Retrograde dye perfusion of the proximal aorta - A postmortem technical study

Introduction: Multiple cardiovascular conditions can lead to unexpected fatality, which is defined as sudden cardiac death. One of these potentially underlying conditions is aortic regurgitation, which can be caused by discrete changes of the geometry of the proximal aorta. To analyze aortic valve competency and furthermore to elucidate underlying pathological alterations of the coronary arteries and the vasa vasorum a perfusion method to simulate a diastolic state was designed. Material and methods: A postmortem approach with retrograde perfusion of the ascending aorta with methylene blue was applied to three bodies. The procedure comprised cannulation of the brachiocephalic trunk, clamping of the aortic arch between brachiocephalic trunk and left carotid artery, infusion of 250 ml of methylene blue, and optical clearing of the superficial tissue layers after perfusion. Organs were examined directly following perfusion and after optical clearing. Results: Assessment and visualization of aortic valve competency and the vasa vasorum were possible in all three instances. Visualization of the coronary perfusion was impaired by postmortem thrombus formation. Optical clearing did not provide additional information. Discussion: The method presented here is a time- and cost-efficient way of visualizing aortic valve competency and the vasa vasorum. The visualization of the vasa vasorum highlights the potential of this method in basic research on diseases of the great arteries and coronaries. However, for a time-efficient functional analysis of the coronaries, other methods must be applied

Forensic, legal, and clinical aspects of deaths associated with implanted cardiac devices

As the population ages, the prevalence of heart failure and individuals wearing an implanted cardiac device is increasing. The combination of different underlying pathophysiologies and (the combination of) implanted cardiac devices can become a challenge with regard to the determination of cause and manner of death in such individuals. Additionally, heart disease is frequently associated with mental disease, ranging from anxiety and depression to suicidality and suicide (attempts). At the same time, the correct diagnosis of cause and manner of death is the basis for quality assurance, further therapeutic advances, legal safety, and suicide prevention. By that, an interdisciplinary field between legal medicine, clinicians, and law enforcement opens up. In this field, the different participants can simultaneously benefit from and need each other. For example, legal medicine experts need investigatory results and clinical expertise for the interpretation of readout data of implanted cardiac devices in order to correctly determine the cause of death. A correctly determined cause of death can assist law enforcement and help clinicians to further improve various therapeutic approaches based on correct mortality data collection. In addition, it is the basis for identification of suicides of device carriers, allowing psychological and psychiatric experts to better understand the burden of mental disease in this particular cohort. Against this interdisciplinary background, this manuscript summarizes information about psychiatric comorbidities and suicidality while being on a device. Thereby, basic information on complications and malfunctions of implanted cardiac devices, device-associated deaths with particular emphasis on device manipulation is displayed as basic information needed for correct determination of the cause of death. Also, legal and ethical issues in this field are outlined. The final result is a proposal of an interdisciplinary assessment workflow for a conjoint approach to improve the diagnosis of deaths associated with implanted cardiac devices. It will allow for a differentiation between an individual who died with or due to the device

iNOS expressing macrophages co-localize with nitrotyrosine staining after myocardial infarction in humans

IntroductionInducible nitric oxide synthase (iNOS) produces micromolar amounts of nitric oxide (NO) upon the right stimuli, whose further reactions can lead to oxidative stress. In murine models of myocardial infarction (MI), iNOS is known to be expressed in infiltrating macrophages, which at early onset enter the infarcted zone and are associated with inflammation. In contrast cardiac tissue resident macrophages are thought to enhance regeneration of tissue injury and re-establish homeostasis. Both detrimental and beneficial effects of iNOS have been described, still the role of iNOS in MI is not fully understood. Our aim was to examine cell expression patterns of iNOS and nitrotyrosine (NT) production in human MI.Material and MethodsWe examined in postmortem human MI hearts the iNOS mRNA expression by means of qPCR. Further we performed immunohistochemical stainings for cell type identification. Afterwards a distance analysis between iNOS and NT was carried out to determine causality between iNOS and NT production.ResultsiNOS mRNA expression was significantly increased in infarcted regions of human MI hearts and iNOS protein expression was detected in resident macrophages in infarcted human hearts as well as in controls hearts, being higher in resident macrophages in MI hearts compared to control. Furthermore in MI and in healthy human hearts cells showing signs of NT production peaked within 10–15 µm proximity of iNOS+ cells.DiscussionThese results indicate that, unexpectedly, resident macrophages are the main source of iNOS expression in postmortem human MI hearts. The peak of NT positive cells within 10–15 µm of iNOS+ cells suggest an iNOS dependent level of NT and therefore iNOS dependent oxidative stress. Our results contribute to understanding the role of iNOS in human MI

Forensic, legal, and clinical aspects of deaths associated with implanted cardiac devices

As the population ages, the prevalence of heart failure and individuals wearing an implanted cardiac device is increasing. The combination of different underlying pathophysiologies and (the combination of) implanted cardiac devices can become a challenge with regard to the determination of cause and manner of death in such individuals. Additionally, heart disease is frequently associated with mental disease, ranging from anxiety and depression to suicidality and suicide (attempts). At the same time, the correct diagnosis of cause and manner of death is the basis for quality assurance, further therapeutic advances, legal safety, and suicide prevention. By that, an interdisciplinary field between legal medicine, clinicians, and law enforcement opens up. In this field, the different participants can simultaneously benefit from and need each other. For example, legal medicine experts need investigatory results and clinical expertise for the interpretation of readout data of implanted cardiac devices in order to correctly determine the cause of death. A correctly determined cause of death can assist law enforcement and help clinicians to further improve various therapeutic approaches based on correct mortality data collection. In addition, it is the basis for identification of suicides of device carriers, allowing psychological and psychiatric experts to better understand the burden of mental disease in this particular cohort. Against this interdisciplinary background, this manuscript summarizes information about psychiatric comorbidities and suicidality while being on a device. Thereby, basic information on complications and malfunctions of implanted cardiac devices, device-associated deaths with particular emphasis on device manipulation is displayed as basic information needed for correct determination of the cause of death. Also, legal and ethical issues in this field are outlined. The final result is a proposal of an interdisciplinary assessment workflow for a conjoint approach to improve the diagnosis of deaths associated with implanted cardiac devices. It will allow for a differentiation between an individual who died with or due to the device

Sensitive and label-free biosensing of RNA with predicted secondary structures by a triplex affinity capture method

A novel biosensing approach for the label-free detection of nucleic acid sequences of short and large lengths has been implemented, with special emphasis on targeting RNA sequences with secondary structures. The approach is based on selecting 8-aminoadenine-modified parallel-stranded DNA tail-clamps as affinity bioreceptors. These receptors have the ability of creating a stable triplex-stranded helix at neutral pH upon hybridization with the nucleic acid target. A surface plasmon resonance biosensor has been used for the detection. With this strategy, we have detected short DNA sequences (32-mer) and purified RNA (103-mer) at the femtomol level in a few minutes in an easy and level-free way. This approach is particularly suitable for the detection of RNA molecules with predicted secondary structures, reaching a limit of detection of 50 fmol without any label or amplification steps. Our methodology has shown a marked enhancement for the detection (18% for short DNA and 54% for RNA), when compared with the conventional duplex approach, highlighting the large difficulty of the duplex approach to detect nucleic acid sequences, especially those exhibiting stable secondary structures. We believe that our strategy could be of great interest to the RNA field

Gender differences in social support among older adults

The purpose of this study was to determine whether exposure to life stress can help explain gender differences in the use of social support. Findings from a longitudinal study suggest that as the number of stressful life events increase, elderly men and women are equally likely to become more involved in their social network, while gender differences emerge only in response to chronic financial strain. Further analysis indicates that elderly women are more likely than elderly men to report that the support they received increased their feelings of personal control.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45591/1/11199_2004_Article_BF00289174.pd

“Well, I’m Going to Have a Baby”: Navigating Safety, Stakeholders, and Strategy in Workplace Pregnancy Disclosures

This study explores how 92 women disclosed their pregnancies in the workplace. Examining workplace pregnancy disclosure broadly rather than taking a dyadic approach (e.g. employee to supervisor) highlighted tensions and outcomes associated with simultaneously navigating disclosures to multiple colleagues and supervisors. Data analysis revealed four themes: (b) timing safely, (c) diffusing selectively, (d) controlling gatherings, and (e) crafting conversational tones. Findings situate workplace pregnancy disclosure as a dynamic multi-stakeholder process. Women’s accounts suggest that risk is understood as linked to potential future disclosures and the importance of emotion in crafting disclosure interactions