title: Lactogenic immunity and vaccines for porcine epidemic diarrhea virus (PEDV): Historical and current concepts

text: Abstract Morbidity, mortality, and loss of productivity from enteric diseases in neonatal piglets cost swine producers millions of dollars annually. In 2013–2014, the porcine epidemic diarrhea virus (PEDV) outbreak led to $900 million to $1.8 billion in annual losses to US swine producers. Passive lactogenic immunity remains the most promising and effective way to protect neonatal suckling piglets from enteric diseases like PEDV. Protecting suckling piglets through lactogenic immunity is dependent on trafficking of pathogen-specific IgA plasmablasts to the mammary gland and accumulation of secretory IgA (sIgA) antibodies in milk, defined as the gut-mammary-sIgA axis. Due to an impermeable placenta, piglets are born agammaglobulinic, and are highly susceptible to a plethora of infectious agents. They rely solely on colostrum and milk antibodies for maternal lactogenic immunity. Previous advances in the development of live and attenuated vaccines for another devastating diarrheal virus of pigs, transmissible gastroenteritis virus (TGEV), provide insights into the mechanisms of maternal immunity and piglet protection. In this chapter, we will review previous research on TGEV-induced lactogenic immunity to provide a historical perspective on current efforts for PEDV control and vaccines in the swine industry. Identifying factors that influence lactogenic immunity and the gut-mammary-sIgA axis may lead to improved vaccine regimens for PEDV and other enteric pathogens in gestating swine and improved overall herd immunity, swine health and industry productivity.


title: Cardiac Surgery in Canada During the COVID-19 Pandemic: A Guidance Statement From the Canadian Society of Cardiac Surgeons

text: Abstract On March 11, 2020, the World Health Organization declared that COVID-19 was a pandemic. 1 At that time, only 118,000 cases had been reported globally, 90% of which had occurred in 4 countries. 1 Since then, the world landscape has changed dramatically. As of March 31, 2020, there are now nearly 800,000 cases, with truly global involvement. 2 Countries that were previously unaffected are currently experiencing mounting rates of the novel coronavirus infection with associated increases in COVID-19–related deaths. At present, Canada has more than 8000 cases of COVID-19, with considerable variation in rates of infection among provinces and territories. 3 Amid concerns over growing resource constraints, cardiac surgeons from across Canada have been forced to make drastic changes to their clinical practices. From prioritizing and delaying elective cases to altering therapeutic strategies in high-risk patients, cardiac surgeons, along with their heart teams, are having to reconsider how best to manage their patients. It is with this in mind that the Canadian Society of Cardiac Surgeons (CSCS) and its Board of Directors have come together to formulate a series of guiding statements. With strong representation from across the country and the support of the Canadian Cardiovascular Society, the authors have attempted to provide guidance to their colleagues on the subjects of leadership roles that cardiac surgeons may assume during this pandemic: patient assessment and triage, risk reduction, and real-time sharing of expertise and experiences. A visual abstract of the main principles underlying our recommended approach is provided in Figure 1.


title: Establishment and reinforcement of the national reference centers for human microbiology in Belgium

text: BACKGROUND: Microbiology reference laboratories are critical in the development of high-quality clinical and public health services. In Belgium, the reference laboratories performed their activities on a voluntary basis and lacked a legal status. METHODS: Pathogens or groups of pathogens necessitating a national reference center (NRC) were prioritized based on diagnostic and epidemiologic relevance. Terms of reference for each of these pathogens were developed. RESULTS: Recently, 40 NRCs for different pathogens or groups of pathogens have been installed in Belgium to fulfill the following core functions: offering reference diagnostics, collecting reference materials, sharing information and scientific advice, participating in national and international networks, collaborating with research workgroups, and contributing to surveillance activities. CONCLUSIONS: These NRCs are important focal points of the national and international network in public health microbiology.


title: The Importance of Mouse Models to Define Immunovirologic Determinants of Progressive Multifocal Leukoencephalopathy

text: Progressive multifocal leukoencephalopathy (PML) is a severely debilitating and often fatal demyelinating disease of the central nervous system (CNS) in immunosuppressed individuals caused by JC polyomavirus (JCV), a ubiquitous human pathogen. Demyelination results from lytically infected oligodendrocytes, whose clearance is impaired in the setting of depressed JCV-specific T cell-mediated CNS surveillance. Although mutations in the viral capsid and genomic rearrangements in the viral non-coding region appear to set the stage for PML in the immunosuppressed population, mechanisms of demyelination and CNS antiviral immunity are poorly understood in large part due to absence of a tractable animal model that mimics PML neuropathology in humans. Early studies using mouse polyomavirus (MPyV) in T cell-deficient mice demonstrated productive viral replication in the CNS and demyelination; however, these findings were confounded by spinal cord compression by virus-induced vertebral bone tumors. Here, we review current literature regarding animal models of PML, focusing on current trends in antiviral T cell immunity in non-lymphoid organs, including the CNS. Advances in our understanding of polyomavirus lifecycles, viral and host determinants of persistent infection, and T cell-mediated immunity to viral infections in the CNS warrant revisiting polyomavirus CNS infection in the mouse as a bona fide animal model for JCV-PML.


title: Contingency plan for the intensive care services for the COVID-19 pandemic

text: Abstract In January 2020, the Chinese authorities identified a new virus of the Coronaviridae family as the cause of several cases of pneumonia of unknown aetiology. The outbreak was initially confined to Wuhan City, but then spread outside Chinese borders. On 31 January 2020, the first case was declared in Spain. On 11 March 2020, The World Health Organization (WHO) declared the coronavirus outbreak a pandemic. On 16 March 2020, there were 139 countries affected. In this situation, the Scientific Societies SEMICYUC and SEEIUC, have decided to draw up this Contingency Plan to guide the response of the Intensive Care Services. The objectives of this plan are to estimate the magnitude of the problem and identify the necessary human and material resources. This is to provide the Spanish Intensive Medicine Services with a tool to programme optimal response strategies.


title: Detection and genotyping of bovine diarrhea virus by reverse transcription-polymerase chain amplification of the 5′ untranslated region

text: Abstract A reverse-transcription polymerase chain reaction (RT-PCR) was developed to differentiate the bovine diarrhea virus (BVDV) from other pestiviruses, and to determine the genotype of the BVDV isolates. For this purpose, primer pairs were selected in the 5′ untranslated region (5′UTR). The primers BE and B2 were located in highly conserved regions and were pestivirus-specific. Two primer pairs named B3B4 and B5B6 were specific of BVDV genotypes I and II, respectively. With this technique, an amplification product of the expected size was obtained with either the B3B4 or the B5B6 primer pairs for the 107 BVDV isolates tested but not for BDV or CSFV. For some isolates that were grouped in the genotype II, sequence analysis of the PCR fragments confirmed their classification into this genotype.


title: Long-term viremia and fecal shedding in pups after modified-live canine parvovirus vaccination

text: Canine parvovirus (CPV) modified live virus vaccines are able to infect vaccinated dogs replicating in the bloodstream and enteric mucosa. However, the exact duration and extent of CPV vaccine-induced viremia and fecal shedding are not known. With the aim to fill this gap, 26 dogs were administered two commercial vaccines containing a CPV-2 or CPV-2b strain and monitored for 28 days after vaccination. By using real-time PCR, vaccine-induced viremia and shedding were found to be long lasting for both vaccinal strains. Vaccinal CPV-2b shedding was detected for a shorter period than CPV-2 (12 against 19 mean days) but with greater viral loads, whereas viremia occurred for a longer period (22 against 19 mean days) and with higher titers for CPV-2b. Seroconversion appeared as early as 7 and 14 days post-vaccination for CPV-2b and CPV-2 vaccines, respectively. With no vaccine there was any diagnostic interference using in-clinic or hemagglutination test, since positive results were obtained only by fecal real-time PCR testing. The present study adds new insights into the CPV vaccine persistence in the organism and possible interference with diagnostic tests.


title: Ribonucleases as antiviral agents

text: Many ribonucleases (RNases) are able to inhibit the reproduction of viruses in infected cell cultures and laboratory animals, but the molecular mechanisms of their antiviral activity remain unclear. The review discusses the well-known RNases that possess established antiviral effects, including both intracellular RNases (RNase L, MCPIP1 protein, and eosinophil-associated RNases) and exogenous RNases (RNase A, BS-RNase, onconase, binase, and synthetic RNases). Attention is paid to two important, but not always obligatory, aspects of molecules of RNases that have antiviral properties, i.e., catalytic activity and ability to dimerize. The hypothetic scheme of virus elimination by exogenous RNases that reflects possible types of interaction of viruses and RNases with a cell is proposed. The evidence for RNases as classical components of immune defense and thus perspective agents for the development of new antiviral therapeutics is proposed.


title: Respiratory infections in Norwegian dairy calves

text: Abstract The aims of this study were to estimate the seroprevalence of respiratory agents in Norwegian dairy calves and to identify risk factors for respiratory disease. The participating 135 herds were randomly selected from those in The Norwegian Dairy Herd Recording System with at least 15 cow years. Each herd was followed for 1 yr. Blood samples from calves of >150 d of age (n = 1,348) were analyzed for antibodies against parainfluenza virus 3, bovine coronavirus (BCoV), bovine respiratory syncytial virus (BRSV), and Mycoplasma bovis. Calves reported to have been on pasture (n = 139) were tested for antibodies against Dictyocaulus viviparus. Seroprevalences for parainfluenza virus 3, BCoV, BRSV, and D. viviparus at the calf level were 50.2, 39.3, 31.2, and 4.3%, respectively. No calves were antibody positive for M. bovis. Calves in herds with BCoV-seropositive calves had an increased risk of respiratory disease compared with herds in which BCoV antibodies were not detected [hazard ratio (HR) = 3.9], as had calves in herds in which the majority (>54%) of the sampled calves were seropositive for BRSV (HR = 2.7). Other factors found to increase the risk of respiratory disease in calves were shared housing with cows during the first week of life compared with separate housing (HR = 16.7), a larger herd size (>50 cow years) compared with smaller herds (HR = 8.2), more than an 8-wk age difference between calves housed together in the same group pen compared with having pen mates of a more similar age (HR = 3.9), previous recordings of diarrhea compared with no recorded diarrhea (HR = 3.9), and leaving calves with dams for >24h after birth compared with earlier separation (HR = 3.5).


title: Beliefs underlying blood donors’ intentions to donate during two phases of an avian influenza outbreak

text: Abstract Using a Theory of Planned Behavior (TPB) framework the current study explored the beliefs of current blood donors (N =172) about donating during a low and high-risk phase of a potential avian influenza outbreak. While the majority of behavioral, normative, and control beliefs identified in preliminary research differed as a function of donors’ intentions to donate during both phases of an avian influenza outbreak, regression analyses suggested that the targeting of different specific beliefs during each phase of an outbreak would yield most benefit in bolstering donors’ intentions to remain donating. The findings provide insight in how to best motivate donors in different phases of an avian influenza outbreak.


title: Coronavirus Disease 2019 (COVID–19): A Short Review on Hematological Manifestations

text: Infection with severe acute respiratory syndrome coronavirus 2 (SARS–CoV–2) is a rapidly spreading and devastating global pandemic. Many researchers are attempting to clarify the mechanisms of infection and to develop a drug or vaccine against the virus, but there are still no proven effective treatments. The present article reviews the common presenting hematological manifestations of coronavirus disease 2019 (COVID–19). Elucidating the changes in hematological parameters in SARS–CoV–2 infected patients could help to understand the pathophysiology of the disease and may provide early clues to diagnosis. Several studies have shown that hematological parameters are markers of disease severity and suggest that they mediate disease progression.


title: Putative progressive and abortive feline leukemia virus infection outcomes in captive jaguarundis (Puma yagouaroundi)

text: BACKGROUND: Feline leukemia virus (FeLV) is an exogenous gammaretrovirus of domestic cats (Felis catus) and some wild felids. The outcomes of FeLV infection in domestic cats vary according to host susceptibility, virus strain, and infectious challenge dose. Jaguarundis (Puma yagouaroundi) are small wild felids from South and Central America. We previously reported on FeLV infections in jaguarundis. We hypothesized here that the outcomes of FeLV infection in P. yagouaroundi mimic those observed in domestic cats. The aim of this study was to investigate the population of jaguarundis at Fundação Parque Zoológico de São Paulo for natural FeLV infection and resulting outcomes. METHODS: We investigated the jaguarundis using serological and molecular methods and monitored them for FeLV-related diseases for 5 years. We retrieved relevant biological and clinical information for the entire population of 23 jaguarundis held at zoo. Post-mortem findings from necropsies were recorded and histopathological and immunohistopathological analyses were performed. Sequencing and phylogenetic analyses were performed for FeLV-positive samples. For sample prevalence, 95% confidence intervals (CI) were calculated. Fisher’s exact test was used to compare frequencies between infected and uninfected animals. P-values <0.05 were considered significant. RESULTS: In total, we detected evidence of FeLV exposure in four out of 23 animals (17%; 95% CI 5–39%). No endogenous FeLV (enFeLV) sequences were detected. An intestinal B-cell lymphoma in one jaguarundi was not associated with FeLV. Two jaguarundis presented FeLV test results consistent with an abortive FeLV infection with seroconversion, and two other jaguarundis had results consistent with a progressive infection and potentially FeLV-associated clinical disorders and post-mortem changes. Phylogenetic analysis of env revealed the presence of FeLV-A, a common origin of the virus in both animals (100% identity) and the closest similarity to FeLV-FAIDS and FeLV-3281 (98.4% identity), originally isolated from cats in the USA. CONCLUSIONS: We found evidence of progressive and abortive FeLV infection outcomes in jaguarundis, and domestic cats were probably the source of infection in these jaguarundis.


title: High COVID‐19 virus replication rates, the creation of antigen–antibody immune complexes and indirect haemagglutination resulting in thrombosis

text: A new pathogenic virus, COVID-19, appeared in 2019, in Wuhan, China, typically causing fever, cough, diarrhea and fatigue and significant mortality (Mao, 2020). COVID-19 has also shown about 80% genetic similarity to the Severe Acute Respiratory Symptom (SARS) virus, which is already known to be derived from a bat virus (Ye, 2020). Arterial thrombosis and venous thrombosis, variously attributed to long term patient immobilizations, inflammation, autoimmune reactions or endothelial cell damage to the blood vessels, have also been reported for COVID-19 infections (Bikdeli, 2020; Kollas, 2020). However, another explanation for thrombosis (blood clots) in some patients infected with COVID-19 is discussed.


title: Policies and technical guidelines for urban planning of high-density cities – air ventilation assessment (AVA) of Hong Kong

text: Abstract In 2003, Hong Kong was hit by severe acute respiratory syndrome (SARS) from which many people died. The Hong Kong Government subsequently set up a Governmental Team Clean Committee to investigate possible urban design policies. Team Clean charged the task to the Planning Department, HKSAR. In 2003, it initiated a study titled: “Feasibility Study for Establishment of Air Ventilation Assessment (AVA) System.” A number of focused studies were conducted. It eventually led to the technical methodology and guidelines of the air ventilation assessment (AVA) system. Unlike many countries with guidelines for dealing with gust wind problems, AVA is a guideline for weak wind conditions specifically designed to deal with congested urban conditions. The AVA system basically establishes a method for project developers to objectively assess their designs. In 2006, the government of Hong Kong officially adopted the system and required all major publicly funded development projects to undertake the assessment. The scientific and implementation processes leading to the AVA system are reported in this paper.


title: Flow-injection chemiluminescence determination of chrysin and baicalein assisted by theoretical prediction of chemiluminescence behavior of chrysin and baicalein

text: Abstract In this paper, the molecular connectivity indices were applied to theoretically predict the direct chemiluminescence (CL) behavior of chrysin and baicalein with our recently proposed discriminant function. Then, combined with flow-injection analysis, a new CL system for determination of chrysin and baicalein was proposed. The method was based on the oxidation of chrysin and baicalein by acidic KMnO4 in the presence of formaldehyde to produce strong CL emission. The present paper suggested a new model to discover new CL analytical system: first, to theoretical predict the CL behavior, and the second, to suggest analytical system.


title: A conceptual model for the outbreak of Coronavirus disease 2019 (COVID-19) in Wuhan, China with individual reaction and governmental action

text: The ongoing Coronavirus Disease 2019 (COVID-19) outbreak, originated in the end of 2019 in Wuhan, China, has claimed more than 2200 lives and posed a huge threat to global public health. The Chinese government has implemented control measures including setting up special hospitals and travel restriction to mitigate the spread. We propose conceptual models for the outbreak in Wuhan with the consideration of individual behavioural reaction and governmental actions, e.g., holiday extension, travel restriction, hospitalisation and quarantine. We employed the estimates of these two key components from the 1918 influenza pandemic in London, United Kingdom, incorporated zoonotic introductions and the emigration, then computed future trends and the reporting ratio. The model is concise in structure, and it successfully captures the course of the COVID-19 outbreak, and thus sheds light on understanding the trends of the outbreak.


title: Chapter 9 Pathogenic agents

text: Publisher Summary This chapter describes the pathogens of humans, animals, and plants that may be present in organic wastes. The recycling of biological wastes by aerobic or anaerobic biotechnological treatment is necessary to protect the environment and to save natural resources. The recycling process may be conducted either in large-scale plants operated mostly in urban industrial areas, or in small plants operated primarily in the rural environment to improve the farmer's income. A relatively large number of pathogens are found in solid and liquid organic wastes and the most prevalent are bacteria, viruses, fungi, and parasites. Fungi present in wastes and materials used for composting are mainly of interest from the point of view of occupational health and phytohygiene. The presence of parasites or their infective stages in wastes or residues of plant, animal, or human origin depends on the nature of the wastes and the level of pretreatment. Parasites are of veterinary and medical importance if the raw materials used for composting are generated in wastewater treatment facilities or in slaughterhouses. Plant pathogenic parasites must also be considered, even if some of them are highly specialized on certain plants, which limit their epidemiological importance. Cyst-forming nematodes are the most relevant because these cysts may survive in the soil for several years.


title: Novel Human Bocavirus in Children with Acute Respiratory Tract Infection

text: Human bocavirus (HBoV) and HBoV2, two human bocavirus species, were found in 18 and 10 of 235 nasopharyngeal aspirates, respectively, from children hospitalized with acute respiratory tract infection. Our results suggest that, like HBoV, HBoV2 is distributed worldwide and may be associated with respiratory and enteric diseases.


title: Clinically Applicable AI System for Accurate Diagnosis, Quantitative Measurements and Prognosis of COVID-19 Pneumonia Using Computed Tomography

text: Summary Many COVID-19 patients infected by SARS-CoV-2 virus develop pneumonia (called novel coronavirus pneumonia, NCP) and rapidly progress to respiratory failure. However, rapid diagnosis and identification of high-risk patients for early intervention are challenging. Using a large computed Tomography (CT) database from 4,154 patients, we developed an AI system that can diagnose NCP and differentiate it from other common pneumonia and normal controls. The AI system can assist radiologists and physicians in performing a quick diagnosis especially when the health system is overloaded. Significantly, our AI system identified important clinical markers that correlated with the NCP lesion properties. Together with the clinical data, our AI system was able to provide accurate clinical prognosis that can aid clinicians to consider appropriate early clinical management and allocate resources appropriately. We have made this AI system available globally to assist the clinicians to combat COVID-19.


title: Epidemiologic report and serologic findings for household contacts of three cases of influenza A (H7N9) virus infection

text: Abstract Background and objective We conducted epidemiologic investigations and serologic assays on household contacts that were extensively exposed to three influenza A (H7N9) virus infected case-patients before infection-control practices were implemented. Study design Data on the early clinical course of each patient and the exposure history for each patient's household contacts were obtained by interviewing household members and by reviewing medical records. Viral RNA in patient samples was tested using real-time reverse transcriptase polymerase chain reaction assay. Antibodies against H7N9 virus in serum samples were tested using hemagglutination inhibition and pseudovirus based neutralization assays. Results All household contacts were extensively exposed to the case-patients without the use of measures to protect against infection. Viral RNA was detected in the specimens from case-patients for approximately 7–11 days after confirmation of infection. However, the results of the analyses of serum specimens taken from the household contacts 15–26 days post exposure revealed no evidence of transmission of H7N9 virus from the case-patients to the contacts. Conclusion Despite ample unprotected exposures to case-patients during the virus shedding period, household members in this report were not infected by the H7N9 virus.


title: Bereavement support on the frontline of COVID-19: Recommendations for hospital clinicians

text: Abstract Deaths due to COVID-19 are associated with risk factors which can lead to prolonged grief disorder, post-traumatic stress and other poor bereavement outcomes among relatives, as well as moral injury and distress in frontline staff. Here we review relevant research evidence, and provide evidence-based recommendations and resources for hospital clinicians to mitigate poor bereavement outcomes and support staff. For relatives, bereavement risk factors include dying in an intensive care unit, severe breathlessness, patient isolation or restricted access, significant patient and family emotional distress, and disruption to relatives’ social support networks. Recommendations include advance care planning; proactive, sensitive and regular communication with family members alongside accurate information provision; enabling family members to say goodbye in person where possible; supporting virtual communication; providing excellent symptom management and emotional and spiritual support; and providing and/or sign-posting to bereavement services. To mitigate effects of this emotionally challenging work on staff, we recommend an organisational and systemic approach which includes access to informal and professional support.


title: Phage P22 tailspike protein: crystal structure of the head-binding domain at 2.3 Å, fully refined structure of the endorhamnosidase at 1.56 Å resolution, and the molecular basis of O-antigen recognition and cleavage 1 1 Edited by K. Nagai

text: Abstract The tailspike protein of Salmonella phage P22 is a viral adhesion protein with both receptor binding and destroying activities. It recognises the O-antigenic repeating units of cell surface lipopolysaccharide of serogroup A, B and D1 as receptor, but also inactivates its receptor by endoglycosidase (endorhamnosidase) activity. In the final step of bacteriophage P22 assembly six homotrimeric tailspike molecules are non-covalently attached to the DNA injection apparatus, mediated by their N-terminal, head-binding domains. We report the crystal structure of the head-binding domain of P22 tailspike protein at 2.3 Å resolution, solved with a recombinant telluromethionine derivative and non-crystallographic symmetry averaging. The trimeric dome-like structure is formed by two perpendicular β-sheets of five and three strands, respectively in each subunit and caps a three-helix bundle observed in the structure of the C-terminal receptor binding and cleaving fragment, reported here after full refinement at 1.56 Å resolution. In the central part of the receptor binding fragment, three parallel β-helices of 13 complete turns are associated side-by-side, while the three polypeptide strands merge into a single domain towards their C termini, with close interdigitation at the junction to the β-helix part. Complex structures with receptor fragments from S. typhimurium, S. enteritidis and S. typhi253Ty determined at 1.8 Å resolution are described in detail. Insertions into the β-helix form the O-antigen binding groove, which also harbours the active site residues Asp392, Asp395 and Glu359. In the intact structure of the tailspike protein, head-binding and receptor-binding parts are probably linked by a flexible hinge whose function may be either to deal with shearing forces on the exposed, 150 Å long tailspikes or to allow them to bend during the infection process.


title: Quantitative immunohistochemical assessment of IgA, IgM, IgG and antigen-specific immunoglobulin secreting plasma cells in pig small intestinal lamina propria

text: Abstract Intestinal immune response plays an important defensive role for pathogens, particularly for those transmitted by the oro-faecal route or for foecal shedding modulation. This work examined three parts of intestine from twelve gilts experimentally infected with PCV2-spiked semen, six vaccinated (V group) and six unvaccinated (NV group) against PCV2, 29 and 53 days post infection (DPI). An immunohistochemical investigation for IgA-, IgG- and IgM-antibody bearing plasma cells (PCs) was run on intestinal samples coupled with a sandwich immunohistochemical method to reveal anti-PCV2 antibody-secreting PCs. Plasma cell density was compared in the two groups of animals at 29 and 53 DPI. The IgA, IgG and IgM PC density did not differ between groups but displayed an increase from the upper (villus) to the lower part of the crypts while a decreasing trend in PC density was identified from duodenum to ileum. In the NV group, no increase in anti-PCV2 PC density was demonstrable in the two sampling moment: the amounts of lamina propria PCV2-specific antibody-producing PCs remained constant, 10.55±4.24 and 10.06±5.01 at 29 DPI and 53 DPI, respectively. In the V group a significant increase in PCV2-specific antibody-producing PCs was observed over time. The amounts of PCV2-specific antibody-producing PCs increased from 9.37±13.36 at 29 DPI to 18.76±15.83 at 53 DPI. The data on IgA, IgM and IgG PC counts can be considered reference values in a population of adult pigs. The sandwich method can be proposed as a technique able to identify specific antibody-secreting PCs in formalin-fixed paraffin-embedded tissues. A practical application of the sandwich method is the demonstration of a “booster-like” response of the lamina propria in vaccinated compared to unvaccinated animals. After virus challenge, vaccination induced an increase in the number of PCs containing specific anti-PCV2 antibodies at the level of intestinal mucosa.


title: Hematopoietic cell transplantation and emerging viral infections

text: Viral infections remain important causes of morbidity and mortality in hematopoietic cell transplant recipients. More recent developments in preparative regimens and graft manipulations, as well as the control of well‐recognized post‐transplant infections by the introduction of prophylaxis and preemptive strategies, have influenced the timing and the epidemiology of infections. As new pathogens, such as human metapneumovirus (HMPV), human bocavirus, human coronaviruses HCoV‐NL63 and HCoV‐HKU1, human herpesviruses HHV‐6 and HHV‐7, and polyomaviruses, have emerged, it is fundamental to determine the significance of the newly discovered viruses and their role in the transplantation field. This article summarizes recent data on epidemiology and laboratory diagnosis of new pathogens, as well as clinical features and management of the associated infectious complications. J. Med. Virol. 82:528–538, 2010. © 2010 Wiley‐Liss, Inc.


title: The origin and global emergence of adamantane resistant A/H3N2 influenza viruses

text: Resistance to the adamantane class of antiviral drugs by human A/H3N2 influenza viruses currently exceeds 90% in the United States and multiple Asian countries. Adamantane resistance is associated with a single amino acid change (S31N) in the M2 protein, which was shown to rapidly disseminate globally in 2005 in association with a genome reassortment event. However, the exact origin of influenza A/H3N2 viruses carrying the S31N mutation has not been characterized, particularly in South-East Asia. We therefore conducted a phylogenetic analysis of the HA, NA, and M1/2 segments of viral isolates collected between 1997-2007 from temperate localities in the Northern hemisphere (New York State, United States, 492 isolates) and Southern hemisphere (New Zealand and Australia, 629 isolates) and a subtropical locality in South-East Asia (Hong Kong, 281 isolates). We find that although the S31N mutation was independently introduced at least 11 times, the vast majority of resistant viruses now circulating globally descend from a single introduction that was first detected in the summer of 2003 in Hong Kong. These resistant viruses were continually detected in Hong Kong throughout 2003-2005, acquired a novel HA through reassortment during the first part of 2005, and thereafter spread globally. The emergence and persistence of adamantane-resistant viruses in Hong Kong further supports a source-sink model of global influenza virus ecology, in which South-East Asia experiences continuous viral activity and repeatedly seeds epidemics in temperate areas.


title: Redefining the BH3 death domain as a “Short Linear Motif”

text: BCL-2-related proteins control programmed cell death through a complex network of protein-protein interactions mediated by BCL-2 homology 3 (BH3) domains. Given their roles as dynamic linchpins, the discovery of novel BH3-containing proteins has attracted considerable attention. However, without a clearly defined BH3 signature sequence, the BCL-2 family has expanded to include a nebulous group of non-homologous BH3-only proteins, now justified by an intriguing twist. We present evidence that BH3s from both ordered and disordered proteins represent a new class of short linear motifs (SLiMs) or molecular recognition features (MoRFs), and are diverse in their evolutionary histories. The implied corollaries are that BH3s have a broad phylogenetic distribution and could potentially bind to non-BCL-2-like structural domains with distinct functions.


title: Asymptomatic patients and asymptomatic phases of Coronavirus Disease 2019 (COVID-19): a population-based surveillance study

text: In this population-based study, we identified 307 confirmed COVID-19 cases from massive surveillance, including 129,551 individuals screened at fever clinics or returning from Hubei and 3710 close contacts of confirmed COVID-19 patients. Among them, 17 patients were asymptomatic at initial clinical assessment. These asymptomatic patients on admission accounted for a small proportion of all patients (5.54%) with relatively weak transmissibility, and the detection rate was 0.35 per 100 close contacts. Moreover, the dynamics of symptoms of the 307 patients showed that the interval from symptom remission to the final negativity of viral nucleic acid was 5.0 days (IQR 2.0 to 11.0 days), with 14 patients (4.56%) having re-detectable viral RNA after discharge. Together, our findings suggested asymptomatic carriers and presymptomatic patients only accounted for a small proportion of COVID-19. Also, the asymptomatic phase in during recovery of COVID-19 urged that negativity in viral RNA is necessary as de-isolation criteria and follow-up is recommended.


title: Spinal Cryptococcoma in an Immunocompetent Cat

text: Summary This report describes an unusual case of primary cryptococcoma in the proximal thoracic spinal cord of an 11-year-old immunocompetent cat from a farm on which there were large numbers of pigeons. This animal was referred for examination with progressive paralysis and shown to be free from feline immunodeficiency virus, feline leukaemia virus, feline coronavirus and Toxoplasma gondii. It died 2 months later. At necropsy, the only lesion detected was a malacic area, 4cm in length, in the spinal cord. Histopathological examination of the spinal cord revealed severe granulomatous inflammation associated with large numbers of encapsulated yeast cells. In addition to the granulomatous host response, necrosis, digestion chambers, Gitter cells, spheroids and lymphocytic perivascular cuffs were features of the malacic areas. Immunohistochemistry confirmed the presence of Cryptococcus neoformans var. grubii yeast cells.


title: The prevalence of Middle East respiratory Syndrome coronavirus (MERS-CoV) infection in livestock and temporal relation to locations and seasons

text: Abstract Background The Middle East respiratory syndrome (MERS) has been reported for the first time infecting a human being since 2012. The WHO was notified of 27 countries have reported cases of MERS, the majority of these cases occur in the Arabian Peninsula, particularly in Saudi Arabia. Dromedary camels are likely to be the main source of Middle East respiratory syndrome virus (MERS-CoV) infection in humans. Methods MERS-CoV infection rates among camels in livestock markets and slaughterhouses were investigated in Saudi Arabia. A total of 698 nasal swabs were collected and examined with Rapid assay and rtRT-PCR. Ten MERS-CoV positive samples were subjected to full genomic sequencing. In addition, the sensitivity and specificity of the Rapid immunochromatographic assay (BioNote, South Korea) was evaluated as a diagnostic tool for MERS-CoV compared to rtRT-PCR. Results The results showed a high percentage of dromedaries (56.4%) had evidence for nasal MERS-CoV infection. Phylogenetic analysis of the ten MERS-CoV isolates showed that the sequences were closely related to the other MERS-CoV strains recovered from camels and human cases. Moreover, the results showed that 195 samples were positive for MERS-CoV by rapid assay compared to 394 positive samples of rtRT-PCR, which showed low rapid assay sensitivity (49.49%) while, the specificity were found to be 100%. Conclusion These findings indicate that these sites are a highly-hazardous to zoonotic diseases.


title: Clinical and molecular features of adenovirus type 2, 3, and 7 infections in children in an outbreak in Taiwan, 2011

text: Abstract Objectives We studied paediatric patients with human adenovirus (HAdV) infection during the 2011 outbreak in northern Taiwan to define the clinical features of different HAdV genotypes in children. Methods Between January and December 2011, 637 patients <19 years of age exhibited culture-confirmed adenoviral infection in Chang Gung Memorial Hospital, and provided specimens available for genotyping by multiplex real-time PCR. Clinical data were collected retrospectively. Results Excluding five cases with multiple genotypes, 632 cases were included for analysis. Three genotypes were identified, including HAdV-3 (429/632; 67.6%), HAdV-7 (144/632; 22.6%) and HAdV-2 (59/632; 9.8%). Median age was 4.58 years (range 2 months to 18 years), with children infected with HAdV-3 significantly older (82.9% >3 years; p <0.001). Of the 621 inpatients, 98.2% had fevers and all exhibited respiratory symptoms, 75 patients (12.1%) had lower respiratory tract infections, 20 (3.2%) required intensive care (HAdV-2: 1; HAdV-3: 8; and HAdV-7: 11), and three died (all HAdV-7-infected). HAdV-3-infected patients were significantly more likely to have upper respiratory symptoms and a high serum C-reactive protein level >100 mg/L, whereas leucocytosis (white blood cell count >15 000/mm3) was more common in HAdV-2-infected patients (p 0.007). HAdV-7 infections were significantly associated with a longer duration of fever, leucopenia (white blood cell count <5000/mm3), thrombocytopenia (platelet count <150 000/mm3), lower respiratory tract infections, a longer length of hospital stay, and requiring intensive care (all p <0.001). Conclusion Childhood HAdV-2, HAdV-3 and HAdV-7 infections may exhibit different clinical manifestations. Although HAdV-3 was the most prevalent genotype observed during the 2011 Taiwan outbreak, HAdV-7 caused more severe disease characteristics and outcomes.


title: A Case-Control Study Assessing the Impact of Nonventilated Hospital-Acquired Pneumonia on Patient Outcomes

text: Background Nonventilated hospital-acquired pneumonia (NVHAP) is a serious nosocomial infection that is increasingly attributed to antibiotic-resistant bacteria. Methods This is a retrospective case-control study comparing patients with and those without NVHAP from January 1, 2014 to December 31, 2014 at Barnes-Jewish Hospital, a 1,300-bed urban academic medical center in St. Louis, Missouri. Results One hundred seventy-four consecutive patients with NVHAP were enrolled. A random sample of 696 control patients matched by age, sex, race, and hospital admission date were selected from a total of 5,322 potential matched control subjects. NVHAP was pathogen-negative in 98 cases (56.3%). Respiratory viruses were identified in 42 patients (24.1%), gram-negative bacteria were seen in 25 patients (14.4%), and gram-positive bacteria were identified in 20 patients (11.5%). Individuals in whom NVHAP developed were more likely to die (15.5% vs 1.6%; P < .01), to require intensive care (56.3% vs 22.8%; P < .01) or mechanical ventilation (19.0% vs 3.9%; P < 0.01), and to have a longer hospital length of stay (15.9 days [range, 9.8-26.3 days] vs 4.4 days [range, 2.9-7.3 days]; P < 0.01). This case-control study identified a strong association between hospital mortality and NVHAP, with patients who acquired NVHAP having an 8.4 times greater odds of death (95% CI, 5.6-12.5). Conclusions The occurrence of NVHAP was associated with significant increases in mortality, the use of intensive care and mechanical ventilation, and hospital length of stay. We also found that respiratory viruses were an important cause of NVHAP. These findings suggest that efforts aimed at the successful prevention of NVHAP could improve patient outcomes and reduce health-care costs.


title: Strategies for the enhanced intracellular delivery of nanomaterials

text: The intracellular delivery of nanomaterials and drugs has been attracting increasing research interest, mainly because of their important effects and functions in several organelles. Targeting specific organelles can help treat or decrease the symptoms of diabetes, cancer, infectious, and autoimmune diseases. Tuning biological and chemical properties enables the creation of functionalized nanomaterials with enhanced intracellular uptake, ability to escape premature lysosome degradation, and to reach a specific target. Here, we provide an update of recent advances in the intracellular delivery mechanisms that could help drugs reach their target more efficiently.


title: Rapid, responsive, relevant (R3) research: a call for a rapid learning health research enterprise

text: Our current health research enterprise is painstakingly slow and cumbersome, and its results seldom translate into practice. The slow pace of health research contributes to findings that are less relevant and potentially even obsolete. To produce more rapid, responsive, and relevant research, we propose approaches that increase relevance via greater stakeholder involvement, speed research via innovative designs, streamline review processes, and create and/or better leverage research infrastructure. Broad stakeholder input integrated throughout the research process can both increase relevance and facilitate study procedures. More flexible and rapid research designs should be considered before defaulting to the traditional two-arm randomized controlled trial (RCT), but even traditional RCTs can be designed for more rapid findings. Review processes for grant applications, IRB protocols, and manuscript submissions can be better streamlined to minimize delays. Research infrastructures such as rapid learning systems and other health information technologies can be leveraged to rapidly evaluate new and existing treatments, and alleviate the extensive recruitment delays common in traditional research. These and other approaches are feasible but require a culture shift among the research community to value not only methodological rigor, but also the pace and relevance of research.


title: A double-blind block randomized clinical trial on the effect of zinc as a treatment for diarrhea in neonatal Holstein calves under natural challenge conditions

text: Abstract Diarrhea is the leading cause of death in neonatal calves and contributes to major economic losses. The objective of this double-blind randomized clinical trial was to evaluate the effect of oral inorganic or organic zinc supplementation as a treatment for neonatal diarrhea in calves. Seventy nine 1 to 8 day old male Holstein calves on a California calf ranch were block randomized to one of 3 treatments within 24h from their first onset of diarrhea. Calves received a daily dose of either a placebo composed of 80mg of zinc-free powder, 381.54mg of zinc methionine (Met) (equivalent to 80mg of zinc), or 99.69mg of zinc oxide (ZO) (equivalent to 80mg of zinc) in 2L of a zinc-free oral rehydration solution (ORS). Calves were treated once daily until normal fecal consistency or for a maximum of 14 days. Upon enrollment and exit, calves were weighed, and blood, feces, and liver biopsies were collected for trace mineral analysis. Fecal samples at enrollment and exit were tested for E. coli K99, Cryptosporidium spp., rotavirus and coronavirus. Pre-treatment liver zinc concentrations for the 71 calves in the placebo, zinc Met, and ZO treatment groups were 710.6 (SEM=147.7), 852.3 (SEM=129.6), and 750.7 (SEM=202.9)mg/kg dry weight (DW), respectively. Exit liver zinc concentrations for the calves in the placebo, zinc Met, and ZO treatment groups were 728.9 (SEM=182.9), 1141.0 (SEM=423.8), and 636.8 (SEM=81.5)mg/kg dry weight, respectively. Although statistically non-significant, there were clinically important findings identified for each of zinc Met and ZO treatments. Calves treated with zinc Met gained on average 40g/day during a diarrhea episode compared to a weight loss of 67g/day on average in the placebo-treated calves (Power 19.9%). Calves treated with ZO had 1.4 times higher hazard of clinical cure compared to calves in the placebo group (Power 5.3%). Calves that were fecal positive to cryptosporidium spp. at enrollment and treated with zinc Met had higher odds of testing negative at exit compared to placebo calves (Odds Ratio (OR)=16.0). In contrast, calves treated with ZO tended to recover (fecal score=1) one day earlier compared to calves treated with a placebo (8.5 d vs. 9.7 d). The current trial identified clinically important findings that warrant further research to investigate zinc's therapeutic effect for calf diarrhea.


title: Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study

text: BACKGROUND: Pneumonia is the leading cause of death among children younger than 5 years. In this study, we estimated causes of pneumonia in young African and Asian children, using novel analytical methods applied to clinical and microbiological findings. METHODS: We did a multi-site, international case-control study in nine study sites in seven countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. All sites enrolled in the study for 24 months. Cases were children aged 1–59 months admitted to hospital with severe pneumonia. Controls were age-group-matched children randomly selected from communities surrounding study sites. Nasopharyngeal and oropharyngeal (NP-OP), urine, blood, induced sputum, lung aspirate, pleural fluid, and gastric aspirates were tested with cultures, multiplex PCR, or both. Primary analyses were restricted to cases without HIV infection and with abnormal chest x-rays and to controls without HIV infection. We applied a Bayesian, partial latent class analysis to estimate probabilities of aetiological agents at the individual and population level, incorporating case and control data. FINDINGS: Between Aug 15, 2011, and Jan 30, 2014, we enrolled 4232 cases and 5119 community controls. The primary analysis group was comprised of 1769 (41·8% of 4232) cases without HIV infection and with positive chest x-rays and 5102 (99·7% of 5119) community controls without HIV infection. Wheezing was present in 555 (31·7%) of 1752 cases (range by site 10·6–97·3%). 30-day case-fatality ratio was 6·4% (114 of 1769 cases). Blood cultures were positive in 56 (3·2%) of 1749 cases, and Streptococcus pneumoniae was the most common bacteria isolated (19 [33·9%] of 56). Almost all cases (98·9%) and controls (98·0%) had at least one pathogen detected by PCR in the NP-OP specimen. The detection of respiratory syncytial virus (RSV), parainfluenza virus, human metapneumovirus, influenza virus, S pneumoniae, Haemophilus influenzae type b (Hib), H influenzae non-type b, and Pneumocystis jirovecii in NP-OP specimens was associated with case status. The aetiology analysis estimated that viruses accounted for 61·4% (95% credible interval [CrI] 57·3–65·6) of causes, whereas bacteria accounted for 27·3% (23·3–31·6) and Mycobacterium tuberculosis for 5·9% (3·9–8·3). Viruses were less common (54·5%, 95% CrI 47·4–61·5 vs 68·0%, 62·7–72·7) and bacteria more common (33·7%, 27·2–40·8 vs 22·8%, 18·3–27·6) in very severe pneumonia cases than in severe cases. RSV had the greatest aetiological fraction (31·1%, 95% CrI 28·4–34·2) of all pathogens. Human rhinovirus, human metapneumovirus A or B, human parainfluenza virus, S pneumoniae, M tuberculosis, and H influenzae each accounted for 5% or more of the aetiological distribution. We observed differences in aetiological fraction by age for Bordetella pertussis, parainfluenza types 1 and 3, parechovirus–enterovirus, P jirovecii, RSV, rhinovirus, Staphylococcus aureus, and S pneumoniae, and differences by severity for RSV, S aureus, S pneumoniae, and parainfluenza type 3. The leading ten pathogens of each site accounted for 79% or more of the site's aetiological fraction. INTERPRETATION: In our study, a small set of pathogens accounted for most cases of pneumonia requiring hospital admission. Preventing and treating a subset of pathogens could substantially affect childhood pneumonia outcomes. FUNDING: Bill & Melinda Gates Foundation.


title: Knowledge and practices of isolation precautions among nurses in Jordan

text: BACKGROUND: Implementation of isolation precautions from the Centers for Disease Control and Prevention (CDC) has been justified through research and clinical evidence. However, nurses' understanding and compliance with these precautions is still unknown. The aim of this study was to assess nurses' knowledge and practices in relation to isolation precautions in Jordan. METHODS: A cross-sectional, descriptive design was used. The study took place in 8 hospitals in Jordan. A self-reported questionnaire and an observational checklist were developed based on the CDC (2007) isolation precautions guidelines. RESULTS: A total of 247 questionnaires were returned out of 400, for a response rate of 61.7%. The results show that most nurses (90%) have good knowledge of isolation precautions. However, only 65% of nurses reported good compliance with isolation precautions. The results of a t test revealed that nurses with Bachelor's degrees perform better in knowledge examinations than nurses with 2-year diplomas (P < .001). However, there was no significant difference in knowledge and self-report practices scores based on nurses' previous training and existence of isolation guidelines in their units or wards (P > .05). The results of the checklists confirm that there is a low compliance with standard isolation practice. In addition, the checklist shows that a high percentage of units and wards do not use isolation signs (46.4%) and posters (34.5%). CONCLUSIONS: This study revealed that educating nurses about isolation is not enough strategy to improve their compliance. It is important to adapt other strategies, such as supporting nurses by giving them a manageable workload, and providing more supplies and reminders of isolation precautions in the hospitals.


title: Isolation and Phylogenetic Characterization of Streptococcus halichoeri from a European Badger (Meles meles) with Pyogranulomatous Pleuropneumonia

text: Summary Clinical and pathological studies in European badgers (Meles meles) are limited. Badgers play a significant role in the epidemiology of bovine tuberculosis (TB) in some countries and an accurate diagnosis is needed for this infection. However, the lesions of bovine TB are similar to those associated with other pathogens, making pathological diagnosis difficult. In the present study, Streptococcus halichoeri was isolated from a European badger with pyogranulomatous pleuropneumonia and suspected of having tuberculosis. TB and other pathogens able to induce similar lesions were ruled out. Comparative 16S rRNA and rpoB gene sequencing studies showed an identity of 99.51% and 98.28%, respectively, with S. halichoeri. This report represents the third description of this bacterium and the first in an animal species other than the grey seal (Halichoerus grypus). It also shows that S. halichoeri can be associated with a pathological process characterized by granulomatous inflammation and resembling tuberculosis.


title: Targeted Deletion of FGL2 Leads to Increased Early Viral Replication and Enhanced Adaptive Immunity in a Murine Model of Acute Viral Hepatitis Caused by LCMV WE

text: Mounting effective innate and adaptive immune responses are critical for viral clearance and the generation of long lasting immunity. It is known that production of inhibitory factors may result in the inability of the host to clear viruses, resulting in chronic viral persistence. Fibrinogen-like protein 2 (FGL2) has been identified as a novel effector molecule of CD4(+)CD25(+) Foxp3(+) regulatory T (Treg) cells that inhibits immune activity by binding to FCγRIIB expressed primarily on antigen presenting cells (APC). In this study, we show that infection of mice with Lymphocytic Choriomeningitis Virus WE (LCMV WE) leads to increased plasma levels of FGL2, which were detected as early as 2 days post-infection (pi) and persisted until day 50 pi. Mice deficient in FGL2 (fgl2(−/−)) had increased viral titers of LCMV WE in the liver early p.i but cleared the virus by day 12 similar to wild type mice. Dendritic cells (DC) isolated from the spleens of LCMV WE infected fgl2(−/−) had increased expression of the DC maturation markers CD80 and MHC Class II compared to wild type (fgl2(+/+)). Frequencies of CD8(+) and CD4(+) T cells producing IFNγ in response to ex vivo peptide re-stimulation isolated from the spleen and lymph nodes were also increased in LCMV WE infected fgl2 (−/−) mice. Increased frequencies of CD8(+) T cells specific for LCMV tetramers GP(33) and NP(396) were detected within the liver of fgl2(−/−) mice. Plasma from fgl2(−/−) mice contained higher titers of total and neutralizing anti-LCMV antibody. Enhanced anti-viral immunity in fgl2(−/−) mice was associated with increased levels of serum alanine transaminase (ALT), hepatic necrosis and inflammation following LCMV WE infection. These data demonstrate that targeting FGL2 leads to early increased viral replication but enhanced anti-viral adaptive T & B cell responses. Targeting FGL2 may enhance the efficacy of current anti-viral therapies for hepatotropic viruses.


Oral hygiene risk factor


title: Extracts of the medicinal herb Sanguisorba officinalis inhibit the entry of human immunodeficiency virus-1

text: Abstract Highly active antiretroviral therapy (HAART) has been successful in reducing human immunodeficiency virus (HIV)-1-associated morbidity and mortality since its introduction in 1996. However, it fails to eradicate HIV-1 infection. The high cost of life-long highly active antiretroviral therapy and the emergence of drug resistance among HIV-1-infected individuals have brought renewed pressure for the discovery of novel antivirals and alternative medicines. Traditional Chinese medicine (TCM) is a complementary and alternative medicine, and serves as a rich resource for new drug development. Despite the almost 100 plant-derived compounds that are in clinical trials, few target HIV-1 infection. In this study, we discovered that Sanguisorba officinalis extract (SOE) has anti-HIV-1 properties. Using a cell-based assay and single-cycle luciferase reporter viruses pseudotyped with envelopes from HIV-1 or control viruses, we found that SOE exhibited significant inhibitory ability against both CCR5 and CXCR4 tropic HIV-1 (ADA and HXB2), with respective IC50 values of 1.91 ± 0.16 μg/mL and 3.70 ± 0.53 μg/mL. SOE also inhibited simian immunodeficiency virus infection but failed to block vesicular stomatitis virus, severe acute respiratory syndrome coronavirus, and influenza H5N1 pseudoviruses. Furthermore, we showed that SOE had no effect on postentry events of HIV-1 replication. Because SOE pretreatment with the virus but not with cell lines expressing viral receptors showed the maximal inhibitory activity, we can state that SOE probably blocks entry by acting on the viral envelope directly. In addition, SOE was able to inhibit reverse transcriptase inhibitor resistant viruses (K103N, Y188L, and K103N/Y188L/G190A) and a protease inhibitor resistant strain (PI-2840). Our findings demonstrate SOE as a novel and specific entry inhibitor, which sheds light on the discovery of anti-HIV-1 drugs from traditional herbal medicines.


29th International Mammalian Genome Conference meeting report


title: Laboratory-based surveillance of hospital-acquired respiratory virus infection in a tertiary care hospital

text: Of 7,772 laboratory-confirmed cases of respiratory viral infection among hospitalized patients, 22.8% were categorized as having hospital-acquired infection. The overall incidence of hospital-acquired respiratory viral infection was 3.9 (95% confidence interval, 3.7-4.1) cases per 1,000 admitted patients. Rhinovirus was the most common virus (30.3%), followed by influenza virus (17.6%) and parainfluenza virus (15.6%).


title: Emerging Attack and Management Strategies for Nuclear Medicine in Responding to COVID-19—ACNM Member Experience and Advice

text: As the World Health Organization declared COVID-19 as “global pandemic,” it is important for everyone, including nuclear medicine personnel, to know how to stop transmission, contain, and prevent the spread of COVID-19. We reach out to our ACNM (American College of Nuclear Medicine) international members from Wuhan, China and Singapore, who have participated in dealing with COVID-19 for the last 2 months, to learn from their lessons and experiences, so to provide advice to all ACNM members for their clinical practice and management strategies in responding to COVID-19.


title: Adapting Orthopaedic Surgery Training Programs During the COVID-19 Pandemic and Future Directions

text: Abstract The COVID-19 pandemic swept across the world, altering the structure and existence of graduate medical education programs across all disciplines. Orthopaedic residency programs can adapt during these unprecedented times to continue providing meaningful education to trainees, and to continue providing high-quality patient care, all while keeping both residents and patients safe from disease. The purpose of this review is to evaluate the literature and describe evidence-based changes that can be taken to an orthopaedic residency program to ensure patient and resident safety, sustaining the principles of graduate medical education, during the COVID-19 pandemic. We describe measures which can be enacted now or with future pandemics, including workforce and occupational modifications, personal protective equipment, telemedicine, online didactic education, resident wellness, return to elective surgery and factors affecting medical students and fellows. After a review of these strategies, programs can make changes for sustainable improvements and adapt to be ready for second wave events or future pandemics.


title: Bat coronavirus phylogeography in the Western Indian Ocean

text: Bats provide key ecosystem services such as crop pest regulation, pollination, seed dispersal, and soil fertilization. Bats are also major hosts for biological agents responsible for zoonoses, such as coronaviruses (CoVs). The islands of the Western Indian Ocean are identified as a major biodiversity hotspot, with more than 50 bat species. In this study, we tested 1,013 bats belonging to 36 species from Mozambique, Madagascar, Mauritius, Mayotte, Reunion Island and Seychelles, based on molecular screening and partial sequencing of the RNA-dependent RNA polymerase gene. In total, 88 bats (8.7%) tested positive for coronaviruses, with higher prevalence in Mozambican bats (20.5% ± 4.9%) as compared to those sampled on islands (4.5% ± 1.5%). Phylogenetic analyses revealed a large diversity of α- and β-CoVs and a strong signal of co-evolution between CoVs and their bat host species, with limited evidence for host-switching, except for bat species sharing day roost sites. Importance This is the first study to report the presence of coronaviruses (CoVs) in bats in Mayotte, Mozambique and Reunion Island, and in insectivorous bats in Madagascar. Eight percent of the tested bats were positive for CoVs, with higher prevalence in continental Africa than on islands. A high genetic diversity of α- and β-CoVs was found, with strong association between bat host and virus phylogenies, supporting a long history of co-evolution between bats and their associated CoVs in the Western Indian Ocean. These results highlight that strong variation between islands does exist and is associated with the composition of the bat species community on each island. Future studies should investigate whether CoVs detected in these bats have a potential for spillover in other hosts.


title: Neutralization of genotype 2 porcine epidemic diarrhea virus strains by a novel monoclonal antibody

text: Abstract Porcine epidemic diarrhea virus (PEDV) has two genotypes, G1 and G2. To research the immunogenicity differences of PEDV G1 and G2 genotype strains and obtain a neutralizing monoclonal antibody (mAb), we inoculated specific-pathogen-free BALB/c mice with a newly emerged strain, PEDV-LNCT2. After immunizations, cells from the spleen of the mice were fused with SP2/0 myeloma cells. Following culturing and subcloning, a strain, 1B9, secreting neutralizing antibody, was obtained. The 1B9 mAb neutralized new variant genotype 2 PEDV strains (LNCT2, LNSY, and Hjms), but it did not neutralize a genotype 1 PEDV strain (CV777), in vitro. Results showed that the epitope recognized by the 1B9 mAb lies in the spike protein, and that it is a conformational epitope. These findings confirm that allelic differences in the PEDV S gene between the G1 and G2 genotype strains led to changes in the S protein and, thus, differences in its immunogenicity.


title: Innate immunity for biodefense: A strategy whose time has come

text: Defense against biothreat agents requires a broad-spectrum approach. Modulation of the innate immune system might fulfill this requirement. Hackett's previous review of innate immune activation as a broad-spectrum biodefense strategy identified several unresolved questions. The current article is a systematic approach to answering those questions with the focused participation of research groups developing this technology. Our team of academic and industry participants reviewed the promising agents and came to the following conclusions. It is feasible to construct a biodefense platform combining synergistic agents that activate the innate immune system against a broad range of pathogens on the basis of conserved microbial components by using a nasal spray for immune activation in the respiratory and gastrointestinal tracts because these are the most likely routes of attack. It might also be possible to include agents that inhibit molecular events leading to septic shock. Innate immune-activating agents designed to activate Toll-like and other receptors will probably provide protection against the biothreat pathogen spectrum for periods ranging from 2 to 14 days for IFNs up to 26 weeks for immunomodulatory oligonucleotides. Initial treatment is proposed on the first index case or biosensor alert. Boost doses would be required. Harmful inflammation is possible, but thus far, only transient fever has been observed. Autoimmune reaction and retroviral activation have not been seen thus far in preclinical and human trials of many of these compounds. Toll-like receptor agonists caused cytokine production in all subjects tested, but genetic polymorphism reduced the response to IFN in African American subjects.


title: COVID 19 in babies: Knowledge for neonatal care

text: Infection is a leading cause of death worldwide in babies under one month of age who are more susceptible to sepsis due to immature host defence mechanisms. Usually, babies may become acutely unwell from infective pathogens due to specific differences in their respiratory and immune systems. However, with the Covid-19 virus, the focus of this paper, it appears that the neonatal population is not significantly affected in the same way as adults. That said, knowledge about this novel virus is rapidly emerging. Therefore, it is vital that neonatal nurses, midwives and other healthcare professionals are adequately informed and educated about the potential impact on neonatal practice. This review paper draws upon key findings and themes from a selection of recent literature to provide an overview of current knowledge on Covid-19 and the implications for care within the neonatal field. The discussion focuses on the nature of Covid-19, its pathophysiology and transmission relevant to maternal and neonatal care. This is followed by implications for practice; namely, maternal issues, the importance of human breast milk, neonatal care relating to parenting and specific management before a final review of the current World Health Organization guidance.


title: Missouri K-12 school disaster and biological event preparedness and seasonal influenza vaccination among school nurses

text: BACKGROUND: School preparedness for bioevents, such as emerging infectious diseases, bioterrorism, and pandemics, is imperative, but historically has been low. METHODS: The Missouri Association of School Nurses members were sent an online survey during the 2013-2014 school year to assess current bioevent readiness. There were 15 and 35 indicators of school disaster and bioevent preparedness, respectively. Multivariate linear regressions were conducted to delineate factors associated with higher school disaster and bioevent preparedness scores. RESULTS: In total, 133 school nurses participated, with a 33.6% response rate. On average, schools had fewer than half of the disaster or bioevent indicators. Disaster and bioevent preparedness scores ranged from 1-12.5 (mean, 6.0) and 5-25 (mean, 13.8), respectively. The least frequently reported plan components included bioterrorism-specific psychological needs addressed (1.5%, n = 2), having a foodservice biosecurity plan (8.3%, n = 11), and having a liberal sick leave policy for bioevents (22.6%, n = 30). Determinants of better bioevent preparedness include perception that the school is well prepared for a pandemic (P = .001) or natural disaster (P < .05), nurse being on the disaster planning committee (P = .001), and school being a closed point of dispensing (P < .05). CONCLUSION: Schools are underprepared for biological events and are not on track to meet state and national biological preparedness goals.


title: Sensitivity and specificity of in vitro diagnostic device used for influenza rapid test in Taiwan

text: Abstract The pandemic influenza A/H1N1 outbreak resulted in 18,449 deaths in over 214 countries. In Taiwan, the influenza rapid test, an in vitro diagnostic device (Flu-IVD), only requires documented reviews for market approval by the Taiwan Food and Drug Administration. The purpose of this study was to investigate the analytical sensitivity and specificity of Flu-IVDs used in Taiwan. Analytical sensitivity and specificity tests were performed for influenza antigens A/California/7/2009 (H1N1) virus, A/Victoria/210/2009 (H3N2) virus, B/Brisbane/60/08 virus, and human coronavirus OC43. A total of seven domestic and 31 imported Flu-IVD samples were collected, of which, 20 samples had inadequate labeling, including those with removed package inserts or incorrect insert information. The analytical sensitivity of Flu-IVDs for A/H1N1, A/H3N2, and Flu B was 500–1000 ng/mL, 1000 ng/mL, and 1000 ng/mL, respectively. For the 50% cell culture infective dose (CCID50) label, the average A/H1N1 and A/H3N2 sensitivity for Flu-IVDs was log10 5.8 ± 0.5 and log10 6.6 ± 0.5 CCID50/mL, respectively. As to the specificity test, no product cross-reacted with human coronavirus OC43. This study provides important information on the Flu-IVD regulation status and can thus help the government formulate policies for the regulation of in vitro diagnostic devices in Taiwan.


title: Pneumonia in children in the developing world: New challenges, new solutions

text: Pneumonia has been a leading cause of death in both developed and developing countries as long as health indicators have been available. Yet the issues of concern for this syndrome are far from static. Improvements in access to health services have lowered infant mortality rates, benefiting children around the world and lowering the fraction of child deaths caused by pneumonia. However, progress has been interrupted repeatedly by the emergence of new pathogens. Landmark randomized controlled trials have now demonstrated the effectiveness of Haemophilus influenzae type b (Hib) and multivalent pneumococcal conjugate vaccines against childhood pneumonia, as well as meningitis and bacteremic disease. Momentum has gathered to tackle long-standing economic obstacles to expand access to new vaccines and programs for the poorest countries of the world. A pressing challenge for the control of pneumonia in developing countries is to identify better metrics for pneumonia. Surveillance tools are needed that will bridge studies of interventions, establish preventable disease burden, and serve as indicators for monitoring new programs.


title: Recent advances on host plants and expression cassettes' structure and function in plant molecular pharming

text: Plant molecular pharming is a promising system to produce important recombinant proteins such as therapeutic antibodies, pharmaceuticals, enzymes, growth factors, and vaccines. The system provides an interesting alternative method to the direct extraction of proteins from inappropriate source material while offering the possibility to overcome problems related to product safety and source availability. Multiple factors including plant hosts, genes of interest, expression vector cassettes, and extraction and purification techniques play important roles in the plant molecular pharming. Plant species, as a biosynthesis platform, are a crucial factor in achieving high yields of recombinant protein in plant. The choice of recombinant gene and its expression strategy is also of great importance in ensuring a high amount of the recombinant proteins. Many studies have been conducted to improve expression, accumulation, and purification of the recombinant protein from molecular pharming systems. Re-engineered vectors and expression cassettes are also pivotal tools in enhancing gene expression at the transcription and translation level, and increasing protein accumulation, stability, retention and targeting of specific organelles. In this review, we report recent advances and strategies of plant molecular pharming while focusing on the choice of plant hosts and the role of some molecular pharming elements and approaches: promoters, codon optimization, signal sequences, and peptides used for upstream design, purification and downstream processing.


COVID‐19 and Anxiety and Depression in 2020


title: The phenylalanine ammonia-lyase gene family in Isatis indigotica Fort.: molecular cloning, characterization, and expression analysis

text: Abstract Phenolic compounds, metabolites of the phenylpropanoid pathway, play an important role in the growth and environmental adaptation of many plants. Phenylalanine ammonia-lyase (PAL) is the first key enzyme of the phenylpropanoid pathway. The present study was designed to investigate whether there is a multi-gene family in I. Indigotic and, if so, to characterize their properties. We conducted a comprehensive survey on the transcription profiling database by using tBLASTn analysis. Several bioinformatics methods were employed to perform the prediction of composition and physicochemical characters. The expression levels of IiPAL genes in various tissues of I. indigotica with stress treatment were examined by quantitative real-time PCR. Protoplast transient transformation was used to observe the locations of IiPALs. IiPALs were functionally characterized by expression with pET-32a vector in Escherichia colis strain BL21 (DE3). Integration of transcripts and metabolite accumulations was used to reveal the relation between IiPALs and target compounds. An new gene (IiPAL2) was identified and both IiPALs had the conserved enzymatic active site Ala-Ser-Gly and were classified as members of dicotyledon. IiPAL1 and IiPAL2 were expressed in roots, stems, leaves, and flowers, with the highest expression levels of IiPAL1 and IiPAL2 being observed in stems and roots, respectively. The two genes responded to the exogenous elicitor in different manners. Subcellular localization experiment showed that both IiPALs were localized in the cytosol. The recombinant proteins were shown to catalyze the conversion of L-Phe to trans-cinnamic acid. Correlation analysis indicated that IiPAL1 was more close to the biosynthesis of secondary metabolites than IiPAL2. In conclusion, the present study provides a basis for the elucidation of the role of IiPALs genes in the biosynthesis of phenolic compounds, which will help further metabolic engineering to improve the accumulation of bioactive components in I. indigotica.


title: Imaging manifestations and pathological analysis of severe pneumonia caused by human infected avian influenza (H7N9)

text: Abstract Objective To investigate the imaging and pathological findings of severe pneumonia caused by human infected avian influenza (H7N9), and therefore to further understand and improve diagnostic accuracy of severe pneumonia caused by human infected avian influenza (H7N9). Methods The relevant clinical and imaging data of 19 cases, including 10 males and 9 females, with pneumonia caused by human infected avian influenza (H7N9) was retrospectively analyzed. One of the cases had received percutaneous lung biopsy, with the clinical, imaging and pathological changes possible to be analyzed. Results The lesions were mainly located at lower lobes and dorsal of lungs, involving multiple lobes and segments. Ground-glass opacities and/or pulmonary opacities were the more often imaging manifestations of severe pneumonia caused by human infected avian influenza (H7N9) in early and evolving phases (19/19,100%). By biopsy following percutaneous lung puncture, exudation of slurry, cellulose, RBC and neutrophils, formation of hyaline membrane, squamous metaplasia and organizing exudates were observable at the alveolar space. Some of alveoli collapsed, and some responded to show compensatory emphysema. Conclusion The imaging features of severe pneumonia caused by human infected avian influenza (H7N9) include obvious ground-glass opacity and pulmonary consolidation, mainly at lower lobes and dorsal of lungs, with rapid changes. The cross-analysis of imaging and pathology preliminary can elucidate the pathological mechanisms of ground-glass opacities and pulmonary consolidation of severe pneumonia. Such an intensive study is beneficial to prompt clinicians to observe and evaluate the progress of the disease. In addition, it is also in favor of managing the symptoms and reducing the mortality rate.


title: Anticardiolipin antibodies and COVID‐19—A case report from America

text: In an effort to unravel the pathological mechanism of COVID-19, several reports and studies have been recently conducted in the frontlines around the world. Some initial clues have been obtained, and among them, the concern for clot formation and the idea of an impaired coagulation has strongly increased. We report a case of pulmonary embolism in a COVID-19 patient who tested positive for anticardiolipin antibodies. This article is protected by copyright. All rights reserved.


title: Investigating the use of sensory information to detect and track prey by the Sunda pangolin (Manis javanica) with conservation in mind

text: Pangolins are of conservation concern as one of the most heavily poached, yet least understood mammals. The Sunda pangolin (Manis javanica) in particular is a critically endangered species. Here, we investigate the behaviour of these pangolins, for the first time, using a battery of cognitive tasks based on a manipulation of available sensory information. In an object-choice task in which only one of two containers was baited with food, the pangolins were able to find the food with olfactory information alone (N = 2), but not with visual or acoustic information alone (N = 1). The single subject tested on all three domains was further tested on how he used smell to find food by providing him with an opportunity to find it from a controlled distance or by using scent trails as a guide. The results suggest that our subject may have the capacity to exploit scent trails left by prey which can be tracked to a final source, though we found no evidence to suggest that he had the ability to initiate hunts based on distant prey odors. Despite the small sample size, this is the first controlled experiment to investigate pangolin foraging behaviour and cognition, which may have implications for the future protection of pangolin habitat based on the location of prey species.


Increased rates of respiratory viral (RV) infections using Flocked Swabs and UTM-RT


title: Aptamers: Uptake mechanisms and intracellular applications

text: Abstract The structural flexibility and small size of aptamers enable precise recognition of cellular elements for imaging and therapeutic applications. The process by which aptamers are taken into cells depends on their targets but is typically clathrin-mediated endocytosis or macropinocytosis. After internalization, most aptamers are transported to endosomes, lysosomes, endoplasmic reticulum, Golgi apparatus, and occasionally mitochondria and autophagosomes. Intracellular aptamers, or “intramers,” have versatile functions ranging from intracellular RNA imaging, gene regulation, and therapeutics to allosteric modulation, which we discuss in this review. Immune responses to therapeutic aptamers and the effects of G-quadruplex structure on aptamer function are also discussed.


Chinese institute makes bold sequencing play


title: Mild versus severe COVID-19: laboratory markers

text: Abstract The number of COVID-19 patients is increasing dramatically worldwide and treatment in intensive care units (ICU) has become a major challenge, the early recognition of severe forms of is absolutely essential for timely triaging of patients. While the clinical status, in particular Peripheral oxygen saturation (SpO2) levels and concurrent comorbidities of COVID-19 patients largely determines the need of their admittance to ICUs, several laboratory parameters may facilitate the assessment of disease severity. In hospitalized patients, clinicians should consider low lymphocyte count as well as the serum levels of CRP, D-dimers, ferritin and IL-6 which may be used in risk stratification to predict severe and fatal COVID-19. The more several or all of these parameters are altered, the more likely it is that the course of the disease will be unfavourable.


title: Thermodynamic modelling of solubility and preferential solvation for ribavirin (II) in co-solvent mixtures of (methanol, n-propanol, acetonitrile or 1,4-dioxane)+water

text: Abstract The equilibrium solubility of ribavirin in solvent mixtures of {methanol (1)+water (2)}, {n-propanol (1)+water (2)}, {acetonitrile (1)+water (2)} and {1,4-dioxane (1)+water (2)} was determined experimentally by using isothermal dissolution equilibrium method within the temperature range from (278.15 to 318.15) K under atmospheric pressure (101.1kPa). At the same temperature and mass fraction of methanol (n-propanol, acetonitrile or 1,4-dioxane), the mole fraction solubility of ribavirin is greater in (methanol+water) than in the other three solvent mixtures. The preferential solvation parameters were derived from their thermodynamic solution properties by means of the inverse Kirkwood–Buff integrals. The preferential solvation parameters for methanol, n-propanol, acetonitrile or 1,4-dioxane (δx 1,3) were negative in the four solvent mixtures with a very wide compositions, which indicated that ribavirin was preferentially solvated by water. Temperature had little effect on the preferential solvation magnitudes. The higher solvation by water could be explained in terms of the higher acidic behaviour of water interacting with the Lewis basic groups of the ribavirin. Besides, the solubility of the drugs was mathematically represented by using the Jouyban-Acree model, van’t Hoff-Jouyban-Acree model and Apelblat-Jouyban-Acree model obtaining average relative deviations lower than 1.57% for correlative studies. It is noteworthy that the solubility data presented in this work contribute to expansion of the physicochemical information about the solubility of drugs in binary solvent mixtures and also allows the thermodynamic analysis of the respective dissolution and specific solvation process.


title: Host dihydrofolate reductase (DHFR)-directed cycloguanil analogues endowed with activity against influenza virus and respiratory syncytial virus

text: We have identified a series of 1-aryl-4,6-diamino-1,2-dihydrotriazines, structurally related to the antimalarial drug cycloguanil, as new inhibitors of influenza A and B virus and respiratory syncytial virus (RSV) via targeting of the host dihydrofolate reductase (DHFR) enzyme. Most analogues proved active against influenza B virus in the low micromolar range, and the best compounds (11, 13, 14 and 16) even reached the sub-micromolar potency of zanamivir (EC(50) = 0.060 μM), and markedly exceeded (up to 327 times) the antiviral efficacy of ribavirin. Activity was also observed for two influenza A strains, including a virus with the S31N mutant form of M2 proton channel, which is the most prevalent resistance mutation for amantadine. Importantly, the compounds displayed nanomolar activity against RSV and a superior selectivity index, since the ratio of cytotoxic to antiviral concentration was >10,000 for the three most active compounds 11, 14 and 16 (EC(50) ∼0.008 μM), far surpassing the potency and safety profile of the licensed drug ribavirin (EC(50) = 5.8 μM, SI > 43).


title: Using Latent Class Analysis to Identify the Complex Needs of Youth on Probation

text: Youth involved with the juvenile justice system have higher rates of unmet social and psychological service needs than the general population. Yet, scant research has addressed the potentially complex needs of youth on probation. This study is thus a first step in improving our ability to promote positive youth development and improved outcomes from youth on probation. It uses administrative data on probation youth from FY2011-2013 in a mid-Atlantic state. We estimated latent class models based on the ordinal scoring (high, moderate, none/low) of the 25 subscales from a standardized assessment administered at intake. In order to test whether groups were distinct, we examined a range of variables, including the official risk classification and recidivism rates measured by officieal rearrests and reconvictions. We report the demographic differences between the estimated groups, as well as adverse childhood experiences, school and employment status, previous legal history, and substance use history. Ultimately, the seven-class model produced four groups that others have noted: a relatively low needs (lowest need), relatively high needs (complex needs), substance use service needs, and mental health service needs. The other three groups that emerged include two gender specific groups (one for male and one for female high-need groups) and a group with skills needs that lacks supportive and protective skills. The analyses will facilitate a better appreciation for the service needs of moderate risk youth. Youth on probation are not a uniform population; they reflect tremendous heterogeneity, and probation systems should embrace systemic responsivity to provide appropriate services to improve youth outcomes. Advancing efforts to provide a broader spectrum of services that address multi-morbid conditions can ensure that youth have opportunities to improve their quality of life during the period of supervision.


title: Prevalence of Isospora suis and Eimeria spp. in suckling piglets and sows in Poland

text: Abstract The aim of this investigation was to determine the prevalence of coccidian infections in suckling piglets and sows in Poland. The research was carried out in 14 out of 16 Polish provinces in the years 2003–2005. The investigation was conducted on three types of farms: large farms (>100 sows), medium farms (25–100 sows) and small farms (<25 sows). Diarrhoea of unweaned piglets was observed on all the examined farms. Overall, 780litters of suckling piglets from 104 farms and 267 mother sows were examined. The faeces were analyzed with the modified McMaster method. Isopsora suis was found in 217 (27.8%) litters from 70 (66.7%) farms. Eimeria spp. was detected only in 20 (2.6%) litters from 12 (11.5%) farms. On the large farms I. suis infection was detected in 31.7% of litters whereas Eimeria spp. in 1.4% of them. On the medium sized farms I. suis was found in 18.1% of litters and Eimeria spp. in 0.6%. On the small farms I. suis was detected in only 13.2% of litters, whereas Eimeria spp. in as many as 28.9%. I. suis and Eimeria spp. oocysts were found in 18 (6.7%) and 16 (6%) sows respectively. From 72 sows producing I. suis infected piglets only 12 (16.7%) shed I. suis oocysts and as little as 4 (5.6%) shed Eimeria oocysts. In the remaining 56 sows (77.8%) no cases of coccidian infections were detected. The results of this investigation demonstrate the high prevalence of I. suis in suckling piglets on the large swine farms in Poland.


title: Coronavirus 2019 and health systems affected by protracted conflict: the case of Syria

text: Abstract Introduction Two thirds of countries globally are unprepared to respond to a health emergency as per the International Health Regulations (2005) with conflict-affected countries like Syria particularly vulnerable. Political influences on outbreak preparedness, response and reporting may also adversely affect control of SARS-CoV-2 in Syria. Syria reported its first case on 22 March 2020 however concerns were raised that this was delayed and that underreporting continues. Main Syria's conflict has displaced more than half its pre-war population leaving 6.7 million people internally displaced; consequent overcrowding with insufficient water, sanitation and healthcare (including laboratory capacity) could lead to conditions which are ideal for spread of SARS-CoV-2 in Syria. Political changes have led to the formation of at least three health systems within Syria's borders, each with their own governance, capacity and planning. This fragmentation with little interaction between them could lead to poor resource allocation and adversely affect control. As such, COVID-19 could overwhelm the health systems (particularly intensive care capacity) leading to high deaths across the population, particularly for the most vulnerable such as detainees. Conclusions Locally implementable interventions which rapidly build WASH and health system capacity are required across Syria to ensure early detection and management of COVID-19 cases.


title: Effects of coronavirus (COVID-19) pandemic on orthopedic residency program in the seventh largest city of the world: Recommendations from a resource-constrained setting

text: The coronavirus (COVID-19) pandemic has hit the entire world hard. Since its inception from Wuhan China the whole world is affected now. Health care facilities and workers are overwhelmed and the situation is changing on daily basis. With the changes in the dynamics of the hospitals, residency and fellowships training programs have also suffered undoubtedly. Due to decreased elective cases and outpatient clinics surgical training gets compromised, however on the other side this physical distancing and isolation have proven to be effective measures in controlling the disease. In this article we share our experience of effect of COVID-19 pandemic on our orthopedic residency program and how we coped along with it. We also discussed some way forwards in the article.


Which medical specialties should be prioritised to fill staffing gaps caused by COVID‐19 in the United Kingdom? A network analysis


title: RT-PCR Detection of Avian Coronaviruses of Galliform Birds (Chicken, Turkey, Pheasant) and in a Parrot

text: Of the many primer combinations that we have investigated for the detection of avian coronaviruses, two have worked better than any of the others: they worked with the largest number of strains/samples of a given coronavirus and the most species of avian coronavirus, and they also produced the most sensitive detection tests. The primer combinations were: oligonucleotide pair 2Bp/4Bm, which is in a region of gene 1 that is moderately conserved among all species of coronavirus (1); and UTR11-/UTR41+, which are in a highly conserved part of the 3′ untranslated region of avian coronaviruses related to infectious bronchitis virus (2). The gene 1 primer pair enabled the detection of a new coronavirus in a green-cheeked Amazon parrot (Amazon viridigenalis Cassin). In this chapter we describe the use of these oligonucleotides in a one-step (single-tube) RT-PCR, and describe the procedure that we used to extract RNA from turkey feces.


title: Serological characterization of guinea pigs infected with H3N2 human influenza or immunized with hemagglutinin protein

text: BACKGROUND: Recent and previous studies have shown that guinea pigs can be infected with, and transmit, human influenza viruses. Therefore guinea pig may be a useful animal model for better understanding influenza infection and assessing vaccine strategies. To more fully characterize the model, antibody responses following either infection/re-infection with human influenza A/Wyoming/03/2003 H3N2 or immunization with its homologous recombinant hemagglutinin (HA) protein were studied. RESULTS: Serological samples were collected and tested for anti-HA immunoglobulin by ELISA, antiviral antibodies by hemagglutination inhibition (HI), and recognition of linear epitopes by peptide scanning (PepScan). Animals inoculated with infectious virus demonstrated pronounced viral replication and subsequent serological conversion. Animals either immunized with the homologous HA antigen or infected, showed a relatively rapid rise in antibody titers to the HA glycoprotein in ELISA assays. Antiviral antibodies, measured by HI assay, were detectable after the second inoculation. PepScan data identified both previously recognized and newly defined linear epitopes. CONCLUSIONS: Infection and/or recombinant HA immunization of guinea pigs with H3N2 Wyoming influenza virus resulted in a relatively rapid production of viral-specific antibody thus demonstrating the strong immunogenicity of the major viral structural proteins in this animal model for influenza infection. The sensitivity of the immune response supports the utility of the guinea pig as a useful animal model of influenza infection and immunization.


title: Patients of COVID-19 may benefit from sustained Lopinavir-combined regimen and the increase of Eosinophil may predict the outcome of COVID-19 progression

text: OBJECTIVES: To explore the epidemiological information, clinical characteristics, therapeutic outcomes and temporal progression of laboratory findings in 2019-coronavirus disease (COVID-19) patients exposed to lopinavir. METHODS: We collected data from ten COVID-19 patients admitted between January 22, 2020 and February 11, 2020 at Xixi hospital in Hangzhou, China. RESULTS: Of ten patients, secondary, tertiary and quartus patients emerged; the incubation period was 3–7 days. Mainly initial symptoms were cough and low fever (37.3–38.0 °C). An asymptomatic case presented normal radiography, the others had ground glass opacities. All cases (three transferred, seven discharged) were exposed to lopinavir on initial hospitalization. Three patients stopped lopinavir because of adverse effects, two of them deteriorated, one was hospitalized longer than others who with sustained lopinavir use. Levels of potassium, albumin, and lymphocytes were low, but increased persistently after treatment. Eosinophil values were low on initial hospitalization, then all returned to normal before discharge. Viral load of SARS-CoV-2, radiography and eosinophil improved continuously in 3–14, 6–8 and 7–9 days, respectively. CONCLUSIONS: Increasing eosinophils may be an indicator of COVID-19 improvement. The COVID-19 patients may benefit from sustained lopinavir use. More research on a larger scale is needed to verify these points.


title: Identification of bovine viral diarrhea virus receptor in different cell types

text: Abstract Anti-idiotypic antibodies (anti-ids) have been used successfully in studies on bovine viral diarrhea virus (BVDV) receptor(s) in our laboratory. The anti-ids specifically bound to cultured cells and identified a 50 kDa cellular membrane protein, which is thought to be a specific receptor for BVDV. In this study, flow cytometric analyses demonstrated that the anti-ids also specifically bound to different cell types, namely MDBK, EBK, BT, PK15, MA104, and Vero. Experiments on virus attachment and replication showed that BVDV adsorbed to all cells and replicated in them except monkey kidney cells MA104 and Vero (non-permissive). Results from plaque reduction assays indicated that cellular membrane proteins from all cell lines competitively inhibited BVDV attachment to cultured MDBK cells, suggesting the presence of BVDV receptor on all cells. Immunoblotting of cell membrane proteins with the anti-ids revealed a 50 kDa protein in both permissive and nonpermissive cells. Subcloned or synchronized MDBK cells demonstrated no significant difference of binding with anti-ids as compared to normal cultured cells.


title: COVID-19: Immunology and treatment options

text: Abstract The novel coronavirus SARS-CoV2 causes COVID-19, a pandemic threatening millions. As protective immunity does not exist in humans and the virus is capable of escaping innate immune responses, it can proliferate, unhindered, in primarily infected tissues. Subsequent cell death results in the release of virus particles and intracellular components to the extracellular space, which result in immune cell recruitment, the generation of immune complexes and associated damage. Infection of monocytes/macrophages and/or recruitment of uninfected immune cells can result in massive inflammatory responses later in the disease. Uncontrolled production of pro-inflammatory mediators contributes to ARDS and cytokine storm syndrome. Antiviral agents and immune modulating treatments are currently being trialled. Understanding immune evasion strategies of SARS-CoV2 and the resulting delayed massive immune response will result in the identification of biomarkers that predict outcomes as well as phenotype and disease stage specific treatments that will likely include both antiviral and immune modulating agents.


title: COVID‐19: a global threat to the nervous system

text: In less than 6 months, the severe acute respiratory syndrome‐coronavirus type 2 (SARS‐CoV‐2) has spread worldwide infecting nearly 6 million people and killing over 350,000. Initially thought to be restricted to the respiratory system, we now understand that coronavirus disease 2019 (COVID‐19) also involves multiple other organs including the central and peripheral nervous system. The number of recognized neurologic manifestations of SARS‐CoV‐2 infection is rapidly accumulating. These may result from a variety of mechanisms including virus‐induced hyper‐inflammatory and hypercoagulable states, direct virus infection of the CNS, and post‐infectious immune mediated processes. Example of COVID‐19 CNS disease include encephalopathy, encephalitis, acute disseminated encephalomyelitis, meningitis, ischemic and hemorrhagic stroke, venous sinus thrombosis and endothelialitis. In the peripheral nervous system COVID‐19 is associated with dysfunction of smell and taste, muscle injury, the Guillain‐Barre syndrome and its variants. Due to its worldwide distribution and multifactorial pathogenic mechanisms, COVID‐19 poses a global threat to the entire nervous system. While our understanding of SARS‐CoV‐2 neuropathogenesis is still incomplete and our knowledge is evolving rapidly, we hope that this review will provide a useful framework and help neurologists in understanding the many neurologic facets of COVID‐19.


title: Genomic Characteristics and Changes of Avian Infectious Bronchitis Virus Strain CK/CH/LDL/97I after Serial Passages in Chicken Embryos

text: BACKGROUND: We previously attenuated the infectious bronchitis virus (IBV) strain CK/CH/LDL/97I and found that it can convey protection against the homologous pathogenic virus. OBJECTIVE: To compare the full-length genome sequences of the Chinese IBV strain CK/CH/LDL/97I and its embryo-passaged, attenuated level to identify sequence substitutions responsible for the attenuation and define markers of attenuation. METHODS: The full-length genomes of CK/CH/LDL/97I P5 and P115 were amplified and sequenced. The sequences were assembled and compared using the MEGALIGN program (DNAStar) and a phylogenetic tree was constructed using MEGA4 software. RESULTS: The CK/CH/LDL/97I virus population contained subpopulations with a mixture of genetic mutants. Changes were observed in nsp4, nsp9, nsp11/12, nsp14, nsp15, nsp16, and ORF3a, but these did not result in amino acid substitutions or did not show functional variations. Amino acid substitutions occurred in the remaining genes between P5 and P115; most were found in the S region, and some of the nucleotide mutations resulted in amino acid substitutions. Among the 9 nsps in the ORF1 region, nsp3 contained the most nucleotide substitutions. CONCLUSIONS: Sequence variations in different genes, especially the S gene and nsp3, in the genomes of CK/CH/LDL/97I viruses might contribute to differences in viral replication, pathogenicity, antigenicity, immunogenicity, and tissue tropism.