title: Cutaneous sıde‐effects of the potential COVID‐19 drugs

text: COVID‐19 disease is a highly contagious and particularly popular problem in all countries. A variety of repurposed drugs and investigational drugs such as remdesivir, chloroquine, hydroxychloroquine, ritonavir, lopinavir, interferon‐beta, and other potential drugs have been studied for COVID19 treatment. We reviewed the potential dermatological side‐effects of these drugs.


title: Novel coronavirus in a 15-day-old neonate with clinical signs of sepsis, a case report

text: Introduction: Novel coronavirus or coronavirus disease (COVID-19) can affect all age groups. The clinical course of the disease in children and infants is milder than in adults. It should be noted that, although typical symptoms may be present in children, non-specific symptoms could be noted in the neonate. The disease is rare in the neonate, so, its suspicion in this group can help to make a quick diagnose. Case report: A 15-day-old neonate was admitted with fever, lethargy, cutaneous mottling, and respiratory distress without cough. His mother had symptoms of Novel coronavirus. So Reverse-Transcription Polymerase Chain Reaction (RT-PCR) assay was done for the neonate and showed to be positive. The newborn was isolated and subjected to supportive care. Antibiotic and antiviral treatment was initiated. Eventually, the baby was discharged in good general condition. Conclusion: When a newborn presents with non-specific symptoms of infection with an added history of COVID-19 in his/her parents, it indicates the need for PCR testing for Novel coronavirus.


title: A precision medicine approach to managing 2019 novel coronavirus pneumonia

text: In December 2019, several patients with pneumonia of an unknown cause were detected in Wuhan, China. On 7 January 2020, the causal organism was identified as a new coronavirus, later named as the 2019 novel coronavirus (2019-nCoV). Genome sequencing found the genetic sequence of 2019-nCoV homologous to that of severe acute respiratory syndrome-associated coronavirus. As of 29 January 2020, the virus had been diagnosed in more than 7000 patients in China and 77 patients in other countries. It is reported that both symptomatic and asymptomatic patients with 2019-nCoV can play a role in disease transmission via airborne and contact. This finding has caused a great concern about the prevention of illness spread. The clinical features of the infection are not specific and are often indistinguishable from those of other respiratory infections, making it difficult to diagnose. Given that the virus has a strong ability to spread between individuals, it is of top priority to identify potential or suspected patients as soon as possible—or the virus may cause a serious pandemic. Therefore, a precision medicine approach to managing this disease is urgently needed for detecting and controlling the spread of the virus. In this article, we present such an approach to managing 2019-nCoV-related pneumonia based on the unique traits of the virus recently revealed and on our experience with coronaviruses at West China Hospital in Chengdu, China.


docid: xdvigpqh

title: Hospital unit safety climate: Relationship with nurses' adherence to recommended use of facial protective equipment

text: BACKGROUND: Despite the existence of formal guidelines for the acute health care sector, nurses' adherence to recommended use of facial protective equipment (FPE) to prevent occupational transmission of communicable respiratory disease remains suboptimal. In addition to individual factors such as knowledge and education, group factors such as shared perceptions of organizational support for safety may influence adherence. These group safety climate perceptions can differ depending on the pace and type of work, local leadership, and organizational structure of each unit. METHODS: An analysis of a data set from a cross-sectional survey of 1,074 nurses in 45 units of 6 acute care hospitals was conducted. Variance components analysis was performed to examine the variance in perceptions of safety climate and adherence between units. Hierarchical linear modeling using unit-level safety climate dimensions was conducted to determine if unit-level safety climate dimensions were predictors of nurses' adherence to FPE. RESULTS: Findings revealed statistically significant unit variances in adherence and 5 of the 6 unit-level safety climate dimensions (P < .05). Furthermore, a hierarchical model suggested that tenure and unit-level communication were significantly associated with increased adherence to FPE (P < .05). CONCLUSION: Unit-level safety climate measures varied significantly between units. Strategies to improve unit-level communication regarding safety should assist in improving adherence to FPE.


docid: nazekxla

title: Hematogenous infection of Sprague-Dawley rats with Mycoplasma pulmonis: development of a model for maternal and fetal infection

text: Objectives The specific objective of this study was to conduct a dose response experiment with Mycoplasma pulmonis in Sprague-Dawley rats to develop a reproducible animal model of maternal and fetal infection that would provide a versatile mechanism to address the innate fetal immune response during intrauterine infection. Study Design Pregnant rats were infected intravenously at gestation day 14 with 0 (control), 101, 103, 105, and 107 colony forming units of M pulmonis and necropsied at gestational day 18. Quantitative culture of maternal and fetal tissues as well as histopathologic examination of the placenta were performed. Results We have characterized a rat model of maternal and fetal infection that can be manipulated by alteration of infectious dose. Colonization of Sprague-Dawley rat dam and fetal tissues by M pulmonis occurred in a dose-dependent manner after intravenous inoculation (P < .001). Placental lesion severity increased with infection dose (P = .0001). The minimum threshold dose required to establish infection of the dam and fetus was at least 103 colony forming units, with consistent colonization of maternal and fetal tissues achieved only with 107 colony forming units. In some instances, rat fetal tissues could be colonized in the absence of concomitant amniotic fluid colonization. Interestingly, there appeared to be a predilection for colonization of the reproductive tissues. Conclusions In the Sprague-Dawley rat, the infection rate of both the dam and fetus can be controlled by the inoculum dose. Our data support the concept that hematogenous spread of M pulmonis to the rat fetus can occur without amniotic fluid infection and suggest that the fetus itself can potentially seed the amniotic fluid with microorganisms. Importantly, manipulation of both the route of infection as well as infection dose provide a reproducible way to study both maternal and fetal immune response to infection during pregnancy.


COVID‐19: opportunities for professional development and disruptive innovation


docid: iuenuigz

title: Thrombosis in Coronavirus disease 2019 (COVID-19) through the prism of Virchow’s triad

text: The pathogenesis of Coronavirus disease 2019 (COVID-19) is gradually being comprehended. A high number of thrombotic episodes are reported, along with the mortality benefits of heparin. COVID-19 can be viewed as a prothrombotic disease. We overviewed the available evidence to explore this possibility. We identified various histopathology reports and clinical case series reporting thromboses in COVID-19. Also, multiple coagulation markers support this. COVID-19 can be regarded as a risk factor for thrombosis. Applying the principles of Virchow’s triad, we described abnormalities in the vascular endothelium, altered blood flow, and platelet function abnormalities that lead to venous and arterial thromboses in COVID-19. Endothelial dysfunction, activation of the renin-angiotensin-aldosterone system (RAAS) with the release of procoagulant plasminogen activator inhibitor (PAI-1), and hyperimmune response with activated platelets seem to be significant contributors to thrombogenesis in COVID-19. Stratifying risk of COVID-19 thromboses should be based on age, presence of comorbidities, D-dimer, CT scoring, and various blood cell ratios. Isolated heparin therapy may not be sufficient to combat thrombosis in this disease. There is an urgent need to explore newer avenues like activated protein C, PAI-1 antagonists, and tissue plasminogen activators (tPA). These should be augmented with therapies targeting RAAS, antiplatelet drugs, repurposed antiinflammatory, and antirheumatic drugs.


title: CFD Simulation of Spread Risks of Infectious Disease due to Interactive Wind and Ventilation Airflows via Window Openings in High‐Rise Buildings

text: One of the concerns is that there may exist multiple infectious disease transmission routes across households in high‐rise residential buildings, one of which is the natural ventilative airflow through open windows between flats, caused by buoyancy effects. This study presents the modeling of this cascade effect using computational fluid dynamics (CFD) technique. It is found that the presence of the pollutants generated in the lower floor is generally lower in the immediate upper floor by two orders of magnitude, but the risk of infection calculated by the Wells‐Riley equation is only around one order of magnitude lower. It is found that, with single‐side open‐window conditions, wind blowing perpendicularly to the building may either reinforce or suppress the upward transport, depending on the wind speed. High‐speed winds can restrain the convective transfer of heat and mass between flats, functioning like an air curtain. Despite the complexities of the air flow involved, it is clear that this transmission route should be taken into account in infection control.


Chapter 23 Approach to the diagnosis and classification of blood diseases


Travel and the globalization of emerging infections


title: Visualizing the effectiveness of face masks in obstructing respiratory jets

text: The use of face masks in public settings has been widely recommended by public health officials during the current COVID-19 pandemic. The masks help mitigate the risk of cross-infection via respiratory droplets; however, there are no specific guidelines on mask materials and designs that are most effective in minimizing droplet dispersal. While there have been prior studies on the performance of medical-grade masks, there are insufficient data on cloth-based coverings, which are being used by a vast majority of the general public. We use qualitative visualizations of emulated coughs and sneezes to examine how material- and design-choices impact the extent to which droplet-laden respiratory jets are blocked. Loosely folded face masks and bandana-style coverings provide minimal stopping-capability for the smallest aerosolized respiratory droplets. Well-fitted homemade masks with multiple layers of quilting fabric, and off-the-shelf cone style masks, proved to be the most effective in reducing droplet dispersal. These masks were able to curtail the speed and range of the respiratory jets significantly, albeit with some leakage through the mask material and from small gaps along the edges. Importantly, uncovered emulated coughs were able to travel notably farther than the currently recommended 6-ft distancing guideline. We outline the procedure for setting up simple visualization experiments using easily available materials, which may help healthcare professionals, medical researchers, and manufacturers in assessing the effectiveness of face masks and other personal protective equipment qualitatively.


title: BEDSIDE TRANSCERVICAL-TRANSTRACHEAL POST-INTUBATION INJURY REPAIR IN A COVID-19 PATIENT

text: Abstract SARS-Co-2 disease 2019 (COVID-19) has rapidly spread worldwide since December 2019. A relevant rate of patients develops an acute respiratory distress syndrome that require hospitalization. Among them, a non-negligible rate (9.8%-15.2%) requires tracheal intubation for invasive ventilation. We report the case of a COVID-19 patient developing pneumomediastinum and subcutaneous emphysema secondary to post-intubation tracheal injury. The management of COVID-19 patient can be challenging due to the risk of disease transmission to caregivers and epidemic spread. We performed a bedside tracheal injury surgical repair, after failure of conservative management, with resolution of pneumomediastinum and subcutaneous emphysema and improvement of patient’s conditions.


title: Isolation and Characterization of Polymorphic Microsatellite Markers for the Masked Palm Civet (Paguma larvata)

text: The masked palm civet (Paguma larvata) has been suspected to be the host of a SARS-like CoV virus that causes severe acute respiratory syndrome in humans. In China, the palm civet lives wild and is farmed, but even though the species is a potential carrier of the virus, its geographic distribution and genetic diversity have never been studied. We report the isolation and characterization of six polymorphic microsatellite markers for P. larvata. To characterize each locus, two farmed masked palm civet populations from Shanxi and Guangxi provinces in China were genotyped. The number of alleles per locus ranged from 3 to 15, and the observed heterozygosity for these populations was 47.1 and 68.7%, respectively.


title: Increase in Middle East Respiratory Syndrome-Coronavirus Cases in Saudi Arabia Linked to Hospital Outbreak With Continued Circulation of Recombinant Virus, July 1–August 31, 2015

text: During July–August 2015, the number of cases of Middle East respiratory syndrome (MERS) reported from Saudi Arabia increased dramatically. We reviewed the 143 confirmed cases from this period and classified each based upon likely transmission source. We found that the surge in cases resulted predominantly (90%) from secondary transmission largely attributable to an outbreak at a single healthcare facility in Riyadh. Genome sequencing of MERS coronavirus from 6 cases demonstrated continued circulation of the recently described recombinant virus. A single unique frameshift deletion in open reading frame 5 was detected in the viral sequence from 1 case.


docid: fuqwciin

title: Assessing the pandemic potential of MERS-CoV


title: Ebola Viral Disease in West Africa: A Threat to Global Health, Economy and Political Stability

text: The West African sub-continent is currently experiencing its first, and ironically, the largest and longest Ebola viral diseases (EVD) outbreak ever documented in modern medical history. The current outbreak is significant in several ways, including longevity, magnitude of morbidity and mortality, occurrence outside the traditional niches, rapid spread and potential of becoming a global health tragedy. The authors provided explicit insights into the current and historical background, drivers of the epidemic, societal impacts, status of vaccines and drugs development and proffered recommendations to halt and prevent future occurrences. The authors reviewed mainly five databases and a hand search of key relevant literature. We reviewed 51 articles that were relevant up until the 18(th) of August 2014. The authors supplemented the search with reference list of relevant articles and grey literature as well as relevant Internet websites. Article searches were limited to those published either in English or French. There are strong indications that the EVD may have been triggered by increased human activities and encroachment into the forest ecosystem spurred by increasing population and poverty-driven forest-dependent local economy. Containment efforts are being hampered by weak and fragile health systems, including public health surveillance and weak governance, certain socio-anthropological factors, fast travels (improved transport systems) and globalization. The societal impacts of the EBV outbreak are grave, including economic shutdown, weakening of socio-political systems, psychological distress, and unprecedented consumption of scarce health resources. The research and development (R&D) pipeline for product against EBV seems grossly insufficient. The outbreak of Ebola and the seeming difficulty to contain the epidemic is simply a reflection of the weak health system, poor surveillance and emergency preparedness/response, poverty and disconnect between the government and the people in many West African countries. Although interventions by the United Nations and other international development agencies could ultimately halt the epidemic, local communities must be engaged to build trust and create demand for the public health interventions being implemented in the Ebola-ravaged populations. In the intermediate and long term, post-Ebola rehabilitation should focus on strengthening of health systems, improving awareness about zoonosis and health behaviors, alleviating poverty and mitigating the impact of triggering factors. Finally, national governments and international development partners should mobilize huge resources and investments to spur or facilitate R&D of disease control tools for emerging and pernicious infectious diseases (not limited to EVD).


title: New Interferons

text: Abstract New interferons (IFNs) include members of the type I IFN family, such as IFN epsilon (IFNε), IFN tau, IFN omega, and IFN kappa, as well as the type III IFN family, also known as the IFN lambdas. By comparison the classical or ‘old’ IFNs comprise the 14 subtypes of IFN alpha and IFN beta, which are all members of the type I IFN family, as well as type II IFN gamma. In this article, we examine the new IFNs and specifically discuss their discovery, comparative structures, functions in physiology and disease, the signaling pathways they initiate, and their regulatory controls. We highlight IFNε that was discovered in our laboratory and characterized for its role in protecting the female reproductive tract from infections.


title: Focal EEG changes indicating critical illness associated cerebral microbleeds in a Covid-19 patient

text: OBJECTIVES: We describe a patient suffering from Covid19-related acute respiratory distress syndrome (ARDS), highlighting the diagnostic role of the EEG in ICU. HISTORY: A Covid-19 patient undergoing mechanical ventilation due to related acute respiratory distress syndrome (ARDS), presented altered mental status in the ICU. Video-EEG revealed a focal monomorphic theta slowing in bilateral frontal-central regions. Concordant with the EEG localization, MRI showed abundant microbleeds located in bilateral white matter junction, various regions of corpus callosum and internal capsule, suggestive of Critical Illness-Associated Cerebral Microbleeds. CSF analysis excluded the presence of encephalitis, SARS-Cov2 RNA-PCR in CSF was negative. Clinical and biological picture was suggestive of cytokine release syndrome. CONCLUSION: This is the first reported case of Critical Illness-associated Cerebral Microbleeds in the context of Covid-19. Knowledge of Covid-19 is still partial and acute neurological complications should be explored systematically. In our case, EEG helped to rule out non-convulsive status epilepticus, but revealed focal dysfunction, justifying further investigations. EEG plays a crucial role in these patients, allowing investigating the presence of focal or diffuse cerebral dysfunction. This is particularly helpful for Covid-19 patients in the ICU, where the neurological examination is challenging by the severity of the respiratory illness.


title: Intervention decision model to prevent spiking mortality of turkeys

text: Abstract Based on the daily records on turkeys' mortalities for the series of flocks placed on different farms in a relatively compact geographical area for the period of approximately 2 yr and other relevant explanatory variables, the goal of the research was to design a decision model to determine whether or not to use the fluorquinolone antibiotic, sarafloxacin, to prevent spiking mortality of turkeys. The core of the designed decision model is the forecasting model that attempts to ex-ante predict the cumulative flock mortality for the period between 8 and 28 d of age. Forecasts were generated with the parameters of the linear regression model where continuous values of daily mortalities served as a dependent variable. The decision variable is a binary (yes/no) choice variable, where “yes” means “go ahead with treatment” and “no” means “do nothing”. If the predicted cumulative mortality for the period between 8 and 28 d of age exceeds 9% of the total initial placement, the model generates a “yes” signal. If the predicted cumulative mortality for the same period is below 9% of the total initial placement, the model generates a “no” signal. The results indicate a reasonable accuracy of the prediction model where the number of correct prediction increases and the number of incorrect predictions falls very fast as the forecasting window shortens. The intervention decision model could help veterinarians in making decisions on whether or not to treat the suspect flocks.


Overzealous hand hygiene during COVID 19 pandemic causing increased incidence of hand eczema among general population


docid: wlnclcvk

title: DC-SIGN (CD209) Promoter −336 A/G Polymorphism Is Associated with Dengue Hemorrhagic Fever and Correlated to DC-SIGN Expression and Immune Augmentation

text: BACKGROUND: The C-type lectin DC-SIGN (CD209) is known to be the major dengue receptor on human dendritic cells, and a single nucleotide polymorphism (SNP) in the promoter region of CD209 (−336 A/G; rs4804803) is susceptible to many infectious diseases. We reason that variations in the DC-SIGN gene might have a broad influence on viral replication and host immune responses. METHODS AND FINDINGS: We studied whether the rs4804803 SNP was associated with a susceptibility to dengue fever (DF) and/or dengue hemorrhagic fever (DHF) through genotyping analysis in a Taiwanese cohort. We generated monocyte-derived dendritic cells (MDDCs) from individuals with AA or AG genotype of rs4804803 to study the viral replication and immune responses for functional validation. A total of 574 DNA samples were genotyped, including 176 DF, 135 DHF, 143 other non-dengue febrile illnesses (OFI) and 120 population controls. A strong association between GG/AG genotypes of rs4804803 and risk of DHF was found when compared among DF, OFI and controls (p = 0.004, 3×10(−5) and 0.001, respectively). The AA genotype was associated with protection against dengue infection compared with OFI and controls (p = 0.002 and 0.020, respectively). Moreover, MDDCs from individuals with AG genotype with a higher cell surface DC-SIGN expression had a significantly higher TNFα, IL-12p40, and IP-10 production than those with AA genotype in response to dengue infection. However, the viral replication in MDDCs with AG genotype was significantly lower than those with AA genotype. With both genotypes, MDDCs revealed an increase in viral replication following the addition of anti-IP-10 neutralizing antibody. CONCLUSIONS/SIGNIFICANCE: The rs4804803 SNP in the CD209 promoter contributed to susceptibility to dengue infection and complication of DHF. This SNP with AG genotype affects the cell surface DC-SIGN expression related to immune augmentation and less viral replication.


docid: nsrbndzk

title: Acute Respiratory Distress Syndrome (ARDS) and Severe Acute Respiratory Syndrome (SARS): Are We Speaking Different Languages?


Crushed by the Wheels of Industry: War, Heroes, and Domestic Recolonization in the Time of Covid-19


title: Epidemiology of Deltacoronaviruses (δ-CoV) and Gammacoronaviruses (γ-CoV) in Wild Birds in the United States

text: Porcine deltacoronavirus (δ-CoV) is the object of extensive research in several countries including the United States. In contrast, the epidemiology of δ-CoVs in wild birds in the US is largely unknown. Our aim was to comparatively assess the prevalence of δ- and γ-CoVs in wild migratory terrestrial and aquatic birds in Arkansas, Illinois, Indiana, Maryland, Mississippi, Missouri, Ohio, Tennessee and Wisconsin. A total of 1236 cloacal/fecal swabs collected during the period 2015–2018 were tested for γ- and δ-CoVs using genus-specific reverse transcription-PCR assays. A total of 61 (4.99%) samples were γ-CoV positive, with up to 29 positive samples per state. In contrast, only 14 samples were positive for δ-CoV (1.14%) with only 1–4 originating from the same state. Thus, unlike previous reports from Asia, γ-CoVs are more prevalent than δ-CoVs in the US, suggesting that δ-CoVs may spread in birds with lower efficiency. This may indicate δ-CoV emerging status and incomplete adaptation to new host species limiting its spread. Phylogenetic analysis of the partial N gene revealed that the newly identified δ-CoV strains were most closely related to the HKU20 (wigeon) strain. Further studies are necessary to investigate the role of aquatic bird δ-CoVs in the epidemiology of δ-CoVs in swine and terrestrial birds.


title: The epidemic of 2019-novel-coronavirus (2019-nCoV) pneumonia and insights for emerging infectious diseases in the future

text: Abstract At the end of December 2019, a novel coronavirus, 2019-nCoV, caused an outbreak of pneumonia spreading from Wuhan, Hubei province, to the whole country of China, which has posed great threats to public health and attracted enormous attention around the world. To date, there are no clinically approved vaccines or antiviral drugs available for these human coronavirus infections. Intensive research on the novel emerging human infectious coronaviruses is urgently needed to elucidate their route of transmission and pathogenic mechanisms, and to identify potential drug targets, which would promote the development of effective preventive and therapeutic countermeasures. Herein, we describe the epidemic and etiological characteristics of 2019-nCoV, discuss its essential biological features, including tropism and receptor usage, summarize approaches for disease prevention and treatment, and speculate on the transmission route of 2019-nCoV.


title: ESMO Management and treatment adapted recommendations in the COVID-19 era: Lung cancer

text: The COVID-19 pandemic, characterised by a fast and global spread during the first months of 2020, has prompted the development of a structured set of recommendations for cancer care management, to maintain the highest possible standards. Within this framework, it is crucial to ensure no disruption to essential oncological services and guarantee the optimal care. This is a structured proposal for the management of lung cancer, comprising three levels of priorities, namely: tier 1 (high priority), tier 2 (medium priority) and tier 3 (low priority)—defined according to the criteria of the Cancer Care Ontario, Huntsman Cancer Institute and Magnitude of Clinical Benefit Scale. The manuscript emphasises the impact of the COVID-19 pandemic on lung cancer care and reconsiders all steps from diagnosis, staging and treatment. These recommendations should, therefore, serve as guidance for prioritising the different aspects of cancer care to mitigate the possible negative impact of the COVID-19 pandemic on the management of our patients. As the situation is rapidly evolving, practical actions are required to guarantee the best patients’ treatment while protecting and respecting their rights, safety and well-being. In this environment, cancer practitioners have great responsibilities: provide timely, appropriate, compassionate and justified cancer care, while protecting themselves and their patients from being infected with COVID-19. In case of shortages, resources must be distributed fairly. Consequently, the following recommendations can be applied with significant nuances, depending on the time and location for their use, considering variable constraints imposed to the health systems. An exceptional flexibility is required from cancer caregivers.


docid: opmleyce

title: Hepatitis C virus infection induces endoplasmic reticulum stress and apoptosis in human fetal liver stem cells

text: The cellular mechanisms by which hepatitis C virus (HCV) replication might mediate cytopathic effects are controversial and not entirely clear. In this study, we found that blood‐borne HCV (bbHCV) infection could lead to endoplasmic reticulum (ER)‐stress and mitochondria‐related/caspase‐dependent apoptosis at the early stages of infection based on use of the highly efficient bbHCV cell culture model established previously. Sections of bbHCV‐infected human fetal liver stem cells (hFLSCs) revealed convolution and nonlinear ER, cell vacuolization, swelling of mitochondria, and numerous double membrane vesicles (DMVs). The percentage of apoptotic hFLSCs infected by bbHCV reached 29.8% at 16 h postinfection, and the amount of cytochrome c increased remarkably in the cytosolic protein fraction. However, over time, apoptosis was inhibited due to the activation of NF‐κB. The expression of NF‐κB‐p65, Bcl‐xL, XIAP, and c‐FLIPL in hFLSCs was increased significantly 24 h after in infection by bbHCV. The accelerated cell death cycles involving apoptosis, regeneration and repair by bbHCV infection might give rise to the development of cirrhosis, and ultimately to hepatocellular carcinogenesis. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


COVID‐19 and ABO blood groups


Zoönosen, voorkomen in Nederland en dreiging voor de toekomst


title: Extensive Partnership, Collaboration, and Teamwork is Required to Stop the COVID-19 Outbreak

text: Abstract The COVID-19 outbreak is a disaster now throughout the world. To stop this outbreak, we appeal through the paper for extensive partnership, collaboration and teamwork among the all levels of workers such as scientist, doctors, medical professionals, social workers, policy makers, governments, pharmaceutical firms, funding aid agencies to stop the pandemic immediately.


title: Baculovirus as a highly efficient expression vector in insect and mammalian cells

text: Baculovirus has been widely used for the production of recombinant proteins in insect cells. Since the finding that baculovirus can efficiently transduce mammalian cells, the applications of baculovirus have been greatly expanded. The prospects and drawbacks of baculovirus-mediated gene expression, either in insect or in mammalian cells, are reviewed. Recent progresses in expanding the applications to studies of gene regulation, viral vector preparation, in vivo and ex vivo gene therapy studies, generation of vaccine vectors, etc are discussed and the efforts directed towards overcoming the existing bottlenecks are particularly emphasized.


docid: fygghrxr

title: Disentangling Interactions in the Microbiome: A Network Perspective

text: Microbiota are now widely recognized as being central players in the health of all organisms and ecosystems, and subsequently have been the subject of intense study. However, analyzing and converting microbiome data into meaningful biological insights remain very challenging. In this review, we highlight recent advances in network theory and their applicability to microbiome research. We discuss emerging graph theoretical concepts and approaches used in other research disciplines and demonstrate how they are well suited for enhancing our understanding of the higher-order interactions that occur within microbiomes. Network-based analytical approaches have the potential to help disentangle complex polymicrobial and microbe–host interactions, and thereby further the applicability of microbiome research to personalized medicine, public health, environmental and industrial applications, and agriculture.


title: Isolated radial nerve palsy in newborns—case report of a bilateral manifestation and literature review

text: Uni- or bilateral radial nerve palsy in newborn is a rare symptom. We report about a case of unusual bilateral radial nerve palsy in a term-born girl who recovered completely after 10 months and review the English-speaking literature about this condition. Review of the literature shows less than 60 reported cases of radial nerve palsy, most of them unilateral. Conclusion: Besides the clinical examination, in most cases, no further diagnostic investigation is necessary. An incomplete restitution is rare as recovery mostly occurs within 3–6 months.


title: Molecular docking, simulation and MM-PBSA studies of nigella sativa compounds: a computational quest to identify potential natural antiviral for COVID-19 treatment

text: Nigella sativa or black seed is used as a medicinal plant around the globe. Oil and seeds have a long tradition of folklore use in various medicinal and food systems. The conventional therapeutic use of Nigella sativa, in different ways, has been reported in several studies to treat different diseases including influenza, headache, hypertension, diabetes, inflammation, eczema, fever, cough, asthma, bronchitis, and fever. Based on previously reported potential therapeutic uses of N. sativa compounds, and keeping in mind the dire need of time for the development of potent antiviral, a combined docking, ADMET properties calculation, molecular dynamics, and MM-PBSA approaches were applied in the current study to check the therapeutic potentials of N. sativa chief constituents against COVID-19. Among the studied compounds, we found that dithymoquinone (DTQ), with binding affinity of −8.6 kcal/mol compared to a positive control (chloroquine, −7.2 kcal/mol) , has the high potential of binding at SARS-CoV-2:ACE2 interface and thus could be predicted as a plausible inhibitor to disrupt viral-host interactions. Molecular dynamics simulation of 100 ns well complemented binding affinity of the compound and revealed strong stability of DTQ at the docked site. Additionally, MM-PBSA also affirms the docking results. Compound DTQ of the present study, if validated in wet lab experiments, could be used to treat COVID-19 and could serve as a lead in the future for development of more effective natural antivirals against COVID-19. Communicated by Ramaswamy H. Sarma


title: Obesity is associated with worse outcomes in COVID‐19: Analysis of Early Data From New York City

text: OBJECTIVE: The 2019 novel coronavirus disease (COVID‐19) has triggered a rapidly‐expanding global pandemic in which patients exhibit a wide spectrum of disease severity. Given the high prevalence of obesity in the United States, we hypothesized that the presence of obesity may play a role in the clinical course of COVID‐19 patients. METHODS: This is a retrospective review of adult patients admitted with confirmed SARS‐CoV‐2. Demographics, clinical characteristics, laboratory data, and clinical outcomes were abstracted. BMI (kg/m(2)) was analyzed with regard to a composite outcome of ICU admission or death, and intubation rate. RESULTS: 770 patients were included (61% male, mean age 63.5 yrs). Obese patients were more likely to present with fever, cough and shortness of breath. Obesity was also associated with a significantly higher rate of ICU admission or death (RR = 1.58, p = 0.002) even after adjusting for age, race and troponin level. CONCLUSIONS: Obese patients had an increased risk of critical illness leading to ICU admission or death compared to normal weight individuals. This study confirms that obesity is a major risk factor for COVID‐19 disease severity, significantly impacting disease presentation and critical care requirements.


title: Vaccine-induced enhancement of viral infections

text: Examples of vaccine-induced enhancement of susceptibility to virus infection or of aberrant viral pathogenesis have been documented for infections by members of different virus families. Several mechanisms, many of which still are poorly understood, are at the basis of this phenomenon. Vaccine development for lentivirus infections in general, and for HIV/AIDS in particular, has been little successful. Certain experimental lentiviral vaccines even proved to be counterproductive: they rendered vaccinated subjects more susceptible to infection rather than protecting them. For vaccine-induced enhanced susceptibility to infection with certain viruses like feline coronavirus, Dengue virus, and feline immunodeficiency virus, it has been shown that antibody-dependent enhancement (ADE) plays an important role. Other mechanisms may, either in the absence of or in combination with ADE, be involved. Consequently, vaccine-induced enhancement has been a major stumble block in the development of certain flavi-, corona-, paramyxo-, and lentivirus vaccines. Also recent failures in the development of a vaccine against HIV may at least in part be attributed to induction of enhanced susceptibility to infection. There may well be a delicate balance between the induction of protective immunity on the one hand and the induction of enhanced susceptibility on the other. The present paper reviews the currently known mechanisms of vaccine-induced enhancement of susceptibility to virus infection or of aberrant viral pathogenesis.


title: Mechanism of Methylprednisolone‐Induced Primary Cilia Formation Disorder and Autophagy in Osteoblasts

text: OBJECTIVE: To study the role of primary cilia formation disorder and osteoblasts autophagy in the pathogenesis of steroid‐induced avascular necrosis of the femoral head (SANFH). METHODS: Osteoblasts were isolated from rabbit bones and treated with 1 μM Methylprednisolone for 0, 12, 24, 48, and 72 h. The Beclin1, MAP1LC3, Atg‐5, Atg‐12, IFT20 and OFD1 mRNAs and proteins were detected by PCR and Western blotting, and their correlation was statistically analyzed. The lengths of osteoblast cilia were measured under a laser confocal microscope, and the autophagy flux was tracked by transfecting the osteoblasts with GFP‐RFP‐LC3 lentivirus. RESULTS: Methylprednisolone significantly upregulated Beclin1, MAP1LC3, Atg‐5, Atg‐12 and OFD1 mRNAs and proteins in a time‐dependent manner, and decreased that of IFT20 (P < 0.05). In addition, the autophagy flux in the osteoblasts also increased and the ciliary length decreased in a time‐dependent manner after Methylprednisolone treatment. The length of the cilia were 5.46 ± 0.11 um at 0 h, 4.08 ± 0.09 um at 12 h, 3.07 ± 0.07 um at 24 h, 2.31 ± 0.10 um at 48 h, and finally 1.15 ± 0.04 um at 72 h. Methylprednisolone treatment also affects primary cilium numbers in cultures, for 0 to 72 h. The autophagy regulatory genes, Beclin1, MAP1LC3, Atg‐5 and Atg‐12, were found to be negatively correlated with IFT20, with an average correlation coefficient of −0.81. A negative correlation was also found between OFD1 and IFT20, with an average correlation coefficient of −0.53. CONCLUSION: Methylprednisolone inhibits primary cilia formation and promotes autophagy, which could be the pathological basis of SANFH. The exact regulatory mechanism needs to be further studied in vivo.


title: 5′-Fluoro-5′-deoxyaristeromycin

text: 5′-Fluoro-5′-deoxyaristeromycin (2) has been prepared via a Mitsunobu coupling of (1S,2S,3R,4S)-2,3-(cyclopentylidenedioxy)-4-fluoromethylcyclopentan-1-ol with N6-bis-boc protected adenine. This procedure is adaptable to preparing a number of 5′-fluoro-5′-deoxycarbocyclic nucleoside analogs with diversity in the heterocyclic base. Antiviral analysis found promising activity for 2 towards measles but no other viruses. No cytotoxicity was observed for 2.


title: Middle East respiratory syndrome: An emerging coronavirus infection tracked by the crowd

text: Abstract In 2012 in Jordan, infection by a novel coronavirus (CoV) caused the first known cases of Middle East respiratory syndrome (MERS). MERS-CoV sequences have since been found in a bat and the virus appears to be enzootic among dromedary camels across the Arabian Peninsula and in parts of Africa. The majority of human cases have occurred in the Kingdom of Saudi Arabia (KSA). In humans, the etiologic agent, MERS-CoV, has been detected in severe, mild and influenza-like illness and in those without any obvious signs or symptoms of disease. MERS is often a lower respiratory tract disease associated with fever, cough, breathing difficulties, pneumonia that can progress to acute respiratory distress syndrome, multiorgan failure and death among more than a third of those infected. Severe disease is usually found in older males and comorbidities are frequently present in cases of MERS. Compared to SARS, MERS progresses more rapidly to respiratory failure and acute kidney injury, is more often observed as severe disease in patients with underlying illnesses and is more often fatal. MERS-CoV has a broader tropism than SARS-CoV, rapidly triggers cellular damage, employs a different receptor and induces a delayed proinflammatory response in cells. Most human cases have been linked to lapses in infection prevention and control in healthcare settings, with a fifth of virus detections reported among healthcare workers. This review sets out what is currently known about MERS and the MERS-CoV, summarises the new phenomenon of crowd-sourced epidemiology and lists some of the many questions that remain unanswered, nearly three years after the first reported case.


A global picture of the diverse links between water and health


title: Covid19 pandemic; A practicing head and neck surgeon’s perspective of an institutional model

text: • Surgery for Mucosal Head and neck Cancers needs special consideration as they are AGP, placing the OT staff at a major risk. • Nevertheless all such procedures are considered semi emergencies and they cannot be postponed indefinitely. • Support Machinery of the Government and the co-operation of the people are the key factors favouring best practice of head and neck cancer surgery amidst the current COVID 19 crisis. • Waiting for atleast a period of 2 weeks would a prudent solution to rule out coexistence of COVID 19 infection in low risk cases without any symptoms.


title: El impacto de la Gran Recesión en la salud mental en España

text: The objective of this article is to identify the effects of the Great Recession on the mental health of people residing in Spain. After presenting a conceptual framework on the mechanisms through which economic crises affect mental health, we describe the main results of 45 papers identified in our search. Studies indicate a worsening of mental health in Spain in the years of economic crisis, especially in men. Working conditions (unemployment, low wages, instability, precariousness) emerge as one of the main channels through which mental health is put at risk or deteriorates. This deterioration occurs with intensity in particularly vulnerable groups, such as immigrant population and families with economic burdens. In the case of suicides, the results were inconclusive. Regarding the use of health care services, an increase in the consumption of certain drugs seems to be identified, although the conclusions of all the studies are not coincidental. Social inequalities in mental health do not seem to have remitted. We conclude that Spain needs to improve information systems to a better understanding of the health effects of economic crises. In terms of public policies, together with the reinforcement of health services aimed at addressing mental health problems, an income guarantee network for people in vulnerable situations should be promoted, as well as the development of policies aimed at the labour market.


title: Cellular entry of the SARS coronavirus

text: Enveloped viruses have evolved membrane glycoproteins (GPs) that mediate entry into host cells. These proteins are important targets for antiviral therapies and vaccines. Several efforts to understand and combat infection by severe acute respiratory syndrome coronavirus (SARS-CoV) have therefore focused on the viral GP, known as spike (S). In a short period of time, important aspects of SARS-CoV S-protein function were unraveled. The identification of angiotensin-converting enzyme 2 (ACE2) as a receptor for SARS-CoV provided an insight into viral tropism and pathogenesis, whereas mapping of functional domains in the S-protein enabled inhibitors to be generated. Vaccines designed on the basis of SARS-CoV S-protein were shown to be effective in animals and consequently are attractive candidates for vaccine trials in humans. Here, we discuss how SARS-CoV S facilitates viral entry into target cells and illustrate current approaches that are used to inhibit this process.


title: Cathepsin C limits acute viral infection independently of NK cell and CD8(+) T‐cell cytolytic function

text: Destruction of target cells by cytotoxic T lymphocytes (CTLs) or natural killer (NK) cells requires the coordinated action of the pore forming protein perforin (Pfp) and the granzyme (Gzm) family of serine proteases. The activation of a number of serine proteases, including GzmA and B, is predominately mediated by cathepsin C (CatC). Deficiencies in CatC‐null mice were therefore expected to replicate the defects observed in GzmAB‐deficient mice. We have previously determined that GzmAB‐deficient mice exhibit increased susceptibility to murine cytomegalovirus (MCMV) infection. Here, we have compared the ability of CatC(−/−) mice to control MCMV infection with that of GzmAB‐deficient animals. We found that CatC(−/−) mice have organ‐specific defects in the ability to control MCMV replication, a phenotype that is distinct to that observed in GzmAB(−/−) mice. Significantly, the cytolytic function of CatC‐deficient NK cells and CTLs elicited during infection was indistinguishable from that of wild‐type cells. Hence, CatC is involved in limiting MCMV replication; however, this effect is independent of its role in promoting effector cytolytic activity. These data provide evidence for a novel and unexpected role of CatC during viral infection.


docid: sjqbfern

title: Accelerated vaccination for Ebola virus haemorrhagic fever in non-human primates

text: Containment of highly lethal Ebola virus outbreaks poses a serious public health challenge. Although an experimental vaccine has successfully protected non-human primates against disease(1), more than six months was required to complete the immunizations, making it impractical to limit an acute epidemic. Here, we report the development of accelerated vaccination against Ebola virus in non-human primates. The antibody response to immunization with an adenoviral (ADV) vector encoding the Ebola glycoprotein (GP) was induced more rapidly than with DNA priming and ADV boosting, but it was of lower magnitude. To determine whether this earlier immune response could nonetheless protect against disease, cynomolgus macaques were challenged with Ebola virus after vaccination with ADV–GP and nucleoprotein (NP) vectors. Protection was highly effective and correlated with the generation of Ebola-specific CD8(+) T-cell and antibody responses. Even when animals were immunized once with ADV–GP/NP and challenged 28 days later, they remained resistant to challenge with either low or high doses of virus. This accelerated vaccine provides an intervention that may help to limit the epidemic spread of Ebola, and is applicable to other viruses. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature01876) contains supplementary material, which is available to authorized users.


title: Comparison of Temporal and Spatial Dynamics of Seasonal H3N2, Pandemic H1N1 and Highly Pathogenic Avian Influenza H5N1 Virus Infections in Ferrets

text: Humans may be infected by different influenza A viruses—seasonal, pandemic, and zoonotic—which differ in presentation from mild upper respiratory tract disease to severe and sometimes fatal pneumonia with extra-respiratory spread. Differences in spatial and temporal dynamics of these infections are poorly understood. Therefore, we inoculated ferrets with seasonal H3N2, pandemic H1N1 (pH1N1), and highly pathogenic avian H5N1 influenza virus and performed detailed virological and pathological analyses at time points from 0.5 to 14 days post inoculation (dpi), as well as describing clinical signs and hematological parameters. H3N2 infection was restricted to the nose and peaked at 1 dpi. pH1N1 infection also peaked at 1 dpi, but occurred at similar levels throughout the respiratory tract. H5N1 infection occurred predominantly in the alveoli, where it peaked for a longer period, from 1 to 3 dpi. The associated lesions followed the same spatial distribution as virus infection, but their severity peaked between 1 and 6 days later. Neutrophil and monocyte counts in peripheral blood correlated with inflammatory cell influx in the alveoli. Of the different parameters used to measure lower respiratory tract disease, relative lung weight and affected lung tissue allowed the best quantitative distinction between the virus groups. There was extra-respiratory spread to more tissues—including the central nervous system—for H5N1 infection than for pH1N1 infection, and to none for H3N2 infection. This study shows that seasonal, pandemic, and zoonotic influenza viruses differ strongly in the spatial and temporal dynamics of infection in the respiratory tract and extra-respiratory tissues of ferrets.


title: Fabrication of an anti-viral air filter with SiO2–Ag nanoparticles and performance evaluation in a continuous airflow condition

text: Abstract In this study, SiO2 nanoparticles surface coated with Ag nanoparticles (SA particles) were fabricated to coat a medium air filter. The pressure drop, filtration efficiency, and anti-viral ability of the filter were evaluated against aerosolized bacteriophage MS2 in a continuous air flow condition. A mathematical approach was developed to measure the anti-viral ability of the filter with various virus deposition times. Moreover, two quality factors based on the anti-viral ability of the filter, and a traditional quality factor based on filtration efficiency, were calculated. The filtration efficiency and pressure drop increased with decreasing media velocity and with increasing SA particle coating level. The anti-viral efficiency also increased with increasing SA particle coating level, and decreased by with increasing virus deposition time. Consequently, SA particle coating on a filter does not have significant effects on filtration quality, and there is an optimal coating level to produce the highest anti-viral quality.


title: Crystallographic Analysis of the Reaction Cycle of 2′,3′-Cyclic Nucleotide 3′-Phosphodiesterase, a Unique Member of the 2H Phosphoesterase Family

text: Abstract 2H phosphoesterases catalyze reactions on nucleotide substrates and contain two conserved histidine residues in the active site. Very limited information is currently available on the details of the active site and substrate/product binding during the catalytic cycle of these enzymes. We performed a comprehensive X-ray crystallographic study of mouse 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase), a membrane-associated enzyme present at high levels in the tetrapod myelin sheath. We determined crystal structures of the CNPase phosphodiesterase domain complexed with substrate, product, and phosphorothioate analogues. The data provide detailed information on the CNPase reaction mechanism, including substrate binding mode and coordination of the nucleophilic water molecule. Linked to the reaction, an open/close motion of the β5–α7 loop is observed. The role of the N terminus of helix α7—unique for CNPase in the 2H family—during the reaction indicates that 2H phosphoesterases differ in their respective reaction mechanisms despite the conserved catalytic residues. Furthermore, based on small-angle X-ray scattering, we present a model for the full-length enzyme, indicating that the two domains of CNPase form an elongated molecule. Finally, based on our structural data and a comprehensive bioinformatics study, we discuss the conservation of CNPase in various organisms.


title: Immunology of COVID-19: current state of the science

text: Abstract The coronavirus disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide, igniting an unprecedented effort from the scientific community to understand the biological underpinning of COVID19 pathophysiology. In this review, we summarize the current state of knowledge of innate and adaptive immune responses elicited by SARS-CoV-2 infection and the immunological pathways that likely contribute to disease severity and death. We also discuss the rationale and clinical outcome of current therapeutic strategies as well as prospective clinical trials to prevent or treat SARS-CoV-2 infection.


title: The rOX‐stars of inflammation: links between the inflammasome and mitochondrial meltdown

text: The nod‐like receptor protein 3 (NLRP3) inflammasome drives inflammation in response to mitochondrial dysfunction. As metabolic powerhouses with prokaryotic ancestry, mitochondria are a cache for danger‐associated molecular patterns and pathogen‐associated molecular pattern‐like molecules that elicit potent innate immune responses. Persistent mitochondrial damage caused by infection, or genetic or environmental factors, can lead to inappropriate or sustained inflammasome signalling. Here, we review the features of mitochondria that drive inflammatory signalling, with a particular focus on mitochondrial activation of the NLRP3 inflammasome. Given that mitochondrial network dynamics, metabolic activity and redox state are all intricately linked to each other and to NLRP3 inflammasome activity, we highlight the importance of a holistic approach to investigations of NLRP3 activation by dysfunctional mitochondria.


title: Evolutionary analysis of SARS-CoV-2: how mutation of Non-Structural Protein 6 (NSP6) could affect viral autophagy

text: Abstract Background SARS-CoV-2 is a new coronavirus that has spread globally, infecting more than 150000 people, and being declared pandemic by the WHO. We provide here bio-informatic, evolutionary analysis of 351 available sequences of its genome with the aim of mapping genome structural variations and the patterns of selection. Methods A Maximum likelihood tree has been built and selective pressure has been investigated in order to find any mutation developed during the SARS-CoV-2 epidemic that could potentially affect clinical evolution of the infection. Finding We have found in more recent isolates the presence of two mutations affecting the Non-Structural Protein 6 (NSP6) and the Open Reding Frame10 (ORF 10) adjacent regions. Amino acidic change stability analysis suggests both mutations could confer lower stability of the protein structures. Interpretation One of the two mutations, likely developed within the genome during virus spread, could affect virus intracellular survival. Genome follow-up of SARS-CoV-2 spread is urgently needed in order to identify mutations that could significantly modify virus pathogenicity.


title: Coronaviruses Induce Entry-Independent, Continuous Macropinocytosis

text: Macropinocytosis is exploited by many pathogens for entry into cells. Coronaviruses (CoVs) such as severe acute respiratory syndrome (SARS) CoV and Middle East respiratory syndrome CoV are important human pathogens; however, macropinocytosis during CoV infection has not been investigated. We demonstrate that the CoVs SARS CoV and murine hepatitis virus (MHV) induce macropinocytosis, which occurs late during infection, is continuous, and is not associated with virus entry. MHV-induced macropinocytosis results in vesicle internalization, as well as extended filopodia capable of fusing with distant cells. MHV-induced macropinocytosis requires fusogenic spike protein on the cell surface and is dependent on epidermal growth factor receptor activation. Inhibition of macropinocytosis reduces supernatant viral titers and syncytia but not intracellular virus titers. These results indicate that macropinocytosis likely facilitates CoV infection through enhanced cell-to-cell spreading. Our studies are the first to demonstrate virus use of macropinocytosis for a role other than entry and suggest a much broader potential exploitation of macropinocytosis in virus replication and host interactions.


title: Viral aetiology influenza like illnesses in Santa Cruz, Bolivia (2010–2012)

text: BACKGROUND: Acute respiratory infections represent a serious public health issue worldwide but virological aetiologies of Influenza Like Illnesses (ILIs) remain largely unknown in developing countries. This study represents the first attempt to characterise viral aetiologies of ILIs in Bolivia. METHODS: It was performed in Santa Cruz city from January 2010 to September 2012, based on 564 naso-pharyngeal swabs collected in a National Reference Laboratory and real-time PCR techniques, viral cultures and phylogenetic analyses. RESULTS: 50.2% of samples were positive for at least one virus with influenza viruses (Flu A: ~15%; Flu B: ~9%), rhinoviruses (~8%), coronaviruses (~5%) and hRSV (~4%) being the most frequently identified. The pattern of viral infections varied according to age groups. The elucidation rate was the highest (>60%) amongst patients under 10 yo and the lowest (<40%) amongst patients ≥60 yo. Nearly 3% of samples showed dual viral infections. Epidemiological peaks were associated with a predominant virus but generally included 30-50% of infections by different viruses. Unexpectedly, the frequency of influenza in the 0–4 yo population was very low and a complete hRSV eclipse occurred in 2011. Genetic analyses indicated that distinct evolutionary lineages of Flu A(H1N1)pdm2009, Flu A/H3N2 and Flu B have co-circulated in Bolivia in the study period, originating from Central and North America, Europe, Asia and Australia. CONCLUSION: Our results emphasise the requirement for a reinforced epidemiological and genetic follow-up of influenza and other ILIs in Bolivia to further inform the preparation of vaccines used in the region, guide vaccination campaigns and improve the medical management of patients.


title: Artificial microRNAs can effectively inhibit replication of Venezuelan equine encephalitis virus

text: Abstract Venezuelan equine encephalitis virus is a member of the alphavirus family and genus togaviridae. VEEV is highly infectious in aerosol form and has been weaponized in the past making it a potential biothreat agent. At present, there are no FDA approved antiviral treatments or vaccines for VEEV. Artificial microRNAs are small molecules which are expressed through endogenous microRNA machinery by RNA polymerase II. These artificial microRNAs effectively inhibit gene expression and are non-toxic to the host cell. VEEV RNA dependent RNA polymerase (RdRp) is central to VEEV replication. Therefore, we hypothesize that targeted inhibition of VEEV RdRp using artificial microRNAs may efficiently inhibit VEEV replication. Five artificial microRNAs were tested in vitro in BHK cells. Three of these artificial miRNAs showed significant inhibition of VEEV replication. Further, these microRNAs were cloned into the expression vector in combination to see the synergistic effect on VEEV replication. Combination of more than one miRNA did not result in significant inhibition of virus replication. In conclusion, we have shown that RNAi through artificial microRNAs effectively inhibits VEEV replication and is significantly less toxic in comparison to siRNAs.


title: Inhibition of porcine transmissible gastroenteritis virus (TGEV) replication in mini-pigs by shRNA

text: Abstract Transmissible gastroenteritis virus (TGEV) is the causative agent of porcine transmissible gastroenteritis (TGE), characterized by high mortality and severely retarded growth in piglets that dramatically affects the porcine industry. Previously, we have identified two shRNA-expressing plasmids pEGFP-U6/P1 and pEGFP-U6/P2 that target RNA-dependent RNA polymerase (RdRP) gene of TGEV with more than 95% of virus inhibition in vitro. In this study, inhibition of the TGEV replication by pEGFP-U6/P1 and pEGFP-U6/P2 was tested in mini-pigs. SPF mini-pigs at 25 days old were injected with the shRNA-expressing plasmids and then infected with TGEV. The results from the analyses of clinical signs, histopathology, indirect immunofluorescence (IIF) and RT-PCR show that the two shRNA-expressing plasmids could significantly decrease the quantity of TGEV in different organs and protect mini-pigs from TGEV infection. These findings illustrate the prospect for TGEV-specific shRNAs to be new anti-TGEV agents.


docid: fanatrfo

title: Inappropriate Antibiotic Consumption as a Possible Cause of Inflammatory Storm and Septic Shock in Patients Diagnosed with Coronavirus-19 Disease (COVID-19)

text: The novel coronavirus (SARS-CoV-2) infection which has been known as Coronavirus diseases 2019 (COVID-19) has become an endemic emergent situation by the World Health Organization. So far, no successful specific treatment has been found for this disease. As has been reported, most of non-survivor patients with COVID-19 (70%) had septic shock which was significantly higher than survived ones. Although the exact pathophysiology of septic shock in these patients is still unclear, it seems to be possible that part of it would be due to the administration of empiric antibiotics with inflammatory properties especially in the absence of bacterial infection. Herein, we have reviewed possible molecular pathways of septic shock in the patients who have received antibiotics with inflammatory properties which mainly is release of interleukin 1β (IL-1β), IL-6, and tumor necrosis factor α (TNF- α) through different routes. Altogether, we highly recommend clinicians to look after those antibiotics with anti-inflammatory activity for both empiric antibiotic therapy and reducing the inflammation to prevent septic shock in patients with diagnosed COVID-19.


title: The Expanding Diversity of RNA Viruses in Vertebrates

text: The diversity of RNA viruses in vertebrates remains largely unexplored. The discovery of 214 novel vertebrate-associated RNA viruses will likely help us to understand the diversity and evolution of RNA viruses in vertebrates.


docid: lyvvtwvg

title: Molecular detection and genomic characteristics of bovine kobuvirus from dairy calves in China

text: Abstract In this study, 96 diarrheic and 77 non-diarrheic fecal samples from dairy calves were collected from 14 dairy farms in 4 provinces to investigate the molecular prevalence and genomic characteristics of Bovine Kobuvirus (BKoV) in China. The results showed that the BKoV positive rate for the diarrheic feces (35.42%) was significantly higher than that for the non-diarrheic feces (11.69%, p < 0.001). Interestingly, three potential novel VP1 lineages were identified from 15 complete VP1 sequences, and a unique triple nucleotide insertion which can result in an aa insertion, was first observed in the 11/12 VP0 fragments with 660 bp long in this study, compared with known BKoV VP0 sequences. Moreover, the first Chinese BKoV genome was successfully obtained from a diarrheic fecal sample, named CHZ/CHINA. The open reading frame (ORF) of the genome from strain CHZ/China shares 87.4%–88.3% nucleotide (nt) and 93.7%–96.4% amino acid (aa) identity, compared with the three known genomes of BKoV. Interestingly, phylogenetic tree based on aa sequences of these genomes showed that CHZ/CHINA was clustered into an independent branch, suggesting the strain may represent a novel BKoV strain. The findings contribute to better understanding the molecular characteristics and evolution of BKoV.


title: Corrigendum to “A Rare Cause of Childhood Cerebellitis-Influenza Infection: A Case Report and Systematic Review of Literature”

text: [This corrects the article DOI: 10.1155/2017/4039358.].


title: CovXNet: A multi-dilation convolutional neural network for automatic COVID-19 and other pneumonia detection from chest X-ray images with transferable multi-receptive feature optimization()

text: With the recent outbreak of COVID-19, fast diagnostic testing has become one of the major challenges due to the critical shortage of test kit. Pneumonia, a major effect of COVID-19, needs to be urgently diagnosed along with its underlying reasons. In this paper, deep learning aided automated COVID-19 and other pneumonia detection schemes are proposed utilizing a small amount of COVID-19 chest X-rays. A deep convolutional neural network (CNN) based architecture, named as CovXNet, is proposed that utilizes depthwise convolution with varying dilation rates for efficiently extracting diversified features from chest X-rays. Since the chest X-ray images corresponding to COVID-19 caused pneumonia and other traditional pneumonias have significant similarities, at first, a large number of chest X-rays corresponding to normal and (viral/bacterial) pneumonia patients are used to train the proposed CovXNet. Learning of this initial training phase is transferred with some additional fine-tuning layers that are further trained with a smaller number of chest X-rays corresponding to COVID-19 and other pneumonia patients. In the proposed method, different forms of CovXNets are designed and trained with X-ray images of various resolutions and for further optimization of their predictions, a stacking algorithm is employed. Finally, a gradient-based discriminative localization is integrated to distinguish the abnormal regions of X-ray images referring to different types of pneumonia. Extensive experimentations using two different datasets provide very satisfactory detection performance with accuracy of 97.4% for COVID/Normal, 96.9% for COVID/Viral pneumonia, 94.7% for COVID/Bacterial pneumonia, and 90.2% for multiclass COVID/normal/Viral/Bacterial pneumonias. Hence, the proposed schemes can serve as an efficient tool in the current state of COVID-19 pandemic. All the architectures are made publicly available at: https://github.com/Perceptron21/CovXNet.


title: Fungal lectin MpL enables entry of protein drugs into cancer cells and their subcellular targeting

text: Lectins have been recognized as promising carrier molecules for targeted drug delivery. They specifically bind carbohydrate moieties on cell membranes and trigger cell internalization. Fungal lectin MpL (Macrolepiota procera lectin) does not provoke cancer cell cytotoxicity but is able to bind aminopeptidase N (CD13) and integrin α3β1, two glycoproteins that are overexpressed on the membrane of tumor cells. Upon binding, MpL is endocytosed in a clathrin-dependent manner and accumulates initially in the Golgi apparatus and, finally, in the lysosomes. For effective binding and internalization a functional binding site on the α-repeat is needed. To test the potential of MpL as a carrier for delivering protein drugs to cancer cells we constructed fusion proteins consisting of MpL and the cysteine peptidase inhibitors cystatin C and clitocypin. The fused proteins followed the same endocytic route as the unlinked MpL. Peptidase inhibitor-MpL fusions impaired both the intracellular degradation of extracellular matrix and the invasiveness of cancer cells. MpL is thus shown in vitro to be a lectin that can enable protein drugs to enter cancer cells, enhance their internalization and sort them to lysosomes and the Golgi apparatus.


Proctology in the COVID‐19 era: handle with care


title: Survivability of porcine epidemic diarrhea virus (PEDV) in bovine plasma submitted to spray drying processing and held at different time by temperature storage conditions

text: Abstract Bovine plasma was inoculated with porcine epidemic diarrhea virus (PEDV) at an average final titer of 4.2 log10 TCID50/mL to determine the effect of spray drying on viral inactivation. Using a laboratory scale drier, inoculated plasma was spray dried at 200°C inlet temperature and either 70 or 80°C throughout substance. Both liquid and dried samples were subjected to three passages on VERO cell monolayers to determine PEDV infectivity. Results indicated liquid samples contained infective virus, but none of the spray dried samples were infectious. Also, survivability of PEDV inoculated on spray dried bovine plasma (SDBP) and stored at 4, 12 or 22°C was determined for 7, 14 and 21 days. Commercial SDBP powder was inoculated with PEDV to an average final titer of 2.8 log10 TCID50/g. Five samples per time and temperature conditions were subjected to three passages on VERO cell monolayers to determine PEDV infectivity. The virus was non-infectious for all samples stored at 22°C at 7, 14 and 21 days. PEDV was infective in 1 out of 5 samples stored at 12°C at 7 days, but none of the samples stored for 14 and 21 days were infectious in cell culture. For samples stored at 4°C, 4 out of 5 samples were infectious at 7 days, 1 out of 5 samples were infectious at 14 days, but none were infectious at 21 days. In summary, PEDV was not infectious on cell culture within 7 days when stored at room temperature and within 21 days when stored at refrigerated temperature.


title: Applying the balanced scorecard to local public health performance measurement: deliberations and decisions

text: BACKGROUND: All aspects of the heath care sector are being asked to account for their performance. This poses unique challenges for local public health units with their traditional focus on population health and their emphasis on disease prevention, health promotion and protection. Reliance on measures of health status provides an imprecise and partial picture of the performance of a health unit. In 2004 the provincial Institute for Clinical Evaluative Sciences based in Ontario, Canada introduced a public-health specific balanced scorecard framework. We present the conceptual deliberations and decisions undertaken by a health unit while adopting the framework. DISCUSSION: Posing, pondering and answering key questions assisted in applying the framework and developing indicators. Questions such as: Who should be involved in developing performance indicators? What level of performance should be measured? Who is the primary intended audience? Where and how do we begin? What types of indicators should populate the health status and determinants quadrant? What types of indicators should populate the resources and services quadrant? What type of indicators should populate the community engagement quadrant? What types of indicators should populate the integration and responsiveness quadrants? Should we try to link the quadrants? What comparators do we use? How do we move from a baseline report card to a continuous quality improvement management tool? SUMMARY: An inclusive, participatory process was chosen for defining and creating indicators to populate the four quadrants. Examples of indicators that populate the four quadrants of the scorecard are presented and key decisions are highlighted that facilitated the process.


title: Ecological determinants of health: food and environment on human health

text: Human health and diseases are determined by many complex factors. Health threats from the human-animal-ecosystems interface (HAEI) and zoonotic diseases (zoonoses) impose an increasing risk continuously to public health, from those emerging pathogens transmitted through contact with animals, food, water and contaminated environments. Immense challenges forced on the ecological perspectives on food and the eco-environments, including aquaculture, agriculture and the entire food systems. Impacts of food and eco-environments on human health will be examined amongst the importance of human interventions for intended purposes in lowering the adverse effects on the biodiversity. The complexity of relevant conditions defined as factors contributing to the ecological determinants of health will be illuminated from different perspectives based on concepts, citations, examples and models, in conjunction with harmful consequential effects of human-induced disturbances to our environments and food systems, together with the burdens from ecosystem disruption, environmental hazards and loss of ecosystem functions. The eco-health literacy should be further promoting under the “One Health” vision, with “One World” concept under Ecological Public Health Model for sustaining our environments and the planet earth for all beings, which is coincidentally echoing Confucian’s theory for the environmental ethics of ecological harmony.


title: Rapid Response of an Academic Surgical Department to the COVID-19 Pandemic: Implications for Patients, Surgeons, and the Community

text: Background As the coronavirus disease 2019 (COVID-19) pandemic continues to spread, swift actions and preparation are critical for ensuring the best outcomes for patients and providers. We aim to describe our hospital and Department of Surgery’s experience in preparing for the COVID-19 pandemic and caring for surgical patients during this unprecedented time. Study Design This is a descriptive study outlining the strategy of a single academic health system for addressing the following 4 critical issues facing surgical departments during the COVID-19 pandemic: developing a cohesive leadership team and system for frequent communication throughout the department; ensuring adequate hospital capacity to care for an anticipated influx of COVID-19 patients; safeguarding supplies of blood products and personal protective equipment to protect patients and providers; and preparing for an unstable workforce due to illness and competing personal priorities, such as childcare. Results Through collaborative efforts within the Department of Surgery and hospital, we provided concise and regular communication, reduced operating room volume by 80%, secured a 4-week supply of personal protective equipment, and created reduced staffing protocols with back-up staffing plans. Conclusions By developing an enabling infrastructure, a department can nimbly respond to crises like COVID-19 by promoting trust among colleagues and emphasizing an unwavering commitment to excellent patient care. Sharing principles and practical applications of these changes is important to optimize responses across the country and the world.


title: Antiviral and Antigenic Properties of Recombinant Porcine Interferon Gamma

text: Abstract Recombinant porcine interferon gamma (rPoIFNγ) induced a dose-dependent inhibition of the cytopathic effect produced by vesicular stomatitis virus (VSV) challenge of both homologous and heterologous (bovine) cell lines. In addition, an antiviral effect of rPoIFNγ was demonstrable against the coronavirus transmissible gastroenteritis virus (TGEV) infection of porcine epithelial cells and of pulmonary macrophages. A rabbit anti-PoIFNγ antiserum was prepared and shown to specifically neutralize the antiviral effects of natural and recombinant porcine IFNγ preparations. This antiserum could also neutralize recombinant bovine IFNγ but not recombinant human IFNγ. These results suggest antigenic homology of porcine and bovine IFNγ but antigenic differences between these molecules and human IFNγ.


title: The Expression of IL-6, TNF-α, and MCP-1 in Respiratory Viral Infection in Acute Exacerbations of Chronic Obstructive Pulmonary Disease

text: Viral infection is a common trigger for acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The aim of this study is to investigate the expression of cytokines in AECOPD. Patients with AECOPD requiring hospitalization were recruited. Meanwhile healthy volunteers of similar age that accepted routine check-ups and showed no clinical symptoms of inflammatory diseases were also recruited. Induced sputum and serum were collected. Induced sputum of participants was processed and tested for thirteen viruses and bacteria. Forty cytokines were assayed in serum using the Quantibody Human Inflammation Array 3 (Ray Biotech, Inc.). The most common virus detected in virus positive AECOPD (VP) was influenza A (16%). No virus was found in controls. Circulating levels of IL-6, TNF-α, and MCP-1 were elevated in VP and coinfection subjects (p < 0.05), while the levels of 37 other cytokines showed no difference, compared with virus negative groups and controls (p > 0.05). Additionally, VP patients were less likely to have received influenza vaccination. VP patients had a systemic inflammation response involving IL-6, TNF-α, and MCP-1 which may be due to virus-induced activation of macrophages. There are important opportunities for further investigating AECOPD mechanisms and for the development of better strategies in the management and prevention of virus-related AECOPD.


title: Autophagy during viral infection — a double-edged sword

text: Autophagy is a powerful tool that host cells use to defend against viral infection. Double-membrane vesicles, termed autophagosomes, deliver trapped viral cargo to the lysosome for degradation. Specifically, autophagy initiates an innate immune response by cooperating with pattern recognition receptor signalling to induce interferon production. It also selectively degrades immune components associated with viral particles. Following degradation, autophagy coordinates adaptive immunity by delivering virus-derived antigens for presentation to T lymphocytes. However, in an ongoing evolutionary arms race, viruses have acquired the potent ability to hijack and subvert autophagy for their benefit. In this Review, we focus on the key regulatory steps during viral infection in which autophagy is involved and discuss the specific molecular mechanisms that diverse viruses use to repurpose autophagy for their life cycle and pathogenesis.


Should we have a universal one-week lockdown every year?


title: Paper-based sensors for the application of biological compound detection

text: Abstract This chapter describes the importance of PADs for biomarker detection. The screening of disease markers and other biomolecules that related to health conditions have play important roles for an indication of the risk from infections and other diseases. Paper-based analytical devices (PADs) is an excellent option for applications of biomarker detection because it contains all advantages which arise from the paper material. Moreover, the uncomplicated techniques including electrochemistry and colorimetry can be easily applied on PADs for the analytical detection. The detection method can be categorized into three main topics: enzymatic methods, immunoassays, and DNA sensors. Following the main context, other interesting applications also present in this chapter.


title: HOW TO DETECT AND TRACK CHRONIC NEUROLOGIC SEQUELAE OF COVID-19? USE OF AUDITORY BRAINSTEM RESPONSES AND NEUROIMAGING FOR LONG-TERM PATIENT FOLLOW-UP.

text: This review intends to provide an overview of the current knowledge on neurologic sequelae of COVID-19 and their possible etiology, and, based on available data, proposes possible improvements in current medical care procedures. We conducted a thorough review of the scientific literature on neurologic manifestations of COVID-19, the neuroinvasive propensity of known coronaviruses (CoV) and their possible effects on brain structural and functional integrity. It appears that around one third of COVID-19 patients admitted to intensive care units (ICU) for respiratory difficulties exhibit neurologic symptoms. This may be due to progressive brain damage and dysfunction triggered by severe hypoxia and hypoxemia, heightened inflammation and SARS-CoV-2 dissemination into brain parenchyma, as suggested by current reports and analyses of previous CoV outbreaks. Viral invasion of the brain may particularly target and alter brainstem and thalamic functions and, consequently, result in sensorimotor dysfunctions and psychiatric disorders. Moreover, data collected from other structurally homologous CoV suggest that SARS-CoV-2 infection may lead to brain cell degeneration and demyelination similar to multiple sclerosis (MS). Hence, current evidence warrants further evaluation and long-term follow-up of possible neurologic sequelae in COVID-19 patients. It may be particularly relevant to evaluate brainstem integrity in recovered patients, as it is suspected that this cerebral area may particularly be dysfunctional following SARS-CoV-2 infection. Because CoV infection can potentially lead to chronic neuroinflammation and progressive demyelination, neuroimaging features and signs of MS may also be evaluated in the long term in recovered COVID-19 patients.


title: Mutational analysis of the RNA pseudoknot component of a coronavirus ribosomal frameshifting signal

text: Abstract The genomic RNA of the coronavirus IBV contains an efficient ribosomal frameshift signal at the junction of the overlapping 1a and 1b open reading frames. The signal is comprised of two elements, a heptanucleotide “slip-site” and a downstream tertiary RNA structure in the form of an RNA pseudoknot. We have investigated the structure of the pseudoknot and its contribution to the frameshift process by analysing the frameshifting properties of a series of pseudoknot mutants. Our results show that the pseudoknot structure closely resembles that which can be predicted from current building rules, although base-pair formation at the region where the two pseudoknot stems are thought to stack co-axially is not a pre-requisite for efficient frameshifting. The stems, however, must be in close proximity to generate a functional structure. In general, the removal of a single base-pair contact in either stem is sufficient to reduce or abolish frameshifting. No primary sequence determinants in the stems or loops appear to be involved in the frameshift process; as long as the overall structure is maintained, frameshifting is highly efficient. Thus, small insertions into the pseudoknot loops and a deletion in loop 2 that reduced its length to the predicted functional minimum did not influence frameshifting. However, a large insertion (467 nucleotides) into loop 2 abolished frameshifting. A simple stem-loop structure with a base-paired stem of the same length and nucleotide composition as the stacked stems of the pseudoknot could not functionally replace the pseudoknot, suggesting that some particular conformational feature of the pseudoknot determines its ability to promote frameshifting.


title: Etiologie des gastro-entérites aiguës infantiles en pratique hospitalière courante

text: Summary The authors report the results of a study of enteric disease etiology from chilfren during one year. These study is about 155 diarrheas, 16 from them content leukocytes. Rotavirus are discovered in 38,1 % diarrheas without leukocytes. Between the bacteria isolated, Salmonellaare the most frequently enteric bacterias. After, Campylobacter, E. colientero pathogenic. The isolation of Yersinia enterocoliticaand Shigellaare frequentless. A particular mention about the associations : rotavirus — bacterias, and about the high frequency of Campylobacter.


title: High-level expression of active recombinant ubiquitin carboxyl-terminal hydrolase of Drosophila melanogaster in Pichia pastoris

text: Abstract Ubiquitin carboxyl-terminal hydrolases (UCHs) are implicated in the proteolytic processing of polymeric ubiquitin. The high specificity for the recognition site makes UCHs useful enzymes for in vitro cleavage of ubiquitin fusion proteins. In this work, an active C-terminal His-tagged UCH from Drosophila melanogaster (DmUCH) was produced as a secretory form in a recombinant strain of the methylotrophic yeast Pichia pastoris. The production of recombinant DmUCH by Muts strain was much higher than that by Mut+ strain, which was confirmed by Western blot analysis. When expression was induced at pH 6.0 in a BMMY/methanol medium, the concentration of recombinant DmUCH reached 210mgl−1. With the (His)6-tag, the recombinant DmUCH was easily purified by Ni-NTA chromatography and 18mg pure active DmUCH were obtained from 100ml culture broth supernatant. Ubiquitin–magainin fusion protein was efficiently cleaved by DmUCH, yielding recombinant magainin with high antimicrobial activity. After removing the contaminants by Ni-NTA chromatography, recombinant magainin was purified to homogeneity easily by reversed-phase HPLC. Analysis of the recombinant magainin by ESI-MS showed that the molecular weight of the purified recombinant magainin was 2465Da, which perfectly matches the mass calculated from the amino acid sequence. The result of mass spectrometry confirmed that the purified His-tagged DmUCH can recognize the ubiquitin–magainin fusion protein and cleave it at the carboxyl terminus of ubquitin precisely. Our results showed that P. pastoris is a robust system to express the secreted form of DmUCH.


title: Antiviral RNAi therapy: emerging approaches for hitting a moving target

text: The field of directed RNA interference (RNAi) has rapidly developed into a highly promising approach for specifically downregulating genes to alleviate disease pathology. This technology is especially well-suited to treating viral infections, and numerous examples now illustrate that a wide range of viruses can be inhibited with RNAi, both in vitro and in vivo. One principle that has arisen from this work is that antiviral RNAi therapies must be tailored to the unique life cycle of each pathogen, including the choice of delivery vehicle, route of administration, gene(s) targeted and regulation and duration of RNAi induction. Although effective strategies will be customized to each virus, all such therapies must overcome similar challenges. Importantly, treatment strategies must compensate for the inevitable fact that viral genome sequences evolve extremely rapidly, and computational and bioinformatics approaches may aid in the development of therapies that resist viral escape. Furthermore, all RNAi strategies involve the delivery of nucleic acids to target cells, and all will therefore benefit from the development of enhanced gene design and delivery technologies. Here, we review the substantial progress that has been made towards identifying effective antiviral RNAi targets and discuss strategies for translating these findings into effective clinical therapies.


Role of cellular immune factors in coronavirus A59 induced demyelination


title: Multi-target QPDR classification model for human breast and colon cancer-related proteins using star graph topological indices

text: Abstract The cancer diagnostic is a complex process and, sometimes, the specific markers can interfere or produce negative results. Thus, new simple and fast theoretical models are required. One option is the complex network graphs theory that permits us to describe any real system, from the small molecules to the complex genetic, neural or social networks by transforming real properties in topological indices. This work converts the protein primary structure data in specific Randic's star networks topological indices using the new sequence to star networks (S2SNet) application. A set of 1054 proteins were selected from previous works and contains proteins related or not with two types of cancer, human breast cancer (HBC) and human colon cancer (HCC). The general discriminant analysis method generates an input-coded multi-target classification model with the training/predicting set accuracies of 90.0% for the forward stepwise model type. In addition, a protein subset was modified by single amino acid mutations with higher log-odds PAM250 values and tested with the new classification if can be related with HBC or HCC. In conclusion, we shown that, using simple input data such is the primary protein sequence and the simples linear analysis, it is possible to obtain accurate classification models that can predict if a new protein related with two types of cancer. These results promote the use of the S2SNet in clinical proteomics.


The Covid-19 epidemic: are there lights at the end of the long tunnel?


title: Cohort study of chest CT and clinical changes in 29 patients with coronavirus disease 2019 (COVID-19)

text: OBJECTIVES: To investigate the imaging findings and clinical time course of COVID-19 pneumonia. METHODS: A total of 113 baseline and follow-up CT scans from 24 January 2020 to 18 February 2020 were longitudinally collected from 29 confirmed COVID-19 patients in a single center. The changes in the clinical and laboratory characteristics, imaging features, lesion-to-muscle ratio (LMR), and pulmonary inflammation index (PII) at baseline, 1–6 days, 7–13 days, and ≥ 14 days were compared. RESULTS: Of the 29 COVID-19 patients enrolled, the baseline chest CT scan was obtained 3 ± 2 (0–9) days after the onset of symptoms, and each patient had an average of 4 ± 1 (3–5) CT scans with a mean interval of 5 ± 2 (1–14) days. The percentage of patients with fever, cough, shortness of breath, and myalgia obviously decreased at 7–13 days with regular treatment (p < 0.05). The lymphocyte count, C-reactive protein, interleukin-6, and oxygenation index worsened within 1–6 days but improved sharply at 7–13 days. Compared with those at the other three time points, the LMR, PII, and number of involved lobes at 1–6 days were the highest, and gradually improved after 7–13 days. CONCLUSIONS: Lung lesion development on chest CT reflects the clinical time course of COVID-19 progression over 1–6 days, followed by clinical improvement and the resorption of lesions. CT imaging may be indicated when patients fail to improve within a week of treatment, but repeated chest CT may be unnecessary when the patients show improvements clinically. KEY POINTS: • Chest CT reflects the development of coronavirus disease 2019 pneumonia (COVID-19). • COVID-19 usually shows progressive lesions over up to 9 days with subsequent resorption. • Unusual clinical time course of COVID-19 may indicate repeated chest CT.


title: An Outbreak of Fatal Bordetella bronchiseptica Bronchopneumonia in Puppies

text: Summary Twenty-two newborn puppies that did not receive colostrum exhibited acute respiratory signs and died at a breeding facility. Pathological examinations were performed on four of the puppies. At necropsy examination, the lungs were firm and mottled dark red, consistent with acute bronchopneumonia. Histopathologically, there was marked infiltration of neutrophils and macrophages into the bronchi and alveoli, and gram-negative coccobacilli were attached diffusely to the cilia of bronchial mucosa. Immunohistochemistry for Bordetella bronchiseptica antigen revealed positive labelling of the bacterial agents. On electron microscopy, a large number of coccobacilli were observed attaching to the cilia of bronchial epithelial cells. Real-time polymerase chain reaction amplified a B. bronchiseptica gene from the affected lung tissue. Based on these findings, the four puppies were diagnosed with fatal B. bronchiseptica bronchopneumonia.


title: Nanopolymers improve delivery of exon skipping oligonucleotides and concomitant dystrophin expression in skeletal muscle of mdx mice

text: BACKGROUND: Exon skipping oligonucleotides (ESOs) of 2'O-Methyl (2'OMe) and morpholino chemistry have been shown to restore dystrophin expression in muscle fibers from the mdx mouse, and are currently being tested in phase I clinical trials for Duchenne Muscular Dystrophy (DMD). However, ESOs remain limited in their effectiveness because of an inadequate delivery profile. Synthetic cationic copolymers of poly(ethylene imine) (PEI) and poly(ethylene glycol) (PEG) are regarded as effective agents for enhanced delivery of nucleic acids in various applications. RESULTS: We examined whether PEG-PEI copolymers can facilitate ESO-mediated dystrophin expression after intramuscular injections into tibialis anterior (TA) muscles of mdx mice. We utilized a set of PEG-PEI copolymers containing 2 kDa PEI and either 550 Da or 5 kDa PEG, both of which bind 2'OMe ESOs with high affinity and form stable nanoparticulates with a relatively low surface charge. Three weekly intramuscular injections of 5 μg of ESO complexed with PEI2K-PEG550 copolymers resulted in about 500 dystrophin-positive fibers and about 12% of normal levels of dystrophin expression at 3 weeks after the initial injection, which is significantly greater than for injections of ESO alone, which are known to be almost completely ineffective. In an effort to enhance biocompatibility and cellular uptake, the PEI2K-PEG550 and PEI2K-PEG5K copolymers were functionalized by covalent conjugation with nanogold (NG) or adsorbtion of colloidal gold (CG), respectively. Surprisingly, using the same injection and dosing regimen, we found no significant difference in dystrophin expression by Western blot between the NG-PEI2K-PEG550, CG-PEI2K-PEG5K, and non-functionalized PEI2K-PEG550 copolymers. Dose-response experiments using the CG-PEI2K-PEG5K copolymer with total ESO ranging from 3–60 μg yielded a maximum of about 15% dystrophin expression. Further improvements in dystrophin expression up to 20% of normal levels were found at 6 weeks after 10 twice-weekly injections of the NG-PEI2K-PEG550 copolymer complexed with 5 μg of ESO per injection. This injection and dosing regimen showed over 1000 dystrophin-positive fibers. H&E staining of all treated muscle groups revealed no overt signs of cytotoxicity. CONCLUSION: We conclude that PEGylated PEI2K copolymers are efficient carriers for local delivery of 2'OMe ESOs and warrant further development as potential therapeutics for treatment of DMD.


title: Dramatic differences in the response of macrophages from B2 and B19 MHC-defined haplotypes to interferon gamma and polyinosinic:polycytidylic acid stimulation

text: Abstract The chicken MHC has been associated with disease resistance, though the mechanisms are not understood. The functions of macrophages, critical to both innate and acquired immunity, were compared between the more infectious bronchitis virus-resistant B2 and the more infectious bronchitis virus-susceptible B19 lines. In vivo peripheral blood concentrations of monocytes were similar in B2 or B19 homozygous haplotypes. Peripheral blood-derived macrophages were stimulated with poly I:C, simulating an RNA virus, or IFNγ, a cytokine at the interface of innate and adaptive immunity. Not only did B2-derived peripheral monocytes differentiate into macrophages more readily than the B19 monocytes, but as determined by NO production, macrophages from B2 and B2 on B19 genetic background chicks were also significantly more responsive to either stimulant. In conclusion, the correlation with resistance to illness following viral infection may be directly linked to a more vigorous innate immune response.


docid: gafogxjv

title: Ribavirin, viramidine and adenosine-deaminase-catalysed drug activation: implication for nucleoside prodrug design


title: Pathology of Gray Wolf Shoulders: Lessons in Species and Aging

text: We examined scapula glenoids (n = 14) and proximal articular humeri (n = 14) of seven gray wolves that were maintained in a sanctuary park setting. Immediately after death, observations were made visually in situ and by radiography. Further observations were made in a museum laboratory setting, prior to and following clearing of soft tissues. Selected dry bone specimens were evaluated using computed tomography. Significant cartilage erosion and osteoarthropathy were identified in all shoulder joints. No single evaluation method yielded maximal information. Plain film radiography revealed only more severe changes. Computed tomography yielded more detail and clarity than standard radiography. Direct examination of articular cartilage informed about joint soft tissue, and dry bone informed about externally visible bone pathology. These data provide a basis for biological, biomedical, ecological, and archaeological scientists to improve retrospective interpretations of bone lesions. They further support developing plausible differential diagnoses for features of ancient and modern animal bones. We noted a dog‐like capacity for wolf longevity in a non‐free‐roaming environment. However, aged wolves' life spans far exceeded those of similar‐sized domestic dogs and breeds, suggesting the possibility of an important species difference that should be explored. We suggest also a hypothesis that the driving force for joint pathology in sheltered non‐domestic species may relate significantly to achieving the longevity that is possible biologically, but is uncommon in the wild because of differential stochastic influences. Anat Rec, 299:1338–1347, 2016. © 2016 Wiley Periodicals, Inc.


title: Part II. High-dose methotrexate with leucovorin rescue for severe COVID-19: An immune stabilization strategy for SARS-CoV-2 induced ‘PANIC’ attack()

text: Here, in Part II of a duology on the characterization and potential treatment for COVID-19, we characterize the application of an innovative treatment regimen for the prevention of the transition from mild to severe COVID-19, as well as detail an intensive immunotherapy intervention hypothesis. We propose as a putative randomized controlled trial that high-dose methotrexate with leucovorin (HDMTX-LR) rescue can abolish ‘PANIC’, thereby ‘left-shifting’ severe COVID-19 patients to the group majority of those infected with the SARS-CoV-2 virus, who are designated as having mild, even asymptomatic, disease. HDMTX-LR is endowed with broadly pleiotropic properties and is a repurposed, generic, inexpensive, and widely available agent which can be administered early in the course of severe COVID-19 thus rescuing the critical and irreplaceable gas-exchange alveoli. Further, we describe a preventative treatment intervention regimen for those designated as having mild to moderate COVID-19 disease, but who exhibit features which herald the transition to the severe variant of this novel Coronavirus. Both of our proposed hypothesis-driven questions should be urgently subjected to rigorous assessment in the context of randomized controlled trials, in order to confirm or refute the contention that the approaches characterized herein, are in fact capable of exerting mitigating, if not abolishing, effects upon the SARS-CoV-2 triggering of the ‘PANIC Attack’. Confirmation of our immunotherapy hypothesis would have far-reaching ramifications for the current pandemic, along with yielding invaluable lessons from which we can more effectively prepare for the next challenge to global health.


Primer for ICU Redeployment of the Non-Critical Care Surgeon: Insights from the Epicenter of the COVID-19 Pandemic