Taxonomy of Coding Techniques for Efficient Network Communications

Internet Research Task Force, Request For Comments (RFC) 8406, https://datatracker.ietf.org/doc/rfc8406/This document summarizes recommended terminology for Network Coding concepts and constructs. It provides a comprehensive set of terms in order to avoid ambiguities in future IRTF and IETF documents on Network Coding. This document is the product of the Coding for Efficient Network Communications Research Group (NWCRG), and it is in line with the terminology used by the RFCs produced by the Reliable Multicast Transport (RMT) and FEC Framework (FECFRAME) IETF working groups

The blood-brain barrier is dysregulated in COVID-19 and serves as a CNS entry route for SARS-CoV-2.

Neurological complications are common in COVID-19. Although SARS-CoV-2 has been detected in patients' brain tissues, its entry routes and resulting consequences are not well understood. Here, we show a pronounced upregulation of interferon signaling pathways of the neurovascular unit in fatal COVID-19. By investigating the susceptibility of human induced pluripotent stem cell (hiPSC)-derived brain capillary endothelial-like cells (BCECs) to SARS-CoV-2 infection, we found that BCECs were infected and recapitulated transcriptional changes detected in vivo. While BCECs were not compromised in their paracellular tightness, we found SARS-CoV-2 in the basolateral compartment in transwell assays after apical infection, suggesting active replication and transcellular transport of virus across the blood-brain barrier (BBB) in vitro. Moreover, entry of SARS-CoV-2 into BCECs could be reduced by anti-spike-, anti-angiotensin-converting enzyme 2 (ACE2)-, and anti-neuropilin-1 (NRP1)-specific antibodies or the transmembrane protease serine subtype 2 (TMPRSS2) inhibitor nafamostat. Together, our data provide strong support for SARS-CoV-2 brain entry across the BBB resulting in increased interferon signaling

Phenotyping of cold allodynia in 18 inbred strains of mice

Hintergrund und Ziele: Chronische Schmerzen verursachen ebenso wie neuropathische Schmerzen eine enorme sozioökonomische Belastung mit einer Prävalenz von schätzungsweise vier bis acht Millionen Patienten in der deutschen Bevölkerung und einem ungefähren wirtschaftlichen Schaden von 38 Milliarden Euro pro Jahr - davon 28 Milliarden aufgrund von Fehlzeiten, reduzierter Produktivität und vorzeitiger Pensionierung. Die Gesundheitsausgaben für chronische Schmerzen machen diese Krankheit zu einer der am meisten beunruhigenden Krankheiten in Deutschland (Aster and Sommer, 2019). Zur Behandlung chronischer Schmerzen stehen nur wenige Medikamente zur Verfügung und die meisten davon haben eine eingeschränkte Wirksamkeit und signifikante Nebenwirkungen (Sisignano et al., 2014). Daher ist es wichtig, neue Forschungsansätze zu nutzen, um neue Zielstrukturen für künftige Medikamente zu finden. Es gilt als sehr wahrscheinlich, dass die bei der Schmerzempfindung beobachteten interindividuellen Unterschiede zwischen Patienten auf teils noch unentdeckten genetischen Merkmalen beruhen. In der folgenden Arbeit wurde die Variabilität der Schmerzreaktionen bei 18 unterschiedlichen Inzuchtmäusestämmen unter Verwendung eines pharmakologischen Schmerzmodells basierend auf dem Ciguatoxin-Fischgift (CTX), quantifiziert. Das CTX wird von tropischen Gambierdiscus toxicus Dinoflagellaten produziert und aus Fischfleisch isoliert, in dem es sich über die Nahrungskette anreichert. CTX verursachen über orale Aufnahme die Fischvergiftung Ciguatera, die zu einer Kaltallodynie bei betroffenen Patienten führt und, injiziert in die oberste Hautschicht von Probanden, eine dosisabhängige lokale Kaltallodynie hervorrufen. Das Ziel der Arbeit ist in Inzuchtmäusestämmen phänotypische Unterschiede in der thermischen Nozizeption nach gezielter intraplantarer Gabe von CTX zu charakterisieren und quantifizieren und letztlich als Grundlage zur Detektion für zukünftige genetische Empfindlichkeitsfaktoren für die Kaltallodynie zu dienen. Methoden: Nach intraplantarer (i.pl). Injektion von CTX in die rechte Hinterpfote und Platzieren der Maus auf einer temperaturgesteuerten Platte (37°C, 15°C), basierend auf ein bereits etabliertes CTX-Mausmodell (Vetter et al., 2012), wurde die Intensität des Schmerzverhaltens bei Männchen und Weibchen bei nicht schmerzhafter Wärme (37°C, Warmallodynie) und nicht schmerzhafter Kälte (15°C, Kaltallodynie) über ein definiertes Zeitintervall von 5 min/pro Stunde über insgesamt sechs Stunden beobachtet und quantifiziert. Ergebnisse und Beobachtungen: Die Ergebnisse zeigten sehr große Unterschiede in der Intensität des Schmerzverhaltens bei 15°C zwischen den Stämmen. Bei allen 18 Mäusestämmen konnte eine Abnahme des Schmerzverhaltens innerhalb der Messzeit beobachtet werden. Zusätzlich konnte festgestellt werden, dass einige wenige Mäusestämme nach i.pl. injiziertem CTX auch ein sensibilisiertes Schmerzverhalten bei Wärme (37°C) aufwiesen. Eine Korrelation zwischen Männchen und Weibchen bei Kälte konnte nicht festgestellt werden. Schlussfolgerung: Die gegensätzlichen Schmerzempfindlichkeiten der verschiedenen Stämme implizieren Genotypabweichungen oder Genexpressionsunterschiede als die wahrscheinliche Quelle für die phänotypischen Unterschiede. Das heißt, dass alle Verhaltensmerkmale eine wesentliche vererbbare Komponente bei Mäusen haben. Beim Vergleich dieser Merkmale wurden homogene Gruppen gebildet, die die Stämme basierend auf ihren Mittelwerten zusammenfassen und damit stark und schwach auf Wärme (37°C) und Kälte (15°C) reagierende Stämme voneinander unterscheiden. Aufgrund interindividueller Unterschiede von Patienten und im Hinblick auf eine zukünftige gezielte Schmerztherapie der Kaltallodynie, wird die Auswirkung einer anknüpfenden genetischen Kartierungsstudie mittels der vorliegenden Daten deutlich.Objectives: Chronic pain, like neuropathic pain, causes an enormous socioeconomic burden with an estimated prevalence of 4 to 8 million patients in the German population and an approximate economic loss of 38 billion euros per year - 28 billion of which is due to absenteeism, reduced productivity and early retirement. Healthcare spending on chronic pain makes it one of the most worrying diseases in Germany (Aster and Sommer, 2019). Few drugs are available to treat chronic pain but most of them have limited efficacy and significant side effects (Sisignano et al., 2014). It is therefore important to use new research approaches to find new targets for future drugs. It is considered highly probable that the interindividual differences between patients observed in pain perception are based on partly undiscovered genetic characteristics. In this study, the variability of pain responses was quantified in 18 different strains of inbred mice using a pharmacological pain model based on the ciguatoxin (CTX) fish poison. The CTX is produced by tropical Gambierdiscus toxicus dinoflagellates and isolated from fish flesh where it accumulates via the food chain. CTX cause the fish poisoning Ciguatera via oral ingestion, which leads to cold allodynia in affected patients and, when injected into the uppermost skin layer of volunteers, causes a dose-dependent local cold allodynia. The aim of this study is to characterize and quantify phenotypic differences in thermal nociception in inbred mouse strains after targeted intraplantar injection of CTX and ultimately to serve as a basis for the detection of future genetic sensitivity factors for cold allodynia. Design & Methods: After intraplantar injection of CTX into the right hind paw and placing the mouse on a temperature controlled plate (37°C, 15°C), based on an already established CTX mouse model (Vetter et al., 2012), the intensity of pain behavior in males and females was observed and quantified at nonpainful heat (37°C, warm allodynia) and nonpainful cold (15°C, cold allodynia) over a defined time interval of 5 min/per hour for a total of 6 hours. Observations & Results: The results showed very large differences in the intensity of pain behavior at 15°C between the strains. In all 18 mouse strains a decrease in pain behavior was observed within the measurement period. In addition, it was found that a few mouse strains also exhibited sensitized pain behavior at heat (37°C) after intraplantar injection of CTX. A correlation between males and females at cold could not be established. Conclusions: The conflicting pain sensitivities of the different strains imply genotype or gene expression differences as the likely source of phenotypic differences. This means that all behavioral traits have an essential heritable component in mice. When comparing these characteristics, homogeneous groups were formed, which group the strains together, based on their mean values and thus distinguish between strains that react as high and low responder to heat (37°C) and cold (15°C). Due to interindividual differences of patients and with regard to a future targeted pain therapy of cold allodynia, the impact of a subsequent genetic mapping study using the available data becomes apparent

Minimally Invasive Tissue Sampling via Post Mortem Ultrasound: A Feasible Tool (Not Only) in Infectious Diseases—A Case Report

In the past years the number of hospital autopsies have declined steadily, becoming almost excluded from medical training. Medicolegal (forensic) autopsies account for almost all autopsies, whereas hospital autopsies are becoming increasingly rare. Minimally invasive tissue sampling (MITS) using post mortem ultrasound offers the opportunity to increase the number of post mortem examinations in a clinical and even forensic context. MITS is a needle-based post mortem procedure that uses (radiological) imaging techniques to examine major organs of the body, acquire tissue samples and aspirate fluid from the body cavities or hollow organs. In this study, MITS was used to determine the presence of other co-existing diseases in a deceased infected 97-year-old woman with severe acute respiratory syndrome coronavirus 2. The examination of her body was carried out using ultrasound as an imaging tool and to gather ultrasound-guided biopsies as conventional autopsy was rejected by the next of kin. Ultrasound and histology identified an intravesical mass leading to an obstruction of the urinary outlet resulting in bilateral hydronephrosis and purulent pyelonephritis, which was unknown during her lifetime. Histopathological examination revealed the tumor mass to be a squamous cell carcinoma. This study has shown that MITS can be used to determine the cause of death and the presence of concomitant diseases in the infectious deceased

Dismemberment and Body Encasement—Case Report and an Empiric Study

The mutilation and encasement of corpses are rare in daily forensic work, but when they occur, close cooperation between different disciplines, such as legal medicine and forensic anthropology, is necessary to obtain the most valuable results. One forensic examination method is the radiological evaluation of victims or body parts by postmortem CT (pmCT) and X-ray images. In relation to a case described in this paper, an empirical study was conducted to figure out the value of radiological imaging and the ability to visualize and temporally classify changes in a corpse encased in concrete. For this purpose, the head and paw of a pig were encased in concrete and scanned regularly over a period of one year. Body parts such as the head and paw are clearly visible on X-ray images. Although decay-related changes are shown, a specific minimum time interval cannot yet be found, as these changes occur continuously in lesser amounts

Ultrasound in legal medicine—a missed opportunity or simply too late? A narrative review of ultrasonic applications in forensic contexts

Objectives!#!Conventional autopsies remain the gold standard of postmortem healthcare quality assurance and help gathering extended knowledge on diseases. In answer to constantly declining autopsy rates non- or minimally invasive autopsy methods were introduced. Ultrasound is a well-established tool for imaging commonly used in clinical practice. This narrative review aims to summarize the current literature regarding the feasibility and validity of ultrasound in a forensic context.!##!Material and methods!#!A PubMed database search was carried out. Abstracts were scanned for pre-defined ex- and inclusion criteria, followed by a snowball search procedure applied to the primarily included articles.!##!Results!#!Forty-five publications met our inclusion criteria. The selected articles concern the feasibility of ultrasound in pre- or postmortem settings, forensic age estimation, and minimally invasive approaches. For imaging, ultrasound was deemed a reliable tool for the examination of epiphyses und superficial wounds, with limitations regarding internal organs and image quality due to postmortem changes. Ultrasound-guided minimally invasive approaches yielded higher success rates for adequate tissue sampling. Many investigations were carried out in low- and middle-income countries focusing on infectious diseases.!##!Conclusion!#!Ultrasound seems a promising but underutilized imaging tool in legal medicine to date. Promising approaches on its feasibility have been conducted. Especially for minimally invasive methods, ultrasound offered significant improvements on qualified biopsy sampling and thus appropriate diagnostics. Moreover, ultrasonic evaluation of epiphyses for age estimation offered valuable results. Nevertheless, further assessment of ultrasonic feasibility in forensic contexts is needed

The handling of SARS-CoV-2 associated deaths - infectivity of the body

The body of a deceased with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is considered infectious. In this study, we present the results of infectivity testing of the body and testing of mortuary staff for SARS-CoV-2. We performed real-time quantitative polymerase chain reaction (RT-qPCR) for SARS-CoV-2 on 33 decedents with ante mortem confirmed SARS-CoV-2 infection. Swabs of the body surface from five different body regions and from the body bag or coffin were examined. A subset of the swabs was brought into cell culture. In addition, screening of 25 Institute of Legal Medicine (ILM) personnel for ongoing or past SARS-CoV-2 infection was performed at two different time points during the pandemic. Swabs from all locations of the body surface and the body environment were negative in cases of negative post mortem nasopharyngeal testing (n=9). When the post mortem nasopharyngeal swab tested positive (n=24), between 0 and 5 of the body surface swabs were also positive, primarily the perioral region. In six of the cases, the body bag also yielded a positive result. The longest postmortem interval with positive SARS-CoV-2 RT-qPCR at the body surface was nine days. In no case viable SARS-CoV-2 was found on the skin of the bodies or the body bags. One employee (autopsy technician) had possible occupational infection with SARS-CoV-2; all other employees were tested negative for SARS-CoV-2 RNA or antibody twice. Our data indicate that with adequate management of general safety precautions, transmission of SARS-CoV-2 through autopsies and handling of bodies is unlikely

Association of cardiac infection with SARS-CoV-2 in confirmed COVID-19 autopsy cases

IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be documented in various tissues, but the frequency of cardiac involvement as well as possible consequences are unknown. OBJECTIVE: To evaluate the presence of SARS-CoV-2 in the myocardial tissue from autopsy cases and to document a possible cardiac response to that infection. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from consecutive autopsy cases from Germany between April 8 and April 18, 2020. All patients had tested positive for SARS-CoV-2 in pharyngeal swab tests. EXPOSURES: Patients who died of coronavirus disease 2019. MAIN OUTCOMES AND MEASURES: Incidence of SARS-CoV-2 positivity in cardiac tissue as well as CD3(+), CD45(+), and CD68(+) cells in the myocardium and gene expression of tumor necrosis growth factor α, interferon γ, chemokine ligand 5, as well as interleukin-6, -8, and -18. RESULTS: Cardiac tissue from 39 consecutive autopsy cases were included. The median (interquartile range) age of patients was 85 (78-89) years, and 23 (59.0%) were women. SARS-CoV-2 could be documented in 24 of 39 patients (61.5%). Viral load above 1000 copies per μg RNA could be documented in 16 of 39 patients (41.0%). A cytokine response panel consisting of 6 proinflammatory genes was increased in those 16 patients compared with 15 patients without any SARS-CoV-2 in the heart. Comparison of 15 patients without cardiac infection with 16 patients with more than 1000 copies revealed no inflammatory cell infiltrates or differences in leukocyte numbers per high power field. CONCLUSIONS AND RELEVANCE: In this analysis of autopsy cases, viral presence within the myocardium could be documented. While a response to this infection could be reported in cases with higher virus load vs no virus infection, this was not associated with an influx of inflammatory cells. Future investigations should focus on evaluating the long-term consequences of this cardiac involvement

Dying of VOC-202012/01 — multimodal investigations in a death case of the SARS-CoV-2 variant

The current pandemic with Severe acute respiratory syndrome-coronavirus-2 has been taking on new dynamics since the emergence of new variants last fall, some of them spreading more rapidly. Many countries currently find themselves in a race to ramp up vaccination strategies that have been initiated and a possible third wave of the pandemic from new variants, such as the Variant of Concern-202012/01 from the B.1.1.7 lineage. Until today, many investigations in death cases of Coronavirus-disease-19 have been conducted, revealing pulmonary damage to be the predominant feature of the disease. Thereby, different degrees of macroscopic and microscopic lung damage have been reported, most of them resembling an Acute Respiratory Distress Syndrome. Far more, systemic complications of the disease such as pulmonary embolisms have been described. However, neither morphologic nor virologic findings of patients dying of the new variants have yet been reported. Here, we report on a comprehensive analysis of radiologic, morphologic, and virologic findings in a fatal case of this variant

Taxonomy of Coding Techniques for Efficient Network Communications

Internet Research Task Force, Request For Comments (RFC) 8406, https://datatracker.ietf.org/doc/rfc8406/This document summarizes recommended terminology for Network Coding concepts and constructs. It provides a comprehensive set of terms in order to avoid ambiguities in future IRTF and IETF documents on Network Coding. This document is the product of the Coding for Efficient Network Communications Research Group (NWCRG), and it is in line with the terminology used by the RFCs produced by the Reliable Multicast Transport (RMT) and FEC Framework (FECFRAME) IETF working groups