title: Political Polarization Drives Online Conversations About COVID‐19 in the United States

text: Since the outbreak in China in late 2019, the novel coronavirus (COVID‐19) has spread around the world and has come to dominate online conversations. By linking 2.3 million Twitter users to locations within the United States, we study in aggregate how political characteristics of the locations affect the evolution of online discussions about COVID‐19. We show that COVID‐19 chatter in the US is largely shaped by political polarization. Partisanship correlates with sentiment toward government measures and the tendency to share health and prevention messaging. Cross‐ideological interactions are modulated by user segregation and polarized network structure. We also observe a correlation between user engagement with topics related to public health and the varying impact of the disease outbreak in different US states. These findings may help inform policies both online and offline. Decision‐makers may calibrate their use of online platforms to measure the effectiveness of public health campaigns, and to monitor the reception of national and state‐level policies, by tracking in real‐time discussions in a highly polarized social media ecosystem.


title: Estimating Workforce-Related Economic Impact of a Pandemic on the Commonwealth of Virginia

text: A pandemic outbreak is one of the major planning scenarios considered by emergency-preparedness policymakers. The consequences of a pandemic can significantly affect and disrupt a large spectrum of workforce sectors in today's society. This paper, motivated by the impact of a pandemic, extends the formulation of the dynamic inoperability input–output model (DIIM) to account for economic perturbations resulting from such an event, which creates a time-varying and probabilistic inoperability to the workforce. A pandemic is a unique disaster, because the majority of its direct impacts are workforce related and it does not create significant direct impact to infrastructure. In light of this factor, this paper first develops a method of translating unavailable workforce into a measure of economic-sector inoperability. While previous formulations of the DIIM only allowed for the specification of an initial perturbation, this paper incorporates the fact that a pandemic can cause direct effects to the workforce over the recovery period. Given the uncertainty associated with the impact of a pandemic, this paper develops a simulation framework to account for the possible variations in realizations of the pandemic. The enhancements to the DIIM formulation are incorporated into a MatLab program and then applied to a case study to simulate a pandemic scenario in the Commonwealth of Virginia.


title: Development of Vaccines and Passive Immunotherapy Against Sars Coronavirus Using Mouse and Scid-PBL/hu Mouse Models

text: We have investigated novel vaccines strategies against severe acute respiratory syndrome (SARS) CoV infection using cDNA constructs encoding the structural antigens; spike (S), membrane (M), envelope (E), or nucleocapsid (N) protein, derived from SARS CoV (strain HKU39849, TW1, or FFM-1). As SARS-CoV is thought to infect the alveolar epithelial cell of the lung,in the present study, a type II alveolar epithelial cell clone, T7, was used to analyze the mechanism of CTL against SARS CoV membrane antigens. Mice vaccinated with SARS CoV (N) DNA or (M) DNA using pcDNA 3.1 (+) plasmid vector showed T-cell immune responses (CTL induction and proliferation) against type II alveolar epithelial cells (T7) transfected with SARS (N) or (M) DNA, respectively. To determine whether these DNA vaccines could induce T-cell immune responses in humans as well as in mice, SCID-PBL/hu mice were immunized with these DNA vaccines. PBL from healthy human volunteers were administered i.p. into IL-2 receptor gamma-chain-disrupted NOD-SCID mice [IL-2R(-/-) NOD-SCID]. SCID-PBL/hu mice thus constructed can be used to analyze the human immune response in vivo. The SCID-PBL/hu mice were immunized with SARS (N) DNA or (M) DNA and analyzed for a human T-cell immune response. The M DNA vaccine enhanced CTL activity and proliferation in the presence of M peptide in SCID-PBL/hu mice. Furthermore, the SARS N DNA vaccine induced CTL activity (IFN-gamma production by recombinant N protein or N protein-pulsed autologous B blast cells) and proliferation of spleen cells in SCID-PBL/hu mice. These results, demonstrate that SARS M and N DNA vaccines induced human CTL and human T-cell proliferative responses. On the other hand, we have developed SARS DNA vaccines that induce human neutralizing antibodies and human monoclonal antibodies against SARS CoV. Transgenic mice expressing SARS-CoV receptor (angiotensin converting enzyme 2) are also under development. These vaccines are expected to induce immune responses specific for SARS CoV in human and should provide useful tool for development of protective vaccines.


title: Analysis of SARS-CoV-2 Antibodies in COVID-19 Convalescent Plasma using a Coronavirus Antigen Microarray

text: The current practice for diagnosis of COVID-19, based on SARS-CoV-2 PCR testing of pharyngeal or respiratory specimens in a symptomatic patient at high epidemiologic risk, likely underestimates the true prevalence of infection. Serologic methods can more accurately estimate the disease burden by detecting infections missed by the limited testing performed to date. Here, we describe the validation of a coronavirus antigen microarray containing immunologically significant antigens from SARS-CoV-2, in addition to SARS-CoV, MERS-CoV, common human coronavirus strains, and other common respiratory viruses. A comparison of antibody profiles detected on the array from control sera collected prior to the SARS-CoV-2 pandemic versus convalescent blood specimens from virologically confirmed COVID-19 cases demonstrates complete discrimination of these two groups. This array can be used as a diagnostic tool, as an epidemiologic tool to more accurately estimate the disease burden of COVID-19, and as a research tool to correlate antibody responses with clinical outcomes.


title: RNA based mNGS approach identifies a novel human coronavirus from two individual pneumonia cases in 2019 Wuhan outbreak

text: From December 2019, an outbreak of unusual pneumonia was reported in Wuhan with many cases linked to Huanan Seafood Market that sells seafood as well as live exotic animals. We investigated two patients who developed acute respiratory syndromes after independent contact history with this market. The two patients shared common clinical features including fever, cough, and multiple ground-glass opacities in the bilateral lung field with patchy infiltration. Here, we highlight the use of a low-input metagenomic next-generation sequencing (mNGS) approach on RNA extracted from bronchoalveolar lavage fluid (BALF). It rapidly identified a novel coronavirus (named 2019-nCoV according to World Health Organization announcement) which was the sole pathogens in the sample with very high abundance level (1.5% and 0.62% of total RNA sequenced). The entire viral genome is 29,881 nt in length (GenBank MN988668 and MN988669, Sequence Read Archive database Bioproject accession PRJNA601736) and is classified into β-coronavirus genus. Phylogenetic analysis indicates that 2019-nCoV is close to coronaviruses (CoVs) circulating in Rhinolophus (Horseshoe bats), such as 98.7% nucleotide identity to partial RdRp gene of bat coronavirus strain BtCoV/4991 (GenBank KP876546, 370 nt sequence of RdRp and lack of other genome sequence) and 87.9% nucleotide identity to bat coronavirus strain bat-SL-CoVZC45 and bat-SL-CoVZXC21. Evolutionary analysis based on ORF1a/1b, S, and N genes also suggests 2019-nCoV is more likely a novel CoV independently introduced from animals to humans.


title: Roles of regulatory T cells and IL-10 in virus-induced demyelination

text: Abstract Neurotropic viruses are important causes of morbidity and mortality in human populations. Some of these viruses preferentially infect oligodendrocytes in the white matter, causing either direct lysis of infected cells, or more commonly myelin damage as a consequence of the host immune response to the virus. Virus-induced demyelination has similarities to the human disease multiple sclerosis. To study this disease process in experimental animals, mice are infected, most commonly, with neurotropic strains of mouse hepatitis virus, a coronavirus or Theiler's murine encephalomyelitis, a picornavirus. While the diseases caused by these two viruses differ in some aspects, in both cases demyelination is a major consequence of the infection. As in autoimmune disease, therapeutic interventions that diminish an overactive immune response would be useful. However, unlike autoimmune disease, complete suppression would result in unchecked virus replication, generally leading to more severe disease. Here we discuss two approaches that dampen but do not fully suppress the host immune response. Regulatory T cells, especially those that are specific for antigens recognized by pathogenic T cells, and IL-10 are two anti-inflammatory/pro-resolution factors that demonstrate efficacy in experimental models of virus-induced demyelination and may be useful in patients infected with viruses that cause demyelination.


title: Pharmacologic Advances in Canine and Feline Reproduction

text: Substantial improvements in therapeutic options for companion animal reproduction and gynecologic emergencies have been made over the last decade. New, alternative drug treatments, with fewer side effects and improved efficacy, are available. This has widened the spectrum of therapeutic possibilities for diseases that were previously treated only by surgical intervention. New drugs are available for estrus induction and pregnancy termination, as well as for the treatment of pyometra. This review summarizes the pharmacology and toxicology of reproductive agents currently in use for contraception, pyometra, dystocia, eclampsia, premature labor, agalactia, mastitis, metritis, and prostatic disorders, and compares their efficacy and safety with newer agents. Drug use and exposure during pregnancy and lactation, and subsequent risks to the fetuses, are also explored, with emphasis on antimicrobials, antifungals, anthelminthics, anesthetics, and vaccinations.


Letter to the editor: Mental health work in the context of the COVID-19 pandemic: What progress have we made so far and what is the next step?


title: Detection of viruses in used ventilation filters from two large public buildings

text: BACKGROUND: Viral and bacterial pathogens may be present in the air after being released from infected individuals and animals. Filters are installed in the heating, ventilation, and air-conditioning (HVAC) systems of buildings to protect ventilation equipment and maintain healthy indoor air quality. These filters process enormous volumes of air. This study was undertaken to determine the utility of sampling used ventilation filters to assess the types and concentrations of virus aerosols present in buildings. METHODS: The HVAC filters from 2 large public buildings in Minneapolis and Seattle were sampled to determine the presence of human respiratory viruses and viruses with bioterrorism potential. Four air-handling units were selected from each building, and a total of 64 prefilters and final filters were tested for the presence of influenza A, influenza B, respiratory syncytial, corona, parainfluenza 1-3, adeno, orthopox, entero, Ebola, Marburg, Lassa fever, Machupo, eastern equine encephalitis, western equine encephalitis, and Venezuelan equine encephalitis viruses. Representative pieces of each filter were cut and eluted with a buffer solution. RESULTS: Attempts were made to detect viruses by inoculation of these eluates in cell cultures (Vero, MDCK, and RK-13) and specific pathogen-free embryonated chicken eggs. Two passages of eluates in cell cultures or these eggs did not reveal the presence of any live virus. The eluates were also examined by polymerase chain reaction or reverse-transcription polymerase chain reaction to detect the presence of viral DNA or RNA, respectively. Nine of the 64 filters tested were positive for influenza A virus, 2 filters were positive for influenza B virus, and 1 filter was positive for parainfluenza virus 1. CONCLUSION: These findings indicate that existing building HVAC filters may be used as a method of detection for airborne viruses. As integrated long-term bioaerosol sampling devices, they may yield valuable information on the epidemiology and aerobiology of viruses in air that can inform the development of methods to prevent airborne transmission of viruses and possible deterrents against the spread of bioterrorism agents.


title: Interleukin-18 expression and the response to treatment in patients with psoriasis

text: INTRODUCTION: The aim of the study was to demonstrate interleukin-18 (IL-18) expression in keratinocytes from psoriatic lesions in comparison to keratinocytes from uninvolved skin and to study the change of expression after therapeutic interventions. MATERIAL AND METHODS: This study included 16 patients of different clinical subtypes of psoriasis. Interleukin-18 gene expression analysis was performed using real time quantitative PCR. Three biopsies were obtained from each patient. Two were taken from the lesional psoriatic skin and from uninvolved skin before starting treatment. A third lesional skin biopsy was taken at the end of 2 months of treatment. The treatment was in the form of topical steroids or oral systemic methotrexate. RESULTS: Of all 16 studied patients, significantly increased IL-18 expression was noted in keratinocytes from psoriatic lesions before and after treatment when compared to keratinocytes from uninvolved skin (p = 0.001 and p = 0.002 respectively). The IL-18 expression in the skin lesions after treatment was significantly lower than lesional skin before treatment (p = 0.023). In psoriatic skin lesions of all studied patients IL-18 expression was significantly correlated with disease duration (r = 0.40 and p = 0.01) and clinical severity of psoriasis (r = 0.72 and p = 0.001). CONCLUSIONS: Increased IL-18 expression in keratinocytes from psoriatic lesions of our patients and its correlation with disease duration and severity supported the concept of psoriasis as a T cell mediated autoimmune disease. This could establish therapeutic and preventive approaches for psoriasis that ultimately lead to improved outcomes for patients.


title: Modeling Regional Disease Spread Over Time Using a Dynamic Spatio-temporal Model – With an Application to Porcine Epidemic Diarrhea Virus data in Iowa, U.S.

text: Regional surveillance is important for detecting the incursion of new pathogens and informing disease monitoring and control programs. Modeling disease distribution over time can provide insight into the development of more efficient regional surveillance approaches. Herein we propose a Bayesian spatio-temporal model to describe the distribution of porcine epidemic diarrhea virus (PEDV) in Iowa USA. Model parameters are estimated through a Bayesian spatio-temporal model approach which can account for missing values. For illustration, we apply the proposed model to PEDV test results from the Iowa State University Veterinary Diagnostic Laboratory (ISU-VDL). A simulation study carried out to evaluate the model showed that the proposed model captured the pattern of PEDV distribution and its spatio-temporal dependence.


title: Safety studies conducted on pecan shell fiber, a food ingredient produced from ground pecan shells

text: Use of pecan shell fiber in human food is presently limited, but could increase pending demonstration of safety. In a 91-day rat study, pecan shell fiber was administered at dietary concentrations of 0 (control), 50 000, 100 000 or 150 000 ppm. There was no effect of the ingredient on body weight of males or females or food consumption of females. Statistically significant increases in food consumption were observed throughout the study in 100 000 and 150 000 ppm males, resulting in intermittent decreases in food efficiency (150 000 ppm males only) that were not biologically relevant. All animals survived and no adverse clinical signs or functional changes were attributable to the test material. There were no toxicologically relevant changes in hematology, clinical chemistry or urinalysis parameters or organ weights in rats ingesting pecan shell fiber. Any macroscopic or microscopic findings were incidental, of normal variation and/or of minimal magnitude for test substance association. Pecan shell fiber was non-mutagenic in a bacterial reverse mutation test and non-clastogenic in a mouse peripheral blood micronucleus test. Based on these results, pecan shell fiber has an oral subchronic (13-week) no observable adverse effect level (NOAEL) of 150 000 ppm in rats and is not genotoxic at the doses analyzed.


Enteric involvement of coronaviruses: is faecal–oral transmission of SARS-CoV-2 possible?


Reinicio De La Actividad Endoscópica En Un Área De Alto Riesgo De Covid-19 (Barcelona): Progresión (O Regresión) Según Los Recursos Necesarios Disponibles Endoscopy


title: Zika virus infection as a cause of congenital brain abnormalities and Guillain-Barré syndrome: systematic review

text: The World Health Organization stated in March 2016 that there was scientific consensus that the mosquito-borne Zika virus was a cause of the neurological disorder Guillain-Barré syndrome and of microcephaly and other congenital brain abnormalities, based on rapid evidence assessments. Decisions about causality require systematic assessment to guide public health actions. The objectives of this study were: to update and re-assess the evidence for causality through a rapid and systematic review about links between Zika virus infection and a) congenital brain abnormalities, including microcephaly, in the foetuses and offspring of pregnant women and b) Guillain-Barré syndrome in any population; and to describe the process and outcomes of an expert assessment of the evidence about causality. The study had three linked components. First, in February 2016, we developed a causality framework that defined questions about the relationship between Zika virus infection and each of the two clinical outcomes in 10 dimensions; temporality, biological plausibility, strength of association, alternative explanations, cessation, dose-response, animal experiments, analogy, specificity and consistency. Second, we did a systematic review (protocol number CRD42016036693). We searched multiple online sources up to May 30, 2016 to find studies that directly addressed either outcome and any causality dimension, used methods to expedite study selection, data extraction and quality assessment, and summarised evidence descriptively. Third, a multidisciplinary panel of experts assessed the review findings and reached consensus on causality. We found 1091 unique items up to May 30, 2016. For congenital brain abnormalities, including microcephaly, we included 72 items; for eight of 10 causality dimensions (all except dose-response relationship and specificity) we found that more than half the relevant studies supported a causal association with Zika virus infection. For Guillain-Barré syndrome, we included 36 items, of which more than half the relevant studies supported a causal association in seven of ten dimensions (all except dose-response relationship, specificity and animal experimental evidence). Articles identified non-systematically from May 30-July 29, 2016 strengthened the review findings. The expert panel concluded that: a) the most likely explanation of available evidence from outbreaks of Zika virus infection and clusters of microcephaly is that Zika virus infection during pregnancy is a cause of congenital brain abnormalities including 61 microcephaly; and b) the most likely explanation of available evidence from outbreaks of Zika virus infection and Guillain-Barré syndrome is that Zika virus infection is a trigger of Guillain-Barré syndrome. The expert panel recognised that Zika virus alone may not be sufficient to cause either congenital brain abnormalities or Guillain-Barré syndrome but agreed that the evidence was sufficient to recommend increased public health measures. Weaknesses are the limited assessment of the role of dengue virus and other possible co-factors, the small number of comparative epidemiological studies, and the difficulty in keeping the review up to date with the pace of publication of new research. Rapid and systematic reviews with frequent updating and open dissemination are now needed, both for appraisal of the evidence about Zika virus infection and for the next public health threats that will emerge. This rapid systematic review found sufficient evidence to say that Zika virus is a cause of congenital abnormalities and is a trigger of Guillain-Barré situation.


China joins investigation of mystery pneumonia


COVID 19 and Surgical Education: Time for Innovations


title: Taste and Smell Impairment in SARS-CoV-2 Recovers Early and Spontaneously: Experimental Data Strongly Linked to Clinical Data

text: [Image: see text] A growing body of literature indicates that smell and taste impairment has frequently occurred during the Severe Acute Respiratory Syndrome (SARS)-like Coronavirus (SARS-CoV-2) outbreak. Experimental studies have mostly found that non-neural-type cells are responsible for SARS-CoV-2-related taste and smell impairment. If this is the case, smell/taste impairment needs to recover early. Literature data from clinical studies indicated a strong correlation between experimental and clinical findings. This article presents clinical studies related to SARS-CoV-2-induced smell/taste impairment that reported recovery rates. Experimental researchers may use these data to observe the dynamics of smell impairment and implement these findings in their research (e.g., correct timing of sampling) to perform further studies.


title: Human Antimicrobial Peptides in Bodily Fluids: Current Knowledge and Therapeutic Perspectives in the Postantibiotic Era

text: Antimicrobial peptides (AMPs) are an integral part of the innate immune defense mechanism of many organisms. Due to the alarming increase of resistance to antimicrobial therapeutics, a growing interest in alternative antimicrobial agents has led to the exploitation of AMPs, both synthetic and isolated from natural sources. Thus, many peptide‐based drugs have been the focus of increasing attention by many researchers not only in identifying novel AMPs, but in defining mechanisms of antimicrobial peptide activity as well. Herein, we review the available strategies for the identification of AMPs in human body fluids and their mechanism(s) of action. In addition, an overview of the distribution of AMPs across different human body fluids is provided, as well as its relation with microorganisms and infectious conditions.


title: Assessing the effects of medium-chain fatty acids and fat sources on PEDV infectivity

text: The overall objective of this study was to compare the efficacy of medium-chain fatty acids (MCFA) to other common fat sources to minimize the risk of porcine epidemic diarrhea virus (PEDV) cross-contamination in a pig bioassay. Treatments were feed with mitigants inoculated with PEDV after application and were: 1) positive control with no chemical treatment; 2) 0.325% commercially available formaldehyde-based product; 3) 1% blend of 1:1:1 caproic (C6), caprylic (C8), and capric acids (C10) and applied with an aerosolizing nozzle; 4) treatment 3 applied directly into the mixer without an aerosolizing nozzle; 5) 0.66% caproic acid; 6) 0.66% caprylic acid; 7) 0.66% capric acid; 8) 0.66% lauric acid; 9) 1% blend of 1:1 capric and lauric acids; 10) 0.3% commercially available dry C12 product; 11) 1% canola oil; 12) 1% choice white grease; 13) 2% coconut oil; 14) 1% coconut oil; 15) 2% palm kernel oil; 16) 1% palm kernel oil; 17) 1% soy oil and four analysis days (0, 1, 3, and 7 post inoculation) as well as 1 treatment of PEDV-negative feed without chemical treatment. There was a treatment × day interaction (P < 0.002) for detectable PEDV RNA. The magnitude of the increase in Ct value from d 0 to 7 was dependent upon the individual treatments. Feed treated with individual MCFA, 1% MCFA blend, or commercial-based formaldehyde had fewer (P < 0.05) detectable viral particles than all other treatments. Commercial-based formaldehyde, 1% MCFA, 0.66% caproic, 0.66% caprylic, and 0.66% capric acids had no evidence of infectivity 10-d old pig bioassay, while there was no evidence the C12 commercial product or longer chain fat sources inhibited PEDV infectivity. Interestingly, pigs given the coconut oil source with the highest composition of caprylic and capric only showed signs of infectivity on the last day of bioassay. These data suggest some MCFA have potential for reducing post feed manufacture PEDV contamination.


title: Crucial steps in the structure determination of a coronavirus spike glycoprotein using cryo‐electron microscopy

text: The tremendous pandemic potential of coronaviruses was demonstrated twice in the last 15 years by two global outbreaks of deadly pneumonia. Entry of coronaviruses into cells is mediated by the transmembrane spike glycoprotein S, which forms a trimer carrying receptor‐binding and membrane fusion functions. Despite their biomedical importance, coronavirus S glycoproteins have proven difficult targets for structural characterization, precluding high‐resolution studies of the biologically relevant trimer. Recent technological developments in single particle cryo‐electron microscopy allowed us to determine the first structure of a coronavirus S glycoprotein trimer which provided a framework to understand the mechanisms of viral entry and suggested potential inhibition strategies for this family of viruses. Here, we describe the key factors that enabled this breakthrough.


title: Chapter 11 Medical Management and Diagnostic Approaches

text: Abstract This chapter reviews the basic principles of medical management of rat colonies and diagnostic approaches to detect infectious diseases of rats. As is the case with all other species, rats are susceptible to a variety of injuries and diseases that can cause distress, morbidity, or mortality. Any facility that houses rats must develop monitoring programs designed to rapidly identify health-related problems so they can be communicated to appropriate veterinary or animal care personnel to be resolved. These programs generally consist of multiple components, some of which are directed toward individual animals and others that assess the health status of rat populations as a whole. Topics include individual animal monitoring and care, signs of illness and distress, colony health management, components of microbiological monitoring programs, including agents commonly targeted and sentinel programs, quarantine, biological material screening, diagnostic testing methodologies, including culture, serology, molecular diagnostic and histopathology, test profiles and interpretation, management of disease outbreaks, and treatment and prevention strategies for infectious agents.


title: Blood Supply Testing for Infectious Diseases

text: Abstract Blood transfusion is a lifesaving intervention that has an essential role in patient management within health care systems. It is the responsibility of governments to ensure that safe and sufficient supplies of blood are available and accessible to all patients requiring transfusion. The provision of safe and efficacious blood for transfusion involves a number of processes, including assessment of the suitability of prospective blood donors to donate blood, blood collection, processing, and testing of blood donations, and the issue of blood and its transfusion to the patients. While blood transfusion can be lifesaving, there are associated risks, particularly the transmission of blood-borne infections including human immunodeficiency virus and hepatitis B and C viruses. Screening for transfusion-transmissible infections (TTIs) to exclude blood donations at risk of transmitting infection from donors to recipients is a critical part of the process of ensuring that transfusion is as safe as possible. Effective screening for evidence of the presence of the most common and dangerous TTIs can reduce the risk of transmission to very low levels. Blood transfusion services should therefore establish efficient systems to ensure that all donated blood is correctly screened for the appropriate TTIs and that only nonreactive blood is issued for transfusion to patients.


title: A Bioweapon or a Hoax? The Link Between Distinct Conspiracy Beliefs About the Coronavirus Disease (COVID-19) Outbreak and Pandemic Behavior

text: During the coronavirus disease pandemic rising in 2020, governments and nongovernmental organizations across the globe have taken great efforts to curb the infection rate by promoting or legally prescribing behavior that can reduce the spread of the virus. At the same time, this pandemic has given rise to speculations and conspiracy theories. Conspiracy worldviews have been connected to refusal to trust science, the biomedical model of disease, and legal means of political engagement in previous research. In three studies from the United States (N = 220; N = 288) and the UK (N = 298), we went beyond this focus on a general conspiracy worldview and tested the idea that different forms of conspiracy beliefs despite being positively correlated have distinct behavioral implications. Whereas conspiracy beliefs describing the pandemic as a hoax were more strongly associated with reduced containment-related behavior, conspiracy beliefs about sinister forces purposefully creating the virus related to an increase in self-centered prepping behavior.


title: Distinct spread of DNA and RNA viruses among mammals amid prominent role of domestic species

text: Emerging infectious diseases arising from pathogen spillover from mammals to humans comprise a substantial health threat. Tracing virus origin and predicting the most likely host species for future spillover events are major objectives in One Health disciplines. However, the species that share pathogens most widely with other mammals, and the role of different wildlife groups in sharing viruses with humans remain poorly identified. To address this challenge, we applied network analysis and Bayesian hierarchical models to a global database of mammal-virus associations. We show that domesticated mammals and some primates hold the most central positions in networks of known mammal-virus associations. We revealed strong evidence that DNA viruses were phylogenetically more host specific than RNA viruses, while the frequencies of sharing viruses among hosts and the proportion of zoonotic viruses in hosts were larger for RNA than DNA viruses. Among entire host-virus networks, Carnivora and Chiroptera hold central positions for mainly sharing RNA viruses with other host species, while network centrality of Primates scored relatively high for sharing DNA viruses. Ungulates hold central positions for sharing both RNA and DNA viruses. Acknowledging the role of domestic species in addition to host and virus traits in patterns of virus sharing is necessary to improve our understanding of virus spread and spillover in times of global change.


Resuscitation and COVID-19–Recalibrating Patient and Family Expectations During a Pandemic


title: A review on Malaysia’s solar energy pathway towards carbon-neutral Malaysia beyond Covid’19 pandemic

text: COVID’19 pandemic has devastated several industries and solar energy is no exception. In its economic relief package, Malaysia has announced approximately US$ 2.9 billion in expenditure for the installation of new grids, LED street lights and rooftop solar panels. The Government will also open the tender for a 1,400 MW solar power project in the year 2020, which is expected to generate 5 billion ringgit (US$1.1 billion) in investments. As these measures are intended to sustain the existing growth of solar energy potential in the country, it is vital to assess its status quo. Hence, this paper aims to review the current status of renewable energy in Malaysia as well as the initiatives taken before the pandemic to promote solar photovoltaic (PV) technology to meet the energy demands through the low-carbon pathway.


title: Thermal stress associated mortality risk and effect modification by sex and obesity in an elderly cohort of Chinese in Hong Kong

text: We assessed the effects of apparent temperature (AT) on mortality and the effect modifications attributable to individual characteristics in Hong Kong with subtropical climate conditions. Two datasets are used for analyses: one from mortality data of the general elderly population in 1998–2009; the other from an elderly cohort with 66,820 subjects recruited in 1998–2001 with mortality outcomes followed up until 2009. We found that AT below 20.8 °C was associated with an increase in mortality risk of 1.99% (95% confidence interval: 0.64%, 2.64%) for all causes, 2.48% (0.57%, 4.36%) for cardiovascular disease, and 3.19% (0.59%, 5.73%) for respiratory disease for every 1 °C decrease in AT over the following 3 days. The associations were modified by sex and body mass index, in particular stronger associations were observed for females and for obese subjects.


title: Expanding the frontiers of existing antiviral drugs: Possible effects of HIV-1 protease inhibitors against SARS and avian influenza

text: Abstract When unexpected diseases such as the severe acute respiratory syndrome (SARS) and avian influenza become a serious threat to public health, an immediate response is imperative. This should take into consideration existing licensed antiviral drugs against other viral diseases already known to be safe for use in humans. In this report, evidence is presented that HIV-1 protease inhibitors (PIs) currently used in anti-HIV-1 therapies might exert some effects on SARS and perhaps, on avian influenza. Evidence for the potential benefits of PIs against the SARS coronavirus (SARS-CoV) is provided by empirical clinical studies, in vivo viral inhibition assays and computational simulations of the docking of these compounds to the active site of the main SARS-CoV protease. As suggested by in silico docking of these molecules to a theoretical model of a subunit of type A influenza virus RNA-dependent RNA polymerase, there also exists a remote possibility that these PIs may have an effect on avian influenza viruses. Although this evidence is still far from being definitive, the results so far obtained suggest that PIs should be seriously taken into consideration for further testing as potential therapeutic agents for SARS and avian influenza.


title: Clinical Characteristics and Outcomes in People Living With Human Immunodeficiency Virus Hospitalized for Coronavirus Disease 2019

text: We describe the characteristics of 31 people living with human immunodeficiency virus hospitalized for severe acute respiratory syndrome coronavirus 2 infection. All patients were on antiretroviral therapy and virologically suppressed at the time of admission. Clinical course and outcomes were similar to those reported in other hospitalized cohorts.


title: COVID‐19 complicated by parainfluenza co‐infection in a patient with chronic lymphocytic leukemia

text: The number of people suffering from the new coronavirus SARS‐CoV‐2 continues to rise. In SARS‐CoV‐2, superinfection with bacteria or fungi seems to be associated with increased mortality. The role of co‐infections with respiratory viral pathogens has not yet been clarified. Here, we report the course of COVID‐19 in a CLL patient with secondary immunodeficiency and viral co‐infection with parainfluenza.


title: Genetic distance of SARS coronavirus from the recent natural case

text: Abstract Phylogenetic analysis of SARS coronavirus isolates based on the spike gene and protein sequence using Neighbor-Joining, maximum likelihood and Bayesian inference methods indicated that a recent human SARS-CoV isolate was closer to some human SARS-CoV isolates from earlier epidemic phase than to the SARS-CoV-like viruses isolated from wild animals during previous epidemic phase. A reasonable judgment based on phylogenetic relationship and sequence variations it is likely that the recent human SARS-CoV isolate is closer to an unknown SARS-CoV predecessor.


Tromboembolismo pulmonar y COVID-19: un cambio de paradigma


title: COVID-19-associated encephalitis mimicking glial tumor: a case report.

text: Abstract Background Reports on neurologic manifestations of coronavirus disease 2019 (COVID-19) have attracted broad attention. We present the unusual case of COVID-19-associated encephalitis mimicking a glial tumor. Case description A 35-year-old woman presented with headache and seizures. T2 fluid-attenuated inverse recovery imaging showed hyperintensities in the left temporal lobe. Magnetic resonance spectroscopy showed an elevated choline peak. Imaging findings were suggestive of high-grade glioma. Antiepileptic medication failed to achieve seizure control. Left anterior temporal lobectomy was performed. The patient had no post-operative deficits and her symptoms completely improved. Histological examination revealed encephalitis. Post-operatively, our patient was tested positive for COVID-19. Conclusions Our case raises awareness of neurologic manifestations of the disease and their potential to mimic glial tumors. For prompt diagnosis and prevention of transmission, clinicians should consider COVID-19 in patients with similar presentation.


docid: wxnabifu

title: President´s Corner (Mitteilungen der Deutschen Schmerzgesellschaft e.V.)


title: Aetiological agents for pulmonary exacerbations in children with cystic fibrosis: An observational study from a tertiary care centre in northern India

text: BACKGROUND & OBJECTIVES: Pulmonary disease is the main cause of morbidity and mortality in cystic fibrosis (CF). The infection occurs with a unique spectrum of bacterial pathogens that are usually acquired in an age-dependent fashion. The objective of this study was to find out the aetiological agents in respiratory specimens from children with CF during pulmonary exacerbation and relate with demographic variables. METHODS: In this observational study, airway secretions from children (n=104) with CF presenting with pulmonary exacerbations were collected and tested for bacteria, fungi, mycobacteria and viral pathogens using appropriate laboratory techniques. The frequencies of isolation of various organisms were calculated and associated with various demographic profiles. RESULTS: Bacteria were isolated in 37 (35.5%) and viral RNA in 27 (29.3%) children. Pseudomonas was the most common bacteria grown in 31 (29.8%) followed by Burkholderia cepacia complex (Bcc) in three (2.8%) patients. Among viruses, Rhinovirus was the most common, identified in 16 (17.4%) samples followed by coronavirus in four (4.3%). Fungi and mycobacteria were isolated from 23 (22.1%) and four (3.8%) children, respectively. Aspergillus flavus was the most common fungus isolated in 13 (12.5%) children. INTERPRETATION & CONCLUSIONS: Pseudomonas was the most common organism isolated during exacerbation. Non-tuberculous mycobacteria were not isolated, whereas infection with Bcc and Mycobacterium tuberculosis was observed, which could probably have a role in CF morbidity. Polymicrobial infections were associated with severe exacerbations.


title: Identification and design of novel small molecule inhibitors against MERS-CoV papain-like protease via high-throughput screening and molecular modeling

text: Abstract The development of new therapeutic agents against the coronavirus causing Middle East Respiratory Syndrome (MERS) is a continuing imperative. The initial MERS-CoV epidemic was contained entirely through public health measures, but episodic cases continue, as there are currently no therapeutic agents effective in the treatment of MERS-CoV, although multiple strategies have been proposed. In this study, we screened 30,000 compounds from three different compound libraries against one of the essential proteases, the papain-like protease (PLpro), using a fluorescence-based enzymatic assay followed by surface plasmon resonance (SPR) direct binding analysis for hit confirmation. Mode of inhibition assays and competition SPR studies revealed two compounds to be competitive inhibitors. To improve upon the inhibitory activity of the best hit compounds, a small fragment library consisting of 352 fragments was screened in the presence of each hit compound, resulting in one fragment that enhanced the IC50 value of the best hit compound by 3-fold. Molecular docking and MM/PBSA binding energy calculations were used to predict potential binding sites, providing insight for design and synthesis of next-generation compounds.


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title: A Mechanism of Virus-Induced Demyelination

text: Myelin forms an insulating sheath surrounding axons in the central and peripheral nervous systems and is essential for rapid propagation of neuronal action potentials. Demyelination is an acquired disorder in which normally formed myelin degenerates, exposing axons to the extracellular environment. The result is dysfunction of normal neuron-to-neuron communication and in many cases, varying degrees of axonal degeneration. Numerous central nervous system demyelinating disorders exist, including multiple sclerosis. Although demyelination is the major manifestation of most of the demyelinating diseases, recent studies have clearly documented concomitant axonal loss to varying degrees resulting in long-term disability. Axonal injury may occur secondary to myelin damage (outside-in model) or myelin damage may occur secondary to axonal injury (inside-out model). Viral induced demyelination models, has provided unique imminent into the cellular mechanisms of myelin destruction. They illustrate mechanisms of viral persistence, including latent infections, virus reactivation and viral-induced tissue damage. These studies have also provided excellent paradigms to study the interactions between the immune system and the central nervous system (CNS). In this review we will discuss potential cellular and molecular mechanism of central nervous system axonal loss and demyelination in a viral induced mouse model of multiple sclerosis.


title: Frontal horn cysts in normal neonates

text: Abstract Frontal horn cysts (FHCs) are elliptical, smooth, thin-walled cysts adjacent to the tip of the anterior horns of the lateral ventricles. Among 3545 terms or near term healthy babies who underwent cranial ultrasound examination in our hospital over a 2-year 5-month period, 18 were found to have FHCs (17 typical and one atypical; seven bilateral and 11 unilateral, of which seven were on the left and four on the right). The female to male ratio was 2:1. The incidence of FHCs in normal term babies was thus 0.5%. Six children had resolution of the cyst within 1 month, and 6 more had resolution on repeat scan from 2 to 11 months of age. Four children did not have subsequent ultrasonography to document resolution, but they had normal growth and development. Two were lost to follow up. The infant with an atypical FHC had an enlarged left frontal horn cyst with a midline shift on follow up, but he had normal development. Our study suggests that FHC may be a normal physiologic variant or a benign pathologic condition that can be expected to resolve spontaneously within a few months. It is reasonable to follow typical FHC by cranial ultrasound examinations at 1 or 2 and 6 months of age. In the case of an atypical cyst, more frequent follow up and further image studies like CT or MRI are necessary.


title: A database of geopositioned Middle East Respiratory Syndrome Coronavirus occurrences

text: As a World Health Organization Research and Development Blueprint priority pathogen, there is a need to better understand the geographic distribution of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and its potential to infect mammals and humans. This database documents cases of MERS-CoV globally, with specific attention paid to zoonotic transmission. An initial literature search was conducted in PubMed, Web of Science, and Scopus; after screening articles according to the inclusion/exclusion criteria, a total of 208 sources were selected for extraction and geo-positioning. Each MERS-CoV occurrence was assigned one of the following classifications based upon published contextual information: index, unspecified, secondary, mammal, environmental, or imported. In total, this database is comprised of 861 unique geo-positioned MERS-CoV occurrences. The purpose of this article is to share a collated MERS-CoV database and extraction protocol that can be utilized in future mapping efforts for both MERS-CoV and other infectious diseases. More broadly, it may also provide useful data for the development of targeted MERS-CoV surveillance, which would prove invaluable in preventing future zoonotic spillover.


When the game changes: Guidance to adjust sarcoidosis management during the COVID-19 pandemic


title: Surgical Mask–the Saviour: from its Invention to the COVID-19 Era

text: The earliest available evidence attributes the discovery of droplets as a mode of transmission of disease to Carl Flügge, a German bacteriologist, a contemporary of Emil Kocher, in 1897. This finding was instrumental in the development of the gauze mask introduced by Johann von Mikulicz Radecki in the same year. A surgical mask has become an indispensable tool in the armamentarium to fight the COVID 19 pandemic. Surgical masks which were once limited to the confines of healthcare setups are now donned by the members of the general public. It has become imperative that a healthcare worker selects the right kind of respiratory protective equipment to protect himself and his patients. The surgical mask has become essential, in a way, for survival.


title: Recommendations for coronavirus disease (COVID-19) prevention and infection control in the radiology department: Chinese experience

text: The coronavirus disease 19 (COVID-19) outbreak, first reported in Wuhan, China, is gradually spreading worldwide. For diagnosis, chest computed tomography is a conventional, noninvasive imaging modality that is very accurate for detection and evaluation of pneumonia and is an important adjunct to real-time reverse transcription polymerase chain reaction diagnosis of the virus. Previous studies have reported typical computed tomography imaging features indicative of COVID-19, such as multifocal ground-glass opacities with or without consolidation. With the sharply increasing demand for computed tomography examination during the outbreak, ensuring appropriate infection control in radiology departments is challenging. Thus, advanced training and education in standardized infection control and prevention practice are essential. The purpose of this brief review is to summarize such training and education for clinical management of this outbreak for radiology department personnel. We will describe standard transmission-based precautions, workflow for computed tomography examination of fever patients, and decontamination management of a radiology department.


title: Detection of IgM responses to bovine respiratory syncytial virus by indirect ELISA following experimental infection and reinfection of calves: abolition of false positive and false negative results by pre-treatment of sera with protein-G agarose

text: Abstract The IgM responses in three panels of sera generated by infection and reinfection of calves with bovine respiratory syncytial virus (BRSV) were measured by indirect ELISA (I-ELISA). The effect of depleting serum IgG by pre-treatment with protein G agarose (PGA) was evaluated. Following primary infection a weak IgM response was detected in the untreated sera of 3 out of 4 calves with maternally derived antibody (MDA). Both the magnitude and duration of the specific IgM responses in these calves were increased by pre-treatment with PGA. In addition, the fourth infected calf tested gave a single positive IgM result following PGA treatment. Transient or persistent IgM responses which were abolished by pre-treatment of sera with PGA were detected in 4/8 calves following reinfection. These were considered to be false positive results, consistent with the influence of IgM rheumatoid factor (IgM-RF). One of these calves and two additional calves showed transient increases in IgM which were resistant to PGA treatment. These were considered to represent specific IgM responses to reinfection. The results indicate the ability of PGA treatment to eliminate both false positive and false negative results and emphasise the necessity for controlling the influence of IgM-RF in IgM-specific indirect ELISAs.


title: Detection of swine-origin influenza A (H1N1) viruses using a localized surface plasmon coupled fluorescence fiber-optic biosensor

text: Swine-origin influenza A (H1N1) virus (S-OIV) was identified as a new reassortant strain of influenza A virus in April 2009 and led to an influenza pandemic. Accurate and timely diagnoses are crucial for the control of influenza disease. We developed a localized surface plasmon coupled fluorescence fiber-optic biosensor (LSPCF-FOB) which combines a sandwich immunoassay with the LSP technique using antibodies against the hemagglutinin (HA) proteins of S-OIVs. The detection limit of the LSPCF-FOB for recombinant S-OIV H1 protein detection was estimated at 13.9 pg/mL, which is 10(3)-fold better than that of conventional capture ELISA when using the same capture antibodies. For clinical S-OIV isolates measurement, meanwhile, the detection limit of the LSPCF-FOB platform was calculated to be 8.25 × 10(4) copies/mL, compared with 2.06 × 10(6) copies/mL using conventional capture ELISA. Furthermore, in comparison with the influenza A/B rapid test, the detection limit of the LSPCF-FOB for S-OIV was almost 50-fold in PBS solution and 25-fold lower in mimic solution, which used nasal mucosa from healthy donors as the diluent. The findings of this study therefore indicate that the high detection sensitivity and specificity of the LSPCF-FOB make it a potentially effective diagnostic tool for clinical S-OIV infection and this technique has the potential to be applied to the development of other clinical microbe detection platforms.


title: Ethical dimensions of stigma and discrimination in Nepal during COVID-19 pandemic

text: ABSTRACT COVID-19 pandemic has ultimately brought down the world in a status of standstill as a result of lockdown as one of the measures to combat the situation and to prevent cross transmission. On the other hand, it has raised issues like ethical obligation of medical doctors and other staff to attend COVID-19 patients without proper PPE and resources increasing the risk to the staff and their family. In addition, it has resulted in compromise of the services provided to the people like non-availability of medical services to chronic and non-urgent patients. Non-COVID-19 patients attending ‘Fever Clinic’ were harmed due to inappropriate management. Medical staff dealing with testing or working in hospitals, isolation wards or quarantine centres have been stigmatized as ‘possibly infected’ and even denied food and accommodation.


title: Beneficial effects of Houttuynia cordata polysaccharides on “two-hit” acute lung injury and endotoxic fever in rats associated with anti-complementary activities

text: Houttuynia cordata Thunb. is a traditional herb used for clearing heat and eliminating toxins, and has also been used for the treatment of severe acute respiratory syndrome (SARS). In vitro, the crude H. cordata polysaccharides (CHCP) exhibited potent anti-complementary activity through both the classical and alternative pathways by acting on components C3 and C4 of the complement system without interfering with the coagulation system. This study was to investigate the preventive effects of CHCP on acute lung injury (ALI) induced by hemorrhagic shock plus lipopolysaccharide (LPS) instillation (two-hit) and LPS-induced fever in rats. CHCP significantly attenuated pulmonary injury in the “two-hit” ALI model by reducing pulmonary edema and protein exudation in bronchoalveolar lavage fluid (BALF). In addition, it reduced the deposit of complement activation products in the lung and improved oxidant-antioxidant imbalance. Moreover, CHCP administration inhibited fever in rats, reduced the number of leukocytes and restored serum complement levels. The inhibition on the inappropriate activation of complement system by CHCP may play an important role in its beneficial effects on inflammatory diseases. The anti-complementary polysaccharides are likely to be among the key substances for the heat-clearing function of H. cordata.


title: Chromatographic analysis of the aminoacyl-trnas which are required for translation of codons at and around the ribosomal frameshift sites of HIV, HTLV-1, and BLV

text: Abstract An examination of the frameshift signals or proposed signals within published sequences of retroviruses and other genetic elements from higher animals shows that each site utilizes a tRNA which normally contains Wybutoxine (Wye) base or Queuine (Q) base in the anticodon loop. We find experimentally that most of the Phe-tRNA present in HIV-1 infected cells lacks the highly modified Wye base in its anticodon loop and most of the Asn-tRNA in HTLV-1 and BLV infected cells lacks the highly modified Q base in its anticodon loop. Interestingly, Phe-tRNA translates a UUU codon within the ribosomal frameshift signal in HIV and Asn-tRNA translates a AAC codon within the proposed frameshift signals in HTLV-1 and BLV. Thus, the lack of a highly modified base in the anticodon loop of tRNAs in retroviral infected cells is correlated with the participation of these undermodified tRNAs in the corresponding frameshift event. This suggests that the “shifty” tRNAs proposed by Jacks et al. (Cell 55, 447–458, 1988) to carry out frameshifting may be hypomodified isoacceptors.


Validation of Coronavirus E Proteins Ion Channels as Targets for Antiviral Drugs


title: Antiproliferative and apoptotic activity of glycyrrhizinic acid in MCF-7 human breast cancer cells and evaluation of its effect on cell cycle, cell migration and m-TOR/PI3K/Akt signalling pathway

text: INTRODUCTION: Glycyrrhizinic acid is a natural product of pharmacological relevance and its anticancer activity against breast cancer cell lines has not been evaluated. Therefore the main purpose of the present study was to investigate the anticancer effects of glycyrrhizinic acid in MCF-7 human breast cancer cells. MATERIAL AND METHODS: The MTT assay was used to evaluate the anticancer effects while a clonogenic assay was used to study its effects on colony formation tendency. Flow cytometry was used to study the effects on cell cycle phase distribution and apoptosis. Western blot assay was used to study changes in protein expression of the m-TOR/PI3K/Akt pathway. RESULTS: The results indicated that glycyrrhizinic acid caused significant (p < 0.01). The growth inhibitory effects MCF-7 human breast cancer cells. The growth inhibitory effects of glycyrrhizinic acid exhibited concentration-dependent as well as time-dependent growth inhibitory trend. Different doses of glycyrrhizinic acid had a tendency to significantly (p < 0.01) inhibit the colony formation tendency of MCF-7 cells. As compared to the control group, glycyrrhizinic acid-treated cells showed a high percentage of apoptotic cells. Cells treated with a 10, 50 and 100 µM dose of glycyrrhizinic acid led to a 24.3%, 41.5% and 82.1% increase in the sub-G1 phase (apoptotic) cells. Glycyrrhizinic acid also led to significant (p < 0.01) inhibition of cell invasion along with downregulation of m-TOR/PI3K/Akt protein expression. CONCLUSIONS: Glycyrrhizinic acid inhibited MCF-7 human breast cancer cell growth and therefore may prove essential lead molecule in the treatment of breast cancer.


title: Detection of foot-and-mouth disease virus infected cattle using infrared thermography

text: Abstract In this study, infrared thermography (IRT) was assessed as a means of detecting foot-and-mouth disease virus (FMDV)-infected cattle before and after the development of clinical signs. Preliminary IRT imaging demonstrated that foot temperatures increased in FMDV-infected animals. The maximum foot temperatures of healthy (n =53), directly inoculated (DI) (n =12), contact (CT) (n =6), and vaccine trial (VT) (n =21) cattle were measured over the course of FMD infection. A cut-off value was established at 34.4°C (sensitivity=61.1%, specificity=87.7%) with the aim of detecting FMDV-infected animals both before and after clinical signs were observed. Seven of 12 (58%) DI and 3/6 (50%) CT animals showed maximum foot temperatures exceeding the 34.4°C cut-off before the development of foot vesicles. In contrast, only 5/21 (24%) VT animals displayed pre-clinical foot temperatures above this cut-off possibly indicating partial vaccine protection of this group. These results show IRT as a promising screening technology to quickly identify potentially infected animals for confirmatory diagnostic testing during FMD outbreaks. Further evaluation of this technology is needed to determine the value of IRT in detecting animals with mild clinical signs or sub-clinical infections.


Many children aged two to five years have a persistent presence of respiratory viruses in their nasopharynx


title: Viral Diarrhoea in a Rural Coastal Region of Karnataka India

text: Abstract. A total of 106 children below 5 years of age admitted to the Kasturba Medical College Hospital Manipal Karnataka (South India) were investigated over a period of 6 months to determine the aetiologkal role of viruses in acute diarrhoea. Viral aetiological agents isolated were Rotaviruses in 12 (11 per cent) cases, Adenoviruses in 3 (3 per cent) cases, corona virus and astroviruses in two (2 per cent) cases each. Non-viral isolates were Cryptosporidium and Salmonella typhimurium in two cases each, and Entamoeba histolyticaand and Shigella flexneri in one case each.


Machine Learning, COVID‐19 (2019‐nCoV), and multi‐OMICS


title: Increased frequency of CD4+CD25high CD127low/ − regulatory T cells in patients with multiple sclerosis

text: Abstract Background Multiple sclerosis (MS), one of the most common diseases of the central nervous system (CNS), is characterized by demyelination and chronic inflammation of the CNS. Failure of immune tolerance and induced autoimmune processes are involved in MS immunopathogenesis. Regulatory T (Treg) cells play an important role in maintaining peripheral tolerance and immune homeostasis. Objective The aim of this study was to evaluate the frequency of CD4+CD25highCD127low/ −Treg cells in MS patients. Methods The study population was composed of 25 healthy controls (HCs), 35 patients with relapsing remitting multiple sclerosis (RRMS) and 25 patients with progressive multiple sclerosis (PMS). Frequency of CD4+CD25highCD127low/ − Treg cells in RRMS and PMS patients was compared with HC by flow cytometry. Results Treg cells frequency in PMS patients was significantly higher compared to RRMS patients (P < 0.001) and HCs (P < 0.001). It was lower in RRMS patients than HCs (P = 0.005). A Significant direct correlation between Treg cells frequency and expanded disability status scale (EDSS) in PMS patients (P = 0.001, r = 0.6) was observed. Reverse correlation between Treg cells frequency and EDSS in RRMS patients was found (P = 0.01, r = −0.4). Conclusion More detailed clarification of the role of Treg cells in MS patients could provide a basis for development of Treg cells-mediated therapeutic strategies.


title: Chapter 4 Ligand-directed Cancer Gene Therapy to Angiogenic Vasculature

text: Abstract Gene therapy strategies in cancer have remained an active area of preclinical and clinical research. One of the current limitations to successful trials is the relative transduction efficiency to produce a therapeutic effect. While intratumoral injections are the mainstay of many treatment regimens to date, this approach is hindered by hydrostatic pressures within the tumor and is not always applicable to all tumor subtypes. Vascular-targeting strategies introduce an alternative method to deliver vectors with higher local concentrations and minimization of systemic toxicity. Moreover, therapeutic targeting of angiogenic vasculature often leads to enhanced bystander effects, improving efficacy. While identification of functional and systemically accessible molecular targets is challenging, approaches, such as in vivo phage display and phage-based viral delivery vectors, provide a platform upon which vascular targeting of vectors may become a viable and translational approach.


title: Supplemental Lactoferrin Improves Health and Growth of Holstein Calves during the Preweaning Phase 1,2

text: Abstract Lactoferrin is a milk protein that exhibits broad-spectrum antimicrobial properties. Previous studies indicated that supplemental lactoferrin may alter the microbial populations in the gut of nonruminants and increase preweaning weight gains in calves. In the present study, 40 Holstein calves were used to examine the effects of supplemental lactoferrin (0, 1, 2, or 3 g/d) on health, growth, and feed intake from 3 d of age to 2 wk postweaning. Lactoferrin was mixed and fed with a nonmedicated milk replacer. Calves were housed in individual pens and offered a textured, nonmedicated starter and water for ad libitum consumption. Body weight and heart girth were measured weekly. Intakes of milk replacer and starter were determined daily. Fecal consistency was monitored three times per week. Calves were weaned when they met certain criteria based on body weight gain and starter intake. Preweaning fecal score responded quadratically, with the group fed 1 g/d of lactoferrin having the lowest score. Overall and preweaning number of days medicated responded in the same manner as fecal score. Preweaning average daily gain and gain-to-feed ratio increased linearly with lactoferrin supplementation, whereas postweaning gain-to-feed ratio decreased linearly with lactoferrin. Overall average daily heart girth gain increased linearly with lactoferrin. Body weight, weaning age, and dry matter intake were not different among treatments. Based on the observed improved gain-to-feed ratios, increased average daily gains, improved fecal scores, and reduced morbidity in preweaned calves, it appears that lactoferrin may be a beneficial supplement in the diets of neonatal calves prior to weaning.


title: Fuelling regional development or exporting value? The role of the gas industry on the Limestone Coast, South Australia

text: Abstract The degree to which host regions benefit from resource extraction is a major issue for research and policy. In Australia and Canada, the dominant narrative of resource extraction is that most of the benefits flow away from host regions. This paper draws on evolutionary economic geography, presenting a case study of the Limestone Coast in South Australia, which previously extracted and distributed gas locally to food and fibre manufacturing industries. New policies seeking to renew the gas industry in the region, provide subsidies for exploration. Scenarios were developed to help inform decisions about the role of gas within this region. Qualitative analysis of the scenarios emphasised that gas needs to be affordable and locally accessible. Quantitative modelling showed that using the gas locally by manufacturing industries as part of broader industrial expansion would lead to greater benefits compared with exporting all gas outside the region. We conclude that policy settings have gone some way towards realising increased benefits for the region. Regional stakeholders clearly favoured the local use scenario but saw it as unlikely in the context of current infrastructure limitations. Stakeholders sought policy support for infrastructure to enable the preferred scenario to be realised.


title: New insights on the role of paired membrane structures in coronavirus replication

text: Abstract The replication of coronaviruses, as in other positive-strand RNA viruses, is closely tied to the formation of membrane-bound replicative organelles inside infected cells. The proteins responsible for rearranging cellular membranes to form the organelles are conserved not just among the Coronaviridae family members, but across the order Nidovirales. Taken together, these observations suggest that the coronavirus replicative organelle plays an important role in viral replication, perhaps facilitating the production or protection of viral RNA. However, the exact nature of this role, and the specific contexts under which it is important have not been fully elucidated. Here, we collect and interpret the recent experimental evidence about the role and importance of membrane-bound organelles in coronavirus replication.


title: Chapter 11 Structural Insight Into the Viral 3C-Like Protease Inhibitors: Comparative SAR/QSAR Approaches

text: Abstract Severe acute respiratory syndrome (SARS), caused by SARS-coronavirus (SARS-CoV), is a dreadful infection worldwide having economic and medical importance and a global threat for health. It was turned into an epidemic in South China followed by a chain of infections across three generations. A number of pathogeneses in human may occur due to the virus. This infection has not been taken into account before the SARS outbreak, and still it is a neglected one. Therefore, there is an urgent need to develop small molecule antivirals to combat the SARS-CoV. No vaccines are available till date though a number of SARS-CoV 3C-like and 3C protease inhibitors were reported. In this chapter, quantitative structure–activity relationship technique is used for development of anti-SARS and anti-HRV drugs and outcome discussed in details. This approach may be a useful strategy to design novel and potential anti-SARS drugs to combat these dreadful viral diseases.


title: Recomendações para Ressuscitação Cardiopulmonar (RCP) de pacientes com diagnóstico ou suspeitos de COVID-19ϯ

text: Resumo A atenção ao paciente vítima de parada cardiorrespiratória em um contexto de pandemia de COVID-19 possui particularidades que devem ser ressaltadas. As seguintes recomendações da Associação Brasileira de Medicina de Emergência (ABRAMEDE), Sociedade Brasileira de Cardiologia (SBC), Associação de Medicina Intensiva Brasileira (AMIB) e Sociedade Brasileira de Anestesiologia (SBA), associações e sociedades representantes oficiais de especialidades afiliadas a Associação Medica Brasileira (AMB), têm por objetivo orientar as diversas equipes assistentes, em um contexto de poucas evidências sólidas, maximizando a proteção das equipes e dos pacientes. É fundamental a paramentação completa com Equipamentos de Proteção Individual (EPIs) para aerossóis durante o atendimento de Parada Cardiorrespiratória (PCR), e imperativo que se considerem e tratem os potenciais causas nesses pacientes, principalmente hipóxia e arritmias causadas por alterações no intervalo QT ou miocardites. A instalação de via aérea invasiva avançada deve ser obtida precocemente e o uso de filtros High Efficiency Particulate Arrestance (HEPA) na interface com a bolsa-válvula é obrigatório; situações de ocorrência de PCR durante a ventilação mecânica e em posição pronada demandam peculiaridades distintas do padrão convencional de PCR. Frente ao atendimento de um paciente com diagnóstico ou suspeito de COVID-19, o atendimento segue em acordo com os protocolos e diretrizes nacionais e internacionais 2015 ILCOR (Aliança Internacional dos Comitês de Ressuscitação), Diretrizes AHA 2019 (American Heart Association) e a Atualização da Diretriz de Ressuscitação Cardiopulmonar e Cuidados de Emergência da Sociedade Brasileira de Cardiologia 2019. Abstract The care for patients suffering from cardiopulmonary arrest in a context of a COVID-19 pandemic has particularities that should be highlighted. The following recommendations from the Brazilian Association of Emergency Medicine (ABRAMEDE), the Brazilian Society of Cardiology (SBC) and the Brazilian Association of Intensive Medicine (AMIB) and the Brazilian Society of Anesthesiology (SBA), associations and societies official representatives of specialties affiliated to the Brazilian Medical Association (AMB), aim to guide the various assistant teams, in a context of little solid evidence, maximizing the protection of teams and patients. It is essential to wear full Personal Protective Equipment (PPE) for aerosols during the care of Cardiopulmonary Resuscitation (CPR) and it is imperative to consider and treat the potential causes in these patients, especially hypoxia and arrhythmias caused by changes in the QT interval or myocarditis. The installation of an advanced invasive airway must be obtained early and the use of High Efficiency Particulate Arrestance (HEPA) filters at the interface with the valve bag is mandatory; situations of occurrence of CPR during mechanical ventilation and in a prone position demand peculiarities that are different from the conventional CPR pattern. Faced with the care of a patient diagnosed or suspected of COVID-19, the care follows the national and international protocols and guidelines 2015 ILCOR (International Alliance of Resuscitation Committees), AHA 2019 Guidelines (American Heart Association) and the Update of the Cardiopulmonary Resuscitation and Emergency Care Directive of the Brazilian Society of Cardiology 2019.


title: Post-translational processing of the glycoproteins of lymphocytic choriomeningitis virus

text: Abstract Intracellular events in the synthesis, glycosylation, and transport of the lymphocytic choriomeningitis virus (LCMV) glycoproteins have been examined. We have shown by N-glycanase digestion that LCMV strain Arm-4 bears five oligosaccharides on GP-1 and two on GP-2. By pulse-chase labeling experiments in the presence of drugs which inhibit N-linked oligosaccharide addition and processing we demonstrate that addition of high mannose precursor oligosaccharides is necessary for transport and cleavage of the viral GP-C glycoprotein. Moreover, in the presence of tunicamycin which inhibits en bloc addition of these mannose-rich side chains, virus budding was substantially decreased and infectious virions were reduced by more than 1000-fold in the supernatant medium. Incubation in the presence of castantospermine, which permits addition of oligomannosyl-rich chains but blocks further processing, restored transport and cleavage of GP-C and maturation of virions. Finally, by temperature block experiments we have determined that maturation of GP-C oligosaccharides to an endoglycosidase H resistant form precedes cleavage to GP-1 and GP-2. The latter process is most likely to occur in the Golgi or post-Golgi compartment.


title: COVID-19 Pneumonia Diagnosis Using a Simple 2D Deep Learning Framework With a Single Chest CT Image: Model Development and Validation

text: BACKGROUND: Coronavirus disease (COVID-19) has spread explosively worldwide since the beginning of 2020. According to a multinational consensus statement from the Fleischner Society, computed tomography (CT) is a relevant screening tool due to its higher sensitivity for detecting early pneumonic changes. However, physicians are extremely occupied fighting COVID-19 in this era of worldwide crisis. Thus, it is crucial to accelerate the development of an artificial intelligence (AI) diagnostic tool to support physicians. OBJECTIVE: We aimed to rapidly develop an AI technique to diagnose COVID-19 pneumonia in CT images and differentiate it from non–COVID-19 pneumonia and nonpneumonia diseases. METHODS: A simple 2D deep learning framework, named the fast-track COVID-19 classification network (FCONet), was developed to diagnose COVID-19 pneumonia based on a single chest CT image. FCONet was developed by transfer learning using one of four state-of-the-art pretrained deep learning models (VGG16, ResNet-50, Inception-v3, or Xception) as a backbone. For training and testing of FCONet, we collected 3993 chest CT images of patients with COVID-19 pneumonia, other pneumonia, and nonpneumonia diseases from Wonkwang University Hospital, Chonnam National University Hospital, and the Italian Society of Medical and Interventional Radiology public database. These CT images were split into a training set and a testing set at a ratio of 8:2. For the testing data set, the diagnostic performance of the four pretrained FCONet models to diagnose COVID-19 pneumonia was compared. In addition, we tested the FCONet models on an external testing data set extracted from embedded low-quality chest CT images of COVID-19 pneumonia in recently published papers. RESULTS: Among the four pretrained models of FCONet, ResNet-50 showed excellent diagnostic performance (sensitivity 99.58%, specificity 100.00%, and accuracy 99.87%) and outperformed the other three pretrained models in the testing data set. In the additional external testing data set using low-quality CT images, the detection accuracy of the ResNet-50 model was the highest (96.97%), followed by Xception, Inception-v3, and VGG16 (90.71%, 89.38%, and 87.12%, respectively). CONCLUSIONS: FCONet, a simple 2D deep learning framework based on a single chest CT image, provides excellent diagnostic performance in detecting COVID-19 pneumonia. Based on our testing data set, the FCONet model based on ResNet-50 appears to be the best model, as it outperformed other FCONet models based on VGG16, Xception, and Inception-v3.


title: Inhibitory effect of antisense aminopeptidase N (APN/CD13) cDNA transfection on the invasive potential of osteosarcoma cells

text: Aminopeptidase N (APN/CD13), a Zn(2+)-dependent ectopeptidase, is localized on the cell surface and functions as a transmembrane protein. Increased expression and activity of APN have been postulated to correlate with the aggressive behavior of several tumor types. In this study, the osteosarcoma cell line MNNG/HOS was stably transfected with an expression vector capable of expressing the antisense transcript of APN. Four stably transfected clones, the control clones and parental cells were characterized. Stable integration of the antisense vector was confirmed by PCR analysis of genomic DNA. Competitive RT-PCR revealed that mRNA expression of antisense-transfectants was decreased to approximately 37% of the control cell line. The activity assay showed that the enzymatic activity of APN was inhibited to approximately 51% of the control cell line. Antisense-transfection had no influence on the cellular proliferation measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, on the motility in Transwell chambers, and on the adhesive potential to collagen I. However, an in vitro invasion assay revealed a significant decrease in the number of cells that migrated through a reconstituted membrane (51% of the control cell line). The adhesive potential to Matrigel was also affected (73% of the control cell line). Furthermore, under in vivo conditions, a reduced potency to metastasize to the lung was shown in an experimental metastasis assay in nude mice. These findings demonstrate that APN plays an active role in the cellular attachment and proteolytic degradation of the extracellular matrix in the metastatic process of osteosarcomas. Abbreviation: GAPDH – glyceraldehyde-3-phosphate dehydrogenase


title: Growth characteristics and protein profiles of prototype and wild-type rat coronavirus isolates grown in a cloned subline of mouse fibroblasts (L2p.176 cells)

text: Abstract Rat coronaviruses (RCVs) infect laboratory rats and confound biomedical research results. In vitro systems developed so far have limited the growth in knowledge about RCVs by not permitting generation of plaque-cloned virus stocks, reliable isolation of RCVs from rat tissues, or growth of high titered stocks of all isolates. Due to the fact that less than 20% of L2(Percy) cells were becoming infected, sublines were produced and selected for maximal growth of RCVs. Screening of 238 cell sublines yielded L2p.176 cells which were highly susceptible to all RCVs tested; however, susceptibility declined after 30 passages in vitro. Low-passaged L2p.176 cells were used to isolate virus from natural outbreaks and to propagate individual RCV plaques into high titered stocks. Proteins from six RCV isolates were immunoblotted using polyclonal rat and mouse antibodies to sialodacryoadenitis virus and polyclonal monospecific rabbit and goat antibodies against the peplomer (S) and nucleocapsid (N) proteins of mouse hepatitis virus (MHV). Proteins of two prototype, one Japanese and three wild type RCVs were examined and found to be similar to those of MHV, although the exact sizes and ratios of protein forms were unique for most RCV isolats. This study reports the development of a continuous cell line which reliably supports RCVs opening an opportunity for further in vivo studies of the biology of these agents. As a first step in the characterization of RCVs, we have shown that RCV proteins are very similar to those of MHV.


title: The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies

text: Abstract Feline infectious peritonitis (FIP) is a common and highly lethal coronavirus disease of domestic cats. Recent studies of diseases caused by several RNA viruses in people and other species indicate that antiviral therapy may be effective against FIP in cats. The small molecule nucleoside analog GS-441524 is a molecular precursor to a pharmacologically active nucleoside triphosphate molecule. These analogs act as an alternative substrate and RNA-chain terminator of viral RNA dependent RNA polymerase. We determined that GS-441524 was non-toxic in feline cells at concentrations as high as 100 uM and effectively inhibited FIPV replication in cultured CRFK cells and in naturally infected feline peritoneal macrophages at concentrations as low as 1 uM. We determined the pharmacokinetics of GS-441524 in cats in vivo and established a dosage that would sustain effective blood levels for 24 h. In an experimental FIPV infection of cats, GS-441524 treatment caused a rapid reversal of disease signs and return to normality with as little as two weeks of treatment in 10/10 cats and with no apparent toxicity.


title: Applications of microarrays in pathogen detection and biodefence

text: The microarray is a platform with wide-ranging potential in biodefence. Owing to the high level of throughput attainable through miniaturization, microarrays have accelerated the ability to respond in an epidemic or crisis. Extending beyond diagnostics, recent studies have applied microarrays as a research tool towards understanding the etiology and pathogenicity of dangerous pathogens, as well as in vaccine development. The original emphasis was on DNA microarrays, but the range now includes protein, antibody and carbohydrate microarrays, and research groups have exploited this diversity to further extend microarray applications in the area of biodefence. Here, we discuss the impact and contributions of the growing range of microarrays and emphasize the concepts that might shape the future of biodefence research.


Sachregister


title: Potentiation of macrophage activity by thymol through augmenting phagocytosis

text: Abstract The potent role of thymol, a natural compound, in modulation of macrophage activity was evaluated by determining all the sequential steps involved during phagocytosis. We found a significant increase in the proliferation of splenocytes in the presence of thymol and it proved to be a good mitogen. Uptake capacity of macrophages was enhanced due to increased membrane fluidity after treatment with thymol and it also increases lysosomal activity of macrophages. Data of superoxide anion generation revealed the involvement of thymol in the generation of respiratory burst as it potentiated this property of macrophages at a concentration of 150μM. In the case of TNF-α, IL-1ß and PGE2 a decreased level of secretion was observed 154ρg/ml, 736.1ρg/ml, and 151ρg/ml respectively when compared with lipopolysaccharide treated cells, where the level of these cytokines was significantly high. We also determined the anti-complementary activity of thymol which showed to be more effective than rosmarinic acid. Thus, the results obtained from the study suggest the potential role of thymol as a natural immunostimulatory drug which can be used in the treatment of various immunological disorders.


title: Thrombosis and COVID-19 pneumonia: the clot thickens!

text: Pulmonary thrombosis appears to be common in Covid-19 pneumonia and takes two forms, proximal pulmonary emboli and/or distal thrombosis. We hypothesise mechanisms and discuss clinical implications.


title: Evolutionary conflicts between viruses and restriction factors shape immunity

text: Host restriction factors are potent, widely expressed intracellular blocks to viral replication that are an important component of the innate immune response to viral infection. However, viruses have evolved mechanisms that antagonize restriction factors. Through evolutionary pressure for both host survival and virus replication, an evolutionary 'arms race' has developed that drives continuous rounds of selection for beneficial mutations in the genes encoding restriction factors and their viral antagonists. Because viruses can evolve faster than their hosts, the innate immune system of modern-day vertebrates is for the most part optimized to defend against ancient viruses, rather than newer viral threats. Thus, the evolutionary history of restriction factors might, in part, explain why humans are susceptible or resistant to the viruses present in the modern world.


title: Frontline Workers in the Backrooms of COVID-19: Caring for the Living and the Dead

text: OBJECTIVES: To review the response to the coronavirus disease 2019 (COVID-19) pandemic in a forensics center that integrates an academic department of pathology with multiple regional county medical examiners’ offices. METHODS: Faculty and staff were asked to volunteer stories, data, and photographs describing their activities from March through May 2020. The information was assembled into a narrative summary. RESULTS: Increased deaths challenged capacity limits in a hospital morgue and a large urban medical examiner’s office (MEO) successfully managed by forensic teams and monitored by an institutional command center. Autopsies of suspected and proven cases of COVID-19 were performed in both facilities. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing of decedents was performed in a MEO serving a large urban area. Scene investigators worked directly with families to meet needs unique to a pandemic. Artful photographs of decedent’s hands and/or tattoos were offered to those unable to have in-person viewings. Pathologists and social workers were available to families of the deceased and created novel solutions to facilitate the grieving process. CONCLUSIONS: Forensic pathology is important to successfully navigating emerging diseases like the COVID-19 pandemic. Direct conversations with families are common in forensic pathology and serve as a model for patient- and family-centered care.


title: Clinical characteristics of older and younger patients infected with SARS-CoV-2

text: Background: SARS-CoV-2 causes high mortality risk in older patients. This study aims to characterize the clinical features of older and younger SARS-CoV-2 infected patients. Results: A total of 239 patients were divided into the younger group (<60 years; n=181) and the older group (≥60 years; n=58). In both groups, fever and cough were common symptoms. However, dyspnea was more frequent in older patients than younger patients (20.7% versus 9.9%, p=0.032). Compared with younger patients, older patients harbored more severe cases (37.9% versus 17.1%, p=0.001) and comorbidities (58.6% versus 21.0%, p<0.001) such as hypertension and diabetes. The baseline values of eosinophils and C-reactive protein were abnormal in older and younger groups. From baseline to day 14, significant decreases of three biomarkers (C-reactive protein, hemoglobin, albumin) and dramatic increases of three biomarkers (lymphocytes, platelets, blood urea nitrogen) were observed in older patients. Conclusion: Older and younger patients exhibited differences in dyspnea, comorbidities, and proportions of severe cases. Moreover, the disease progression of SARS-CoV-2 in older patients is observed with the dynamics of laboratory biomarkers, supporting their potential use in disease monitoring. Methods: We retrieved clinical symptoms, laboratory findings, comorbidities, and hospitalization information of SARS-CoV-2 cases in Changsha.


title: Role of RNA chaperones in virus replication

text: Abstract RNA molecules are functionally diverse in part due to their extreme structural flexibility that allows rapid regulation by refolding. RNA folding could be a difficult process as often molecules adopt a spatial conformation that is very stable but not biologically functional, named a kinetic trap. RNA chaperones are non-specific RNA binding proteins that help RNA folding by resolving misfolded structures or preventing their formation. There is a large number of viruses whose genome is RNA that allows some evolutionary advantages, such as rapid genome mutation. On the other hand, regions of the viral RNA genomes can adopt different structural conformations, some of them lacking functional relevance and acting as misfolded intermediates. In fact, for an efficient replication, they often require RNA chaperone activities. There is a growing list of RNA chaperones encoded by viruses involved in different steps of the viral cycle. Also, cellular RNA chaperones have been involved in replication of RNA viruses. This review briefly describes RNA chaperone activities and is focused in the roles that viral or cellular nucleic acid chaperones have in RNA virus replication, particularly in those viruses that require discontinuous RNA synthesis.


title: The COVID-19 Serology Studies Workshop: Recommendations and Challenges

text: Summary The development, validation and appropriate application of serological assays to detect antibodies to SARS-CoV-2 are essential to determining seroprevalence of this virus in the United States and globally and in guiding government leadership and the private sector on back-to-work policies. An interagency working group of the U.S. Department of Health and Human Services convened a virtual workshop to identify knowledge gaps and key outstanding scientific issues and to develop strategies to fill them. Key outcomes of the Workshop included recommendations for: 1) advancing serology assays as a tool to better understand SARS-CoV-2 infection; and 2) conducting crucial serology field studies to advance an understanding of immunity to SARS-CoV-2 leading to protection and duration of protection, including the correlation between serological test results and risk of reinfection.


title: Transient diabetes mellitus in a neonatal Thoroughbred foal

text: Objective – To describe the clinical presentation, treatment, and outcome of a neonatal foal diagnosed with transient Type 1 diabetes mellitus. Case Summary – A 3‐day‐old Thoroughbred foal presented with a 24‐hour history of diarrhea and depression. Coronavirus particles were observed in the feces via electron microscopy. During hospitalization the foal developed hyperglycemia concomitantly with low insulin concentration and an adequate response to exogenous insulin therapy supported a diagnosis of Type 1 diabetes mellitus. The foal required SC insulin for 26 days, but developed complications associated with insulin therapy that resolved with appropriate care. On follow up assessment the foal was found to be a healthy euglycemic animal with normal insulin concentration at 11 months of age. New or Unique Information Provided – To our knowledge this is the first report of Type 1 diabetes in this age group and the first report of transient neonatal diabetes mellitus in horses. Type 1 diabetes mellitus should be considered a differential diagnosis for hyperglycemia in equine neonates and that it can be transient and managed successfully.


title: Emerging evidence to support not always “just saying no” to SARS‐CoV‐2 positive donors

text: We are gratified to see the broad discussion of our manuscript, "Use of SARS-CoV-2 infected deceased organ donors: Should we always 'just say no?'" and the companion manuscript by Shah et al., "Utilization of deceased donors during a pandemic: An argument against using SARS-CoV-2 positive donors."1,2 Our viewpoint argues that the risk of SARS-CoV-2 transmission from asymptomatic or minimally symptomatic donors is likely very low. For selected patients with imminently life-threatening organ failure, transplants from deceased donors with asymptomatic or mild SARS-CoV-2 infection may offer a favorable risk/benefit balance, although factors beyond transmission risk must also be considered.


title: Capacity of Public Health Surveillance to Comply with Revised International Health Regulations, USA

text: Public health surveillance is essential for detecting and responding to infectious diseases and necessary for compliance with the revised International Health Regulations (IHR) 2005. To assess reporting capacities and compliance with IHR of all 50 states and Washington, DC, we sent a questionnaire to respective epidemiologists; 47 of 51 responded. Overall reporting capacity was high. Eighty-one percent of respondents reported being able to transmit notifications about unknown or unexpected events to the Centers for Disease Control and Prevention (CDC) daily. Additionally, 80% of respondents reported use of a risk assessment tool to determine whether CDC should be notified of possible public health emergencies. These findings suggest that most states have systems in place to ensure compliance with IHR. However, full state-level compliance will require additional efforts.


Low prevalence of IgG antibodies to SARS‐CoV‐2 in cancer patients with COVID‐19


docid: ynulxpto

title: Molecular Biology and Inhibitors of Hepatitis A Virus

text: Hepatitis A virus (HAV) is a faeco‐orally transmitted picornavirus and is one of the main causes of acute hepatitis worldwide. An overview of the molecular biology of HAV is presented with an emphasis on recent findings. Immune evasion strategies and a possible correlation between HAV and atopy are discussed as well. Despite the availability of efficient vaccines, antiviral drugs targeting HAV are required to treat severe cases of fulminant hepatitis, contain outbreaks, and halt the potential spread of vaccine‐escape variants. Additionally, such drugs could be used to shorten the period of illness and decrease associated economical costs. Several known inhibitors of HAV with various mechanisms of action will be discussed. Since none of these molecules is readily useable in the clinic and since the availability of an anti‐HAV drug would be of clinical importance, increased efforts should be targeted toward discovery and development of such antivirals.


title: Bacterial Pathogen Emergence Requires More than Direct Contact with a Novel Passerine Host

text: While direct contact may sometimes be sufficient to allow a pathogen to jump into a new host species, in other cases, fortuitously adaptive mutations that arise in the original donor host are also necessary. Viruses have been the focus of most host shift studies, so less is known about the importance of ecological versus evolutionary processes to successful bacterial host shifts. Here we tested whether direct contact with the novel host was sufficient to enable the mid-1990s jump of the bacterium Mycoplasma gallisepticum from domestic poultry to house finches (Haemorhous mexicanus). We experimentally inoculated house finches with two genetically distinct M. gallisepticum strains obtained either from poultry (Rlow) or from house finches (HF1995) during an epizootic outbreak. All 15 house finches inoculated with HF1995 became infected, whereas Rlow successfully infected 12 of 15 (80%) inoculated house finches. Comparisons among infected birds showed that, relative to HF1995, Rlow achieved substantially lower bacterial loads in the host respiratory mucosa and was cleared faster. Furthermore, Rlow-infected finches were less likely to develop clinical symptoms than HF1995-infected birds and, when they did, displayed milder conjunctivitis. The lower infection success of Rlow relative to HF1995 was not, however, due to a heightened host antibody response to Rlow. Taken together, our results indicate that contact between infected poultry and house finches was not, by itself, sufficient to explain the jump of M. gallisepticum to house finches. Instead, mutations arising in the original poultry host would have been necessary for successful pathogen emergence in the novel finch host.


title: Diagnosis and Treatment of Colonic Disease in AIDS

text: The colon is a frequent site of gastrointestinal complications in patients with HIV infection, and these colonic disorders increase in frequency as immunodeficiency worsens. The most common clinical manifestations of colonic disease in AIDS are diarrhea, lower gastrointestinal bleeding, and abdominal pain. Toxic megacolon, intussuseption, typhlitis, idiopathic colonic ulcer, and pneumatosis intestinalis also have been described. In the HIV-infected patient with preserved immunity, the most common cause of colitis is bacterial, but as the degree of immunodeficiency worsens, opportunistic pathogens (CMV, protozoa, mycobacteria, fungi) and neoplasms become more frequent. The frequent use of antibiotics, chemotherapeutic agents, and frequent hospitalization increase the susceptibility to Clostridium difficule colitis. Endoscopy plays an integral role in the management of many colonic disorders in AIDS.


title: Increased susceptibility to mouse hepatitis virus 3 of peritoneal macrophages exposed to dieldrin

text: Abstract Interaction of a single dose (36 mg/kg body wt) of the organochlorine pesticide dieldrin with mouse peritoneal macrophages was examined in C57Bl 6 , ( C57Bl 6 × A J )F1 , and A J strains of different genetic resistance to mouse hepatitis virus 3 (MHV3) infection. In vivo studies showed increased susceptibility to MHV3 acute disease of C57Bl 6 and ( C57Bl 6 × A J )F1 animals challenged with the pesticide. Significant decrease of mean time of death in dieldrin-exposed, MHV3-infected susceptible C57Bl 6 mice was observed similarly upon po or ip administration of a single, sublethal dose of dieldrin. In addition, decrease of humoral response to the virus was quantified by determination of anti-MHV3 IgG antibodies in spleen cell supernatant fractions and in blood sera of dieldrin-exposed C57Bl 6 mice. A single dose of dieldrin did not alter the in vivo resistance of A J animals to acute MHV3 disease. The resistant A J mice, however, showed increased mortality upon two subsequent exposures to dieldrin followed by infection with high lethal doses of MHV3. Phagocytic activity, cell adherence capacity, and attachment and uptake of 3H-radiolabeled MHV3 by C57Bl 6 peritoneal macrophages were determined by in vitro studies. These affector activities of peritoneal macrophages were slightly decreased or unchanged in cells originating from animals exposed to the pesticide. However, the intrinsic activity of MHV3 restriction appeared to be affected in macrophages derived from dieldrin-treated animals: (i) peritoneal C57Bl 6 macrophages collected from the early phase of acute MHV3 disease contained increased MHV3 antigen and (ii) increased cytolysis was observed after in vitro MHV3 infection of macrophages originating from dieldrin-exposed C57Bl 6 mice.


title: Antitumor and antiviral activities of 4-substituted 1,2,3-triazolyl-2,3-dibenzyl-L-ascorbic acid derivatives

text: Two series of 6-(1,2,3-triazolyl)-2,3-dibenzyl-l-ascorbic acid derivatives with the hydroxyethylene (8a−8u) and ethylidene linkers (10c−10p) were synthesized and evaluated for their antiproliferative activity against seven malignant tumor cell lines and antiviral activity against a broad range of viruses. Conformationally unrestricted spacer between the lactone and 1,2,3-triazole units in 8a−8u series had a profound effect on antitumor activity. Besides, the introduction of a long side chain at C-4 of 1,2,3-triazole that led to the synthesis of decyl-substituted 2,3-dibenzyl-l-ascorbic acid 8m accounted for a selective and potent antiproliferative activity on breast cancer MCF-7 cells cells in the nM range. Further analysis showed that compound 8m strongly enhanced expression of hypoxia inducible transcription factor 1 α (HIF-1α) and to some extent decreased expression of nitric oxide synthase 2 (NOS2) suggesting its role in regulating HIF-1α signalling pathway. The p-methoxyphenyl-substituted derivative 10g displayed specific anti-cytomegalovirus (CMV) potential, whereas aliphatic-substituted derivatives 8l and 8m had the most potent, yet relatively non-specific, anti-varicella-zoster (VZV) activity.


title: Tracking sources of Staphylococcus aureus hand contamination in food handlers by spa typing

text: We aimed to identify the source of Staphylococcus aureus contaminating hands of food handlers. Nasal samples and direct fingertip imprints were collected on 2 occasions from food handlers and characterized to determine likely sources of hand contamination. Most hand contamination was attributable to nasal isolates of persistently colonized coworkers who had presumably contaminated the environment. Regular handwashing should be supplemented by effective environmental disinfection.