title: Enhanced inhibition of foot-and-mouth disease virus by combinations of porcine interferon-α and antiviral agents

text: Abstract Foot-and-mouth disease (FMD) is an economically significant animal disease because of the speed of its transmission. The current FMD vaccine provides no protection until 7days after the vaccination, which reduces its effectiveness in the case of an outbreak. Therefore, to find an alternative method of applying antiviral agents for rapid and enhanced inhibition of the FMD virus (FMDV), we compared the antiviral effects of promising antiviral agents and attempted to apply them in combination. First, we measured and compared the 50% effective concentration (EC50) to the mean inhibition effects of FMDV, and the 50% cytotoxic concentration (CC50) to the mean cytotoxicity of antiviral agents such as ribavirin, guanidine-hydrochloride (guanidine-HCl), 6-azauridine, and recombinant adenovirus expressing three small interference RNAs (Ad-siRNA) or porcine interferon-α (Ad-porcine IFN-α) in swine kidney cells (IBRS-2). The selectivity indices of ribavirin (35.2) and 6-azauridine (34.6) were higher than that of guanidine-HCl (26.9). The selectivity indices of Ad-siRNA or Ad-porcine IFN-α were 7×103 or 7×104 based on the adenoviral titer. Next, we tested the combined effects of the FMDV inhibition agents. Enhanced inhibition effects were observed in the IBRS-2 cells and in suckling mice from the combination of Ad-porcine IFN-α and Ad-siRNA or ribavirin. The combined application of these recombinant adenoviruses and ribavirin may enhance their inhibitory effect on FMDV and overcome FMDV resistance against antiviral agents.


title: Human metapneumovirus associated with community‐acquired pneumonia in children in Beijing, China,

text: Community‐acquired pneumonia is a major cause of morbidity and mortality in children worldwide. However, few studies have been conducted on the infection of human metapneumovirus (hMPV) associated with pediatric community‐acquired pneumonia in China. Nasopharyngeal aspirates were collected between July 2008 and June 2010 from 1,028 children, aged ≤16.5 years, who were diagnosed with community‐acquired pneumonia in Beijing, China. Reverse‐transcriptase polymerase chain reaction was used to screen the samples for hMPV and common respiratory viruses. hMPV was detected in 6.3% of the patients with community‐acquired pneumonia. This detection rate is the third highest for a respiratory virus in children with community‐acquired pneumonia, after that of rhinovirus (30.9%) and respiratory syncytial virus (30.7%). The detection rate of hMPV in 2008/2009 (42/540, 7.8%) was significantly higher than in 2009/2010 (23/488, 4.7%; χ(2) = 4.065, P = 0.044). The hMPV subtypes A2, B1, and B2 were found to co‐circulate, with A2 being most prevalent. These results indicate that hMPV plays a substantial role in pediatric community‐acquired pneumonia in China. Overall, these findings provide a better understanding of the epidemiological and clinical features of hMPV infections. J. Med. Virol. 85:138–143, 2012. © 2012 Wiley Periodicals, Inc.


title: A system of protein target sequences for anti-RNA-viral chemotherapy by a vitamin B6-Derived zinc-Chelating trioxa-adamantane-triol

text: Abstract The synthesis of the structurally unusual heterotricyclic compound 1-[3-hydroxy-5-(hydroxymethyl)-2-methyl-4-pyridinyl]-2,8,9-trioxaadamantane-3,5,7-triol (trivially named bananin, BN) from pyridoxylidenephloroglucinol and a theoretical prospect on possible biological activities of BN are presented in this report. Pyridoxylidenephloroglucinol is synthesized by Knoevenagel condensation of the vitamin B6 aldehyde pyridoxal with phloroglucinol. Pyridoxylidenephloroglucinol rearranges to light-yellow (4′RS)-1′,4′-dihydrobananin by refluxing in 5M hydrochloric acid. Air oxidation subsequently forms BN in the heat which immediately yields orange-yellow (4′RS)-4′-chloro-1′,4′-dihydrobananin by 1,4-addition of hydrogen chloride. This intermediate could be isolated but, interestingly, not a BN hydrochloride. Brown BN is finally achieved by base-catalyzed elimination of hydrogen chloride from (4′RS)-4′-chloro-1′,4′-dihydrobananin. Regarding possible biological activities, it was demonstrated that BN acts as zinc (Zn2+) chelator. Therefore, a target of interest could be the human immunodeficiency virus type 1 (HIV-1) zinc finger HIV-1 RNA-binding nucleocapsid protein p7 (NCp7). Through suggested zinc ejection from HIV-1 genomic RNA ψ-element-binding and HIV-1–RNA-duplex packaging NCp7 by BN, thus rendering NCp7 functionally obsolete, it is deduced that HIV-1 replication and effective infectious virion encapsidation could be inhibited by BN. Furthermore, theoretical and structural considerations propose that BN is converted into bananin 5′-monophosphate (BNP) by the cell type-ubiquitous human enzyme pyridoxal kinase (EC 2.7.1.35). Together with the putative antilentiviral retinoid vitamin A–vitamin B6 conjugate analogue B6RA (Kesel, A. J. Biochem. Biophys. Res. Comm. 2003, 300, 793), BNP is postulated to serve as effector in a system of protein target sequences RX(D/E) of RNA virus components. Human immunodeficiency Retroviridae (HIVs) could possibly be influenced by B6RA and BNP. In addition, candidate targets of B6RA and BNP could be adsorption, transcription and/or viral RNA replication of an interestingly wide RNA virus selection including Picornaviridae (poliovirus, human coxsackievirus, hepatitis A virus), Flaviviridae (yellow fever virus, Dengue virus, West Nile virus, Kunjin virus, St. Louis encephalitis virus, hepatitis C virus), Togaviridae (rubella virus), Coronaviridae (human coronavirus, human SARS-associated coronavirus), Rhabdoviridae (rabies virus), Paramyxoviridae (human parainfluenza virus, measles virus, human respiratory syncytial virus), Filoviridae (Marburg virus, Ebola virus), Bornaviridae (Borna disease virus), Bunyaviridae (Hantaan virus), Arenaviridae (Lassa virus), and Reoviridae (human rotavirus). The postulated scope of ‘metabolically trapped’ BNP might resemble the antiviral spectrum of the RNA-viral virustatic ribavirin.


title: An effective screening and management process in the outpatient clinic for patients requiring hospitalization during the COVID‐19 pandemic

text: We have described the screening and management process for patients who present to the out‐patient clinics in China. We believe that our study makes a significant contribution to the literature because we have little reliable literature to refer to with regard to the COVID‐19 pandemic and this protocol has been admirably efficient in China. This article is protected by copyright. All rights reserved.


title: Chapter 4 Demyelination in multiple sclerosis

text: Abstract This review, focused on demyelination in multiple sclerosis, is divided in two parts. The first part addresses the many and not exclusive mechanisms leading to demyelination in the central nervous system. Although the hypothesis that a primary oligodendrocyte or myelin injury induces a secondary immune response in the central nervous system is still a matter of debate, most recent advances underline the influence of a primary immune response against myelin antigen(s), with a diversity of potential targets. Whereas multiple sclerosis was long considered as a T cell-mediated disease, the role of B lymphocytes is now increasingly recognized, and the influence of antibodies on tissue damage actively investigated. The second part of the review describes the axonal consequences of demyelination. Segmental demyelination results in conduction block or slowing of conduction through adaptative responses, notably related to modifications in the distribution of voltage gated sodium channels along the denuded axon. If demyelination persists, these changes, as well as the loss of trophic and metabolic support, will lead to irreversible axonal damage and loss. In this respect, favouring early myelin repair, during a window of time when axonal damage is still reversible, might pave the way for neuroprotection.


Loneliness and Social Isolation in Older Adults During the Covid-19 Pandemic: Implications for Gerontological Social Work


title: Health response to Hajj mass gathering from emergency perspective, narrative review

text: Hajj is a unique gathering with Mecca and Kaaba being spiritually important to many faiths across the globe, especially Muslims. This is because of the proclamation of the prophet's father, Ibrahaam, when he called all mankind to perform Hajj. That is why all Muslims on Earth feel that they have to visit Mecca and Kaaba on a specific date and time, and that is the reason this small location hosts one of the largest human gatherings in the world. Hajj is one of the five pillars of Islam that every financially and physically able Muslim must perform once in his/her lifetime. For 14 centuries countless millions of Muslim men and women from the four corners of the earth have undertaken pilgrimage to Mecca. In conclusion this review article confirm that Hajj is oldest and largest mass gathering in all mankind and there is some issues influence the health response such as size of gathering. diversity of population, climate and health facilities around hajj site, also we discuss the infectious and non infectious related illness in hajj and their prevention methods.


title: Innovation in plant-based transient protein expression for infectious disease prevention and preparedness

text: Addressing new challenges in global health and biosecurity requires responsive and accessible platforms for the manufacture of preventative or therapeutic interventions. Transient protein expression in plants has evolved into a technology that offers a unique combination of rapid expression, inherent scalability, and flexibility in gene stacking with the capability to produce complex proteins and protein assemblies. Technical developments that have driven the progress of transient expression in plants include advanced expression systems, protein engineering and synthetic biology approaches to transiently, or stably, modify host plants. The plasticity of transient expression in plants, speed of scalability and relatively low capital costs, highlight the great potential of this technology in the future of human and animal health.


title: The acute phase response of haptoglobin and serum amyloid A (SAA) in cattle undergoing experimental infection with bovine respiratory syncytial virus

text: Abstract The ability of a pure virus infection to induce an acute phase protein response is of interest as viral infections are normally considered to be less efficient in inducing an acute phase protein response than bacterial infections. This was studied in a bovine model for infection with bovine respiratory syncytial virus (BRSV), analysing the induction of the two most dominant bovine acute phase proteins haptoglobin and serum amyloid A (SAA). Strong and reproducible acute phase responses were detected for both proteins, peaking at around 7–8 days after inoculation of BRSV, while no response was seen in mock-inoculated control animals. The serum concentrations reached for SAA and haptoglobin during the BRSV-induced acute phase response were generally the same or higher than previously reported for bacterial infections in calves. The magnitude and the duration of the haptoglobin response was found to correlate well with the severity of clinical signs (fever) and with the extent of lung consolidation while SAA responded most rapidly to infection.


title: Human bocavirus in children with acute respiratory infections in Vietnam

text: Acute respiratory infections are the major cause of morbidity and mortality globally. Human bocavirus (HBoV), a novel virus, is recognized to increasingly associate with previously unknown etiology respiratory infections in young children. In this study, the epidemiological, clinical, and molecular characteristics of HBoV infections were described in hospitalized Vietnamese pediatric patients. From April 2010 to May 2011, 1,082 nasopharyngeal swab samples were obtained from patients with acute respiratory infections at the Children's Hospital 2, Ho Chi Minh City, Vietnam. Samples were screened for HBoV by PCR and further molecularly characterized by sequencing. HBoV was found in 78 (7.2%) children. Co‐infection with other viruses was observed in 66.7% of patients infected with HBoV. Children 12–24 months old were the most affected age group. Infections with HBoV were found year‐round, though most cases occurred in the dry season (December–April). HBoV was possible to cause severe diseases as determined by higher rates of hypoxia, pneumonia, and longer hospitalization duration in patients with HBoV infection than in those without (P‐value <0.05). Co‐infection with HBoV did not affect the disease severity. The phylogenetic analysis of partial VP1 gene showed minor variations and all HBoV sequences belonged to species 1 (HBoV1). In conclusion, HBoV1 was circulating in Vietnam and detected frequently in young children during dry season. Acute respiratory infections caused by HBoV1 were severe enough for hospitalization, which implied that HBoV1 may have an important role in acute respiratory infections among children. J. Med. Virol. 86:988–994, 2014. © 2013 Wiley Periodicals, Inc.


title: Fulminant Tritrichomonas foetus ‘feline genotype’ infection in a 3-month old kitten associated with viral co-infection

text: Abstract Tritrichomonas foetus is a flagellate protist which commonly causes a waxing and waning large bowel diarrhoea in young cats. We report severe T. foetus infection of the colon, cecum and ileum with concurrent feline enteric coronavirus (FCoV) and feline panleukopenia virus (FPV) in a 3-month-old Bengal kitten with an 8-day history of vomiting, diarrhoea, failure to thrive and coughing. Protozoa filling the lumen and crypts and occasional invading into lamina propria were identified within the affected colon and confirmed by PCR as T. foetus ‘feline genotype’. Assessment of faeces by PCR revealed concurrent infection with FCoV and FPV. It is possible that immunosuppression by FPV played a role in the unprecedented T. foetus infection intensity observed histologically. Studies during and after resolution of FPV infection, will be critical to determine if T. foetus co-infection affects long-term prognosis of FPV survivors.


title: Vision Based Wall Following Framework: A Case Study With HSR Robot for Cleaning Application

text: Periodic cleaning of all frequently touched social areas such as walls, doors, locks, handles, windows has become the first line of defense against all infectious diseases. Among those, cleaning of large wall areas manually is always tedious, time-consuming, and astounding task. Although numerous cleaning companies are interested in deploying robotic cleaning solutions, they are mostly not addressing wall cleaning. To this end, we are proposing a new vision-based wall following framework that acts as an add-on for any professional robotic platform to perform wall cleaning. The proposed framework uses Deep Learning (DL) framework to visually detect, classify, and segment the wall/floor surface and instructs the robot to wall follow to execute the cleaning task. Also, we summarized the system architecture of Toyota Human Support Robot (HSR), which has been used as our testing platform. We evaluated the performance of the proposed framework on HSR robot under various defined scenarios. Our experimental results indicate that the proposed framework could successfully classify and segment the wall/floor surface and also detect the obstacle on wall and floor with high detection accuracy and demonstrates a robust behavior of wall following.


Leveraging existing quality improvement communication strategies during the COVID-19 crisis: Creation of an Emergency Department COVID-19 Case Conference


title: Detailed structural analysis of a genome rearrangement in bovine rotavirus

text: Abstract A genome rearrangement involving RNA segment 11 of a bovine rotavirus has been analysed by molecular cloning and sequencing. This revealed that the rearranged genome segment was generated by a head to tail concatemerisation of two almost full length copies of segment 11. The upstream copy of the gene has lost its 3' end and the downstream copy its 5' end. The truncation of the upstream copy of the gene occurs within the termination codon for VP11 converting it from a UAG to a UGA, the rearranged gene is therefore still able to encode a normal VP11. The possible mechanisms by which this rearrangement may have been generated are discussed.


COVID‐19 and spatio‐temporal disjuncture in the experience of danger


title: Chinese experts’ consensus on the Internet of Things-aided diagnosis and treatment of coronavirus disease 2019 (COVID-19)

text: Abstract The aim is to diagnose COVID-19 earlier and to improve its treatment by applying medical technology, the “COVID-19 Intelligent Diagnosis and Treatment Assistant Program (nCapp)” based on the Internet of Things. Terminal eight functions can be implemented in real-time online communication with the “cloud” through the page selection key. According to existing data, questionnaires, and check results, the diagnosis is automatically generated as confirmed, suspected, or suspicious of 2019 novel coronavirus (2019-nCoV) infection. It classifies patients into mild, moderate, severe or critical pneumonia. nCapp can also establish an online COVID-19 real-time update database, and it updates the model of diagnosis in real time based on the latest real-world case data to improve diagnostic accuracy. Additionally, nCapp can guide treatment. Front-line physicians, experts, and managers are linked to perform consultation and prevention. nCapp also contributes to the long-term follow-up of patients with COVID-19. The ultimate goal is to enable different levels of COVID-19 diagnosis and treatment among different doctors from different hospitals to upgrade to the national and international through the intelligent assistance of the nCapp system. In this way, we can block disease transmission, avoid physician infection, and epidemic prevention and control as soon as possible.


title: Efflux pumps and antimicrobial resistance: Paradoxical components in systems genomics

text: Abstract Efflux pumps play a major role in the increasing antimicrobial resistance rendering a large number of drugs of no use. Large numbers of pathogens are becoming multidrug resistant due to inadequate dosage and use of the existing antimicrobials. This leads to the need for identifying new efflux pump inhibitors. Design of novel targeted therapies using inherent complexity involved in the biological network modeling has gained increasing importance in recent times. The predictive approaches should be used to determine antimicrobial activities with high pathogen specificity and microbicidal potency. Antimicrobial peptides, which are part of our innate immune system, have the ability to respond to infections and have gained much attention in making resistant strain sensitive to existing drugs. In this review paper, we outline evidences linking host-directed therapy with the efflux pump activity to infectious disease.


title: Inpatient Care of Patients with COVID-19: A Guide for Hospitalists

text: Abstract Since its emergence in December 2019, the virus known as severe acute respiratory syndrome coronavirus 2 has quickly caused a pandemic. This virus causes a disease now known as coronavirus disease 2019, or COVID-19. As an increasing proportion of the at-risk population becomes infected, and patients with severe illness are hospitalized, it is essential for hospitalists to remain current on how to best care for people with suspected or confirmed disease. Establishing a system for logistical planning, and accurate information sharing is strongly recommended. Infection control remains the ultimate goal. As such, healthcare workers should be educated on universal and isolation precautions, and the appropriate use of personal protective equipment. Social distancing should be encouraged to prevent the spread of infection, and creative and innovative ways to reduce contact may need to be considered. Moreover, it is imperative to prepare for contingencies as medical staff will inevitably get sick or become unavailable. Hospitalists have the difficult task of caring for patients, while also adapting to the many logistical and social elements of a pandemic.


title: Comparison of the Luminex xTAG Respiratory Viral Panel Fast v2 Assay With Anyplex II RV16 Detection Kit and AdvanSure RV Real-Time RT-PCR Assay for the Detection of Respiratory Viruses

text: BACKGROUND: The accurate and rapid identification of the causative viruses is important for the timely diagnosis and management of respiratory infections. Multiplex molecular diagnostic techniques have been widely adopted to detect respiratory viruses. We compared the results of a newly upgraded, multiplex, molecular bead-based respiratory viral panel (RVP) assay with the results of Anyplex II RV16 detection kit and AdvanSure RV real-time RT-PCR assay. METHODS: We tested 254 respiratory specimens and cultured viral strains using the Luminex xTAG RVP Fast v2 assay (Luminex Molecular Diagnostics, Canada) and Anyplex II RV16 detection kit and compared the results. Specimens showing discordant results between the two assays were tested with a AdvanSure RV real-time RT-PCR assay. RESULTS: Of the 254 respiratory specimens, there was total agreement in the results between the xTAG RVP Fast v2 assay and the other real-time PCR assay in 94.1–100% of the specimens. The agreement levels were relatively low (94.1–97.6%) for specimens of adenovirus, coronavirus NL63, and parainfluenza type 3. In comparison to the other assay, the xTAG RVP Fast v2 assay detected a higher number of parainfluenza type 3 (4 cases) and metapneumovirus (9 cases). CONCLUSIONS: The xTAG RVP Fast v2 assay showed comparable capabilities compared with the other assays; it will be useful for identifying respiratory viral infections in patients with respiratory symptoms. Clinicians should be aware of the characteristics of the assays they use, since different assays show different detectability for each virus.


title: Mechanisms of Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury

text: Systems biology offers considerable promise in uncovering novel pathways by which viruses and other microbial pathogens interact with host signaling and expression networks to mediate disease severity. In this study, we have developed an unbiased modeling approach to identify new pathways and network connections mediating acute lung injury, using severe acute respiratory syndrome coronavirus (SARS-CoV) as a model pathogen. We utilized a time course of matched virologic, pathological, and transcriptomic data within a novel methodological framework that can detect pathway enrichment among key highly connected network genes. This unbiased approach produced a high-priority list of 4 genes in one pathway out of over 3,500 genes that were differentially expressed following SARS-CoV infection. With these data, we predicted that the urokinase and other wound repair pathways would regulate lethal versus sublethal disease following SARS-CoV infection in mice. We validated the importance of the urokinase pathway for SARS-CoV disease severity using genetically defined knockout mice, proteomic correlates of pathway activation, and pathological disease severity. The results of these studies demonstrate that a fine balance exists between host coagulation and fibrinolysin pathways regulating pathological disease outcomes, including diffuse alveolar damage and acute lung injury, following infection with highly pathogenic respiratory viruses, such as SARS-CoV.


COVID-19 pandemic. Impact on hysteroscopic procedures. A consensus statement from the Global Congress of Hysteroscopy Scientific Committee


title: Coagulopathy and Plausible Benefits of Anticoagulation Among COVID-19 Patients

text: The exceptional outbreak of COVID-19 pandemic has let the scientific community to work closely and quickly learnt things in a very short period of time. This has let us recognise that thromboembolic complications are responsible morbidity and mortality among the COVID-19 infected patients. Available data have suggested a possible multifactorial basis of this complications, and while efforts are being made to treat this infection, preventive measure with the use of systemic anticoagulation were quickly adopted to deal with this complication. Despite obvious benefits as appeared with the use of systemic anticoagulation, most of the emerged data were retrospective, and hence raise questions on the possible interplay of the confounders as well as long term benefits and safety of systemic anticoagulation.


title: Assessment of Acute Acral Lesions in a Case Series of Children and Adolescents During the COVID-19 Pandemic

text: IMPORTANCE: A novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently been identified as the cause of a pandemic called coronavirus disease 2019 (COVID-19). In this context, some associated skin diseases have been described. Cutaneous lesions referred to as acute acro-ischemia have been reported as a possible sign of COVID-19 in adolescents and children. OBJECTIVE: To evaluate the pathogenesis of these newly described acute acral lesions. DESIGN, SETTING, AND PARTICIPANTS: This prospective case series was conducted at La Fe University Hospital, a tertiary referral hospital in Valencia, Spain, between April 9 and April 15, 2020. Among 32 referred patients, 20 children and adolescents with new-onset inflammatory lesions did not have a diagnosis. EXPOSURES: Patients were not exposed to any drug or other intervention. MAIN OUTCOMES AND MEASURES: We performed reverse transcriptase–polymerase chain reaction for SARS-CoV-2 and a range of blood tests for possible origins of the lesions. Skin biopsies were performed in 6 patients. RESULTS: Of the 20 patients enrolled, 7 were female and 13 were male, with an age range of 1 to 18 years. Clinical findings fit into the following patterns: acral erythema (6 patients), dactylitis (4 patients), purpuric maculopapules (7 patients), and a mixed pattern (3 patients). None of the patients had remarkable hematologic or serologic abnormalities, including negative antibodies to SARS-CoV-2. Biopsies performed in 6 patients showed histologic findings characteristic of perniosis. CONCLUSIONS AND RELEVANCE: The clinical, histologic, and laboratory test results were compatible with a diagnosis of perniosis, and no evidence was found to support the implication of SARS-CoV-2 infection.


[Image: see text] In focus in HCB


title: Ruptured abdominal aortic aneurysm treated with endovascular repair in a patient with active COVID-19 infection during the pandemic

text: We report a patient that presented with acute abdominal pain during the COVID-19 pandemic. His workup revealed rupture of a 5.8 cm abdominal aortic aneurysm. He presented with fever, cough, and shortness of breath and radiologic evidence of COVID-19 infection. After careful consideration, he underwent successful endovascular repair under local anesthesia with good short-term results.


title: COVID-19: socio-environmental challenges of Rohingya refugees in Bangladesh

text: Multifaceted international and national collaborative responses and progress have sustained the world’s largest densely populated refugee camps in the Cox’s Bazar district, Bangladesh. Yet, the Rohingyas remain in an extremely precarious situation during the COVID-19 pandemic. The refugees are living in highly challenging circumstances of water, sanitation, and hygiene (WASH), natural disasters of the monsoon season as well as existing health and educational challenges of HIV, malnutrition and other diseases. Particulate matter PM(2.5) in the sampling camps varied from 44 μg/m(3) to 546 μg/m(3), whereas PM(10) in the sampling camps varied from 125 μg/m(3) to 1122 μg/m(3). Due to lock-down of Cox’s Bazar, aid workers in and out of the camps were restrained with the only continuation of emergency food and medical service supplies. Largely dependent on aid during the ongoing pandemic, an investigation of the socio-environmental challenges of the refugee camps will identify the anticipatory impacts and needs.


title: Novel Stem Cells and Nucleic Acid-Based Vaccine Trials Against Viral Outbreak: A Systematic Evaluation During COVID-2019 Pandemic

text: The current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) outbreak, the cause of coronavirus disease (COVID-19), has influenced health globally. So far, there are no established management options and prophylaxis for those who have been exposed to SARS-CoV-2, and those who develop COVID-19. Documented scientific evidences in similar viral outbreaks in past suggested few therapy regimens. These rather have not shown promising results in management of current pandemic. So, in the current review, we are exploring novel treatment strategies and therapies that are being explored and are in clinical and preclinical stages of research. To explore more about the same, we directed our search towards stem cell based, DNA based, or RNA based vaccines against COVID-19 under development by various universities, institutes or pharmaceutical companies. The current scientific literature and database search were performed by exploring various Trials registry (NIH: https://clinicaltrials.gov/ and https://www.coronavirus.gov) and Chinese clinical trial registry http://www.chictr.org.cn/) and for preclinical trials various University, Institutions, Pharmaceutical companies websites and news bulletins along with google search were checked routinely from 3rd March 2020 to 16 May 2020. The term “Stem Cell therapy and COVID-19”, “Mesenchymal stem cell and corona 2019 virus”, “DNA Vaccines and COVID-19, RNA Vaccines and COVID-19” and “Cell-based therapy with SARS-CoV-2, University/Institutions and COVID-19 research” were used. The vaccine trials (Stem Cells/DNA/RNA) which were cancelled were not included in this review. Similarly, few others like repurposing of drugs, Nano Vaccines, other miscellaneous trials of Herbs, Music therapy etc., were also excluded. In the present review, we have included the various novel therapies like stem cell therapy, DNA or RNA vaccines which are under development and if proven successful may have a lasting impact on the health industry.


title: COVID‐19: Emergence of Infectious Diseases, Nanotechnology Aspects, Challenges, and Future Perspectives

text: Wuhan, a city of China, is the epicenter for the pandemic outbreak of coronavirus disease‐2019 (COVID‐19). It has become a severe public health challenge to the world and established a public health emergency of international worry. This infectious disease has pulled down the economy of almost all top developed nations. The coronaviruses (CoVs) known for various epidemics caused time to time. Infectious diseases such as severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS), followed by COVID‐19, are all coronaviruses led outbreaks that scourged the history of mankind. CoVs evolved themselves to more infectious, transmissible, and more pandemic with time. To prevent the spread of the SARS‐CoV‐2, many countries have ordered the complete lockdown to combat the outbreak. This paper briefly discussed the historical background of CoVs and the evolution of human coronaviruses (HCoVs), the case studies and the development of their antiviral medications. The viral infection encountered with present‐day challenges and futuristic approaches with the help of nanotechnology to minimize the spread of infectious viruses. The antiviral drugs and their clinical advances, along with herbal medicines for viral inhibition and immunity boosters, are described. Elaboration of tables related to CoVs for the compilation of the literature has been adopted for the better understanding.


title: Epstein-Barr virus-induced gene 3 negatively regulates neuroinflammation and T cell activation following coronavirus-induced encephalomyelitis

text: Epstein-Barr virus-induced gene 3 (EBI3) associates with p28 and p35 to form the immunomodulatory cytokines IL-27 and IL-35, respectively. Infection of EBI3−/− mice with the neuroadapted JHM strain of mouse hepatitis virus (JHMV) resulted in increased mortality that was not associated with impaired ability to control viral replication but enhanced T cell and macrophage infiltration into the CNS. IFN-γ secretion from virus-specific CD4+ and CD8+ T cells isolated from infected EBI3−/− mice was augmented while IL-10 expression muted in comparison to infected WT mice. These data demonstrate a regulatory role for EBI3-associated cytokines in controlling host responses following CNS viral infection.


title: Risk factors for bobby calf mortality across the New Zealand dairy supply chain

text: Abstract The objective of this study was to identify risk factors for morbidity and mortality of bobby calves across the whole dairy supply chain in New Zealand. A case-control study was carried out in the 2016 spring calving season. A total of 194 bobby calves, comprising 38 cases (calves that died or were condemned for health or welfare reasons before the point of slaughter) and 156 controls (calves deemed acceptable and presented for slaughter) were included in the study. Case and control calves were selected by veterinarians located at 29 processing premises across New Zealand. Information regarding management of selected calves on-farm, during transport and at the processor was obtained retrospectively via questionnaires administered to supplying farmers, transport operators and processing premises personnel. Associations between management variables and calf mortality (death or condemnation) were examined using multivariable logistic regression models. Factors associated with an increased risk of calf mortality included time in the farm of origin’s calving season, duration of travel from farm to the processor and processing slaughter schedule (same day or next day). Every additional week into the farm’s calving season increased the odds of mortality by a factor of 1.2 (95%CI 1.06, 1.35). Similarly, each additional hour of travel time increased the odds of mortality by a factor of 1.45 (95% CI 1.18, 1.76). Risk of mortality was significantly greater for calves processed at premises with a next day slaughter schedule than those processed at premises with a same day slaughter schedule (OR 3.82, 95% CI 1.51, 9.67). However, when the data set was limited to those cases that died or were condemned in the yards (i.e. excluding calves that were dead or condemned on arrival) the effect of same day slaughter was not significant. In order to reduce bobby calf mortality and morbidity, transport duration should be kept as short as possible and a same day slaughter schedule applied. While these factors can be regulated, New Zealand’s pastoral dairy system means that calves will inevitably be transported for slaughter across several months each spring. Although farm management factors did not apparently influence the risk of mortality in this study, the effect of time in farm’s calving season suggests there may be farm-management related factors that change over the season. This requires further investigation.


title: Acute viral gastroenteritis

text: Abstract Two virus-like particles have been found to be associated with acute viral gastroenteritis. One, a 270-nm parvovirus-like particle (the Norwalk agent), was visualized and recognized by immune electron microscopy in an infectious stool filtrate derived from a community outbreak of nonbacterial gastroenteritis. It appears to be one of the etiologic agents of a usually self-limited form of gastroenteritis which commonly occurs in community outbreaks. The other, a 70-nm reovirus-like particle, has been observed by electron microscopy in specimens from infants and children with severe diarrhea in many parts of the world. The reovirus-like particle may emerge as a major etiologic agent of diarrhea of infants and young children.


title: Olfactory Device for Large Scale Pre-screening for COVID-19

text: Recent pandemic caused by COVID-19 has motivated lockdown in several countries for long duration and will have a long lasting impact on the social life and economics world wide. India is no exception although showing relatively delayed increase in number of cases. Multilayered diagnostics for mass scaled screening is inevitable during and especially after the peak is passed and life is moving towards normalcy. First level of screening currently used in India is mainly based on temperature and has possibility of false positives and false negative (fever as a symptom has not yet been developed although infected). We propose here another augmentation or an intermediate level of screening, depending on the usage, based on assessing olfactory functions. It is established with multiple publications reporting degrading (hyposmia) or loss of sense (anosmia) of smell for infected patients. This paper presents a recently developed technology and device that uses olfactory sense detection using a novel device that is capable of generating precise level of smell digitally, and repeatedly in contactless manner. The device is designed to work with a mobile app that can trigger selected smell or combinations and further can be programmed to give standard or customised smell tests. Estimated capital and running cost are low since one (out of 25) canister filled with of 0.1 ml volume of essential smell oil can serve hundreds of tests. The prototype is tested to work for a desired smell generation and is available for further tweaking for rapid screening of subjects as per the requirements.


COVID-19 Is Further Subdivided Into COVIP-19 and COVII-19


title: Human Metapneumovirus Infections Following Hematopoietic Cell Transplantation: Factors Associated With Disease Progression

text: Background. Human metapneumovirus (HMPV) is a newly identified pulmonary pathogen that can cause fatal lower respiratory tract disease (LRD) in hematopoietic cell transplantation (HCT) recipients. Little is known about progression rates from upper respiratory tract infection (URI) to LRD and risk factors associated with progression. Methods. A total of 118 HCT recipients receiving transplantation between 2004 and 2014 who had HMPV detected in nasopharyngeal, bronchoalveolar lavage, or lung biopsy samples by real-time reverse transcription polymerase chain reaction were retrospectively analyzed. Results. More than 90% of the cases were identified between December and May. Among the 118 HCT patients, 88 and 30 had URI alone and LRD, respectively. Among 30 patients with LRD, 17 patients progressed from URI to LRD after a median of 7 days (range, 2–63 days). The probability of progression to LRD within 40 days after URI was 16%. In Cox regression analysis, steroid use ≥1 mg/kg prior to URI diagnosis (hazard ratio [HR], 5.10; P = .004), low lymphocyte count (HR, 3.43; P = .011), and early onset of HMPV infection after HCT (before day 30 after HCT; HR, 3.54; P = .013) were associated with higher progression to LRD. The median viral load in nasal wash samples was 1.1 × 10(6) copies/mL (range, 3.3 × 10(2)–1.7 × 10(9)) with no correlation between the viral load and progression. Conclusions. Progression from URI to LRD occurred in up to 60% of HCT recipients with risk factors such as systemic corticosteroid use or low lymphocyte counts. Further studies are needed to define the role of viral load in the pathogenesis of progressive disease.


title: Influenza-associated Deaths in Tropical Singapore

text: We used a regression model to examine the impact of influenza on death rates in tropical Singapore for the period 1996–2003. Influenza A (H3N2) was the predominant circulating influenza virus subtype, with consistently significant and robust effect on mortality rates. Influenza was associated with an annual death rate from all causes, from underlying pneumonia and influenza, and from underlying circulatory and respiratory conditions of 14.8 (95% confidence interval 9.8–19.8), 2.9 (1.0–5.0), and 11.9 (8.3–15.7) per 100,000 person-years, respectively. These results are comparable with observations in the United States and subtropical Hong Kong. An estimated 6.5% of underlying pneumonia and influenza deaths were attributable to influenza. The proportion of influenza-associated deaths was 11.3 times higher in persons age >65 years than in the general population. Our findings support the need for influenza surveillance and annual influenza vaccination for at-risk populations in tropical countries.


title: Labor and delivery guidance for COVID-19

text: This document addresses the current coronavirus disease 2019 (COVID-19) pandemic for providers and patients in labor and delivery (L&D). The goals are to provide guidance regarding methods to appropriately screen and test pregnant patients for COVID-19 prior to, and at admission to L&D reduce risk of maternal and neonatal COVID-19 disease through minimizing hospital contact and appropriate isolation; and provide specific guidance for management of L&D of the COVID-19–positive woman, as well as the critically ill COVID-19–positive woman. The first 5 sections deal with L&D issues in general, for all women, during the COVID-19 pandemic. These include Section 1: Appropriate screening, testing, and preparation of pregnant women for COVID-19 before visit and/or admission to L&D Section 2: Screening of patients coming to L&D triage; Section 3: General changes to routine L&D work flow; Section 4: Intrapartum care; Section 5: Postpartum care; Section 6 deals with special care for the COVID-19–positive or suspected pregnant woman in L&D and Section 7 deals with the COVID-19–positive/suspected woman who is critically ill. These are suggestions, which can be adapted to local needs and capabilities.


title: Identifying and hurdling obstacles to translational research

text: Although there is overwhelming pressure from funding agencies and the general public for scientists to bridge basic and translational studies, the fact remains that there are significant hurdles to overcome in order to achieve this goal. The purpose of this Opinion article is to examine the nature of these hurdles and to provide food for thought on the main obstacles that impede this process.


title: COVID-19 challenges to Pakistan: Is GIS analysis useful to draw solutions?

text: Abstract The outbreak of novel coronavirus (COVID-19) is a public health emergency that had caused disastrous results in more than 100 countries. The ability to detect disease outbreaks in the early stages is a key component of efficient disease control and prevention. With the increased availability of electronic health-care data and spatial analysis techniques, there is great potential to develop algorithms to enable more effective disease surveillance. The research focuses to develop a transparent user-friendly method to simulate the outbreak data. The paper describes the GIS tools to identify and define the field of investigation which requires consideration of the strengths and limitations of data collection instruments, facility of locational data collection, accuracy of locational data, and pertinent attributes for understanding disease risk. Using such information, it is quite easy for authorities to locate the highly effected area and take appropriate actions in that particular areas. However, GIS techniques, resources, and methods can be used in Pakistan for more effective investigation of vulnerable geographical locations.


title: Molecular characterization of a new PToV strain. Evolutionary implications

text: Abstract Toroviruses are emergent viruses, belonging to the Nidovirales order, that remain mostly ignored, despite they are able to infect different species of domestic animals and humans, causing enteric diseases and diarrhea. Thus far, only five variants of porcine torovirus (PToV) have been identified. In this report we describe the identification and partial characterization of a new strain of porcine torovirus (PToV-BRES) that was detected by RT-PCR in a swine faecal specimen from a farm in Brescia (Italy). The complete genes coding for the nucleocapsid (N), hemagglutinin-esterase (HE) and membrane (M) proteins were amplified, and sequence analysis showed that PToV-BRES is a new PToV strain that, based on the HE gene sequence, is phylogenetically related to P4 strain, that was up to now the only member of a distinct PToV lineage. The nucleocapsid protein from PToV-BRES was expressed in insect cells as a his-tagged protein, purified by affinity chromatography and used to develop an ELISA method to detect antibodies against PToV. This assay was evaluated using a serum collection including 45 samples from three commercial farms from Spain. High antibody prevalence against PToV was observed in the three farms, both in adult animals and in piglets, which could suggest that PToV might be endemic in Spanish porcine population. The ELISA method developed in this work could be useful in future epidemiological surveys about toroviruses.


title: Improving VOCs control strategies based on source characteristics and chemical reactivity in a typical coastal city of South China through measurement and emission inventory

text: Abstract In China, the corresponding control directives for volatile organic compounds (VOCs) have been based on primary emissions, rarely considering reactive speciation. To seek more effective VOCs control strategies, we investigated 107 VOC species in a typical coastal city (Beihai) of South China, from August to November 2018. Meanwhile, a high-resolution anthropogenic VOCs monthly emission inventory (EI) was established for 2018. For source apportionments (SAs) reliability, comparisons of source structures derived from positive matrix factorization (PMF) and EI were made mainly in terms of reaction losses, uncertainties and specific ratios. Finally, for the source–end control, a comprehensive reactivity control index (RCI) was established by combing SAs with reactive speciation profiles. Ambient measurements showed that the average concentration of VOCs was 26.38 ppbv, dominated by alkanes (36.7%) and oxygenated volatile organic compounds (OVOCs) (29.4%). VOC reactivity was estimated using ozone formation potential (52.35 ppbv) and propylene-equivalent concentration (4.22 ppbv). EI results displayed that the entire VOC, OFP, and propylene-equivalent emissions were 40.98 Gg, 67.98 Gg, and 105.93 Gg, respectively. Comparisons of source structures indicated that VOC SAs agreed within ±100% between two perspectives. Both PMF and EI results showed that petrochemical industry (24.0% and 33.0%), food processing and associated combustion (19.1% and 29.2%) were the significant contributors of anthropogenic VOCs, followed by other industrial processes (22.2% and 13.3%), transportation (18.9% and 12.0%), and solvent utilization (9.1% and10.5%). Aimed at VOCs abatement according to RCI: for terminal control, fifteen ambient highly reactive species (predominantly alkenes and alkanes) were targeted; for source control, the predominant anthropogenic sources (food industry, solvent usage, petrochemical industry and transportation) and their emitted highly reactive species were determined. Particularly, with low levels of ambient VOC and primary emissions, in this VOC and NOx double-controlled regime, crude disorganized emission from food industry contributed a high RCI.


title: Detection of SARS-CoV-2-specific humoral and cellular immunity in COVID-19 convalescent individuals

text: Summary The World Health Organization has declared SARS-CoV-2 virus outbreak a world-wide pandemic. However, there is very limited understanding on the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. Here, we collected blood from COVID-19 patients who have recently become virus-free and therefore were discharged, and detected SARS-CoV-2-specific humoral and cellular immunity in 8 newly discharged patients. Follow-up analysis on another cohort of 6 patients 2 weeks post discharge also revealed high titers of IgG antibodies. In all 14 patients tested, 13 displayed serum neutralizing activities in a pseudotype entry assay. Notably, there was a strong correlation between neutralization antibody titers and the numbers of virus-specific T cells. Our work provides a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases. It has also implications in developing an effective vaccine to SARS-CoV-2 infection.


title: COVID-19 Outpatient Screening: a Prediction Score for Adverse Events

text: BACKGROUND. We sought to develop an automatable score to predict hospitalization, critical illness, or death in patients at risk for COVID-19 presenting for urgent care during the Massachusetts outbreak. METHODS. Single-center study of adult outpatients seen in respiratory illness clinics (RICs) or the emergency department (ED), including development (n = 9381, March 7-May 2) and prospective (n = 2205, May 3–14) cohorts. Data was queried from Partners Enterprise Data Warehouse. Outcomes were hospitalization, critical illness or death within 7 days. We developed the COVID-19 Acuity Score (CoVA) using automatically extracted data from the electronic medical record and learning-to-rank ordinal logistic regression modeling. Calibration was assessed using predicted-to-observed ratio (E/O). Discrimination was assessed by C-statistics (AUC). RESULTS. In the development cohort, 27.3%, 7.2%, and 1.1% of patients experienced hospitalization, critical illness, or death, respectively; and in the prospective cohort, 26.1%, 6.3%, and 0.5%. CoVA showed excellent performance in the development cohort (concurrent validation) for hospitalization (E/O: 1.00, AUC: 0.80); for critical illness (E/O: 1.00, AUC: 0.82); and for death (E/O: 1.00, AUC: 0.87). Performance in the prospective cohort (prospective validation) was similar for hospitalization (E/O: 1.01, AUC: 0.76); for critical illness (E/O 1.03, AUC: 0.79); and for death (E/O: 1.63, AUC=0.93). Among 30 predictors, the top five were age, diastolic blood pressure, blood oxygen saturation, COVID-19 testing status, and respiratory rate. CONCLUSIONS. CoVA is a prospectively validated automatable score to assessing risk for adverse outcomes related to COVID-19 infection in the outpatient setting.


title: The epidemiologic and clinical features of suspected and confirmed cases of imported 2019 novel coronavirus pneumonia in north Shanghai, China.

text: Background A recent cluster of pneumonia cases in Wuhan (China) is known to be caused by a novel beta-coronavirus named the corona virus disease 2019 (COVID-19) and can be spread through human-to-human transmission. Methods Data of 21 patients with laboratory-confirmed COVID-19 and 84 patients with suspected COVID-19 were analyzed by RT-PCR. The epidemiologic and clinical features as well as clinical outcomes were compared between the confirmed and suspected cases. Results Altogether 105 patients had been enrolled in this study by February 15, 2020 in north Shanghai, including 21 confirmed cases and 84 suspected cases of COVID-19. The incubation period of these confirmed patients with imported COVID-19 was 17.6 days (IQR 5-34 days) and the median time from symptom onset to diagnosis was 145.64 h (IQR 21-441 h). More than 50% of the confirmed patients were older than 51 (range, 51-60) years. Fifty (59.5%) of the 84 probably patients were younger than 40 years, including 27 (32%) patients younger than 30 years. Most confirmed patients were men (61.9%, 13/21), and less than 50% of them had underlying diseases, including diabetes (9.5%, 2/21), hypertension (19%, 4/21), COPD (23.8%, 5/21), and CD (23.8%, 5/21). In addition, 10 (47.6%) of the 21 confirmed patients were ordinary employees, and 12 (57.2%) of them had recently been to Wuhan or had close contacts with people from Wuhan. Of the 84 suspected patients, 28 (33.3%) were retired employees; 69 (82.1%) had recently been to supermarkets and groceries or had a history of traveling abroad or to other cities of China. The common onset symptoms of the patients in both groups were fever and cough. The symptom of Sputum production was more pronounced in probably patients (40.5%, 34/84) than that in confirmed patients (9.5%, 2/21). More than 50% imported patients (53.3%, 56/105) had one and two affected lobes. Twenty-nine (27.6%) of the 105 imported patients had been discharged, no patient had died, and all the other patients are still in hospital. Conclusions The overall incubation period in this cohort of imported confirmed COVID-19 patients was longer than that in Wuhan, mostly infecting older men. The disease onset of imported COVID-19 infection was occult, and the clinical symptoms were usually mild, mostly presenting as low fever, fatigue, light cough, and mild dyspnea.


title: Ligation-mediated amplification for effective rapid determination of viral RNA sequences (RDV)

text: Abstract Background Emerging infectious diseases pose a significant risk to public health. Methods for rapid detection of pathogens are needed to effectively treat these diseases. Recently, we developed new methods for the rapid determination of viral RNA sequences, RDV ver1.0 and ver2.0. We demonstrated that these methods were able to simultaneously detect cDNA fragments of many different viruses without using sequence specific primers. However, some species of viruses, including the Yokose virus (YOKV), a flavivirus, could not be detected using the conventional procedures. Objective The RDV method was further modified to reduce the candidate PCR primer sets. Study design Primer sets were reduced to 256 sets in the improved RDV ver3.0, and theoretically, all viral cDNA fragments ligated by two kinds of adaptors after digestion by two restriction enzymes could be amplified in the PCR step for direct sequencing. Results We succeeded in obtaining 118 YOKV cDNA fragments of the 141 sequence fragments. The cDNA fragments covered diverse range of viral genome. Conclusion We were able to reduce the combinations of PCR primer sets used in the RDV method. This RDV method ver3.0 has a potential to detect viral cDNA fragments of both known and unknown RNA viruses rapidly and conveniently.


title: Dipeptidyl peptidase 4 inhibitors and their potential immune modulatory functions

text: Abstract Dipeptidyl peptidase 4 (DPP4) inhibitors (DPP4is) are oral anti-diabetic drugs (OADs) for the treatment of type 2 diabetes mellitus (T2DM) through inhibiting the degradation of incretin peptides. Numerous investigations have been focused on the effects of DPP4is on glucose homeostasis. However, there are limited evidences demonstrating their Potential modulatory functions in the immune system. DPP4, originally known as the lymphocyte cell surface protein CD26, is widely expressed in many types of immune cells including CD4(+) and CD8(+) T cells, B cells, NK cells, dendritic cells, and macrophages; and regulate the functions of these cells. In addition, DPP4 is capable of modulating plenty of cytokines, chemokines and peptide hormones. Accordingly, DPP4/CD26 is speculated to be involved in various immune/inflammatory diseases and DPP4is may become a new drug class applied in these diseases. This review focuses on the regulatory effects of DPP4is on immune functions and their possible underlying mechanisms. Further clinical studies will be necessitated to fully evaluate the administration of DPP4is in diabetic patients with or without immune diseases.


title: Pleiotropic roles of the ubiquitin-proteasome system during viral propagation

text: Abstract Protein ubiquitination is a highly conserved post-translational modification affecting various biological processes including viral propagation. Ubiquitination has multiple effects on viral propagation, including viral genome uncoating, viral replication, and immune evasion. Ubiquitination of viral proteins is triggered by the ubiquitin-proteasome system (UPS). This involves the covalent attachment of the highly conserved 76 amino acid residue ubiquitin protein to target proteins by the consecutive actions of E1, E2 and E3 enzymes, and the 26S proteasome that together form a multiprotein complex that degrades target proteins. The UPS is the primary cytosolic proteolytic machinery for the selective degradation of various forms of proteins including viral proteins, thereby limiting viral growth in host cells. To combat this host anti-viral machinery, viruses have evolved the ability to employ or subvert the UPS to inactivate or degrade cellular proteins to favour viral propagation. This review highlights our current knowledge on the different roles of the UPS during viral propagation.


title: The Emerging Roles of Viroporins in ER Stress Response and Autophagy Induction during Virus Infection

text: Viroporins are small hydrophobic viral proteins that oligomerize to form aqueous pores on cellular membranes. Studies in recent years have demonstrated that viroporins serve important functions during virus replication and contribute to viral pathogenicity. A number of viroporins have also been shown to localize to the endoplasmic reticulum (ER) and/or its associated membranous organelles. In fact, replication of most RNA viruses is closely linked to the ER, and has been found to cause ER stress in the infected cells. On the other hand, autophagy is an evolutionarily conserved “self-eating” mechanism that is also observed in cells infected with RNA viruses. Both ER stress and autophagy are also known to modulate a wide variety of signaling pathways including pro-inflammatory and innate immune response, thereby constituting a major aspect of host-virus interactions. In this review, the potential involvement of viroporins in virus-induced ER stress and autophagy will be discussed.


title: MT-PCR panel detection of canine parvovirus (CPV-2): Vaccine and wild-type CPV-2 can be difficult to differentiate in canine diagnostic fecal samples

text: Abstract Canine parvovirus (CPV-2) remains an important cause of devastating enteritis in young dogs. It can be successfully prevented with live attenuated CPV-2 vaccines when given at the appropriate age and in the absence of maternal antibody interference. Rapid diagnosis of parvoviral enteritis in young dogs is essential to ensuring suitable barrier nursing protocols within veterinary hospitals. The current diagnostic trend is to use multiplexed PCR panels to detect an array of pathogens commonly responsible for diarrhea in dogs. The multiplexed PCR assays do not distinguish wild from vaccine CPV-2. They are highly sensitive and detect even a low level of virus shedding, such as those caused by the CPV-2 vaccine. The aim of this study was to identify the CPV-2 subtypes detected in diagnostic specimens and rule out occult shedding of CPV-2 vaccine strains. For a total of 21 samples that tested positive for CPV-2 in a small animal fecal pathogens diagnostic multiplexed tandem PCR (MT-PCR) panel during 2014–2016 we partially characterized the VP2 gene of CPV-2. Vaccine CPV-2 strain, wild type CPV-2a subtypes and vaccine-like CPV-2b subtypes were detected. High copy number was indicative of wild-type CPV-2a presence, but presence of vaccine-like CPV-2b had a variable copy number in fecal samples. A yardstick approach to a copy number or Ct-value to discriminate vaccine strain from a wild type virus of CPV-2 can be, in some cases, potentially misleading. Therefore, discriminating vaccine strain from a wild type subtype of CPV-2 remains ambitious.


title: Encoded metal nanoparticle-based molecular beacons for multiplexed detection of DNA

text: In this paper we describe a molecular beacon format assay in which encoded nanowire particles are used to achieve multiplexing. We demonstrate this principle with the detection of five viral pathogens; Hepatitis A virus, Hepatitis C virus, West Nile Virus, Human Immune Deficiency virus and Severe Acute Respiratory Syndrome virus. Oligonucleotides are designed complementary to a target sequence of interest containing a 3′ universal fluorescence dye. A 5′ thiol causes the oligonucleotides to self-assemble onto the metal nanowire. The single-stranded oligonucleotide contains a self-complementary hairpin stem sequence of 10 bases that forces the 3′ fluorophore to come into contact with the metallic nanowire surface, thereby quenching the fluorescence. Upon addition of target DNA, there is hybridization with the complementary oligonucleotides. The resulting DNA hybrid is rigid, unfolds the hairpin structure, and causes the fluorophore to be moved away from the surface such that it is no longer quenched. By using differently encoded nanowires, each conjugated with a different oligonucleotide sequence, multiplexed DNA assays are possible using a single fluorophore, from a multiplexed RT-PCR reaction.


title: The Main Biological Hazards in Animal Biosafety Level 2 Facilities and Strategies for Control

text: Concern about the biological hazards involved in microbiological research, especially research involving laboratory animals, has increased in recent years. Working in an animal biosafety level 2 facility (ABSL-2), commonly used for research on infectious diseases, poses various biological hazards. Here, the regulations and standards related to laboratory biosafety in China are introduced, the potential biological hazards present in ABSL-2 facilities are analyzed, and a series of strategies to control the hazards are presented.


Cruise Ships, Nursing Homes and Prisons as COVID-19 Epicenters: A ‘Wicked Problem” with Breakthrough Solutions?


title: HIV infection and antiretroviral therapy lead to unfolded protein response activation

text: BACKGROUND: The unfolded protein response (UPR) is one of the pathways triggered to ensure quality control of the proteins assembled in the endoplasmic reticulum (ER) when cell homeostasis is compromised. This mechanism is primarily composed of three transmembrane proteins serving as stress sensors: PKR-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1 (IRE1). These three proteins’ synergic action elicits translation and transcriptional downstream pathways, leading to less protein production and activating genes that encode important proteins in folding processes, including chaperones. Previous reports showed that viruses have evolved mechanisms to curtail or customize this UPR signaling for their own benefit. However, HIV infection’s effect on the UPR has scarcely been investigated. METHODS: This work investigated UPR modulation by HIV infection by assessing UPR-related protein expression under in vitro and in vivo conditions via Western blotting. Antiretroviral (ARV) drugs’ influence on this stress response was also considered. RESULTS: In in vitro and in vivo analyses, our results confirm that HIV infection activates stress-response components and that ARV therapy contributes to changes in the UPR’s activation profile. CONCLUSIONS: This is the first report showing UPR-related protein expression in HIV target cells derived directly from HIV-infected patients receiving different ARV therapies. Thus, two mechanisms may occur simultaneously: interference by HIV itself and the ARV drugs’ pharmacological effects as UPR activators. New evidence of how HIV modulates the UPR to enhance its own replication and secure infection success is also presented. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0298-0) contains supplementary material, which is available to authorized users.


Surge capacity and updated admission criteria: response of the NHS-commissioned national respiratory ECMO network to the COVID-19 pandemic


title: A rapid, inexpensive yeast-based dual-fluorescence assay of programmed—1 ribosomal frameshifting for high-throughput screening

text: Programmed −1 ribosomal frameshifting (−1 PRF) is a mechanism that directs elongating ribosomes to shift-reading frame by 1 base in the 5′ direction that is utilized by many RNA viruses. Importantly, rates of −1 PRF are fine-tuned by viruses, including Retroviruses, Coronaviruses, Flavivriuses and in two endogenous viruses of the yeast Saccharomyces cerevisiae, to deliver the correct ratios of different viral proteins for efficient replication. Thus, −1 PRF presents a novel target for antiviral therapeutics. The underlying molecular mechanism of −1 PRF is conserved from yeast to mammals, enabling yeast to be used as a logical platform for high-throughput screens. Our understanding of the strengths and pitfalls of assays to monitor −1 PRF have evolved since the initial discovery of −1 PRF. These include controlling for the effects of drugs on protein expression and mRNA stability, as well as minimizing costs and the requirement for multiple processing steps. Here we describe the development of an automated yeast-based dual fluorescence assay of −1 PRF that provides a rapid, inexpensive automated pipeline to screen for compounds that alter rates of −1 PRF which will help to pave the way toward the discovery and development of novel antiviral therapeutics.


title: Smilax guianensis Vitman extract prevents LPS-induced inflammation by inhibiting the NF-κB pathway in RAW 264.7 cells

text: Nutraceutical treatments can reduce inflammation and prevent the development of inflammatory diseases In this study, the anti-inflammatory effects of Smilax guianensis Vitman extract (SGE) were examined SGE suppressed lipopolysaccharide (LPS)-mediated nitrite production in RAW 264 7 cells SGE also prevented the LPS-induced expression of inducible nitric oxide synthase (iNOS) but not cyclooxygenase (COX)-2 Western blot analysis showed that SGE attenuated LPS-induced phosphorylation of IκB kinase, inhibitor of kappa B (IκB), and p65 Additionally, SGE inhibited LPS-induced IκB degradation in RAW 264 7 cells Western blot analysis of the cytosolic and nuclear fractions, as well as immunofluorescence assay results, revealed that SGE suppressed LPS-induced p65 nuclear translocation in RAW 264 7 cells Moreover, SGE reduced LPS-induced interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) mRNA expression and IL-1β and IL-6 protein expression in RAW 264 7 cells Collectively, these results indicate that SGE suppresses the NF-κB signaling pathway and thereby inhibits the production of NO, IL-1β, and IL-6


title: Hospital management of adults with severe acute respiratory syndrome (SARS) if SARS re-emerges—updated 10 February 2004

text: Abstract Severe Acute Respiratory Syndrome (SARS) is a potentially severe and highly infectious disease to which healthcare workers involved in the management of cases are particularly vulnerable. These guidelines briefly summarise optimal and safe practice for clinicians involved in the emergency care of patients with probable or confirmed SARS.


title: Identification of a Bacillus thuringiensis Cry11Ba toxin-binding aminopeptidase from the mosquito, Anopheles quadrimaculatus

text: BACKGROUND: Aminopeptidase N (APN) type proteins isolated from several species of lepidopteran insects have been implicated as Bacillus thuringiensis (Bt) toxin-binding proteins (receptors) for Cry toxins. We examined brush border membrane vesicle (BBMV) proteins from the mosquito Anopheles quadrimaculatus to determine if APNs from this organism would bind mosquitocidal Cry toxins that are active to it. RESULTS: A 100-kDa protein with APN activity (APN(Anq )100) was isolated from the brush border membrane of Anopheles quadrimaculatus. Native state binding analysis by surface plasmon resonance shows that APN(Anq )100 forms tight binding to a mosquitocidal Bt toxin, Cry11Ba, but not to Cry2Aa, Cry4Ba or Cry11Aa. CONCLUSION: An aminopeptidase from Anopheles quadrimaculatus mosquitoes is a specific binding protein for Bacillus thuringiensis Cry11Ba.


title: Antiproliferative cyclodepsipeptides from the marine actinomycete Streptomyces sp. P11-23B downregulating the tumor metabolic enzymes of glycolysis, glutaminolysis, and lipogenesis

text: Abstract Two cyclodepsipeptides and a known cyclodepsipeptide valinomycin were isolated from a culture of the marine actinomycete Streptomyces sp. P11-23B. Their structures were established based on NMR, HRESIMS, and MS-MS spectroscopic interpretation as well as by chemical degradation. Both streptodepsipeptides P11A and P11B inhibited proliferation of different glioma cell lines, with IC50 values ranging from 0.1 μM to 1.4 μM. Streptodepsipeptide P11A was found to block the cell cycle at the G0/G1 phase and induce apoptosis in glioma cells. Further investigation demonstrated that streptodepsipeptide P11A downregulated expression of HK2, PFKFB3, PKM2, GLS, and FASN, important tumor metabolic enzymes. Data from this study suggested that targeting multiple tumor metabolic regulators might be one anti-glioma mechanism of streptodepsipeptide P11A. A possible mechanism for this class of streptodepsipeptides is reported herein.


title: Burden of influenza infection in hospitalised children below 6 months of age and above in Hong Kong from 2005 to 2011()

text: The World Health Organization recommends vaccination of pregnant women for seasonal influenza that can also protect infants aged below 6 months. We estimated incidence and disease burden of influenza in hospitalised children below and above 6 months of age in Hong Kong during a 6 year period. Discharge diagnoses for all admissions to public Hong Kong Hospital Authority hospitals, recorded in a central computerised database (Clinical Management System, CMS), were analysed for the period April 2005 to March 2011. Incidence estimates of influenza disease by age group were derived from CMS ICD codes 487–487.99. Laboratory-confirmed influenza infections from a single surveillance hospital were then linked to the CMS entries to assess possible over- and under-diagnosis of influenza based on CMS codes alone. Influenza was recorded as any primary or any secondary diagnosis in 1.3% (1158/86,582) of infants aged above 6 days to below 6 months and 4.3% (20,230/471,482) of children above 6 days to below 18 years. The unadjusted incidence rates per 100,000 person-years based on any CMS diagnosis of influenza in all admission to Hong Kong public hospitals were 627 in the below 2 months of age group and 1762 in the 2 month to below 6 month group. Incidence of hospitalisation for influenza in children was highest from 2 months to below 6 months. In the absence of vaccines for children below 6 months of age, effective vaccination of pregnant women may have a significant impact on reducing influenza hospitalisations in this age group.


title: Viral survival

text: How long do viruses like cold, flu and coronavirus survive outside the body? What factors affect this? Douglas Fairchild, Two Harbors, Minnesota, US


title: Implicaciones de la pandemia por COVID-19 para el paciente con insuficiencia cardiaca, trasplante cardiaco y asistencia ventricular. Recomendaciones de la Asociación de Insuficiencia Cardiaca de la Sociedad Española de Cardiología

text: Resumen La irrupción de la pandemia por COVID-19 está suponiendo un verdadero reto social y sanitario. Su rápida expansión hace que sean muchos los pacientes afectos que desarrollan clínica asociada, incluyendo síntomas cardiológicos. Los pacientes con afectación cardiaca son un grupo especialmente vulnerable, por su mayor riesgo de contagio y gravedad de la enfermedad. La insuficiencia cardiaca, incluyendo al trasplante cardiaco y las asistencias ventriculares, supone un grupo relevante dentro de los pacientes cardiológicos. Por ello, la Asociación de Insuficiencia Cardiaca de la Sociedad Española de Cardiología ha elaborado una serie de recomendaciones para el abordaje de estos pacientes, en los diferentes escenarios en los que se pueden encontrar: ambulatorio y hospitalizado, con y sin COVID-19. Abstract The outbreak of the COVID-19 pandemic is a real social and healthcare system challenge. Its rapid expansion implies that many affected patients develop associated symptoms, including cardiological symptoms. Patients with cardiological diseases are at increased risk of being infected and the severity of the disease. Heart failure, including heart transplantation and ventricular assist devices, is a relevant group within the cardiological patients. For this reason, the following text has been intended to give a series of recommendations for the management of these patients, in the different scenarios in which they can be found: outpatient and hospitalized, with and without COVID-19.


title: Gastrointestinal Diseases of Rabbits

text: Gastrointestinal stasis syndrome is a very common presentation of an ill rabbit to the veterinarian. The causes involved in this syndrome are often multifactorial, and an inappropriate diet puts the rabbit at a greater risk of developing this syndrome. Complications of this disorder can lead to gastrointestinal obstruction, a life-threatening condition that necessitates aggressive medical and in some case surgical therapy. Rabbits may also be presented with signs of diarrhea. However, abnormal cecotrophs must be differentiated from true intestinal diarrhea. The common causes, diagnosis and management of diarrhea including dysbiosis and enteritis are discussed. Other important causes of gastrointestinal disease are infectious disease and liver lobe torsion. Rabbit hemorrhagic disease virus has a new variant that has been identified in mainland Europe, the United Kingdom, and Australia. Subclinical infection of intestinal coccidiosis is a common cause of weight loss in adult rabbits. Liver lobe torsion is a challenging condition to diagnose in rabbits; this chapter discusses the presenting signs, diagnostic techniques, and therapeutic options.


title: The effect of grafted methoxypoly(ethylene glycol) chain length on the inhibition of respiratory syncytial virus (RSV) infection and proliferation

text: Abstract Respiratory syncytial virus (RSV) is a significant cause of morbidity in humans. To date, no effective treatments exist and current prophylactic therapy access is limited and is only ∼50% effective. To attenuate the risk of RSV infection, we hypothesized that bioengineering of either the virus particle or host cell via the covalent grafting of methoxypoly(ethylene glycol) [mPEG] would prevent infection. To this end, the anti-viral effects of grafting concentration, linker chemistry and polymer length on RSV infection was assessed. For viral modification, short chain polymers (2kDa) were significantly more effective than long chain (20kDa) polymers. In contrast, modification of host cells with small polymers provided no (∼0%) protection while long chain polymers effectively prevented infection. For example, at 48hours post-infection at a multiplicity of infection of 0.5 and grafting concentrations of 5, 7.5, and 15mm, 20kDa mPEG decreased infection by 45, 83, and 91%, respectively. Importantly, both viral and host cell PEGylation strategies were able to provide near complete protection against RSV infection of both non-polarized and polarized cells. In conclusion, mPEG-modification of either RSV or the host cell is a highly effective prophylactic strategy for preventing viral infection.


title: Host gene expression profiles in ferrets infected with genetically distinct henipavirus strains

text: Henipavirus infection causes severe respiratory and neurological disease in humans that can be fatal. To characterize the pathogenic mechanisms of henipavirus infection in vivo, we performed experimental infections in ferrets followed by genome-wide gene expression analysis of lung and brain tissues. The Hendra, Nipah-Bangladesh, and Nipah-Malaysia strains caused severe respiratory and neurological disease with animals succumbing around 7 days post infection. Despite the presence of abundant viral shedding, animal-to-animal transmission did not occur. The host gene expression profiles of the lung tissue showed early activation of interferon responses and subsequent expression of inflammation-related genes that coincided with the clinical deterioration. Additionally, the lung tissue showed unchanged levels of lymphocyte markers and progressive downregulation of cell cycle genes and extracellular matrix components. Infection in the brain resulted in a limited breadth of the host responses, which is in accordance with the immunoprivileged status of this organ. Finally, we propose a model of the pathogenic mechanisms of henipavirus infection that integrates multiple components of the host responses.


title: EMS in Taiwan: Past, present, and future

text: Abstract Taiwan is a small island country located in East Asia. From around 1995 modern concepts of the EMS were imported and supported by legislation. Considerable progress has since been made towards the construction of an effective pre-hospital care system. This article introduces the current status of the EMS in Taiwan, including the systems, response configurations, funding, personnel, medical directorship, and outcome research. The features and problems of in-hospital emergency care are also discussed. Key areas for further development in the country vary depending on regional differences in available resource and population density. An analysis of the strength, weakness, opportunity, and threats of the evolving EMS in Taiwan could be an example for other countries where the EMS is undergoing a similar process of development and optimisation.


COVID-19: immense necessity and challenges in meeting the needs of minorities, especially asylum seekers and undocumented migrants


Magdeleine of Martinique


title: A Recombinant Avian Infectious Bronchitis Virus Expressing a Heterologous Spike Gene Belonging to the 4/91 Serotype

text: We have shown previously that replacement of the spike (S) gene of the apathogenic IBV strain Beau-R with that from the pathogenic strain of the same serotype, M41, resulted in an apathogenic virus, BeauR-M41(S), that conferred protection against challenge with M41 [1]. We have constructed a recombinant IBV, BeauR-4/91(S), with the genetic backbone of Beau-R but expressing the spike protein of the pathogenic IBV strain 4/91(UK), which belongs to a different serogroup as Beaudette or M41. Similar to our previous findings with BeauR-M41(S), clinical signs observations showed that the S gene of the pathogenic 4/91 virus did not confer pathogenicity to the rIBV BeauR-4/91(S). Furthermore, protection studies showed there was homologous protection; BeauR-4/91(S) conferred protection against challenge with wild type 4/91 virus as shown by the absence of clinical signs, IBV RNA assessed by qRT-PCR and the fact that no virus was isolated from tracheas removed from birds primarily infected with BeauR-4/91(S) and challenged with IBV 4/91(UK). A degree of heterologous protection against M41 challenge was observed, albeit at a lower level. Our results confirm and extend our previous findings and conclusions that swapping of the ectodomain of the S protein is a precise and effective way of generating genetically defined candidate IBV vaccines.


title: A three-dimensional A549 cell culture model to study respiratory syncytial virus infections

text: Abstract Background Respiratory syncytial virus (RSV) is a primary cause of morbidity and mortality worldwide, affecting infants, young children, and immune-compromised patients; however, currently no vaccine is available for prevention of RSV infections. The overwhelming majority of our knowledge of how RSV causes infection is based upon studies that have been carried out using traditional 2D methods, with cells cultured on flat plastic dishes. Although these simplified culture systems are essential to gain an insight into the fundamentals of host-pathogen interactions, cells in 2D are not exposed to the same conditions as cells in 3D tissues in the body and are therefore a poor representation of thein vivo microenvironment. In this study, we aim to develop the first 3D culture model for RSV infection using A549 cells to test its utility for RSV pathogenesis. Methods To generate spheroids, A549 cells were cultured using ultra-low attachment plates to generate 25 × 103 cell spheroids. The viability of the spheroids was assessed by trypan blue exclusion assay and flow cytometry showing prominent live cells throughout the spheroids confirming high viability over seven days of incubation. Results Immunostaining of A549 spheroids inoculated with RSV, showed time-dependent dissemination of the viral antigen RSV-F within the spheroid, resulting in syncytia formation and a 3-fold increase in mucin secretion compared to the uninfected cells. Additionally, RSV successfully replicated in the spheroids producing infectious virus as early as day one post-inoculation and was sustained for up to 7 days post-inoculation. Conclusions Results show that A549 spheroids are susceptible and permissive for RSV since they exhibit the characteristics of RSV infection including syncytia formation and mucin overexpression, suggesting that A549 spheroids can be used a promising model for studying RSV in vitro.


title: SARS outbreaks in Ontario, Hong Kong and Singapore: the role of diagnosis and isolation as a control mechanism

text: Abstract In this article we use global and regional data from the SARS epidemic in conjunction with a model of susceptible, exposed, infective, diagnosed, and recovered classes of people (“SEIJR”) to extract average properties and rate constants for those populations. The model is fitted to data from the Ontario (Toronto) in Canada, Hong Kong in China and Singapore outbreaks and predictions are made based on various assumptions and observations, including the current effect of isolating individuals diagnosed with SARS. The epidemic dynamics for Hong Kong and Singapore appear to be different from the dynamics in Toronto, Ontario. Toronto shows a very rapid increase in the number of cases between March 31st and April 6th, followed by a significant slowing in the number of new cases. We explain this as the result of an increase in the diagnostic rate and in the effectiveness of patient isolation after March 26th. Our best estimates are consistent with SARS eventually being contained in Toronto, although the time of containment is sensitive to the parameters in our model. It is shown that despite the empirically modeled heterogeneity in transmission, SARS’ average reproductive number is 1.2, a value quite similar to that computed for some strains of influenza (J. Math. Biol. 27 (1989) 233). Although it would not be surprising to see levels of SARS infection higher than 10% in some regions of the world (if unchecked), lack of data and the observed heterogeneity and sensitivity of parameters prevent us from predicting the long-term impact of SARS. The possibility that 10 or more percent of the world population at risk could eventually be infected with the virus in conjunction with a mortality rate of 3–7% or more, and indications of significant improvement in Toronto support the stringent measures that have been taken to isolate diagnosed cases.


Organisations for patients with cancer feel the brunt of COVID-19 pandemic


title: Modeling and forecasting the COVID-19 pandemic in India

text: In India, 1,00,340 confirmed cases and 3,155 confirmed deaths due to COVID-19 were reported as of May 18, 2020. Due to absence of specific vaccine or therapy, non-pharmacological interventions including social distancing, contact tracing are essential to end the worldwide COVID-19. We propose a mathematical model that predicts the dynamics of COVID-19 in 17 provinces of India and the overall India. A complete scenario is given to demonstrate the estimated pandemic life cycle along with the real data or history to date, which in turn divulges the predicted inflection point and ending phase of SARS-CoV-2. The proposed model monitors the dynamics of six compartments, namely susceptible (S), asymptomatic (A), recovered (R), infected (I), isolated infected (I(q)) and quarantined susceptible (S(q)), collectively expressed SARII(q)S(q). A sensitivity analysis is conducted to determine the robustness of model predictions to parameter values and the sensitive parameters are estimated from the real data on the COVID-19 pandemic in India. Our results reveal that achieving a reduction in the contact rate between uninfected and infected individuals by quarantined the susceptible individuals, can effectively reduce the basic reproduction number. Our model simulations demonstrate that the elimination of ongoing SARS-CoV-2 pandemic is possible by combining the restrictive social distancing and contact tracing. Our predictions are based on real data with reasonable assumptions, whereas the accurate course of epidemic heavily depends on how and when quarantine, isolation and precautionary measures are enforced.


SARS‐CoV2 as a potential trigger of neurodegenerative diseases


title: Challenges posed by new and re-emerging infectious diseases in livestock production, wildlife and humans

text: Abstract In today's world, emerging and re-emerging diseases have a significant impact on global economies and public health, and with bioterrorism a constant threat this has become a very topical subject in recent years. Bernard Vallat, director general of the OIE, made the statement, “As a result of globalisation and climate change we are currently facing an unprecedented worldwide impact of emerging and re-emerging animal diseases and zoonoses”. He is not alone in this thinking, but are we facing an unprecedented impact of diseases and are globalisation and climate change the main driving forces? This paper examines some historical disease outbreaks and the factors that played a role in their emergence and compares these with recent emerging diseases. In doing so it highlights certain challenges that face livestock producers and decision makers today as they grapple with emerging diseases. One of the driving forces for the emergence of diseases is translocation of people and their livestock and this has often been coupled with invading armies or peoples, political unrest and a concurrent environment of socio-economic upheaval. Contact between wild animals, domestic animals and people is another driving force involving the interaction between naïve population groups that induces the emergence of new diseases. Pandemics are not new to human society and nor are many of the driving forces that caused them to occur in the past; what has changed is our increased knowledge and awareness of disease dynamics, allowing identification of challenges for the future and ways of addressing these. Modern farming practices often serve to amplify emerging infectious diseases and modern trade and transport mechanisms and routes have served to sometimes accelerate the spread of disease. How can we reduce the risks and should we only be worried about emerging infectious diseases or are emerging non-communicable diseases just as important in our modern society? This paper serves to explain some of the reasons for the emergence of diseases and to try and answer some of the pressing questions that confront livestock producers today.


title: An enzyme-linked immunosorbent assay using canine coronavirus-infected CRFK cells as antigen for detection of anti-coronavirus antibody in cat

text: Abstract From the reasons that canine coronavirus (CCV) grows more efficiently than feline coronavirus in a cell culture and they are mutually related in their antigenicities, an enzyme-linked immunosorbent assay (ELISA) using CCV-infected feline kidney (CRFK) cells as substrate antigens was developed for detection of anti-coronavirus antibodies in cats. It was indispensable for generating coronavirus-specific ELISA antibody activities that the sample was applied to the mock-infected, normal CRFK cells in parallel with the CCV-infected cells and then the optical density values given by the mock-infected cell antigen were subtracted from those given by the virus-infected cell antigen. On the basis of ELISA antibody titers obtained in sera from the cats experimentally infected with CCV and from the spontaneous feline infectious peritonitis (FIP) cases, the ELISA described in the present study was found to be applicable as a simple and easy serologic test which was able to detect anti-coronavirus antibodies as efficiently as the indirect immunofluorescence assay with homologous FIP virus.


title: Effects of Methylprednisolone Pulse Therapy on Refractory Mycoplasma pneumoniae Pneumonia in Children

text: PURPOSE: Mycoplasma pneumoniae (M. pneumoniae) is one of the most common causes of community-acquired pneumonia in children. The clinical course is typically self-limited and benign; however, rare cases of severe pneumonia can develop despite appropriate antibiotic therapy. We studied the effects of methylprednisolone pulse therapy on severe refractory M. pneumoniae pneumonia in children. METHODS: The clinical effects of methylprednisolone therapy were evaluated retrospectively in 12 children with severe refractory M. pneumoniae pneumonia, which was diagnosed serologically. All patients developed respiratory distress, high fever, and initial lobar pneumonic consolidation based on radiological findings. All clinical symptoms deteriorated despite appropriate antibiotic therapy. Thus, children were treated with intravenous methylprednisolone pulse therapy in addition to antibiotics. RESULTS: The average febrile period before admission was 4.9±1.7 days, and fever persisted in all children until steroid administration. Methylprednisolone pulse therapy (30 mg/kg) was given 5.4±2.5 days after admission. After methylprednisolone pulse therapy, clinical symptoms improved in all patients without adverse events. The fever subsided 0-2 h after initiation of corticosteroid therapy. The abnormal radiological findings resolved within 2.6±1.3 days, and the high C-reactive protein levels (6.7±5.9 mg/dL) on admission decreased to 1.3±1.7 mg/dL within 3.0±1.1 days after starting corticosteroid therapy. CONCLUSIONS: Three-day methylprednisolone pulse therapy could be applied to treatment of refractory M. pneumoniae pneumonia despite appropriate antibiotic therapy and appeared to be efficacious and well-tolerated.


title: Associations between Single Nucleotide Polymorphisms in Cellular Viral Receptors and Attachment Factor-Related Genes and Humoral Immunity to Rubella Vaccination

text: BACKGROUND: Viral attachment and cell entry host factors are important for viral replication, pathogenesis, and the generation and sustenance of immune responses after infection and/or vaccination, and are plausible genetic regulators of vaccine-induced immunity. METHODS: Using a tag-SNP approach in candidate gene study, we assessed the role of selected cell surface receptor genes, attachment factor-related genes, along with other immune genes in the genetic control of immune response variations after live rubella vaccination in two independent study cohorts. RESULTS: Our analysis revealed evidence for multiple associations between genetic variants in the PVR, PVRL2, CD209/DC-SIGN, RARB, MOG, IL6 and other immune function-related genes and rubella-specific neutralizing antibodies after vaccination (meta p-value <0.05). CONCLUSION: Our results indicate that multiple SNPs from genes involved in cell adhesion, viral attachment, and viral entry, as well as others in genes involved in signaling and/or immune response regulation, play a role in modulating humoral immune responses following live rubella vaccination.


title: Innovative “Bring-Service-Near-Your-Home” Operations under Corona-Virus (COVID-19/SARS-CoV-2) Outbreak: Can Logistics Become the Messiah?

text: Abstract The corona virus (COVID-19/SARS-CoV-2) outbreak has created serious disruptions to many business operations. Among them, many service operations, which require customers to travel and visit a place indoor, become almost infeasible to run in a crowded city like Hong Kong. Motivated by a recent reported real case on an innovative service operation in Hong Kong, we build analytical models to explore how logistics and technologies together can transform the “static service operations” to become the “bring-service-near-your-home” mobile service operations. We also highlight how the government may provide the subsidy to support the above mentioned mobile service operation (MSO) to make it financially viable. We specifically show that the government may adopt the fixed-cost-subsidy (FCS) scheme, operations-cost-subsidy (OCS) scheme or safety-technology-support (STS) scheme to help. We further uncover that the OCS scheme would bring a larger consumer surplus than the FCS scheme and is hence more preferable. In the extended models, we first study the case when service fee cannot be changed because of corona virus outbreak (CVO). We then explore the feasibility of adopting MSO in the long run as a financially self-sustainable service operation and derive the analytical conditions under which MSO is a win-win business model for both the service provider and consumers. Finally, we study the optimal safety technology investment problem.


title: Characterization of anti-porcine epidemic diarrhea virus neutralizing activity in mammary secretions

text: Abstract Porcine epidemic diarrhea virus (PEDV) causes a severe clinical enteric disease in suckling neonates with up to 100% mortality, resulting in devastating economic losses to the pork industry in recent years. Maternal immunity via colostrum and milk is a vital source to neonates of passive protection against diarrhea, dehydration and death caused by PEDV. Comprehensive information on neutralizing activity (NA) against PEDV in mammary secretions is critically important for assessing the protective capacity of sows. Therefore, the objectives of this study were to characterize anti-PEDV neutralizing activity in mammary secretions. Anti-PEDV NA was present in colostrum, milk and serum from PEDV-infected sows as determined both by immunofluorescence and ELISA-based neutralizing assays, with neutralization levels higher in colostrum and milk than in serum. The highest NA was observed in colostrum on day 1, and decreased rapidly in milk at day 3, then gradually declined from day 3 to day 19 post-farrowing. Notably, the NA in mammary secretions showed various patterns of decline over time of lactation that may contribute to variation in sow protective capacities. The kinetics of NA decline were associated with total IgA and IgG antibody levels. Neutralizing activity significantly correlated with specific IgA primarily to spike domain 1 (S1) and domain 2 (S2) proteins of PEDV rather than to specific IgG in colostrum. Subsequently, the NA in milk was mainly related to specific IgA to S1 and S2 during lactation.


title: The first confirmed case of COVID-19 in Tanzania: recommendations based on lesson learned from China

text: As the coronavirus disease (COVID-19) takes its course outside China, the number of imported cases to other countries is on the rise. Currently, Tanzania has received the first imported case on 16 March 2020. This letter serves to describe this specific event and put forth a number of recommendations including establishing more testing points, discouraging all forms of public and religious gatherings, and tailoring a unique model for lockdown and social distancing to prevent further spread of the disease. The letter has also suggested ways to further improve the efforts already in place so as to strengthen the prevention and control system.


title: COVID-19: A Revelation – A reply to Ian Mitroff

text: Abstract This is a rejoinder of Dr. Ian Mitroff's perspective titled "Corona Virus: A Prime Example of A Wicked Mess". While I agree with Dr. Mitroff on the complexity of the COVID-19 outbreak and the urgency to address it, I disagree with him on points related to the role of wet market in this specific outbreak and whether China had acknowledged the existence of the outbreak. I also consider key highlights of the outbreak are the importance of collaboration across national and state borders and a balance between privacy and public health under such situations.


title: Conduction abnormalities in hydroxychloroquine add on therapy to lopinavir/ritonavir in COVID‐19

text: COVID-19 is a contagious disease caused by Severe Adult Respiratory Syndrome Corona Virus-2 (SARS-CoV-2). Currently the role of HCQ in COVID-19 remains controversial but HCQ continued to be used in the absence of any effective therapy. We showed that cardiac conduction abnormalities were common in patients with HCQ added on to lopinavir/ritonavir. After starting HCQ, there were 5 (45.5%) new events of which four (36.3%) were attributed to HCQ: QTc prolongations in 3 patients with additional development of conduction blocks (fascicular block and right bundle brunch block in one patient respectively) and one patient with bradycardia. All conduction abnormalities settled after discontinuation of HCQ. Therefore monitoring is recommended when considering HCQ in treating patients with COVID-19. This article is protected by copyright. All rights reserved.


title: The influence of stabilizers and rates of freezing on preserving of structurally different animal viruses during lyophilization and subsequent storage

text: AIMS: To make a comparative evaluation of the effects of different stabilizers and freezing rates on structurally different viruses during lyophilization and storage. METHODS AND RESULTS: Two virus strains from each of six animal virus families, including both enveloped and nonenveloped viruses, were lyophilized in (i) culture medium, (ii) with the addition of gelatine–sucrose and (iii) skim milk–sodium glutamate. All the virus suspensions were frozen (i) at −80°C or (ii) in liquid nitrogen before lyophilization. Virus titre assay after lyophilization and after 8 months storage at 4°C revealed that the efficacy of stabilizers depended on virus structure. Generally, the best protective quality for enveloped viruses was achieved with gelatine–sucrose, which best maintained their infectivity and envelope morphology. Even additive‐free culture medium proved adequate for nonenveloped viruses. Differences in stabilizer efficacy were also found between virus families and were expressed immediately after lyophilization; the activity of stabilizers in the course of storage was very similar. Freezing in liquid nitrogen proved beneficial for picornaviruses. CONCLUSIONS: The choice of an appropriate stabilizer with respect to virus type is crucial for effective lyophilization. SIGNIFICANCE AND IMPACT OF THE STUDY: This study contributes to the establishment of general guidelines for animal virus lyophilization, with particular respect to differences in virus structure.