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In murine models, the expression of inducible nitric oxide synthase (iNOS) in myocardial infarction (MI) has been reported to be the result of tissue injury and inflammation. In the present study, mRNA expression of iNOS, hypoxia-inducible factor-1α (HIF-1α), and vascular endothelial growth factor (VEGF) was investigated in postmortem human infarction hearts. Since HIF-1α is the inducible subunit of the transcription factor HIF-1, which regulates transcription of iNOS and VEGF, the interrelation between the three genes was observed, to examine the molecular processes during the emergence of MI. iNOS and VEGF mRNAs were found to be significantly upregulated in the affected regions of MI hearts in comparison to healthy controls. Upregulation of HIF-1α was also present but not significant. Correlation analysis of the three genes indicated a stronger and significant correlation between HIF-1α and iNOS mRNAs than between HIF-1α and VEGF. The results of the study revealed differences in the expression patterns of HIF-1 downstream targets. The stronger transcription of iNOS by HIF-1 in the affected regions of MI hearts may represent a pathological process, since no correlation of iNOS and HIF-1α mRNA was found in non-affected areas of MI hearts. Oxidative stress is considered to cause molecular changes in MI, leading to increased iNOS expression. Therefore, it may also represent a forensic marker for detection of early changes in heart tissue.
Sudden cardiac death (SCD) in adolescents and young adults may be the first manifestation of an inherited arrhythmic syndrome. Thus identification of a genetic origin in sudden death cases deemed inconclusive after a comprehensive autopsy and may help to reduce the risk of lethal episodes in the remaining family. Using next-generation sequencing (NGS), a large number of variants of unknown significance (VUS) are detected. In the majority of cases, there is insufficient evidence of pathogenicity, representing a huge dilemma in current genetic investigations. Misinterpretation of such variants may lead to inaccurate genetic diagnoses and/or the adoption of unnecessary and/or inappropriate therapeutic approaches. In our study, we applied current (ACMG) recommendations for variant classification in post-mortem genetic screening of a cohort of 56 SCD victims. We identified a total 53 rare protein-altering variants (MAF < 0.2%) classified as VUS or worse. Twelve percent of the cases exhibited a clinically actionable variant (pathogenic, likely pathogenic or VUS – potentially pathogenic) that would warrant cascade genetic screening in relatives. Most of the variants detected by means of the post-mortem genetic investigations were VUS. Thus, genetic testing by itself might be fairly meaningless without supporting background data. This data reinforces the need for an experienced multidisciplinary team for obtaining reliable and accountable interpretations of variant significance for elucidating potential causes for SCDs in the young. This enables the early identification of relatives at risk or excludes family members as genetic carriers. Also, development of adequate forensic guidelines to enable appropriate interpretation of rare genetic variants is fundamental.
Fragestellung: Die meniscofemoralen Ligamente (MFL) ant. (Humphry) und post. (Wrisberg) begleiten inkonstant das hintere Kreuzband vom lateralen Meniskus zur medialen Femurkondyle, sie üben eine Außenmeniskusstellfunktion aus. Bisherige Literatur gibt eine stark variierende Inzidenzrate der MFL an, die durch eine hohe Fallzahl von untersuchten Kniegelenken in dieser Arbeit verifiziert werden soll.
Methoden: 122 frische, unversehrte Kniegelenke von 31 männlichen und 30 weiblichen Leichen des Sektionsgutes der Rechtsmedizin Frankfurt, wurden auf Inzidenz und Morpholgie von ant. und post. MFL untersucht, ein ventraler (n.Souryal) und dorsaler Nochweitenindex (NWI) erstellt sowie eine morphologische Typisierung der vorhandenen ant. und post. MFL vorgenommen
Ergebnisse: 96% der Kniegelenke zeigten ein oder beide MFL, davon post. MFL in 82% und ant. MFL in 58%. Beide Ligamente in beiden Knien einer Leiche kamen zu 33% vor. Statistisch wurde keine Korrelation zwischen Alter, Geschlecht, Seite und der Inzidenz der Ligamente gefunden. vNWI: w 0,22; m 0,24. dorsaler NWI: w 0,26; m 0,28. Einteilung des post. MFL (Wrisberg): Typ I Strang, Typ II Fächer, Typ III kein meniskaler Ansatz.
Schlussfolgerungen: Die Inzidenz und damit auch klinische Relevanz beider MFL liegt höher als bisher angenommen, z.B. in der Beurteilung von Knie-MRTs als falschpos. Rupturen oder in der klinischen Untersuchung als Abschwächung einer hinteren Schublade. Die Typisierung zeigt einen Zusammenhang des post. MFL mit einem dritten Kreuzband auf: nach Evolution des aufrechten Ganges und damit weniger Rotation im Kniegelenk bildet es sich zurück.
Mongolian spots (MS) are congenital dermal conditions resulting from neural crest-derived melanocytes migration to the skin during embryogenesis. MS incidences are highly variable in different populations. Morphologically, MS present as hyperpigmented maculae of varying size and form, ranging from round spots of 1 cm in diameter to extensive discolorations covering predominantly the lower back and buttocks. Due to their coloring, which is also dependent on the skin type, MS may mimic hematoma thus posing a challenge on the physician conducting examinations of children in cases of suspected child abuse. In the present study, MS incidences and distribution, as well as skin types, were documented in a collective of 253 children examined on the basis of suspected child abuse. From these data, a classification scheme was derived to document MS and to help identify cases with a need for recurrent examination for unambiguous interpretation of initial findings alongside the main decisive factors for re-examination such as general circumstances of the initial examination (e. g., experience of the examiner, lighting conditions) and given dermatological conditions of the patient (e. g., diaper rash).