The sinus node (SN) is the heart's primary pacemaker. Key ion channels (mainly the funny channel, HCN4) and Ca2+-handling proteins in the SN are responsible for its function. Transcription factors (TFs) regulate gene expression through inhibition or activation and microRNAs (miRs) do this through inhibition. There is high expression of macrophages and mast cells within the SN connective tissue. 'Novel'/unexplored TFs and miRs in the regulation of ion channels and immune cells in the SN are not well understood. Using RNAseq and bioinformatics, the expression profile and predicted interaction of key TFs and cell markers with key miRs in the adult human SN vs. right atrial tissue (RA) were determined. 68 and 60 TFs significantly more or less expressed in the SN vs. RA respectively. Among those more expressed were ISL1 and TBX3 (involved in embryonic development of the SN) and 'novel' RUNX1-2, CEBPA, GLI1-2 and SOX2. These TFs were predicted to regulate HCN4 expression in the SN. Markers for different cells: fibroblasts (COL1A1), fat (FABP4), macrophages (CSF1R and CD209), natural killer (GZMA) and mast (TPSAB1) were significantly more expressed in the SN vs. RA. Interestingly, RUNX1-3, CEBPA and GLI1 also regulate expression of these cells. MiR-486-3p inhibits HCN4 and markers involved in immune response. In conclusion, RUNX1-2, CSF1R, TPSAB1, COL1A1 and HCN4 are highly expressed in the SN but not miR-486-3p. Their complex interactions can be used to treat SN dysfunction such as bradycardia. Interestingly, another research group recently reported miR-486-3p is upregulated in blood samples from severe COVID-19 patients who suffer from bradycardia.

Towards the end of 2019, a novel coronavirus was identified as the culprit for a cluster of pneumonia cases in Wuhan, China. Since then, it has rapidly spread worldwide, affecting more than 43 million people, and in March 2020, the World Health Organization (WHO) declared it a pandemic. The purpose of the study is to present the findings of 15 forensic autopsies performed in Romania, on SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) positive subjects, and to present the case of one SARS-CoV-2 infected patient who experienced a violent death, as established during their autopsy. A total of 11 male and 4 female patients were autopsied, and SARS-CoV-2 infection was diagnosed post-mortem in two cases. The most frequent symptoms before death were dry cough, dyspnoea, and fever. Hypertension, ischemic cardiac disease, and a history of stroke were the most frequent associated diseases. The mean duration from the symptoms’ debut to a RT-PCR positive SARS-CoV-2 test was 3.7 days, while the mean survival time from the RT-PCR positive test was 4.2 days. A histological examination was performed in seven cases and revealed, in most of them, hyaline membranes, and mixed inflammatory cell infiltration of the interstitium, alveoli, and perivascular areas. In addition, all of the examined cases developed small vessel thrombosis. A case of violent death was also reported, regarding a 87-year-old male subject who suffered a femur fracture (domestic fall) and was diagnosed with SARS-CoV-2 infection the following day after surgery. After transfer to a COVID-19 (coronavirus disease-19) support hospital, during an episode of behavioral disorder, the patient jumped from the first floor window. Death occurred a few days later, and the cause was established as bronchopneumonia superimposed on SARS-CoV-2 infection. In conclusion, autopsies should be conducted while providing a safe environment for professionals to perform them, because they are crucial procedures that can help gain a better understanding of the role of SARS-CoV-2 infection in thanatogenesis.

The sinus node is an intensively researched structure in terms of anatomical, histological, electrophysiological, molecular and genetic approach. For postmortem diagnosis it is still difficult to investigate due to a still reduced accessibility. In this study we tried and succeed to apply molecular biology techniques on postmortem tissues in order to widen the range of postmortem forensic investigation and provide information related to the diagnostic of cardiac arrhythmia. I described the stages of this investigation, with dissection, preservation and analysis that included classical histology, immunohistochemistry, confocal microscope, microdissection, RIN testing, mRNA expression obtaining a precise morphofunctional location of the sinus node.

Tracheal rupture in the newborn represents a rare but severe injury with a difficult therapeutic management and causality interpretation. Here we present the case of a macrosomic female newborn who presented after a dystocic delivery with a series of complications: respiratory impairment, subcutaneous emphysema, pneumothorax, anemia, and finally a diagnosed tracheal tear, which led to a short survival despite the continuous emergency care. The same issues encountered here were also found in the literature and are represented by the delayed diagnosis, the nonspecific initial clinical signs, the lack of a commonly accepted appropriate treatment, the assessment of the mechanism of rupture, the anatomical characteristics of the injury, and the patient management within the whole clinical context.

(1) Background: The sinus node (SN) is the main pacemaker of the heart. It is characterized by pacemaker cells that lack mitochondria and contractile elements. We investigated the possibility that transcription factors (TFs) and microRNAs (miRs) present in the SN can regulate gene expression that affects SN morphology and function. (2) Methods: From human next-generation sequencing data, a list of mRNAs that are expressed at lower levels in the SN compared with the right atrium (RA) was compiled. The mRNAs were then classified into contractile, mitochondrial or glycogen mRNAs using bioinformatic software, RStudio and Ingenuity Pathway Analysis. The mRNAs were combined with TFs and miRs to predict their interactions. (3) Results: From a compilation of the 1357 mRNAs, 280 contractile mRNAs and 198 mitochondrial mRNAs were identified to be expressed at lower levels in the SN compared with RA. TFs and miRs were shown to interact with contractile and mitochondrial function-related mRNAs. (4) Conclusions: In human SN, TFs (MYCN, SOX2, NUPR1 and PRDM16) mainly regulate mitochondrial mRNAs (COX5A, SLC25A11 and NDUFA8), while miRs (miR-153-3p, miR-654-5p, miR-10a-5p and miR-215-5p) mainly regulate contractile mRNAs (RYR2, CAMK2A and PRKAR1A). TF and miR-mRNA interactions provide a further understanding of the complex molecular makeup of the SN and potential therapeutic targets for cardiovascular treatments.

View of Volume 66, Special Issue, September 2021 Introduction. In Romania legal medicine suppose professional activities as forensic pathologist and legal doctor are facing victims that request documenting traumatic lesions if any or sexual abuses, prejudices, working capacity, malpraxis, etc. Objective. The objective of our work is to determine the special kind of doctor-patient relationship in clinical legal medicine and to analyze the ethical influences. Material and methods. More than 1500 cases of medico-legal examinations are performed in the National Institute of Legal Medicine Mina Minovici in Bucharest each year. Most of them are domestic violence requests or car accidents. Discussions. In the late 30 years (Ezechiel JE, Linda LE, JAMA 1992) found out 4 different relationship models that may be applied in medical practice; the paternalistic model (the patient accepts his doctor as his legal and moral representative), informative model (the patient expresses his autonomy), interpretative model (the doctor is a good friend in need) and the deliberative model of self-construction of the knowledge that the patient must have in order to have a voluntary decision. Conclusions. In clinical legal medicine the patient is not only a patient but a victim also. Therefore, the relationship is double folded. With his patient the legal doctor develops initially an informative model, then an interpretative model. With his victim the doctor develops initially a paternalistic approach (passive character type) or an informative one (active character type), usually an interpretative model as most highly requested (What would you do if you were I?) or the deliberative model when evaluating prejudices, etc.