Plxnd1 Expression in Thymocytes Regulates Their Intrathymic Migration While That in Thymic Endothelium Impacts Medullary Topology

An important role for plexinD1 in thymic development is inferred from studies of germline Plxnd1 knockout (KO) mice where mislocalized CD69+ thymocytes as well as ectopic thymic subcapsular medullary structures were observed. Given embryonic lethality of the Plxnd1−/− genotype, fetal liver transplantation was employed in these prior analyses. Such embryonic hematopoietic reconstitution may have transferred Plxnd1 KO endothelial and/or epithelial stem cells in addition to Plxnd1 KO lymphoid progenitors, thereby contributing to that phenotype. Here we use Plxnd1flox/flox mice crossed to pLck-Cre, pKeratin14-Cre, or pTek-Cre transgenic animals to create cell-type specific conditional knockout (CKO) lines involving thymocytes (D1ThyCKO), thymic epithelium (D1EpCKO), and thymic endothelium (D1EnCKO), respectively. These CKOs allowed us to directly assess the role of plexinD1 in each lineage. Loss of plexinD1 expression on double positive (DP) thymocytes leads to their aberrant migration and cortical retention after TCR-mediated positive selection. In contrast, ectopic medulla formation is a consequence of loss of plexinD1 expression on endothelial cells, in turn linked to dysregulation of thymic angiogenesis. D1EpCKO thymi manifest neither abnormality. Collectively, our findings underscore the non-redundant roles for plexinD1 on thymocytes and endothelium, including the dynamic nature of medulla formation resulting from crosstalk between these thymic cellular components

Distinct Compartments of the Proepicardial Organ Give Rise to Coronary Vascular Endothelial Cells

SummaryThe proepicardial organ is an important transient structure that contributes cells to various cardiac lineages. However, its contribution to the coronary endothelium has been disputed, with conflicting data arising in chick and mouse. Here we resolve this conflict by identifying two proepicardial markers, Scleraxis (Scx) and Semaphorin3D (Sema3D), that genetically delineate heretofore uncharacterized proepicardial subcompartments. In contrast to previously fate-mapped Tbx18/WT-1-expressing cells that give rise to vascular smooth muscle, Scx- and Sema3D-expressing proepicardial cells give rise to coronary vascular endothelium both in vivo and in vitro. Furthermore, Sema3D+ and Scx+ proepicardial cells contribute to the early sinus venosus and cardiac endocardium, respectively, two tissues linked to vascular endothelial formation at later stages. Taken together, our studies demonstrate that the proepicardial organ is a molecularly compartmentalized structure, reconciling prior chick and mouse data and providing a more complete understanding of the progenitor populations that establish the coronary vascular endothelium

Cardiopulmonary resuscitation (CPR) training strategies in the times of COVID-19: A systematic literature review comparing different training methodologies

Background: Traditional, instructor led, in-person training of CPR skills has become more challenging due to COVID-19 pandemic. We compared the learning outcomes of standard in-person CPR training (ST) with alternative methods of training such as hybrid or online-only training (AT) on CPR performance, quality, and knowledge among laypersons with no previous CPR training.Methods: We searched PubMed and Google Scholar for relevant articles from January 1995 to May 2020. Covidence was used to review articles by two independent researchers. Effective Public Health Practice Project (EPHPP) Quality Assessment Tool was used to assess quality of the manuscripts.Results: Of the 978 articles screened, twenty met the final inclusion criteria. All included studies had an experimental design and moderate to strong global quality rating. The trainees in ST group performed better on calling 911, time to initiate chest compressions, hand placement and chest compression depth. Trainees in AT group performed better in assessing scene safety, calling for help, response time including initiating first rescue breathing, adequate ventilation volume, compression rates, shorter hands-off time, confidence, willingness to perform CPR, ability to follow CPR algorithm, and equivalent or better knowledge retention than standard teaching methodology.Conclusion: AT methods of CPR training provide an effective alternative to the standard in-person CPR for large scale public training

Using network theory to identify the causes of disease outbreaks of unknown origin.

The identification of undiagnosed disease outbreaks is critical for mobilizing efforts to prevent widespread transmission of novel virulent pathogens. Recent developments in online surveillance systems allow for the rapid communication of the earliest reports of emerging infectious diseases and tracking of their spread. The efficacy of these programs, however, is inhibited by the anecdotal nature of informal reporting and uncertainty of pathogen identity in the early stages of emergence. We developed theory to connect disease outbreaks of known aetiology in a network using an array of properties including symptoms, seasonality and case-fatality ratio. We tested the method with 125 reports of outbreaks of 10 known infectious diseases causing encephalitis in South Asia, and showed that different diseases frequently form distinct clusters within the networks. The approach correctly identified unknown disease outbreaks with an average sensitivity of 76 per cent and specificity of 88 per cent. Outbreaks of some diseases, such as Nipah virus encephalitis, were well identified (sensitivity = 100%, positive predictive values = 80%), whereas others (e.g. Chandipura encephalitis) were more difficult to distinguish. These results suggest that unknown outbreaks in resource-poor settings could be evaluated in real time, potentially leading to more rapid responses and reducing the risk of an outbreak becoming a pandemic

Using Mathematical Models In A Unified Approach To Predicting The Next Emerging Infectious Disease

Emerging infectious diseases (EIDs) pose a significant threat to human health, global economies, and conservation (Smolinski et al. 2003). They are defined as diseases that have recently increased in incidence (rate of the development of new cases during a given time period), are caused by pathogens that recently moved from one host population to another, have recently evolved, or have recently exhibited a change in pathogenesis (Morse 1993; Krause 1994). Some EIDs threaten global public health through pandemics with large-scale mortality (e.g., HN/AIDS). Others cause smaller outbreaks but have high case fatality ratios or lack effective therapies or vaccines (e.g. Ebola virus or methicillin-resistant Staphylococcus aureus). As a group, EIDs cause hundreds of thousands of deaths each year, and some outbreaks (e.g., SARS, H5N1) have cost the global economy tens of billions of dollars. Emerging diseases also affect plants, livestock, and wildlife and are recognized as a Significant threat to the conservation of biodiversity (Daszak et al. 2000). Approximately 60% of emerging human disease events are zoonotic, and over 75% of these diseases originate in wildlife (Jones et al. 2008). The global response to such epidemics is frequently reactive, and the effectiveness of conventional disease control operations is often too little, too late\u27: With rising globalization, the ease with which diseases spread globally has increased dramatically in recent times. Also, interactions between humans and wildlife have intensified through trade markets, agricultural intensification, logging and mining, and other forms of development that encroach into wild areas. Rapid human population growth, land use change, and change in global trade and travel require a shift toward a proactive, predictive, and preventive approaches for the next zoonotic pandemic

Possibility for reverse zoonotic transmission of SARS-CoV-2 to free-ranging wildlife: a case study of bats

The COVID-19 pandemic highlights the substantial public health, economic, and societal consequences of virus spillover from a wildlife reservoir. Widespread human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also presents a new set of challenges when considering viral spillover from people to naïve wildlife and other animal populations. The establishment of new wildlife reservoirs for SARS-CoV-2 would further complicate public health control measures and could lead to wildlife health and conservation impacts. Given the likely bat origin of SARS-CoV-2 and related beta-coronaviruses (β-CoVs), free-ranging bats are a key group of concern for spillover from humans back to wildlife. Here, we review the diversity and natural host range of β-CoVs in bats and examine the risk of humans inadvertently infecting free-ranging bats with SARS-CoV-2. Our review of the global distribution and host range of β-CoV evolutionary lineages suggests that 40+ species of temperate-zone North American bats could be immunologically naïve and susceptible to infection by SARS-CoV-2. We highlight an urgent need to proactively connect the wellbeing of human and wildlife health during the current pandemic and to implement new tools to continue wildlife research while avoiding potentially severe health and conservation impacts of SARS-CoV-2 "spilling back" into free-ranging bat populations

Possibility for reverse zoonotic transmission of SARS-CoV-2 to free-ranging wildlife: a case study of bats

The COVID-19 pandemic highlights the substantial public health, economic, and societal consequences of virus spillover from a wildlife reservoir. Widespread human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also presents a new set of challenges when considering viral spillover from people to naïve wildlife and other animal populations. The establishment of new wildlife reservoirs for SARS-CoV-2 would further complicate public health control measures and could lead to wildlife health and conservation impacts. Given the likely bat origin of SARS-CoV-2 and related beta-coronaviruses (β-CoVs), free-ranging bats are a key group of concern for spillover from humans back to wildlife. Here, we review the diversity and natural host range of β-CoVs in bats and examine the risk of humans inadvertently infecting free-ranging bats with SARS-CoV-2. Our review of the global distribution and host range of β-CoV evolutionary lineages suggests that 40+ species of temperate-zone North American bats could be immunologically naïve and susceptible to infection by SARS-CoV-2. We highlight an urgent need to proactively connect the wellbeing of human and wildlife health during the current pandemic and to implement new tools to continue wildlife research while avoiding potentially severe health and conservation impacts of SARS-CoV-2 "spilling back" into free-ranging bat populations