledge of the risks and abnormalities associated with trisomy 21 are helpful in medicolegal assessments, particularly, in relation to medical malpractice charges.

Eicosanoids are lipid-mediator molecules with key roles in inflammatory skin diseases, such as psoriasis. Eicosanoids are released close to the source of inflammation, where they elicit local pleiotropic effects and dysregulations. Monitoring inflammatory mediators directly in skin lesions could provide new insights and therapeutic possibilities. Here, we analyzed dermal interstitial fluid samples obtained by dermal open-flow microperfusion in a rat model of skin inflammation. We developed a solid-phase extraction ultra-HPLC/MS/MS method to reliably and precisely analyze small-volume samples and quantified 11 eicosanoids [thromboxane B(2), prostaglandin (PG) E(2), PGD(2), PGF(2α), leukotriene B(4), 15-HETE, 12-HETE, 5-HETE, 12-hydroxyeicosapentaenoic acid, 13-HODE, and 17-hydroxydocosahexaenoic acid]. Our method achieved a median intraday precision of approximately 5% and interday precision of approximately 8%. All calibration curves showed excellent linearity between 0.01 and 50 ng/ml (R(2) > 0.980). In the rat model, eicosanoids were significantly increased in imiquimod-treated inflamed skin sites compared with untreated control sites. Oral treatment with an anti-inflammatory glucocorticoid decreased eicosanoid concentrations. These results show that a combination of tissue-specific sampling with LC/MS analytics is well suited for analyzing small sample volumes from minimally invasive sampling methods such as open-flow microperfusion or microdialysis to study local inflammation and the effect of treatments in skin diseases.

Zusammenfassung Misshandlung und sexueller Missbrauch von Kindern hinterlassen u.a. physische Verletzungen. Diese können bei zeitnaher Dokumentation entscheidend sein für eine Beweisführung u.a. vor Gericht. Dabei werden körperliche Untersuchungen von verschiedenen Institutionen in Auftrag gegeben (Jugendamt, Polizei, Staatsanwaltschaft, Gericht) und es werden Gewaltformen unterschieden: stumpfe Gewalt (z.B. Schläge), thermische Gewalt (z.B. Verbrennen durch eine Zigarette), scharfe Gewalt (z.B. durch ein Messer). Hinzu kommen spezielle Formen der Kindesmisshandlung: u.a. das Schütteltrauma-Syndrom und das Münchhausen-Syndrom by proxy.

Die Untersuchung der Ossifikation des Schildknorpels ist nicht nur in Form von anatomischer und morphologischer Grundlagenforschung, sondern auch fur rechtsmedizinische Uberlegungen von Belang. Ziel war es, einen Geschlechts- und Alterspolymorphismus mittels Mikro-Computertomographie (µCT) nachzuweisen. An 53 autoptisch asservierten Kehlkopfpraparaten wurde eine mikrocomputertomographische Bildgebung durchgefuhrt. Die µCT eignet sich durch ihre hohe raumliche Auflosung und das nichtdestruktive Erschaffen dreidimensionaler Volumendatensatze zur quantitativen Analytik von Knochenstrukturparametern und zur Visualisierung von Unterschieden und Veranderungen der trabekularen Knochenstruktur. Dabei wurden u. a. Parameter bestimmt wie z. B. die Knochendichte, das Knochen- und Gesamtvolumen und ein eigens entwickelter Score fur die Art der Verknocherung. Sowohl ein Alters- als auch ein Geschlechtspolymorphismus konnten nachgewiesen werden. Die mannlichen und die alteren Schildknorpel sind deutlich starker trabekular und vollstandiger verknochert und weisen ein groseres Knochen- und Gesamtvolumen auf als die jungeren und die weiblichen Schildknorpel. Damit lasst sich ein Nutzen fur die Rechtsmedizin aufzeigen, mit dem Schildknorpel als Pradiktor fur das Geschlecht und das Alter eines Knochen- bzw. Leichenfundes.

Introduction The estimation of age-at-death of unidentified cadavers is a central aspect of the identification process. With increasing age, the incidence of glomerulosclerosis and the thickness of the carotid wall have been observed to also increase. This correlation has been demonstrated in various international histological studies. The aim of our study was to assess whether these correlations also apply to a Western European population. Methodology In this retrospective observational study, kidney and common carotid artery samples from 216 cases autopsied at the Institute of Legal Medicine at the Justus-Liebig University in Giessen, Germany, were examined. Only cases with available tissue samples from both body sides were included. Exclusion criteria were poor sample quality and an age younger than 21 years. After histological processing, the tissue samples were assessed and digitally evaluated. Regression and classification analyses were used to investigate the correlation between age-at-death and intima-media thickness and age-at-death and the incidence of renal glomerular sclerosis. Results Of the 216 autopsy cases, 183 were included for evaluation. Analysis of the carotid artery segments showed a strong correlation (Pearson correlation coefficient r = 0.887) between the intima-media-complex thickness and chronological age. Classification of the glomerulosclerotic incidence showed a correlation of 37.7–43.1% with the predicted age group. Discussion Both the intima-media thickness and the proportion of sclerotic glomeruli can be used to estimate age in Western European cadavers. On the basis of these results, both methods are suited to supplement other already established methods for age-at-death estimation in the identification of an unknown cadaver.

Objective: To implement OFM-recirculation and OFM-suction capable of direct and absolute in-vivo quantification of albumin in the ISF of pigs. Approach: OFM-recirculation and OFM-suction were used to collect ISF in-vivo in pigs and lymph was collected from the same pigs after OFM sampling. Blood was collected before and after OFM sampling, plasma was isolated and mean albumin plasma concentrations per pig were used to yield albumin ISF-to-plasma ratios. We characterized the quality of the collected undiluted ISF via (1) stable albumin ISF-to-plasma ratio in OFM-recirculation and in OFM-suction samples, (2) comparison of albumin ISF-to-plasma ratios from OFM-recirculation and OFM-suction and (3) comparison of normalized albumin concentrations in the ISF and lymph. Main results: Both advanced OFM methods were successfully implemented and albumin was quantified from the collected ISF samples. OFM-recirculation reached stable albumin ISF-to-plasma ratios after 20 recirculation cycles. Absolute ISF albumin concentrations were 11.2 mg ml−1 (OFM-recirculation) and 14.2 mg ml−1 (OFM-suction). Albumin ISF-to-plasma ratios were 0.39 ± 0.04 (OFM -recirculation) and 0.47 ± 0.1 (OFM-suction). Significance: Knowledge of the ISF protein content is of major importance when assessing PK/PD effects, especially of highly protein bound drugs. Up to now, only blood albumin values have been available to determine the degree of protein binding in several tissues. OFM-recirculation and OFM-suction allow direct, absolute quantification of albumin in ISF for the first time and enable investigation of the degree of protein binding of a drug directly in its target tissue.

The treatment of macular diseases requires frequent monitoring by optical coherence tomography (OCT). Home monitoring would reduce the burden of frequent clinical visits and increase therapy adherence. In a pilot study with 47 patients having different macular diseases we tested a proprietary self-examination low-cost full-field OCT (SELFF-OCT). For comparison, scans with a standard clinical spectral domain OCT were taken. Data was graded by a reading center. Patients were able to successfully acquire images that were clinically gradable for 85% of the included eyes. The sensitivity and specificity for an anti-VEGF treatment decision based on the SELFF-OCT was 0.94 and 0.95, respectively.

Purpose New lasers with a continuous wave power exceeding 15 W are currently investigated for retinal therapies, promising highly localized effects at and close to the Retinal Pigment Epithelium (RPE). The goal of this work is to evaluate mechanisms and thresholds for RPE cell damage by means of pulse durations up to 50 µs. Methods A diode laser with a wavelength of 514 nm, a power of 15 W, and adjustable pulse durations between 2 µs and 50 µs was used. Porcine RPE-choroidal explants (ex vivo) and chinchilla bastard rabbits (in vivo) were irradiated to determine threshold radiant exposures for RPE damage \({\bar H_{Cell}}\) by calcein vitality staining and fluorescence angiography, respectively. Thresholds for microbubble formation (MBF) \({\bar H_{MBF}}\) were evaluated by time-resolved optoacoustics. Exemplary histologies support the findings. Results \({\bar H_{{{MBF}}}}\) is significantly higher than \({\bar H_{Cell}}\) at pulse durations ≥ 5 µs (P < 0.05) ex vivo, while at 2 µs, no statistically significant difference was found. The ratios between \({\bar H_{{{MBF}}}}\) and \({\bar H_{Cell}}\) increase with pulse duration from 1.07 to 1.48 ex vivo and 1.1 to 1.6 in vivo, for 5.2 and 50 µs. Conclusions Cellular damage with and without MBF related disintegration are both present and very likely to play a role for pulse durations ≥ 5 µs. With the lower µs pulses, selective RPE disruption might be possible, while higher values allow achieving spatially limited thermal effects without MBF. However, both modi require a very accurate real-time dosing control in order to avoid extended retinal disintegration in this power range.