title: Some aspects of humoral and cellular immunity in naturally occuring feline infectious peritonitis

text: Abstract Haematology, antibody titers and serum protein electrophoresis from 48 cats (34 effusive and 14 noneffusive forms) affected with feline infectious peritonitis (FIP) were studied and compared with those of 20 healthy cats. In the effusive form, antibody titers and protein electrophoresis in the effusions were analyzed. The distribution of the immune cells and of the virus in FIP lesions were also investigated immunohistochemically with the avidin–biotin complex (ABC) method, using antibodies against the FIP virus (FIPV), myelomonocytic (MAC387) and lymphoid (CD3, CD4 and CD8 for T-cells and IgM and IgG for B-cells) antigens. Seropositive animals (antibody titer>1:100) were present among both the FIP infected cats (73%) and the healthy cats (70%). Cats with effusive FIP had neutrophilic leukocytosis (P>0.05), lymphopenia (P<0.01) and eosinopenia (P<0.001). In both effusive and noneffusive forms decreased albumin/globulin ratio (P<0.001) with hypoalbuminemia (P<0.001), hyperglobulinemia (P<0.001) and increased α2- (P<0.05), β- (P<0.05) and γ-globulins (P<0.001) were found. Hypergammaglobulinemia was not related to the antibody titers, suggesting the presence of other proteins with γ-motility (e.g. complement fractions). The electrophoretic pattern of the effusions was always similar to that of the corresponding serum. Antibody titers higher than those of the corresponding serum were often detected in the effusions. Immunohistochemical findings were not related to the antibody titers, but they were related to the histological aspect of the lesions. In cellular foci of FIP lesions many virus-infected macrophages and few lymphocytes, mainly CD4+, were found. Extracellular viral and myelomonocytic antigens were also detectable in the foci with intercellular necrosis. Only few FIPV-infected cells were present at the periphery of the larger necrotic foci: in these lesions MAC387+ cells were mainly neutrophils, with many MAC387− macrophages, probably due to their activated state; a small number of lymphocytes, with an increasing percentage of CD8+ cells was present. Lymphocytes were more abundant when cellular foci and FIP-infected macrophages were centered around neoformed vessels. IgM and IgG exposing B-cells were always few and scattered. In conclusion the simultaneous analysis of body fluids and of the cellular composition of the lesions showed a complex immune status, on which type III and type IV hypersensitivity could coexist.


title: Predictors of MERS-CoV infection: A large case control study of patients presenting with ILI at a MERS-CoV referral hospital in Saudi Arabia

text: Summary Background A case control study to better characterize the clinical features, laboratory, and radiological abnormalities associated with MERS-CoV infection in order to help with early identification of this syndrome from other respiratory infections. Methods Eighty patients admitted to a hospital in Riyadh, diagnosed with MERS-CoV infection based on RT-PCR were matched on age, sex, and the presence of a co-morbid condition on a basis of 1:2 to other patients admitted with respiratory symptoms and tested negative for MERS-CoV on RT-PCR. Results None of the reported MERS-CoV presenting symptoms was significantly associated with being infected with MERS-CoV. On the other hand, WBC count was significantly lower in patients with confirmed MERS-CoV infection (median 5.7 vs 9.3, P: 0.0004). Neutrophil count was as well significantly lower in MERS-CoV patients (median 3.7 vs 6.7, P: 0.0001). Both AST, and ALT values were significantly higher in MERS-CoV infected group (AST median 42 vs 36, P: 0.03, and ALT median 33 vs 28, P: 0.003). Overall our MERS-CoV mortality rate was (10%) below the national figure of (40%). Conclusions None of the presenting symptoms are specific for MERS-CoV infection. And out of all the investigations WBC, neutrophil counts, AST and ALT values have some predictive utility.


title: Enteric coronavirus infection in adult horses

text: Abstract A new enteric virus of adult horses, equine coronavirus (ECoV), has recently been recognized. It is associated with fever, lethargy, anorexia, and less frequently, colic and diarrhea. This enteric virus is transmitted via the feco-oral route and horses become infected by ingesting fecally contaminated feed and water. Various outbreaks have been reported since 2010 from Japan, Europe and the USA. While the clinical signs are fairly non-specific, lymphopenia and neutropenia are often seen. Specific diagnosis is made by the detection of ECoV in feces by either quantitative real-time PCR, electron microscopy or antigen-capture ELISA. Supportive treatment is usually required, as most infections are self-limiting. However, rare complications, such as endotoxemia, septicemia and hyperammonemia-associated encephalopathy, have been reported, and have been related to the loss of barrier function at the intestinal mucosa. This review article will focus on the latest information pertaining to the virus, epidemiology, clinical signs, diagnosis, pathology, treatment and prevention of ECoV infection in adult horses.


French ICUs fight back: an example of regional ICU organisation to tackle the SARS Cov-2 outbreak


title: What Dentists Need to Know about COVID-19

text: Abstract This article aims at collecting all information needed for dentists regarding the COVID-19 pandemic throughout the world by reviewing articles published by now. In late 2019, a pneumonia outbreak of uncertain etiology happened in Wuhan, China. There were many reports related to a live-animal and seafood market, supporting that the pathogens were transferred from animals to humans, rapidly evolving into transmission from human to human. The pathogen was classified as 2019 Novel Corona Virus (2019-nCoV), and the disease was named COrona VIrus Disease 2019 (COVID-19). Given that COVID-19 has lately been detected in infected patients’ saliva, the COVID-19 outbreak is an alert that all dental and other health professionals must be vigilant in defending against the infectious disease spread, and it may enable to assess whether non-invasive saliva diagnostic for COVID-19. There has so far been no evidence from randomized controlled trials to prescribe any particular anti-nCoV treatment or vaccine, and COVID-19 management has been widely supportive. Since the ACE-2 was expressing on oral cavity mucosa, there is a potentially huge COVID-19 infectious vulnerability risk for oral cavity and brought up a proof for the future prevention procedure in dental practice and daily life. As a result, the whole dental teams should be vigilant and keep patients and themselves in a safe environment by following the guideline in this study.


title: The impact of synthetic biology on drug discovery

text: The emergence of synthetic biology is holding great hopes for providing solutions to the unmet needs of humankind. This review article describes how synthetic biology can deliver on this promise in the field of drug discovery by providing novel opportunities throughout the entire drug discovery process. Synthetic biology tools enable disease mechanisms and target identification to be elucidated and also provide avenues to discover small chemotherapeutic molecules or design novel biopharmaceuticals. Furthermore, synthetic biologists can design cost-effective microbial production processes for complex natural products, which could help overcome global drug shortages. These impressive advances have been achieved in only a few years, and are an indicator for the potential of synthetic biology.


title: Chapter Twelve Policy Support and Resources Mobilization for the National Schistosomiasis Control Programme in The People's Republic of China

text: Abstract Schistosomiasis remains a public health problem in many developing countries around the world. After the founding of The People's Republic of China, from 1949 till date, all levels of government, from central to local, have been attaching great importance to schistosomiasis control in The People's Republic of China. With considerable policy support and resources mobilization, the national schistosomiasis control programmes have been implemented during the past 65years. Here, we summarize the successful experience of schistosomiasis control during the process. Recommendations for the future management of the Chinese national schistosomiasis elimination programme are put forward after considering the remaining challenges, shortcomings and lessons learnt from 65years of schistosomiasis control drives in The People's Republic of China. They will help to sustain past achievements, foster the attainment of the ultimate goal of schistosomiasis elimination for the country and provide reference for schistosomiasis control programme in other countries.


title: Phylogeny of Viruses☆

text: Abstract Biological species, including viruses, change through generations and over time in the process known as evolution. Viruses may evolve at high, uneven, and fluctuating rates among genome sites. The accumulated changes, through either mutation or recombination with other species, are first fixed in the genome of successful individuals that give rise to genetic lineages. The relationship between biological lineages related by common descent is called ‘phylogeny’. For inferring phylogeny, the differences between aligned sequences of genomes and proteins are quantified and depicted in the form of a tree, in which contemporary species and their intermediate and common ancestors occupy, respectively, the terminal nodes, internal nodes, and the root. The tree is characterized by a topology, length of branches, shape, and the root position. A complex mathematical apparatus has been developed for phylogeny inference that can evaluate inter-species differences, facilitate tree building and comparison of trees, and assess the fit between data and tree through, typically, computationally intensive calculations. A reconstructed tree is an approximation of the true phylogeny that practically remains unknown. The phylogenetic analysis is used in applied and fundamental virus research, including epidemiology, diagnostics, forensic studies, phylogeography, evolutionary studies, and virus taxonomy. It can provide an evolutionary perspective on variation of any trait that can be measured for a group of viruses.


title: Effects of plane of milk-replacer nutrition on the health, behavior, and performance of high-risk Holstein bull calves from a commercial calf ranch

text: ABSTRACT Objective This research study aimed to determine whether preweaning plane of milk-replacer nutrition influences health, standing and oral behaviors, and performance of high-risk calves. Materials and Methods Thirty-six Holstein bull calves (1 d of age) from a commercial calf ranch were assigned to either a high plane of milk-replacer nutrition (HPN; n = 18; 20 and 28% DM lipid and protein, respectively, Cow’s Match, Land O’Lakes Animal Milk Protein Co., Shoreview, MN) or a low plane of milk-replacer nutrition (LPN; n = 18; 20% DM lipid and protein, Herd Maker, Land O’Lakes Animal Milk Protein Co.) through weaning. Total serum protein concentrations confirmed that 72 and 76% of calves had failure of passive transfer (<5.2 g/dL) in HPN and LPN, respectively. All calves were bottle fed twice daily. The LPN were fed 455 g of DM/d of milk replacer (MR) until weaning, and the HPN calves were fed 830 g of DM/d of milk replacer during the first 10 d and 1,080 g from 11 d until weaning. Calf starter and water were offered ad libitum. Calves were step-down weaned beginning at 51 d and completely weaned after 58 d when consuming 1 kg of calf starter (as-fed basis). Data are reported as HPN versus LPN throughout, respectively. Results and Discussion Risk for bloat and scouring were greater for calves fed the HPN, but there was no difference in antibiotic treatment or mortality. The HPN calves had greater performance over the preweaning period including final BW, ADG, and feed:gain (total kg of milk replacer + calf starter, kg of DM/kg of BW gain), but weaning was more stressful for HPN calves. Implications and Applications In conclusion, the high-risk calves fed a HPN had increased preweaning ADG, but there was also an increased incidence of scours. There may be differences in the health status of calves that may affect the ability to consume and use high MR levels. When feeding high-risk calves there may be a need for alternate strategies when determining the quality and quantity of MR being fed when compared with low-risk calves. Differences in gut integrity may influence the ability of high-risk calves to handle high levels of MR early in life. Potential issues with high-risk calves being fed a HPN might be reduced with increased feeding times per day, a gradual step-up method, or other nutritional strategies that improve gastrointestinal development and function.


title: Nuclear Factor-κB: a Key Regulator in Health and Disease of Lungs

text: Rel/NF-κB transcription factors play a key role in modulating the response of immunoregulatory genes including cytokines and chemokines, cell adhesion molecules, acute phase proteins, and anti-microbial peptides. Furthermore, an array of genes important for angiogenesis, tumor invasion and metastasis is also regulated by nuclear factor-κB (NF-κB). Close association of NF-κB with inflammation and tumorigenesis makes it an attractive target for basic research as well as for pharmaceutical industries. Studies involving various animal and cellular models have revealed the importance of NF-κB in pathobiology of lung diseases. This review (a) describes structures, activities, and regulation of NF-κB family members; (b) provides information which implicates NF-κB in pathogenesis of pulmonary inflammation and cancer; and (c) discusses information about available synthetic and natural compounds which target NF-κB or specific components of NF-κB signal transduction pathway and which may provide the foundation for development of effective therapy for lung inflammation and bronchogenic carcinomas.


title: Integrated centrifugal reverse transcriptase loop-mediated isothermal amplification microdevice for influenza A virus detection

text: Abstract An integrated reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) microdevice which consists of microbead-assisted RNA purification and RT-LAMP with real-time monitoring by a miniaturized optical detector was demonstrated. The integrated RT-LAMP microdevice includes four reservoirs for a viral RNA sample (purified influenza A viral RNA or lysates), a washing solution (70% ethanol), an elution solution (RNase-free water), and an RT-LAMP cocktail, and two chambers (a waste chamber and an RT-LAMP reaction chamber). The separate reservoirs for a washing solution, an elution solution, and an RT-LAMP cocktail were designed with capillary valves for stable storage. Three influenza A virus strains (A/H1N1, A/H3N2, and A/H5N1) were used for RNA templates, and RT-LAMP primer sets were designed to detect hemagglutinin (HA) and conserved M gene. Sequential sample flow to the microbeads for RNA purification was achieved by centrifugal force with optimization of capillary valves and a siphon channel. Furthermore, the purified RNA solution was successfully isolated from the waste solution by changing the rotational direction, and combined with the RT-LAMP cocktail in the RT-LAMP reaction chamber for target gene amplification. Total process from the sample injection to the result was completed in 47min. Influenza A H1N1 virus was confirmed on the integrated RT-LAMP microdevice even with 10 copies of viral RNAs, which revealed 10-fold higher sensitivity than that of a conventional RT-PCR. Subtyping and specificity test of influenza A H1N1 viral lysates were also performed and clinical samples were successfully genotyped to confirm influenza A virus on our proposed integrated microdevice.


title: Role of Cytomegalovirus Infection in the Incidence of Viral Acute Respiratory Infections in Children Attending Day-Care Centers

text: In a prospective study carried out in Lyon, France, the association between the excretion of cytomegalovirus (CMV) and the increasing frequency and severity of viral respiratory infections in children attending day-care centers was evaluated. Urine samples were collected in November 1992 (S1) and 4 months later in February 1993 (S4). A total of 246 children aged 6–12 months attending 29 day-care centers from 1 November to 28 February were screened for the excretion of CMV in urine. The diagnosis of viral acute respiratory infection was performed in the case of outbreaks only. Forty-eight (19.5%) children were both S1 and S4 positive for CMV, 30 (12.4%) became CMV positive (S1–/S4+), 4 (1.6%) became negative (S1+/S4–) and 164 (66.7%) remained negative. The percentage of children becoming CMV positive was significantly (P<0.001) higher in day-care centers where more than 40 children were enrolled. Nine outbreaks due to respiratory syncytial virus, rhinovirus and enterovirus were recorded in 8 of 29 (27.6%) day-care centers. Viral acute respiratory infections were significantly (P<0.05) more frequently recorded in day-care centers in which CMV and respiratory viruses cocirculated and were significantly (P<0.001) more frequently reported in CMV-infected children. These findings suggest that viral acute respiratory infections are significantly more likely to occur in CMV-infected children.


title: First detection of bovine group B rotavirus in Japan and sequence of its VP7 gene

text: An epizootic outbreak of diarrhea occurred in adult cows on a dairy farm in Hokkaido, Japan. One colostrum-fed calf inoculated with pooled feces of the 5 affected cows, developed mild diarrhea, and shed rotavirus-like parti cles which reacted with antiserum to group B rotavirus in immune electron microscopy. Cell culture immunofluorescence tests, RNA-polyacrylamide gel electrophoresis and RT-PCR confirmed that this virus was bovine group B rota virus, which was designated the Nemuro strain. Additional 2 colostrum-deprived calves inoculated with feces of the first calf also developed diarrhea and shed virus, suggesting that this group B rotavirus might be the etiological agent of the outbreak of adult cow diarrhea. The identities of the nucleotide (nt) and deduced amino acid (aa) sequences of the Nemuro VP7 gene were high (93–95% in nt and 96–97% in aa) and low (61–63% in nt and 49–61% in aa) compared to those of the published corresponding genes from 3 bovine and 2 other mammalian (human and rat) strains of group B rotaviruses, respectively. To our knowledge, this is the first report on the presence of bovine group B rotavirus in Japan.


title: Gene and cytokine profile analysis of macrolide-resistant Mycoplasma pneumoniae infection in Fukuoka, Japan

text: BACKGROUND: Recent epidemiologic data suggest that the prevalence of macrolide resistant Mycoplasma pneumoniae (MR-M. pneumoniae) is increasing rapidly worldwide. This study assessed the present status of M. pneumoniae infection in Japan and clinical end-points to distinguish children with MR-M. pneumoniae. METHODS: During an outbreak of M. pneumoniae infections in Fukuoka, Japan in 2010–11, a total of 105 children with clinically suspected M. pneumoniae infection were enrolled. M. pneumoniae was analyzed for macrolide resistance in domain V of the 23S rRNA gene. Sixty -five patients with PCR positive for M. pneumoniae were analyzed with regard to clinical symptoms, efficacy of several antimicrobial agents and several laboratory data. RESULTS: Causative pathogens were detected in 81.0% (85 of 105) and M. pneumoniae was identified 61.9% (65 of 105). The resistance rate of M. pneumoniae was 89.2% (58 of 65) in this general pediatric outpatient setting. Patients infected with MR-M. pneumoniae showed longer times to resolution of fever and required frequent changes of the initially prescribed macrolide to another antimicrobial agent. We observed three different genotypes of M. pneumoniae including the rarely reported A2063T mutation (A2063G: 31 strains, A2063T: 27 strains, no mutation: 7 strains). Drug susceptibility testing showed different antimicrobial susceptibility profiles for each genotype. Serum IFN-gamma, IL-6 and IP-10 levels were higher in patients with MR-genotypes than in those infected with no-mutation strains (p < 0.001). CONCLUSIONS: Macrolide resistance is more common than previously thought and a small epidemic of rarely reported A2063T mutation was observed in Fukuoka, Japan. Furthermore our results reveal the possibility that levels of certain inflammatory cytokines may be a candidate to predict MR-M.pneumoniae infection.


title: Visualization of HTLV-1–Specific Cytotoxic T Lymphocytes in the Spinal Cords of Patients With HTLV-1–Associated Myelopathy/Tropical Spastic Paraparesis

text: Activated human T-lymphotropic virus type-1 (HTLV-1)–specific CD8-positive cytotoxic T lymphocytes (CTLs) are markedly increased in the periphery of patients with HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP), an HTLV-1–induced inflammatory disease of the CNS. Although virus-specific CTLs play a pivotal role to eliminate virus-infected cells, the potential role of HTLV-1–specific CTLs in the pathogenesis of HAM/TSP remains unclear. To address this issue, we evaluated the infiltration of HTLV-1–specific CTLs and the expression of HTLV-1 proteins in the spinal cords of 3 patients with HAM/TSP. Confocal laser scanning microscopy with our unique staining procedure made it possible to visualize HTLV-1–specific CTLs infiltrating the CNS of the HAM/TSP patients. The frequency of HTLV-1–specific CTLs was more than 20% of CD8-positive cells infiltrating the CNS. In addition, HTLV-1 proteins were detected in CD4-positive infiltrating T lymphocytes but not CNS resident cells. Although neurons were generally preserved, apoptotic oligodendrocytes were frequently in contact with CD8-positive cells; this likely resulted in demyelination. These findings suggest that the immune responses of the CTLs against HTLV-1–infected CD4-positive lymphocytes migrating into the CNS resulted in bystander neural damage.


title: Design, synthesis, antiviral and cytostatic activity of ω-(1H-1,2,3-triazol-1-yl)(polyhydroxy)alkylphosphonates as acyclic nucleotide analogues

text: Abstract The efficient synthesis of a new series of polyhydroxylated dibenzyl ω-(1H-1,2,3-triazol-1-yl)alkylphosphonates as acyclic nucleotide analogues is described starting from dibenzyl ω-azido(polyhydroxy)alkylphosphonates and selected alkynes under microwave irradiation. Selected O,O-dibenzylphosphonate acyclonucleotides were transformed into the respective phosphonic acids. All compounds were evaluated in vitro for activity against a broad variety of DNA and RNA viruses and for cytostatic activity against murine leukemia L1210, human T-lymphocyte CEM and human cervix carcinoma HeLa cells. Compound (1S,2S)-16b exhibited antiviral activity against Influenza A H3N2 subtype (EC50 =20μM—visual CPE score; EC50 =18μM—MTS method; MCC >100μM, CC50 >100μM) in Madin Darby canine kidney cell cultures (MDCK), and (1S,2S)-16k was active against vesicular stomatitis virus and respiratory syncytial virus in HeLa cells (EC50 =9 and 12μM, respectively). Moreover, compound (1R,2S)-16l showed activity against both herpes simplex viruses (HSV-1, HSV-2) in HEL cell cultures (EC50 =2.9 and 4μM, respectively) and feline herpes virus in CRFK cells (EC50 =4μM) but at the same time it exhibited cytotoxicity toward uninfected cell (MCC⩾4μM). Several other compounds have been found to inhibit proliferation of L1210, CEM as well as HeLa cells with IC50 in the 4–50μM range. Among them compounds (1S,2S)- and (1R,2S)-16l were the most active (IC50 in the 4–7μM range).


title: Persistence of lymphocytopenia with CT abnormalities among patients with critical H7N9 swine-origin influenza A virus infection

text: PURPOSE: H7N9 is an emerging pathogen with associated morbidity and mortality, and a broader understanding of the chest radiographic characteristics associated with human H7N9 infections is needed. This study was performed to determine the time course of recovery from lymphocytopenia and resolution of pneumonitis of critical H7N9 infection patients. MATERIALS AND METHODS: We performed chest X-ray and computed tomography (CT) for patients with H7N9 influenza. Lesion patterns, distributions, and changes at follow-up chest X-ray and/or CT were investigated. The time to progression on chest CT image, and the time to resolution of the chest CT findings were assessed. RESULTS: Lymphocytopenia was a common laboratory test abnormality. The most common CT findings were lobar consolidation with air bronchogram and ground-glass opacities. For 7 recovering patients, the time to resolution of the chest CT findings was 10–90 days. Fibrosis and traction bronchiectasis were the main features on the CT scans of recovering patients. Interestingly, the time to recovery from lymphopenia was highly consistent with time to resolution of the chest CT findings. CONCLUSIONS: We have shown the presence of radiographic abnormalities among H7N9 patients. Monitoring of the variation of lymphocytes for H7N9 patients has important clinical significance, especially for prediction of the resolution of pneumonitis.


title: Transmissible gastroenteritis coronavirus: surface antigens induced by virulent and attenuated strains

text: Summary Three strains of the transmissible gastroenteritis virus (TGEV) possessing different degrees of pathogenicity for piglets were examined for their capacity to express M and S glycoproteins on the infected cell surface using a microwell immunoperoxidase test. These two viral glycoproteins were easily detected on the plasma membrane of 0.1 % paraformaldehyde-fixed swine testis (ST) or pig kidney (RP.D) cells which were infected with high-passaged Purdue-115 and low-passaged D-52 strains and a high-passaged attenuated (188-SG) mutant of TGEV. No significant differences were found between attenuated and virulent strains with regard to the viral antigen expression on the membrane of infected cells over a 14-h period.


title: Antiviral effect of amiloride on replication of foot and mouth disease virus in cell culture

text: Abstract Recently, amiloride was shown to potently suppress Coxsackievirus B3 (CVB3) replication. In the current study, we investigated whether amiloride could also exhibit antiviral activity against foot-and-mouth disease virus (FMDV), which belongs to the same family (Picornaviridae) as CVB3. We found that amiloride exerted antiviral activity in a dose-dependent manner against two strains of FMDV in IBRS-2 cells, with slight cytotoxicity at 1000 μM. Besides, amiloride did not inhibit the attachment and entry of FMDV in IBRS-2 cells, but prevented early viral replication. These data implied that amiloride could be a promising candidate for further research as a potential antiviral drug against FMDV infection.


title: Redescription of Hepatozoon felis (Apicomplexa: Hepatozoidae) based on phylogenetic analysis, tissue and blood form morphology, and possible transplacental transmission

text: BACKGROUND: A Hepatozoon parasite was initially reported from a cat in India in 1908 and named Leucocytozoon felis domestici. Although domestic feline hepatozoonosis has since been recorded from Europe, Africa, Asia and America, its description, classification and pathogenesis have remained vague and the distinction between different species of Hepatozoon infecting domestic and wild carnivores has been unclear. The aim of this study was to carry out a survey on domestic feline hepatozoonosis and characterize it morphologically and genetically. METHODS: Hepatozoon sp. DNA was amplified by PCR from the blood of 55 of 152 (36%) surveyed cats in Israel and from all blood samples of an additional 19 cats detected as parasitemic by microscopy during routine hematologic examinations. Hepatozoon sp. forms were also characterized from tissues of naturally infected cats. RESULTS: DNA sequencing determined that all cats were infected with Hepatozoon felis except for two infected by Hepatozoon canis. A significant association (p = 0.00001) was found between outdoor access and H. felis infection. H. felis meronts containing merozoites were characterized morphologically from skeletal muscles, myocardium and lungs of H. felis PCR-positive cat tissues and development from early to mature meront was described. Distinctly-shaped gamonts were observed and measured from the blood of these H. felis infected cats. Two fetuses from H. felis PCR-positive queens were positive by PCR from fetal tissue including the lung and amniotic fluid, suggesting possible transplacental transmission. Genetic analysis indicated that H. felis DNA sequences from Israeli cats clustered together with the H. felis Spain 1 and Spain 2 sequences. These cat H. felis sequences clustered separately from the feline H. canis sequences, which grouped with Israeli and foreign dog H. canis sequences. H. felis clustered distinctly from Hepatozoon spp. of other mammals. Feline hepatozoonosis caused by H. felis is mostly sub-clinical as a high proportion of the population is infected with no apparent overt clinical manifestations. CONCLUSIONS: This study aimed to integrate new histopathologic, hematologic, clinical, epidemiological and genetic findings on feline hepatozoonosis and promote the understanding of this infection. The results indicate that feline infection is primarily caused by a morphologically and genetically distinct species, H. felis, which has predilection to infecting muscular tissues, and is highly prevalent in the cat population studied. The lack of previous comprehensively integrated data merits the redescription of this parasite elucidating its parasitological characteristics.


title: Identification of a Contiguous 6-Residue Determinant in the MHV Receptor That Controls the Level of Virion Binding to Cells

text: Abstract Murine carcinoembryonic antigens serve as receptors for the binding and entry of the enveloped coronavirus mouse hepatitis virus (MHV) into cells. Numerous receptor isoforms are now known, and each has extensive differences in its amino terminal immunoglobulin-like domain (NTD) to which MHV binds via its protruding spike proteins. Some of these receptor alterations may affect the ability to bind viral spikes. To identify individual residues controlling virus binding differences, we have used plasmid and vaccinia virus vectors to express two forms of MHV receptor differing only in their NTD. The two receptors, designated biliary glycoproteins (Bgp) 1aand 1b NTD, varied by 29 residues in the 107 amino acid NTD. When expressed from cDNAs in receptor-negative HeLa cells, these two Bgp molecules were displayed on cell surfaces to equivalent levels, as both were equally modified by a membrane-impermeant biotinylation reagent. Infectious center assays revealed that the 1aisoform was 10 to 100 times more effective than 1b NTDin its ability to confer sensitivity to MHV (strain A59) infection. Bgp1awas also more effective than Bgp1b NTDin comparative virus adsorption assays, binding 6 times more MHV (strain A59) and 2.5 times more MHV (strain JHMX). Bgp1awas similarly more effective in promoting the capacity of viral spikes to mediate intercellular membrane fusion as judged by quantitation of syncytia following cocultivation of spike and receptor-bearing cells. To identify residues influencing these differences, we inserted varying numbers of 1bresidues into the Bgp1abackground via restriction fragment exchange and site-directed mutagenesis. Analysis of the resulting chimeric receptors showed that residues 38 to 43 of the NTD were key determinants of the binding and fusion differences between the two receptors. These residues map to an exposed loop (C-C′ loop) in a structural model of the closely related human carcinoembryonic antigen.


title: Intracellular processing of the porcine coronavirus transmissible gastroenteritis virus spike protein expressed by recombinant vaccinia virus

text: Abstract The Spike (S) protein from a virulent British field isolate of porcine transmissible gastroenteritis virus (TGEV) FS772/70 was constructed from cDNA and inserted into the vaccinia virus (VV) thymidine kinase gene locus under the control of the VV early/late gene P7.5K promoter. Recombinant S protein was synthesized as an endo-β-N-acetylglucosamini-dase H (Endo H)-sensitive glycoprotein with high mannose simple oligosaccharides (gp190) that underwent post-translational modification to an Endo H-resistant glycoprotein with complex oligosaccharides (gp210). Immunofluorescence analysis demonstrated that the majority of recombinant S protein was retained at the Golgi but some S protein was expressed on the plasma membrane. Monoclonal antibodies (mAbs) raised against native S protein reacted with this recombinant S protein; also, mice infected with the recombinant vaccinia virus (rVV) expressing the S protein induced TGEV neutralizing antibodies. A truncated S protein (SΔ) was also expressed in rVV-infected cells by introducing a deletion into the S protein cDNA that removed 292 amino acids from the C-terminus. The SΔ protein (gpl70) was shown to be antigenically similar to TGEV S protein by immunofluorescence and immunoprecipitation tests but was retained in the endoplasmic reticulum and not expressed on the cell surface.


title: Performance evaluation of the Panther Fusion® respiratory tract panel

text: Abstract Background Respiratory tract infections are among the most common infections during winter season. Rapid diagnostics is required for clinical decision making regarding isolation of patients and appropriate therapy. Objectives The aim of this study was to evaluate the analytical and clinical performance characteristics of the Panther Fusion® respiratory panel using published laboratory-developed real-time PCR assays (LDT). Study design Analytical sensitivity of Panther Fusion® Flu A/B/RSV was assessed by testing dilutions of cell culture isolates. Clinical performance assessment included the complete Panther Fusion® respiratory panel (Flu-A/B/RSV, PIV 1-4 and AdV/hMPV/RV) and consisted of a retrospective and a prospective study-arm. The retrospective evaluation included 201, stored (−80 °C) samples collected between February 2006 and January 2017. Prospective evaluation was performed on 1045 unselected pretreated respiratory tract samples from patients presented to our hospital between November 2017 and May 2018. Results Analytical sensitivity was generally slightly lower for the Panther Fusion® assays. Clinical specificity and sensitivity was between 96 %–100 % and 71.9 %–100 %, respectively. Discrepant results were found in 146 samples of which 88 samples tested LDT positive / Panther Fusion® negative and 58 samples were LDT negative / Panther Fusion® positive. A total of ten discrepant samples with Ct-values <30 were sequenced to confirm the presence of 7 RV-C not-detected by LDT and 1 RV-A and 2 ADV-2 not detected by Panther Fusion®. Conclusions The Panther Fusion® provides a random-access system with continuous loading and much shorter sample-to-answer times compared to LDT, albeit with a slightly less clinical sensitivity compared to the LDT.


title: Upper Respiratory Tract Infections (Including Otitis Media)

text: Upper respiratory tract infections (including otitis media) are the most common illnesses affecting children. Most illnesses are mild and resolve completely without specific treatment, but the frequency of infection and association with fever and constitutional symptoms creates significant distress for the child and the family. By understanding the evidence available from high-quality studies, the clinician can advise the families on appropriate action. The goal of this article is to support clinicians in answering the following questions: (1) What happened to children with these conditions when no additional treatment was provided? (2) Which interventions have been assessed in well-designed studies? (3) Which interventions have been shown to improve outcomes? (4) How large is the overall benefit?


COVID-19 Digestive Symptoms Mimicking Internal Hernia Presentation After Roux-en-Y-Gastric Bypass; Comment on “Internal Hernia in the Times of COVID-19: to Laparoscope or Not to Laparoscope?”


docid: fcwdbvks

title: First Clinical Use of Lenzilumab to Neutralize GM-CSF in Patients with Severe and Critical COVID-19 Pneumonia

text: Background: In COVID-19, high levels of granulocyte macrophage-colony stimulating factor (GM-CSF) and inflammatory myeloid cells correlate with disease severity, cytokine storm, and respiratory failure. With this rationale, we used lenzilumab, an anti-human GM-CSF monoclonal antibody, to treat patients with severe COVID-19 pneumonia. Methods: Hospitalized patients with COVID-19 pneumonia and risk factors for poor outcomes were treated with lenzilumab 600 mg intravenously for three doses through an emergency single-use IND application. Patient characteristics, clinical and laboratory outcomes, and adverse events were recorded. All patients receiving lenzilumab through May 1, 2020 were included in this report. Results: Twelve patients were treated with lenzilumab. Clinical improvement was observed in 11 out of 12 (92%), with a median time to discharge of 5 days. There was a significant improvement in oxygenation: The proportion of patients with SpO2/FiO2 < 315 at the end of observation was 8% vs. compared to 67% at baseline (p=0.00015). A significant improvement in mean CRP and IL-6 values on day 3 following lenzilumab administration was also observed (137.3 mg/L vs 51.2 mg/L, p = 0.040; 26.8 pg/mL vs 16.1 pg/mL, p = 0.035; respectively). Cytokine analysis showed a reduction in inflammatory myeloid cells two days after lenzilumab treatment. There were no treatment-emergent adverse events attributable to lenzilumab, and no mortality in this cohort of patients with severe COVID-19 pneumonia. Conclusions: In high-risk COVID-19 patients with severe pneumonia, GM-CSF neutralization with lenzilumab was safe and associated with improved clinical outcomes, oxygen requirement, and cytokine storm.


title: Ascertaining the 2004–2006 HIV type 1 CRF07_BC outbreak among injecting drug users in Taiwan

text: Summary Objective To ascertain the explosive 2004–2006 outbreak of HIV-1 CRF07_BC among intravenous drug users (IDU) in Taiwan, which more than doubled the total number of reported HIV cases in less than 3 years, resulting in a 45-fold increase in cumulative IDU/HIV cases and a 40-fold increase in previously seldom-reported female IDU/HIV cases. Methods A mathematical model was utilized to fit the monthly case data, in order to estimate the turning points (peak incidence) and the reproduction number R of the outbreak. Furthermore, correlation analysis was carried out to assess the correlation between infections among the male and female IDUs. Results Model fit revealed a two-wave epidemic during April 2004–March 2007. The larger second wave started shortly after May 2005 and peaked in October 2005 before gradually subsiding. R was estimated to be 3.15 (3.14–3.16) and 27.21 (26.73–28.05) for the two respective waves. The time series of monthly differences in male and female case data were found to be most significantly correlated at lag 0 (i.e., r >0.7) with r =0.906 and 0.804, respectively in each direction. The Granger causality test indicated that the male time series caused the corresponding female time series with a lag of 2 months or less. Conclusions The modeling results revealed the presence of a small first wave in 2004, before an explosion of cases after May 2005. Furthermore, a harm reduction program implemented in August 2005 contributed to the downturn in the epidemic after October. Correlation results also suggest that the upsurge in male HIV cases led to the subsequent drastic surge in female cases.


title: Progress and Challenges toward the Development of Vaccines against Avian Infectious Bronchitis

text: Avian infectious bronchitis (IB) is a widely distributed poultry disease that has huge economic impact on poultry industry. The continuous emergence of new IBV genotypes and lack of cross protection among different IBV genotypes have been an important challenge. Although live attenuated IB vaccines remarkably induce potent immune response, the potential risk of reversion to virulence, neutralization by the maternal antibodies, and recombination and mutation events are important concern on their usage. On the other hand, inactivated vaccines induce a weaker immune response and may require multiple dosing and/or the use of adjuvants that probably have potential safety risks and increased economic burdens. Consequently, alternative IB vaccines are widely sought. Recent advances in recombinant DNA technology have resulted in experimental IB vaccines that show promise in antibody and T-cells responses, comparable to live attenuated vaccines. Recombinant DNA vaccines have also been enhanced to target multiple serotypes and their efficacy has been improved using delivery vectors, nanoadjuvants, and in ovo vaccination approaches. Although most recombinant IB DNA vaccines are yet to be licensed, it is expected that these types of vaccines may hold sway as future vaccines for inducing a cross protection against multiple IBV serotypes.


title: Weak binder for MHC molecule is a potent Mycobacterium tuberculosis-specific CTL epitope in the context of HLA-A24 allele

text: Abstracts Tuberculosis causes serious health problem for the world population. Antigenic peptides selected by pathogen-specific cytotoxic T lymphocytes (CTLs) are presented by major histocompatibility complex (MHC; or human leukocyte antigen [HLA] in humans) molecules, and HLA-A restricted responses may be of interest for vaccine development and the understanding of cellular immunity. A series of peptides derived from the 10-KDa culture filtrate protein (CFP10) and the 6 kDa early secretory antigenic target (ESAT-6) in the Mycobacterium tuberculosis (Mtb) have been screened and a CTL epitope restricted by the human leukocyte antigen HLA-A24, a common HLA allele in Asian people, has been identified. In this study, we studied a panel of CFP10 and ESAT-6-derived peptides to identify those with binding motifs for HLA-A24 molecules. The antigenicity of candidate peptides was assessed with in vitro refolding tests and an enzyme-linked immunospot (ELISPOT) assay, and by tetramer staining to determine the capacity to stimulate CTLs from peripheral blood mononuclear cells (PBMCs) of HLA-A24-positive TB Patients. We report that one novel candidate peptide at positions 5–14 of ESAT-6 of Mtb could induce peptide-specific CTLs from PBMCs of HLA-A24-positive patients, but not from HLA-A24-negative patients and HLA-A24-positive healthy controls. Identified epitope is a weak binder for HLA-A24 molecule in a mini MHC refolding assay. Since the peptide is presented by a common HLA class I molecule, it may be useful for immunotherapy against Mtb infection and vaccine development in the large population of Mtb-infected patients.


title: Sars‐CoV‐2 infection: the same virus can cause different cutaneous manifestations: reply from authors

text: Dr Drago et al. are right to point out that our paper did not provide data on enanthems(1,2). As the data collection form did not include the description of mucous membranes, they might have not been explored in many patients. We have reported and included in the supplementary material a few cases that were noticed by their doctors and were the first descriptions of enanthem in COVID‐19. Given the low number of cases and their non‐systematic acquisition, we avoided any analysis of these data.


title: Exploration on the feasibility of moxibustion in prevention and treatment of COVID-19 from the perspective of modern medical mechanism

text: Novel coronavirus pneumonia (COVID-19) is rampant in many countries and regions and there is no time to delay the exploration of the scheme for its prevention and control. The pathogenic characteristics of novel coronavirus and the effect of moxibustion for warming up yang and strengthening the antipathogenic qi were analyzed in this paper. From the perspective of modern medical mechanism, during the prevention and treatment of novel coronaviral infection, moxibustion may be able to prevent and treat COVID-19 by improving the body's immunity so as to conquer virus, by anti-inflammation to alleviate the inflammatory response of COVID-19 and by improving lung function to inhibit pulmonary fibrosis.


title: Virus like particle-based vaccines against emerging infectious disease viruses

text: Emerging infectious diseases are major threats to human health. Most severe viral disease outbreaks occur in developing regions where health conditions are poor. With increased international travel and business, the possibility of eventually transmitting infectious viruses between different countries is increasing. The most effective approach in preventing viral diseases is vaccination. However, vaccines are not currently available for numerous viral diseases. Virus-like particles (VLPs) are engineered vaccine candidates that have been studied for decades. VLPs are constructed by viral protein expression in various expression systems that promote the selfassembly of proteins into structures resembling virus particles. VLPs have antigenicity similar to that of the native virus, but are non-infectious as they lack key viral genetic material. VLP vaccines have attracted considerable research interest because they offer several advantages over traditional vaccines. Studies have shown that VLP vaccines can stimulate both humoral and cellular immune responses, which may offer effective antiviral protection. Here we review recent developments with VLP-based vaccines for several highly virulent emerging or re-emerging infectious diseases. The infectious agents discussed include RNA viruses from different virus families, such as the Arenaviridae, Bunyaviridae, Caliciviridae, Coronaviridae, Filoviridae, Flaviviridae, Orthomyxoviridae, Paramyxoviridae, and Togaviridae families.


title: Acinetobacter baumannii: emergence and spread in Israeli hospitals 1997–2002

text: Summary The incidence of multi-drug-resistant Acinetobacter baumannii bloodstream infections (BSIs) increased two- to four-fold in three Israeli hospitals between 1997 and 2002, accounting for 3.5–18% of all hospital-acquired BSIs. This was associated with increasing carbapenem resistance reaching 35–54%, and by a dramatic increase in carbapenem consumption. In-hospital fatality rates ranged between 47% and 58% and were significantly higher than those seen with other nosocomial Gram-negative pathogens. A. baumannii was not restricted to intensive care units, but had spread to all hospital wards. Multi-drug-resistant A. baumannii has the potential to reach endemicity in hospitals and warrants more vigorous and innovative efforts to limit its spread.


title: Pregnant and postpartum women with SARS‐CoV‐2 infection in intensive care in Sweden

text: The Public Health Agency of Sweden has analysed how many pregnant and postpartum women with SARS‐CoV‐2 infection have been treated in intensive care units (ICU) in Sweden between the March 19 and April 20, 2020, compared with non‐pregnant women of similar age. Cases were identified in a special reporting module within the Swedish Intensive Care Registry (SIR). Fifty‐three women aged 20‐45 years with SARS‐CoV‐2 were reported in SIR, and thirteen (n=13) of these women were either pregnant or postpartum (<1 week). The results indicate that the risk of being admitted to ICU may be higher in pregnant and postpartum women with laboratory‐confirmed SARS‐CoV‐2 in Sweden, compared to non‐pregnant women of similar age.


title: Chest computed tomography for the diagnosis of patients with coronavirus disease 2019 (COVID-19): a rapid review and meta-analysis.

text: Background The outbreak of the coronavirus disease 2019 (COVID-19) has had a massive impact on the whole world. Computed tomography (CT) has been widely used in the diagnosis of this novel pneumonia. This study aims to understand the role of CT for the diagnosis and the main imaging manifestations of patients with COVID-19. Methods We conducted a rapid review and meta-analysis on studies about the use of chest CT for the diagnosis of COVID-19. We comprehensively searched databases and preprint servers on chest CT for patients with COVID-19 between 1 January 2020 and 31 March 2020. The primary outcome was the sensitivity of chest CT imaging. We also conducted subgroup analyses and evaluated the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results A total of 103 studies with 5,673 patients were included. Using reverse transcription polymerase chain reaction (RT-PCR) results as reference, a meta-analysis based on 64 studies estimated the sensitivity of chest CT imaging in COVID-19 was 99% (95% CI, 0.97-1.00). If case reports were excluded, the sensitivity in case series was 96% (95% CI, 0.93-0.99). The sensitivity of CT scan in confirmed patients under 18 years old was only 66% (95% CI, 0.15-1.00). The most common imaging manifestation was ground-glass opacities (GGO) which was found in 75% (95% CI, 0.68-0.82) of the patients. The pooled probability of bilateral involvement was 84% (95% CI, 0.81-0.88). The most commonly involved lobes were the right lower lobe (84%, 95% CI, 0.78-0.90) and left lower lobe (81%, 95% CI, 0.74-0.87). The quality of evidence was low across all outcomes. Conclusions In conclusion, this meta-analysis indicated that chest CT scan had a high sensitivity in diagnosis of patients with COVID-19. Therefore, CT can potentially be used to assist in the diagnosis of COVID-19.


title: Antibiotics nonadherence and knowledge in a community with the world’s leading prevalence of antibiotics resistance: Implications for public health intervention

text: BACKGROUND: Community determinants of antibiotics nonadherence, an important contributor of antibiotics resistance, remained unclear. OBJECTIVES: Our objective was to investigate whether deficient antibiotics knowledge could contribute to nonadherence in a community with high prevalence of antibiotics resistance. METHODS: We recruited 465 people by random sampling from 5 urban areas in Hong Kong. A structured questionnaire was used to assess antibiotics knowledge and adherence. Adherence was defined as completing the most recent course of antibiotics entirely according to physicians’ instructions. An antibiotics knowledge score ranging from 0 to 3 (highest) was composed based on the number of correctly answered questions. RESULTS: Of the 465 participants interviewed, 96.3% had heard of the term “antibiotics,” and 80.6% recalled having previously received antibiotics prescription. Among the eligible 369 subjects, 32.9% showed nonadherence. Percentages of participants with antibiotics knowledge scores of 0, 1, 2, and 3 were 11%, 27%, 33%, and 29%, respectively. There was a higher prevalence of nonadherence among people with lower antibiotics knowledge score (P < .001). Furthermore, people with nonadherence had a significantly lower mean antibiotics knowledge score (1.3 ± 1.0 versus 2.0 ± 0.9, P < .001), with no interaction with education (P < .05). Adjusted for potential confounders, antibiotics knowledge scores of 2, 1, and 0 independently predicted increased risk of nonadherence by 1-fold (odds ratio [OR], 2.00; 95% confidence interval [CI]: 1.01-3.94; P = .047), 4-fold (OR, 4.77; 95% CI: 2.30-9.92; P < .001), and 17-fold (OR, 18.41; 95% CI: 6.92-48.97; P < .001) respectively, compared with the maximum score of 3. CONCLUSION: Lack of antibiotics knowledge is a critical determinant of nonadherence independent of education in the community.


title: Overwhelming Mutations or SNPs of SARS-CoV-2: A Point of Caution

text: • Mutation studies hits cause for the superior infectious rate of SARS-CoV-2. • SARS-CoV-2 is evolving rapidly with number of mutations and SNPs. • Mutations were found in the ACE2 binding region of SARS-CoV-2 spike glycoprotein. • ORF1ab, ORF8 and spike glycoprotein regions of SARS-CoV-2 are highly mutated. • Overwhelming mutations or SNPs of SARS-CoV-2 alerts drug treatment options.


title: Lessons from SARS-CoV-2 Pandemic: Evolution, Disease Dynamics and Future

text: The COVID-19 pandemic is rising at an unprecedented rate. The surging number of deaths every day, global lockdown and travel restrictions have resulted in huge losses to society. The impact is massive and will leave a historical footprint. The Spanish Flu of 1918, which was the last pandemic that had a similar impact, was shadowed under the consequences of World War I. All the brilliance, strength and economies of countries worldwide are aimed at fighting the COVID-19 pandemic. The knowledge about coronavirus dynamics, its nature and epidemiology are expanding every day. The present review aims to summarize the structure, epidemiology, symptoms, statistical status of the disease status, intervention strategies and deliberates the lessons learnt during the pandemic. The intervention approaches, antiviral drug repurposing and vaccine trials are intensified now. Statistical interpretations of disease dynamics and their projections may help the decision-makers.


title: La obesidad como factor de riesgo en personas con COVID-19: Posibles mecanismos e implicaciones

text: Resumen Varios artículos recientes sugieren que la obesidad es un factor de riesgo para una enfermedad más grave por coronavirus. En este artículo se resume la evidencia científica disponible sobre el papel de la obesidad en COVID-19, con especial atención en las personas más jóvenes y los mecanismos biológicos propuestos para explicar tanto el mayor riesgo observado, como la posible mayor contagiosidad de esta población. Se consideran varias implicaciones de la pandemia sobre las personas con obesidad, en relación con las posibles dificultades en el manejo de los pacientes ingresados, las implicaciones del confinamiento sobre el control y tratamiento de la obesidad, y el estigma que sufren estas personas por su condición, y que puede verse aumentado si se confirma la relación de la obesidad con COVID-19. Comprender el papel de la obesidad en COVID-19 debería ser una prioridad de salud pública, dada la alta prevalencia de esta condición en nuestro país.


title: Environment and body contamination: A comparison of two different removal methods in three types of personal protective clothing

text: BACKGROUND: This study aimed to examine the body contamination rates and environmental contamination levels during the removal of 3 types of personal protective clothing (PPC) by the individual accustomed removal method (IARM) and gown removal methods recommended by the Centers for Disease Control and Prevention (CDC). METHODS: Fifty participants performed IARM and CDC-recommended gown removal methods to remove 3 types of PPC (ie, cotton gown, water resistant gown, and plastic apron) in random order at 2 separate sessions after applying Glo Germ simulated germ lotion on the gown's surface. A video demonstrating the CDC-recommended gown removal method was shown between the 2 sessions. After PPC removal, fluorescent stains were counted by an ultraviolet scan under dim light. RESULTS: Following IARM, contaminants were splashed in the surroundings, particularly on the front part of the subject. The plastic apron and cotton gown obtained the highest and lowest contaminative hazards, respectively, to the hands, shoes, and environment. Females, nurses, and senior staff had serious hand or shoe contamination. The CDC removal method more significantly reduced body and environmental contamination of small fluorescent stains (<1 cm(2)), but not of large patches (>1 cm(2)), than IARM. CONCLUSION: The effect of gown removal, PPC type, discarding PPC location, training of infection control measures, hand hygiene, and special work shoes should be considered daily.


title: Special considerations for elderly patients with head and neck cancer during the COVID‐19 pandemic

text: Elderly patients with head and neck cancer are at increased risk of adverse outcomes during and after treatment of head and neck cancer. COVID‐19 severity and mortality can be expected to be significantly greater in elderly patients with head and neck cancer, given that increased age, comorbidities, and presence of malignancy are known risk factors for disease severity and mortality in patients with COVID‐19. Therefore, their management requires multidisciplinary consensus and patient input. A thorough geriatric assessment, which has been shown to be beneficial prior to the COVID‐19 pandemic, could be particularly helpful in this patient population with the added dimension of COVID‐19 risk. In many cases, prudent treatment plan modification may allow for overall best outcomes. Furthermore, recruitment of social services and, when appropriate, palliative care, may allow for optimal management of these patients.


title: Isolation of Middle East Respiratory Syndrome Coronavirus from a Patient of the 2015 Korean Outbreak

text: During the 2015 outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Korea, 186 persons were infected, resulting in 38 fatalities. We isolated MERS-CoV from the oropharyngeal sample obtained from a patient of the outbreak. Cytopathic effects showing detachment and rounding of cells were observed in Vero cell cultures 3 days after inoculation of the sample. Spherical virus particles were observed by transmission electron microscopy. Full-length genome sequence of the virus isolate was obtained and phylogenetic analyses showed that it clustered with clade B of MERS-CoV.


Universal Precautions Studios Presents: ID Creature Features


title: Azithromycin for episodes with asthma-like symptoms in young children aged 1–3 years: a randomised, double-blind, placebo-controlled trial

text: Summary Background Bacteria and viruses are equally associated with the risk of acute episodes of asthma-like symptoms in young children, suggesting antibiotics as a potential treatment for such episodes. We aimed to assess the effect of azithromycin on the duration of respiratory episodes in young children with recurrent asthma-like symptoms, hypothesising that it reduces the duration of the symptomatic period. Methods In this randomised, double-blind, placebo-controlled trial, we recruited children aged 1–3 years, who were diagnosed with recurrent asthma-like symptoms from the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort; a birth cohort consisting of the general Danish population of Zealand, including Copenhagen. Exclusion criteria were macrolide allergy, heart, liver, neurological, and kidney disease, and, before each treatment, one or more clinical signs of pneumonia (respiratory frequency of ≥50 breaths per min; fever of ≥39°C; C-reactive protein concentration of ≥476·20 nmol/L [≥50 mg/L]). Each episode of asthma-like symptoms lasting at least 3 days was randomly allocated to a 3-day course of azithromycin oral solution of 10 mg/kg per day or placebo after thorough examination by a study physician at the Copenhagen Prospective Studies on Asthma research unit. Each episode was randomly allocated independently of previous treatment from a computer-generated list of random numbers in blocks of ten (generated at the Pharmacy of Glostrup). Investigators and children were masked until the youngest child turned 3 years of age and throughout the data validation and analysis phases. The primary outcome was duration of the respiratory episode after treatment, verified by prospective daily diaries and analysed with Poisson regression. Analyses were per protocol (excluding those without a primary outcome measure or who did not receive treatment). This trial is registered with ClinicalTrials.gov, number NCT01233297. Findings Between Nov 17, 2010, and Jan 28, 2014, we randomly allocated 158 asthma-like episodes in 72 children (79 [50%] to azithromycin and 79 [50%] to placebo). The mean duration of the episode after treatment was 3·4 days for children receiving azithromycin compared with 7·7 days for children receiving placebo. Azithromycin caused a significant shortening of the episode of 63·3% (95% CI 56·0–69·3; p<0·0001). The effect size increased with early initiation of treatment, showing a reduction in episode duration of 83% if treatment was initiated before day 6 of the episode compared with 36% if initiated on or after day 6 (p<0·0001). We noted no differences in clinical adverse events between the azithromycin (18 [23%] of 78 episodes included in final analysis) and placebo (24 [30%] of 79) groups (p=0·30), but we did not investigate bacterial resistance patterns after treatment. Interpretation Azithromycin reduced the duration of episodes of asthma-like symptoms in young children, suggesting that this drug could have a role in acute management of exacerbations. Further research is needed to disentangle the inflammatory versus antimicrobial aspects of this relation. Funding Lundbeck Foundation, Danish Ministry of Health, Danish Council for Strategic Research, Capital Region Research Foundation.


title: Mechanisms of Accountability for the Realization of the Right to Health in China

text: China ratified the International Covenant on Economic, Social and Cultural Rights in 2001. It thus bears obligations under Article 12 of the covenant to take appropriate measures at the domestic level to realize the right to health in China. Accountability is an important component of the right to health. This article examines whether the Western concept of accountability, recently imported into China, has the potential to improve the protection of the right to health within China’s existing political, legal, and cultural framework. In so doing, it reviews current Chinese institutional mechanisms and considers the use of less formal mechanisms by which duty-bearers might be held accountable in China. More specifically, this article provides an overview of a range of health-related accountability mechanisms, including judicial, political, administrative, professional, and social accountability arrangements. It concludes that although there is the basis of an accountability framework for the right to health in China, the effective operation of accountability mechanisms is hindered by longstanding cultural and political barriers.


Foreword to the Virus Research Special issue on “Retroviral RNA, protein co-factors and chaperones”


title: Potential pitfalls of routine SARS‐CoV‐2 serology for mass screening

text: There are potential pitfalls of routine SARS-CoV-2 serology for mass screening. This article is protected by copyright. All rights reserved.


title: Evaluation of two singleplex reverse transcription-Insulated isothermal PCR tests and a duplex real-time RT-PCR test for the detection of porcine epidemic diarrhea virus and porcine deltacoronavirus

text: Abstract Recent outbreaks of porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV) in multiple countries have caused significant economic losses and remain a serious challenge to the swine industry. Rapid diagnosis is critical for the implementation of efficient control strategies before and during PEDV and PDCoV outbreaks. Insulated isothermal PCR (iiPCR) on the portable POCKIT™ device is user friendly for on-site pathogen detection. In the present study, a singleplex PEDV RT-iiPCR, a singleplex PDCoV RT-iiPCR, and a duplex PEDV/PDCoV real-time RT-PCR (rRT-PCR) commercial reagents targeting the M gene were compared to an N gene-based PEDV rRT-PCR and an M gene-based PDCoV rRT-PCR that were previously published and used as reference PCRs. All PCR assays were highly specific and did not cross react with other porcine enteric pathogens. Analytical sensitivities of the PEDV RT-iiPCR, PDCoV RT-iiPCR and duplex PEDV/PDCoV rRT-PCR were determined using in vitro transcribed RNA as well as viral RNA extracted from ten-fold serial dilutions of PEDV and PDCoV cell culture isolates. Performance of each PCR assay was further evaluated using 170 clinical samples (86 fecal swabs, 24 feces, 19 intestines, and 41 oral fluids). Compared to the reference PEDV rRT-PCR, the sensitivity, specificity and accuracy of the PEDV RT-iiPCR were 97.73%, 98.78%, and 98.24%, respectively, and those of the duplex PEDV/PDCoV rRT-PCR were 98.86%, 96.34%, and 97.65%, respectively. Compared to the reference PDCoV rRT-PCR, the sensitivity, specificity and accuracy of the PDCoV RT-iiPCR were 100%, 100%, and 100%, respectively, and those of the PEDV/PDCoV duplex rRT-PCR were 96.34%, 100%, and 98.24%, respectively. Overall, all three new PCR assays were comparable to the reference rRT-PCRs for detection of PEDV and/or PDCoV. The PEDV and PDCoV RT-iiPCRs are potentially useful tools for on-site detection and the duplex PEDV/PDCoV rRT-PCR provides a convenient method to simultaneously detect the two viruses and differentiate PEDV from PDCoV.


title: Sequencing of the human IG light chain loci from a hydatidiform mole BAC library reveals locus-specific signatures of genetic diversity

text: Germline variation at immunoglobulin (IG) loci is critical for pathogen-mediated immunity, but establishing complete haplotype sequences in these regions has been problematic because of complex sequence architecture and diploid source DNA. We sequenced BAC clones from the effectively haploid human hydatidiform mole cell line, CHM1htert, across the light chain IG loci, kappa (IGK) and lambda (IGL), creating single haplotype representations of these regions. The IGL haplotype generated here is 1.25 Mb of contiguous sequence, including four novel V alleles and one novel C allele and an 11.9 kb insertion. The CH17 IGK haplotype consists of two 644 kb proximal and 466 kb distal contigs separated by a large gap of unknown size; these assemblies added 49 kb of unique sequence extending into this gap. Our analysis also resulted in the characterization of seven novel IGKV alleles and a 16.7 kb region exhibiting signatures of interlocus sequence exchange between distal and proximal IGKV gene clusters. Genetic diversity in IGK/IGL was compared to that of the IG heavy chain (IGH) locus within the same haploid genome, revealing 3-fold (IGK) and 6-fold (IGL) higher diversity in the IGH locus, potentially associated with increased levels of segmental duplication and the telomeric location of IGH.


title: Histological assessment of cellular immune response to the phytohemagglutinin skin test in Brazilian free-tailed bats (Tadarida brasiliensis)

text: Bats are known reservoirs for numerous emerging infectious diseases, occupy unique ecological niches, and occur globally except for Antarctica. Given their impact on human and agricultural health, it is critical to understand the mechanisms underlying immunocompetence in this reservoir host. To date, few studies have examined immune function in the Order Chiroptera, particularly among natural colonies of bats. The phytohemagglutinin (PHA) skin test has been widely used to measure delayed-type cellular immune response in a wide variety of vertebrates, and has been routinely employed in immunoecological studies. Although this test is frequently described as a measure of T cell proliferation, recent studies indicate it may represent a combination of immune responses. In mammals, the immune response is differentially, temporally and spatially regulated, therefore, we characterized the infiltrating leukocyte response to the PHA skin test in bats by examining a time-series of histological sections from PHA and saline injection areas in 41 Brazilian free-tailed bats (Tadarida brasiliensis). Results suggest that bats exhibit diverse leukocyte traffic within 6 h, and up to 24 h following subcutaneous PHA injection. There was a significant presence of lymphocytes and neutrophils, as well as eosinophils, basophils, and macrophages observed in the PHA-injected tissues, compared with saline-injected control tissues. We observed a highly significant negative correlation between the number of lymphocytes and neutrophils in PHA-injected tissue, with peak lymphocyte response at 12 h, and peak neutrophil response at 24 h post-injection. These results indicate substantial variation in the immune response of individuals, and may aid our understanding of disease emergence in natural populations of bats.


title: 12 Lessons Learned from the Management of the Coronavirus Pandemic

text: The Coronavirus SARS-CoV-2 has spread rapidly since the first cases hit Wuhan, China at the end of 2019, and has now landed in almost every part of the world. By mid-February 2020, China, South Korea, Singapore, Taiwan, and – to some extent – Japan began to contain and control the spread of the virus, while conversely, cases increased rapidly in Europe and the United States. In response to the pandemic, many countries have had to introduce drastic legally mandated lockdowns to enforce physical separation, which are ravaging economies worldwide. Although it will be many months or even years before the final verdict can be reached, we believe that it is already possible to identify 12 key lessons that we can learn from to reduce the tremendous economic and social costs of this pandemic and which can inform responses to future crises. These include lessons around the importance of transparency, solidarity, coordination, decisiveness, clarity, accountability and more.


Pulmonary thromboembolism in criticall ill COVID-19 patients


title: Prednisolone reduces recurrent wheezing after a first wheezing episode associated with rhinovirus infection or eczema

text: Background Rhinovirus-induced early wheezing has been suggested as a new important risk factor for recurrent wheezing. Objective We sought to investigate the risk factors for recurrent wheezing and to determine post hoc the efficacy of prednisolone in risk groups. Methods We followed for 1 year 118 children (median age, 1.1 years) who had had their first episode of wheezing and had participated in a trial comparing prednisolone with placebo in hospitalized children. Demographics and laboratory data were obtained at study entry. The follow-up outcome was recurrent wheezing (3 physician-confirmed episodes). Results Recurrent wheezing was diagnosed in 44 (37%) children. Independent risk factors were age < 1 year, atopy, and maternal asthma. The probability of recurrent wheezing was higher in rhinovirus than respiratory syncytial virus (RSV)–affected children among placebo recipients (hazard ratio, 5.05; 95% CI, 1.00-25.41). Prednisolone decreased the probability of recurrent wheezing in children with eczema (0.15; 95% CI, 0.04-0.63) but not in those without eczema (1.89; 95% CI, 0.83-4.29; P = .007 for interaction). Prednisolone was associated with less recurrent wheezing in the rhinovirus group (0.19; 95% CI, 0.05-0.71), but not in the RSV (2.12; 95% CI, 0.46-9.76) or in the RSV/rhinovirus-negative groups (2.03; 95% CI, 0.83-5.00; P = .017 for interaction). Conclusion Rhinovirus-induced early wheezing is a major viral risk factor for recurrent wheezing. Prednisolone may prevent recurrent wheezing in rhinovirus-affected first-time wheezers. The presence of eczema may also influence the response to prednisolone. Clinical implications A prospective trial is needed to test the hypothesis that prednisolone reduces recurrent wheezing in rhinovirus-affected wheezing children.


title: Are the cutaneous manifestations during or due to SARS-CoV-2 infection/COVID-19 frequent or not? Revision of possible pathophysiologic mechanisms

text: BACKGROUND: SARS-Cov-2 is a single-stranded RNA virus, a Betacoronavirus, composed of 16 non-structural proteins, with specific roles in replication of coronaviruses. The pathogenesis of COVID-19 is not yet fully understood. The virus and host factors interplay among distinct outcomes of infected patients. METHODS: Using MeSH (Medical Subject Headings) in PubMed, authors searched for articles cotaining information on COVID-19 and the skin. RESULTS: The pathophysiology of the disease is multifactorial: association with innate immune response, hypercoagulability state, lung tissue damage, neurological and/or gastrointestinal tract involvement, monocytic/macrophage activation syndrome, culminating in exaggerated cytokine secretion, called “cytokine storm”, which leads to worsening and death. These systemic conditions may be associated with cutaneous lesions, that have polymorphic aspects, where at histopathological level show involvement in different skin changes. These lesions may be associated with multisystemic manifestations that could occur due to angiotensin-converting enzyme 2 receptor and transmembrane serine protease action, allowing the pulmonary infection and possibly skin manifestation. Several reports in literature show cutaneous lesions similar to chilblain, urticarial eruptions, diffuse or disseminated erythema, livedo racemosa, blue toe syndrome, retiform purpura, vesicle trunk, purpuric exanthema or exanthema with clinical aspects of symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) and others. CONCLUSIONS: This review describes the complexity of Covid-19, pathophysiological and clinical aspects, dermatological finding and other dermatological conditions associated with SARS-CoV-2 infection or COVID-19.


title: Overview of Serological Techniques for Influenza Vaccine Evaluation: Past, Present and Future

text: Serological techniques commonly used to quantify influenza-specific antibodies include the Haemagglutination Inhibition (HI), Single Radial Haemolysis (SRH) and Virus Neutralization (VN) assays. HI and SRH are established and reproducible techniques, whereas VN is more demanding. Every new influenza vaccine needs to fulfil the strict criteria issued by the European Medicines Agency (EMA) in order to be licensed. These criteria currently apply exclusively to SRH and HI assays and refer to two different target groups—healthy adults and the elderly, but other vaccine recipient age groups have not been considered (i.e., children). The purpose of this timely review is to highlight the current scenario on correlates of protection concerning influenza vaccines and underline the need to revise the criteria and assays currently in use. In addition to SRH and HI assays, the technical advantages provided by other techniques such as the VN assay, pseudotype-based neutralization assay, neuraminidase and cell-mediated immunity assays need to be considered and regulated via EMA criteria, considering the many significant advantages that they could offer for the development of effective vaccines.


title: The European Union of Medical Specialties core training curriculum in infectious diseases: overview of national systems and distribution of specialists

text: ABSTRACT The European Union of Medical Specialities (UEMS) Section of Infectious Diseases agreed on an infectious disease training programme in 1999, which was updated in 2002. Although the provision of infection services throughout Europe is not uniform, with variation in the roles of infectious disease physicians and microbiologists, there are, nonetheles, physicians with a predominant responsibility for clinical infectious diseases (and tropical medicine) in most countries. However, infectious diseases is formally recognised as a specific discipline by most, but not yet all, European countries. There has been consensus from national representatives to the UEMS on the content of the published curriculum. There are clear areas of overlap in training between different infection disciplines, and exploration of possible areas for closer liaison and collaboration between them has been initiated. The increased movement of medical staff within Europe will place greater demands on those responsible for training, monitoring and quality assurance. The Board and Section of Infectious Diseases have established core training programmes with a generic logbook to assist those countries without a written curriculum or record book and facilitate the development of common standards of training. The duration of training varies across Europe; 4 years is the UEMS standard, or longer if the training is combined with general internal medicine. The numbers of infection specialists (infectious diseases and microbiology) per million population show considerable variation. The UEMS Sections have recognised the importance of working closely with European specialist societies involved with training. The Section for Infectious Diseases has, in partnership with the ESCMID, established a Board for the accreditation of continuing medical education/continuing professional development.


title: Decreased expression of type I (IFN-β) and type III (IFN-λ) interferons and interferon-stimulated genes in patients with chronic rhinosinusitis with and without nasal polyps

text: Background Little is known about antiviral responses in the sinonasal mucosal tissue of patients with chronic rhinosinusitis (CRS). Objective we investigated the presence of virus and the expression of Toll-like receptor (TLR) 3, TLR7, and interferon and interferon-stimulated genes (ISGs) in healthy mucosal tissue of control subjects and the inflammatory sinus mucosal tissue of CRS patients, and evaluated whether levels of interferons and ISGs might be affected by CRS-related cytokines and by treatment with macrolides, dexamethasone, or TLR3 and TLR7 agonists. Methods The presence of virus in the sinonasal mucosa was evaluated with real-time PCR. The expression of interferons and ISGs in the sinonasal mucosa and in cultured epithelial cells treated with TH1 and TH2 cytokines, macrolides, dexamethasone, or TLR3 and TLR7 agonists were evaluated with real-time PCR and Western blotting. The expression of TLR3 and TLR7 in the sinonasal mucosa were evaluated with immunohistochemistry. Results Respiratory viruses were detected in 15% of samples. Interferons and ISGs are expressed in normal mucosa, but their levels were decreased in patients with CRS. Interferon and ISG levels were upregulated in cells treated with macrolides, dexamethasone, or TLR3 agonist, but some were decreased in cytokine-treated cells. TLR3 and TLR7 levels showed no significant difference between normal and inflammatory sinus mucosal tissue. Conclusion These results suggest that decreased levels of interferons and ISGs in patients with CRS might contribute to impairment of the antiviral innate response in inflammatory sinonasal epithelial cells. Macrolides and glucocorticoids might provide positive effects on the treatment of CRS by upregulating interferon and ISG expression.


title: Inactivation of SARS Coronavirus by Means of Povidone-Iodine, Physical Conditions and Chemical Reagents

text: The efficacy of several povidone-iodine (PVP-I) products, a number of other chemical agents and various physical conditions were evaluated for their ability to inactivate the severe acute respiratory syndrome coronavirus (SARS-CoV). Treatment of SARS-CoV with PVP-I products for 2 min reduced the virus infectivity from 1.17 × 10(6) TCID(50)/ml to below the detectable level. The efficacy of 70% ethanol was equivalent to that of PVP-I products. Fixation of SARS-CoV-infected Vero E6 cells with a fixative including formalin, glutaraldehyde, methanol and acetone for 5 min or longer eliminated all infectivity. Heating the virus at 56°C for 60 min or longer reduced the infectivity of the virus from 2.6 × 10(7) to undetectable levels. Irradiation with ultraviolet light at 134 μW/cm(2) for 15 min reduced the infectivity from 3.8 × 10(7) to 180 TCID(50)/ml; however, prolonged irradiation (60 min) failed to eliminate the remaining virus, leaving 18.8 TCID(50)/ml.


docid: bisnmjlr

title: A propos d’une patiente apyrétique, suivie pour un Lymphome du Manteau, présentant une infection pulmonaire COVID19+

text: Abstract A 72-year-old woman underwent a FDG PET-CT, while under treatment for a mantle cell lymphoma and COVID19 positive, because of biological inflammatory syndrom, without any fever ; this exam discarded lymphoma progression but found a bilateral pulmonary infection, whose aspect was suggestive of COVID-19 linked pneumopathy. Résumé La TEP-TDM au 18F-FDG réalisée à cette patiente de 72 ans en cours de traitement pour un Lmphome du Manteau, testée positive au COVID-19, et adressée pour syndrome inflammatoire biologique persistant, sans fièvre, a permis d’éliminer une progression de sa lymphopathie mais a retrouvé une infection pulmonaire bilatérale, dont l’aspect fait évoquer une pneumopathie liée au coronavirus.


title: Virome of crab-eating (Cerdocyon thous) and pampas foxes (Lycalopex gymnocercus) from southern Brazil and Uruguay

text: Crab-eating (Cerdocyon thous) and Pampas foxes (Lycalopex gymnocercus) are wild canids distributed in South America. Domestic dogs (Canis lupus familiaris) and wild canids may share viral pathogens, including rabies virus (RABV), canine distemper virus (CDV), and canine parvovirus 2 (CPV-2). To characterize the virome of these wild canid species, the present work evaluated the spleen and mesenteric lymph node virome of 17 crab-eating and five Pampas foxes using high-throughput sequencing (HTS). Organ samples were pooled and sequenced using an Illumina MiSeq platform. Additional PCR analyses were performed to identify the frequencies and host origin for each virus detected by HTS. Sequences more closely related to the Paramyxoviridae, Parvoviridae and Anelloviridae families were detected, as well as circular Rep-encoding single-stranded (CRESS) DNA viruses. CDV was found only in crab-eating foxes, whereas CPV-2 was found in both canid species; both viruses were closely related to sequences reported in domestic dogs from southern Brazil. Moreover, the present work reported the detection of canine bocavirus (CBoV) strains that were genetically divergent from CBoV-1 and 2 lineages. Finally, we also characterized CRESS DNA viruses and anelloviruses with marked diversity. The results of this study contribute to the body of knowledge regarding wild canid viruses that can potentially be shared with domestic canids or other species.


title: Rotavirus incidence in hospitalised Hong Kong children: 1 July 1997 to 31 March 2011

text: Sentinel laboratory surveillance from one hospital and passive discharge diagnosis (Clinical Management System, CMS) data from all public Hospital Authority (HA) hospitals were used to estimate disease burden and incidence of rotavirus in hospitalised Hong Kong children over 14 rotavirus seasons (1 July 1997 to 31 March 2011). A primary diagnosis of a gastroenteritis-related disorder was noted in 9.8% of children aged below 5 years, and a primary or secondary diagnosis in 11.8%. Any CMS diagnosis of rotavirus (ICD 008.61) was initially used to derive incidence estimates of rotavirus by age group. Rotavirus was recorded as any primary or any secondary diagnosis in 1.6% of children below 5 years of age. The unadjusted incidence rates per 100,000 person-years based on any CMS diagnosis of rotavirus were: 249 (0 to <1m); 612 (1 to <2m); 1066 (2 to <6m); 1383 (6 to <11m); 959 (1 to <2y); 406 (2 to <3y); 233 (3 to <4y); 124 (4 to <5y). Overall the rotavirus incidence was 1071 in children below 2 years and 542 in children below 5 years of age, with the incidence rates trending up during the time period (p = 0.001). A similar but less marked upward trend (p = 0.046) was noted for the incidence of all-cause gastroenteritis. Laboratory results from a single surveillance hospital (1 July 2000 to 31 March 2011) were then linked to these CMS codes to derive adjustment factors for possible over- and under-diagnosis of rotavirus based on CMS codes alone. This analysis suggested that a CMS diagnosis of rotavirus alone likely under-reported true incidence by a factor of between 1.59 and 2.02 in children below 5 years of age. Despite the availability of rotavirus vaccines in the private sector since 2006, no reduction in the incidence of hospitalisation for either rotavirus or all-cause gastroenteritis was noted in Hong Kong children below 5 years of age over 14 rotavirus seasons (1997–2011).


title: Protective immunity after COVID-19 has been questioned: what can we do without SARS-CoV-2-IgG detection?

text: Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a severe acute respiratory syndrome that is called COVID-19. Clinical manifestations of COVID-19 include diarrhea, pneumonia, lymphopenia, exhausted lymphocytes, and pro-inflammatory cytokine production. Immunology is part of the process of clinical evolution, but there are some questions around immunity-based protection: (1) why some infected people have only mild symptoms of the disease or are asymptomatic; (2) why delayed and weak antibody responses are associated with severe outcomes; and (3) why positivity in molecular tests does not represent protective antibody IgG. Perhaps T cell responses may be the key to solving those questions. SARS-CoV-2-specific memory T cells persist in peripheral blood and may be capable of providing effective information about protective immunity. The T cells studies can be helpful in elucidating the pathways for development of vaccines, therapies, and diagnostics for COVID-19 and for filling these immunology knowledge gaps.


title: Evidence that the leukocyte-common antigen is required for antigen-induced T lymphocyte proliferation

text: Abstract The leukocyte-common antigen (L-CA) is a family of large molecular weight glycoproteins uniquely expressed on the surface of all nucleated cells of hematopoletic origin. The glycoprotein consists of a heavily glycosylated exterior domain, a single membrane spanning region, and a large cytoplasmic domain that contains tyrosine phosphatase activity. To investigate the function of this family, we generated T cell clones that lacked L-CA (L-CA−). The expression of the αβ T cell receptor, CD3, CD4, IL-2 receptor (p55), LFA-1, Thy-1, and Pgp-1 (CD44) was normal. The L-CA− T cell clones failed to proliferate in response to antigen or cross-linked CD3; however, they could still proliferate in response to IL-2. An L-CA+ revertant was obtained and the ability to proliferate in response to antigen and cross-linked CD3 was restored. These data indicate that L-CA is required for T cells to enter into cell cycle in response to antigen.


title: Public health might be endangered by possible prolonged discharge of SARS-CoV-2 in stool

text: • The published data, which showed the COVID-19 patients with low digestive. • manifestation, might be misleading. Case with negative URT test showed positive in. • rectal scarab which challenge the isolation protocol. • As fomite transmission caused clusters of infection of SARS, adequate disinfection. • operations should be adopted in SARS-CoV-2 outbreak.


title: Disassembly of the cystovirus ϕ6 envelope by montmorillonite clay

text: Prior studies of clay–virus interactions have focused on the stability and infectivity of nonenveloped viruses, yielding contradictory results. We hypothesize that the surface charge distribution of the clay and virus envelope dictates how the components react and affect aggregation, viral stability, and infectivity. The bacteriophage Cystoviridae species φ6 used in this study is a good model for enveloped pathogens. The interaction between φ6 and montmorillonite (MMT) clay (the primary component of bentonite) is explored by transmission electron microscopy. The analyses show that MMT–φ6 mixtures undergo heteroaggregation, forming structures in which virtually all the virions are either sequestered between MMT platelet layers or attached to platelet edges. The virions swell and undergo disassembly resulting in partial or total envelope loss. Edge-attached viral envelopes distort to increase contact area with the positively charged platelet edges indicating that the virion surface is negatively charged. The nucleocapsid (NCs) remaining after envelope removal also exhibit distortion, in contrast to detergent-produced NCs which exhibit no distortion. This visually discernible disassembly is a mechanism for loss of infectivity previously unreported by studies of nonenveloped viruses. The MMT-mediated sequestration and disassembly result in reduced infectivity, suggesting that clays may reduce infectivity of enveloped pathogenic viruses in soils and sediments.


title: The Influence of Meteorology on the Spread of Influenza: Survival Analysis of an Equine Influenza (A/H3N8) Outbreak

text: The influences of relative humidity and ambient temperature on the transmission of influenza A viruses have recently been established under controlled laboratory conditions. The interplay of meteorological factors during an actual influenza epidemic is less clear, and research into the contribution of wind to epidemic spread is scarce. By applying geostatistics and survival analysis to data from a large outbreak of equine influenza (A/H3N8), we quantified the association between hazard of infection and air temperature, relative humidity, rainfall, and wind velocity, whilst controlling for premises-level covariates. The pattern of disease spread in space and time was described using extraction mapping and instantaneous hazard curves. Meteorological conditions at each premises location were estimated by kriging daily meteorological data and analysed as time-lagged time-varying predictors using generalised Cox regression. Meteorological covariates time-lagged by three days were strongly associated with hazard of influenza infection, corresponding closely with the incubation period of equine influenza. Hazard of equine influenza infection was higher when relative humidity was <60% and lowest on days when daily maximum air temperature was 20–25°C. Wind speeds >30 km hour(−1) from the direction of nearby infected premises were associated with increased hazard of infection. Through combining detailed influenza outbreak and meteorological data, we provide empirical evidence for the underlying environmental mechanisms that influenced the local spread of an outbreak of influenza A. Our analysis supports, and extends, the findings of studies into influenza A transmission conducted under laboratory conditions. The relationships described are of direct importance for managing disease risk during influenza outbreaks in horses, and more generally, advance our understanding of the transmission of influenza A viruses under field conditions.


title: Family Cluster of Middle East Respiratory Syndrome Coronavirus Infections, Tunisia, 2013

text: In 2013 in Tunisia, 3 persons in 1 family were infected with Middle East respiratory syndrome coronavirus (MERS-CoV). The index case-patient’s respiratory tract samples were negative for MERS-CoV by reverse transcription PCR, but diagnosis was retrospectively confirmed by PCR of serum. Sequences clustered with those from Saudi Arabia and United Arab Emirates.


title: Polymorphisms of interferon-inducible genes OAS-1 and MxA associated with SARS in the Vietnamese population

text: Abstract We hypothesized that host antiviral genes induced by type I interferons might affect the natural course of severe acute respiratory syndrome (SARS). We analyzed single nucleotide polymorphisms (SNPs) of 2′,5′-oligoadenylate synthetase 1 (OAS-1), myxovirus resistance-A (MxA), and double-stranded RNA-dependent protein kinase in 44 Vietnamese SARS patients with 103 controls. The G-allele of non-synonymous A/G SNP in exon 3 of OAS-1 gene showed association with SARS (p =0.0090). The G-allele in exon 3 of OAS-1 and the one in exon 6 were in strong linkage disequilibrium and both of them were associated with SARS infection. The GG genotype and G-allele of G/T SNP at position −88 in the MxA gene promoter were found more frequently in hypoxemic group than in non-hypoxemic group of SARS (p =0.0195). Our findings suggest that polymorphisms of two IFN-inducible genes OAS-1 and MxA might affect susceptibility to the disease and progression of SARS at each level.


docid: nvilxnzl

title: Comprehensive detection and identification of human coronaviruses, including the SARS-associated coronavirus, with a single RT-PCR assay

text: Abstract The SARS-associated human coronavirus (SARS-HCoV) is a newly described, emerging virus conclusively established as the etiologic agent of the severe acute respiratory syndrome (SARS). This study presents a single-tube RT-PCR assay that can detect with high analytical sensitivity the SARS-HCoV, as well as several other coronaviruses including other known human respiratory coronaviruses (HCoV-OC43 and HCoV-229E). Species identification is provided by sequencing the amplicon, although a rapid screening test by restriction enzyme analysis has proved to be very useful for the analysis of samples obtained during the SARS outbreak in Toronto, Canada.


title: XMRV as a Human Pathogen?

text: XMRV has been proposed to be associated with Prostate Cancer and Chronic Fatigue Syndrome. This proposition has been controversial because many investigators have failed to replicate the reported associations. Here, we explore whether XMRV is an authentic human pathogen in the light of recent findings that indicate otherwise.


title: CD13

text: Publisher Summary This chapter focuses on the tissue distribution, structure, and functions of the leucocyte antigen CD13. CD13 is expressed by granulocytes and monocytes and their precursors. CD13 is a marker for most acute myeloid leukaemias and a smaller proportion of acute lymphoid leukaemias. Various nonhematopoietic cells express CD13, including epithelial cells from renal proximal tubules and intestinal brush border, endothelial cells, fibroblasts, brain cells, bone marrow stromal cells, osteoclasts, and cells lining the biliary caniculae. CD13 is a member of a group of type II integral membrane metalloproteases that includes the leucocyte antigens CD10, CD26, CD73, and BP-1. The CD13 glycoprotein has a short N-terminal cytoplasmic tail, a transmembrane region that functions as a signal peptide, and a large C-terminal extracellular region that contains 11 N-linked glycosylation sites and also O-linked glycosylation. CD13 is a receptor for coronaviruses, RNA viruses that cause respiratory diseases in humans and several species of animals. The binding site on CD 13 for the swine coronavirus TGEV (transmissible gastroenteritis virus) is distinct from the enzymatic site. CD13 is a zinc-binding metalloprotease that plays a role in cell surface antigen presentation by trimming the N-terminal amino acids from MHC Class II-bound peptides.


title: Queries on the COVID‐19 quick publishing ethics

text: The Editorial titled "COVID19: Why justice and transparency in hospital triage policies are paramount" by Schuklenk, which appeared in Bioethics, is striking as it features the importance of honesty and openness in research ethics. Ethics, of course, is an integral part of research, and the publication ethics is even more crucial to sustain the quality of scientific output.


title: Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling

text: Severe Acute Respiratory Syndrome- Coronavirus 2 (SARS-Cov-2) has caused over 5,000,000 cases of Coronavirus disease (COVID-19) with significant fatality rate.(1–3) Due to the urgency of this global pandemic, numerous therapeutic and vaccine trials have begun without customary safety and efficacy studies.(4) Laboratory mice have been the stalwart of these types of studies; however, they do not support infection by SARS-CoV-2 due to the inability of its spike (S) protein to engage the mouse ortholog of its human entry receptor angiotensin-converting enzyme 2 (hACE2). While hACE2 transgenic mice support infection and pathogenesis,(5) these mice are currently limited in availability and are restricted to a single genetic background. Here we report the development of a mouse model of SARS-CoV-2 based on adeno associated virus (AAV)-mediated expression of hACE2. These mice support viral replication and antibody production and exhibit pathologic findings found in COVID-19 patients as well as non-human primate models. Moreover, we show that type I interferons are unable to control SARS-CoV2 replication and drive pathologic responses. Thus, the hACE2-AAV mouse model enables rapid deployment for in-depth analysis following robust SARS-CoV-2 infection with authentic patient-derived virus in mice of diverse genetic backgrounds. This represents a much-needed platform for rapidly testing prophylactic and therapeutic strategies to combat COVID-19.


title: Characterization of the stimulators of protein-directed ribosomal frameshifting in Theiler's murine encephalomyelitis virus

text: Many viruses utilize programmed –1 ribosomal frameshifting (–1 PRF) to express additional proteins or to produce frameshift and non-frameshift protein products at a fixed stoichiometric ratio. PRF is also utilized in the expression of a small number of cellular genes. Frameshifting is typically stimulated by signals contained within the mRNA: a ‘slippery’ sequence and a 3′-adjacent RNA structure. Recently, we showed that −1 PRF in encephalomyocarditis virus (EMCV) is trans-activated by the viral 2A protein, leading to a temporal change in PRF efficiency from 0% to 70% during virus infection. Here we analyzed PRF in the related Theiler's murine encephalomyelitis virus (TMEV). We show that 2A is also required for PRF in TMEV and can stimulate PRF to levels as high as 58% in rabbit reticulocyte cell-free translations and 81% during virus infection. We also show that TMEV 2A trans-activates PRF on the EMCV signal but not vice versa. We present an extensive mutational analysis of the frameshift stimulators (mRNA signals and 2A protein) analysing activity in in vitro translation, electrophoretic mobility shift and in vitro ribosome pausing assays. We also investigate the PRF mRNA signal with RNA structure probing. Our results substantially extend previous characterization of protein-stimulated PRF.