title: Evaluation of the Xpert Flu A Panel nucleic acid amplification-based point-of-care test for influenza A virus detection and pandemic H1 subtyping

text: Abstract Background Influenza antigenic point-of-care (POC) tests are too insensitive for individual reliable diagnosis of influenza virus infections without additional laboratory confirmation. Molecular POC tests could be a valuable alternative. Objectives To evaluate the first influenza molecular POC test commercially available, the Cepheid Xpert Flu A Panel designed to simultaneously detect influenza A virus and subtype A(H1N1) 2009 pandemic virus, and compare it with in-house real-time RT-PCR (qRT-PCR). Study design Clinical specimens positive for influenza virus and influenza virus isolates with different viral loads and of different type and subtype were used to determine the analytical reactivity and sensitivity. A panel of pathogen negative specimens and isolates of 19 different respiratory pathogens were used to determine the analytical specificity. Results Except A(H9N2) virus the Xpert Flu A Panel detected A(H1N1) seasonal and 2009 pandemic, A(H3N2), A(H5N2), A(H5N1) and A(H7N7) viruses and correctly subtyped A(H1N1) 2009 virus. Analytical sensitivity was similar to qRT-PCR in the range of 400–5000 viral particles per ml. However, of most subtypes some specimens with cycle threshold values greater than 30 in qRT-PCR and A(H1N1) 2009 specimens with inconsistent results in the qRT-PCR due to primer or probe mismatches were not detected in the Xpert Flu A Panel. Analytical specificity was 100%. Conclusions The Xpert Flu A Panel is the first commercially available POC molecular test for detection of influenza A virus and determination of the H1 2009 subtype and is analytically reasonable sensitive compared with qRT-PCR and highly specific and therefore a welcome alternative to antigenic POC tests.


title: Cross-crystal averaging with search models to improve molecular replacement phases

text: The application of molecular replacement (MR) in macromolecular crystallography can be limited by the “model bias” problem. Here we propose a strategy to reduce model bias when only part of a new structure is known: after the MR search, structure determination of the unknown part of the new structure can be facilitated by cross-crystal averaging of the known part of the new structure with the search model. This strategy dramatically improves electron density in the unknown part of the new structure. It has enabled us to determine the structures of two coronavirus receptor-binding domains each complexed with their receptor at moderate resolutions. In a test case, it also enabled automated model building when over 50% of an antigen-antibody complex was absent. These results suggest that this averaging strategy can be routinely used after MR to enhance the interpretability of electron density associated with missing model.


title: Synergistic antiviral effect of a combination of mouse interferon‐α and interferon‐γ on mouse hepatitis virus

text: Although interferon (IFN)‐α and IFN‐γ have been reported to exhibit a synergistic antiviral effect through the different signaling pathways in vitro, their therapeutic efficacy is not well defined in vivo. The current study was carried out to investigate the combined antiviral effect in a model of mouse hepatitis virus Type 2 (MHV‐2) infection, in which fulminant hepatitis is developed. MHV‐2 was injected intraperitoneally into 4‐week‐old ICR mice, IFN or the vehicle was administered intramuscularly for 5 days, and the antiviral effect was evaluated based on survival periods, liver histology, serum alanine transaminase (ALT) levels, and MHV‐2 virus titers in the liver tissues. The animals in the group treated with a combination of IFN‐α and IFN‐γ survived for longer periods than the groups treated with IFN‐α alone and IFN‐γ alone (IFN‐α 10(3) (IU/mouse)/‐γ 10(3) vs. IFN‐α 10(3), P < 0.005; IFN‐α 10(3)/‐γ 10(3) vs. IFN‐γ 10(3), P < 0.001). This is consistent with the lower levels of hepatocellular necrosis and serum ALT and the decreased titers of MHV‐2 virus in the liver tissues (48 hr, P < 0.001; 72 hr, P < 0.001). These findings indicate that a combination of IFN‐α and IFN‐γ exhibits a synergistic antiviral effect on MHV‐2 infection. The biology of MHV‐2 is quite different from that of human hepatitis viruses; however, these results suggest the beneficial combined therapy of IFN‐α and IFN‐γ for the treatment of human viral hepatitis. J. Med. Virol. 69:188–194, 2003. © 2003 Wiley‐Liss, Inc.


title: Clinical Screening Tools to Diagnose Group A Streptococcal Pharyngotonsillitis in Primary Care Clinics to Improve Prescribing Habits

text: This review highlights the clinical scoring tools used for the management of acute pharyngotonsillitis in primary care clinics. It will include the prevalence of group A pharyngotonsillitis among children and adults worldwide and the selective tests employed for diagnosing group A streptococcal pharyngotonsillitis. Pharyngotonsillitis is one of the common reasons for visits to primary care clinics worldwide, and physicians tend to prescribe antibiotics according to the clinical symptoms, which leads to overprescribing antibiotics. This in turn may lead to serious health impacts and severe reactions and may promote antibiotic resistance. These significantly add on to the health care costs. The available information from health organisations and previous studies has indicated the need to manage the diagnosis of pharyngotonsillitis to improve prescribing habits in primary care clinics.


title: Modifiable Areal Unit Problem

text: Abstract The modifiable areal unit problem, MAUP, is ever-present although not always appreciated. Through real examples, this article outlines the basic causes of MAUP, namely changes in the size, shape, and/or orientation of spatial categories/polygons used to map areal data. The visual effects of changes to mapped data are obvious even though the impacts on our understanding of the world are profound. The article concludes with a discussion of technical and broader strategic approaches for confronting the effects of MAUP on our treatment and interpretation of areal data.


title: Characteristics of physical blocking on co-occupant’s exposure to respiratory droplet residuals

text: Existed evidences show that airborne transmission of human respiratory droplets may be related with the spread of some infectious disease, such as severe acute respiratory syndrome (SARS) and H1N1 pandemic. Non-pharmaceutical approaches, including ventilation system and personal protection, are believed to have certain positive effects on the reduction of co-occupant’s inhalation. This work then aims to numerically study the performances of mouth covering on co-occupant’s exposure under mixing ventilation (MV), under-floor air distribution (UFAD) and displacement ventilation (DV) system, using drift-flux model. Desk partition, as one generally employed arrangement in plan office, is also investigated under MV. The dispersion of 1, 5 and 10 μm droplet residuals are numerically calculated and CO(2) is used to represent tracer gas. The results show that using mouth covering by the infected person can reduce the co-occupant’s inhalation greatly by interrupting direct spread of the expelled droplets, and best performance can be achieved under DV since the coughed air is mainly confined in the microenvironment of the infected person. The researches under MV show that the two interventions, mouth covering and desk partition, achieve almost the same inhalation for fine droplets while the inhalation of the co-occupant is lower when using mouth covering for large droplets.


title: Returning to paradise: Investigating issues of tourism crisis and disaster recovery on the island of Bali

text: Abstract The past decade has seen the rapid proliferation of theory, literature, and research, in the field of tourism disaster and crisis management, however very few empirical studies of destination recovery consider the pre-crisis context, or extend beyond a particular crisis catalyst and subsequent return to “business as usual”. As a longitudinal case study, the island destination of Bali provides insight into tourism crisis vulnerability, particularly in relation to issues of unplanned development and host community over-dependence on tourism revenue. Furthermore, the experience of two separate targeted terrorist attacks on the island reveals a number of challenges and tangible lessons for stakeholders engaged in destination disaster management and crisis recovery. While the restoration of consumer confidence and arrival numbers are often considered to be indicators of successful tourism recovery, the broader disaster management literature advocates for proactive vulnerability reduction premised in sustainable development and comprehensive, integrated disaster risk reduction.


Chilblains are a common cutaneous finding during the COVID-19 pandemic: a retrospective nationwide study from France


title: The development of a GeXP-based multiplex reverse transcription-PCR assay for simultaneous detection of sixteen human respiratory virus types/subtypes

text: BACKGROUND: Existing standard non-molecular diagnostic methods such as viral culture and immunofluorescent (DFA) are time-consuming, labor intensive or limited sensitivity. Several multiplex molecular assays are costly. Therefore, there is a need for the development of a rapid and sensitive diagnosis of respiratory viral pathogens. METHODS: A GeXP-based multiplex RT-PCR assay (GeXP assay) was developed to detect simultaneously sixteen different respiratory virus types/subtypes. Seventeen sets of chimeric primers were used to initiate the RT-PCR, and one pair of universal primers was used for the subsequent cycles of the RT-PCR. The specificity of the GeXP assay was examined with positive controls for each virus type/subtype. The sensitivity was evaluated by performing the assay on serial ten-fold dilutions of in vitro-transcribed RNA of all RNA viruses and the plasmids containing the Adv and HBoV target sequence. GeXP assay was further evaluated using 126 clinical specimens and compared with Luminex xTAG RVP Fast assay. RESULTS: The GeXP assay achieved a sensitivity of 20–200 copies for a single virus and 1000 copies when all of the 16 pre-mixed viral targets were present. Analyses of 126 clinical specimens using the GeXP assay demonstrated that GeXP assay and the RVP Fast assay were in complete agreement for 109/126 (88.51%) of the specimens. GeXP assay was more sensitive than the RVP Fast assay for the detection of HRV and PIV3, and slightly less sensitive for the detection of HMPV, Adv, RSVB and HBoV. The whole process of the GeXP assay for the detection of 12 samples was completed within 2.5 hours. CONCLUSIONS: In conclusion, the GeXP assay is a rapid, cost-effective, sensitive, specific and high throughput method for the detection of respiratory virus infections.


title: SARS vaccine based on a replication-defective recombinant vesicular stomatitis virus is more potent than one based on a replication-competent vector

text: Abstract A SARS vaccine based on a live-attenuated vesicular stomatitis virus (VSV) recombinant expressing the SARS-CoV S protein provides long-term protection of immunized mice from SARS-CoV infection (Kapadia, S.U., Rose, J. K., Lamirande, E., Vogel, L., Subbarao, K., Roberts, A., 2005. Long-term protection from SARS coronavirus infection conferred by a single immunization with an attenuated VSV-based vaccine. Virology 340(2), 174–82.). Because it is difficult to obtain regulatory approval of vaccine based on live viruses, we constructed a replication-defective single-cycle VSV vector in which we replaced the VSV glycoprotein (G) gene with the SARS-CoV S gene. The virus was only able to infect cells when pseudotyped with the VSV G protein. We measured the effectiveness of immunization with the single-cycle vaccine in mice. We found that the vaccine given intramuscularly induced a neutralizing antibody response to SARS-CoV that was approximately ten-fold greater than that required for the protection from SARS-CoV infection, and significantly greater than that generated by the replication-competent vector expressing SARS-CoV S protein given by the same route. Our results, along with earlier studies showing potent induction of T-cell responses by single-cycle vectors, indicate that these vectors are excellent alternatives to live-attenuated VSV.


title: Asymmetric dependence between stock market returns and news during COVID19 financial turmoil

text: • I investigate the stock market's reaction to coronavirus news in the top six most affected countries by the pandemic. • The fake news exerts a negative nonlinear influence on the inferior and the middle quantiles throughout the distribution of returns. • The media coverage leads to a decrease in returns across middle and superior quantiles and has no effects on the inferior ones. • During COVID19 turmoil superior quantiles of returns distribution exhibit negative dependence on past performances, while inferior and middle quantiles are not affected by this phenomenon. • The gold return has a positive correlation with the stock markets, which amplifies during extreme bearish and bullish periods indicating that it does not behave as a “Safe Havens” asset.


title: Global comparison of changes in the number of test-positive cases and deaths by coronavirus infection (COVID-19) in the world

text: Global differences in changes in the numbers of population-adjusted daily test-positive cases (NPDP) and deaths (NPDD) by COVID-19 were analyzed for 49 countries, including developed and developing countries. The changes as a proportion of national population were compared, adjusting by the beginning of test-positive cases increase (BPI) or deaths increase (BDI). Remarkable regional differences of more than 100-fold in NPDP and NPDD were observed. The trajectories of NPDD after BDI increased exponentially within 20 days in most countries. Machine learning analysis suggested that NPDD on 30 days after BDI was the highest in developed Western countries (1180 persons per hundred million), followed by countries in the Middle East (128), Latin America (97), and Asia (7). Furthermore, in Western countries with positive rates of the PCR test of less than 7.0%, the increase in NPDP was slowing-down two weeks after BPI, and subsequent NPDD was only 15% compared with those with higher positive rates, which suggested that the situation of testing might have affected the velocity of COVID-19 spread. The causes behind remarkable differences between regions possibly include genetic factors of inhabitants because distributions of the race and of the observed infection increasing rates were in good agreement globally.


title: Sequence analysis of human coronavirus 229E mRNAs 4 and 5: evidence for polymorphism and homology with myelin basic protein

text: Abstract Human coronaviruses (HCV) are important pathogens responsible for respiratory, gastrointestinal and possibly neurological disorders. To better understand the molecular biology of the prototype HCV-229E strain, the nucleotide sequence of the 5'-unique regions of mRNAs 4 and 5 were determined from cloned cDNAs. Sequence analysis of the cDNAs synthesized from mRNA 4 revealed a major difference with previously published results. However, polymerase chain reaction amplification of this region showed that the sequenced cDNAs were produced from minor RNA species, an indication of possible genetic polymorphism in this region of the viral genome. The mutated messenger RNA 4 contains two ORFs: (1) ORF4a consisting of 132 nucleotides which potentially encodes a 44-amino acid polypeptide of 4653 Da; this coding sequence is preceded by a consensus transcriptional initiation sequence, CUAAACU, similar to the ones found upstream of the N and M genes; (2) ORF4b of 249 nucleotides potentially encoding an 83-amino acid basic and leucine-rich polypeptide of 9550 Da. On the other hand, mRNA 5 contains one single ORF of 231 nucleotides which could encode a 77-amino acid basic and leucine-rich polypeptide of 9046 Da. This putative protein presents a significant degree of amino acid homology (33%) with its counterpart found in transmissible gastroenteritis coronavirus (TGEV). The proteins in the two different viruses exhibit similar molecular weights and are extremely hydrophobic. Interestingly, a sequence homology of five amino acids was found between the protein encoded by ORF4b of HCV-229E and an immunologically important region of human myelin basic protein.


title: Human arrogance and epidemics Michael Merson Stephen Inrig

text: Unknown


title: Advocacy to provide good quality oncology services during the COVID-19 pandemic – Actions at 3-Levels

text: Abstract The COVID-19 pandemic is a devastating catastrophe to the whole world, China is the first country seriously affected. This review shows that it is possible to stop wide-spread infection in the country and to provide good quality oncology services even during this challenging period, through concerted efforts with well-organized actions at all levels (National/Municipal, Hospital and Department). The key strategies leading to successful impacts are summarized for sharing. In addition to making practice changes to cope with the adverse realities, oncologists should also work together to raise pragmatic suggestions to policy makers and be strong advocates to protect our patients from the detrimental effect of delay or compromised treatment.


title: Quantitative assay for measuring the Taura syndrome virus and yellow head virus load in shrimp by real-time RT-PCR using SYBR Green chemistry

text: Abstract Taura syndrome virus (TSV) and yellow head virus (YHV) are the two RNA viruses infecting penaeid shrimp (Penaeus sp.) that have caused major economic losses to shrimp aquaculture. A rapid and highly sensitive detection and quantification method for TSV and YHV was developed using the GeneAmp® 5700 Sequence Detection System and SYBR Green chemistry. The reverse transcriptase polymerase chain reaction (RT-PCR) mixture contained a fluorescent dye, SYBR Green, which exhibits fluorescence enhancement upon binding to double strand cDNA. The enhancement of fluorescence was found to be proportional to the initial concentration of the template cDNA. A linear relationship was observed between input plasmid DNA and cycle threshold (C T) values for 106 down to a single copy of both viruses. To control for the variation in sample processing and in reverse transcription reaction among samples, shrimp β-actin and elongation factor-1α (EF-1α) genes were amplified in parallel with the viral cDNA. The sensitivity and the efficiency of amplification of EF-1α was greater than β-actin when compared to TSV and YHV amplification efficiency suggesting that EF-1α is a better internal control for the RT-PCR detection of TSV and YHV. In addition, sample to sample variation in EF-1α C T value was lower than the variation in β-actin C T value of the corresponding samples. The specificity of TSV, YHV, EF-1α and β-actin amplifications was confirmed by analyzing the dissociation curves of the target amplicon. The C T values of TSV and YHV samples were normalized against EF-1α C T values for determining the absolute copy number from the standard curve of the corresponding virus. The method described here is highly robust and is amenable to high throughput assays making it a useful tool for diagnostic, epidemiological and genetic studies in shrimp aquaculture.


title: Preparedness and vulnerability of African countries against importations of COVID-19: a modelling study

text: BACKGROUND: The novel coronavirus disease 2019 (COVID-19) epidemic has spread from China to 25 countries. Local cycles of transmission have already occurred in 12 countries after case importation. In Africa, Egypt has so far confirmed one case. The management and control of COVID-19 importations heavily rely on a country's health capacity. Here we evaluate the preparedness and vulnerability of African countries against their risk of importation of COVID-19. METHODS: We used data on the volume of air travel departing from airports in the infected provinces in China and directed to Africa to estimate the risk of importation per country. We determined the country's capacity to detect and respond to cases with two indicators: preparedness, using the WHO International Health Regulations Monitoring and Evaluation Framework; and vulnerability, using the Infectious Disease Vulnerability Index. Countries were clustered according to the Chinese regions contributing most to their risk. FINDINGS: Countries with the highest importation risk (ie, Egypt, Algeria, and South Africa) have moderate to high capacity to respond to outbreaks. Countries at moderate risk (ie, Nigeria, Ethiopia, Sudan, Angola, Tanzania, Ghana, and Kenya) have variable capacity and high vulnerability. We identified three clusters of countries that share the same exposure to the risk originating from the provinces of Guangdong, Fujian, and the city of Beijing, respectively. INTERPRETATION: Many countries in Africa are stepping up their preparedness to detect and cope with COVID-19 importations. Resources, intensified surveillance, and capacity building should be urgently prioritised in countries with moderate risk that might be ill-prepared to detect imported cases and to limit onward transmission. FUNDING: EU Framework Programme for Research and Innovation Horizon 2020, Agence Nationale de la Recherche.


title: Whole Genome Sequencing and Progress Toward Full Inbreeding of the Mouse Collaborative Cross Population

text: Two key features of recombinant inbred panels are well-characterized genomes and reproducibility. Here we report on the sequenced genomes of six additional Collaborative Cross (CC) strains and on inbreeding progress of 72 CC strains. We have previously reported on the sequences of 69 CC strains that were publicly available, bringing the total of CC strains with whole genome sequence up to 75. The sequencing of these six CC strains updates the efforts toward inbreeding undertaken by the UNC Systems Genetics Core. The timing reflects our competing mandates to release to the public as many CC strains as possible while achieving an acceptable level of inbreeding. The new six strains have a higher than average founder contribution from non-domesticus strains than the previously released CC strains. Five of the six strains also have high residual heterozygosity (>14%), which may be related to non-domesticus founder contributions. Finally, we report on updated estimates on residual heterozygosity across the entire CC population using a novel, simple and cost effective genotyping platform on three mice from each strain. We observe a reduction in residual heterozygosity across all previously released CC strains. We discuss the optimal use of different genetic resources available for the CC population.


title: Distinct usage of three C-type lectins by Japanese encephalitis virus: DC-SIGN, DC-SIGNR, and LSECtin

text: Infection with West Nile virus and dengue virus, two mosquito-borne flaviviruses, is enhanced by two calcium-dependent lectins: dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), and its related molecule (DC-SIGNR). The present study examined the relationship between Japanese encephalitis virus (JEV) infection and three lectins: DC-SIGN, DC-SIGNR, and liver sinusoidal endothelial cell lectin (LSECtin). Expression of DC-SIGNR resulted in robust JEV proliferation in a lymphoid cell line, Daudi cells, which was otherwise non-permissive to infection. DC-SIGN expression caused moderate JEV proliferation, with effects that varied according to the cells in which JEV was prepared. LSECtin expression had comparatively minor, but consistent, effects, in all cell types used in JEV preparation. While DC-SIGN/DC-SIGNR-mediated JEV infection was inhibited by yeast mannan, LSECtin-mediated infection was inhibited by N-acetylglucosamine β1-2 mannose. Although involvement of DC-SIGN/DC-SIGNR in infection seems to be a common characteristic, this is the first report on usage of LSECtin in mosquito-borne flavivirus infection.


title: Immigration Policy and Justice in the Era of COVID-19

text: The U.S. immigration system has not escaped the challenges presented by the COVID-19 pandemic. Concerns have been raised about policy changes, enforcement actions, immigrant detention, and deportation practices during the outbreak. In response, dozens of lawsuits have been brought against the government on behalf of undocumented immigrants and detainees, ranging from the conditions of ICE detention facilities to the public charge rule. While most cases continue to move through the federal court system, a number of district court judges have already ruled in favor of the plaintiffs. This paper focuses on three particular areas of immigration policy and practice during COVID: ICE enforcement actions, immigrant detention, and deportations. We summarize the current state of extant data and evidence on each of these and examine questions that remain for further research.


title: Kein ungezielter Einsatz von Antibiotika: Akute Bronchitis

text: Die akute Bronchitis kann durch eine Vielzahl verschiedener Errreger ausgelöst werden, die Abgrenzung zu anderen Atemwegserkrankungen ist oft schwierig bis unmöglich. Es gibt daher keine spezifische Therapie. Für eine eindeutige Diagnose müssen Asthma, COPD- Exazerbationen, Pneumonie und die gewöhnliche Grippe ausgeschlossen werden. Meist sind Virusinfekte ursächlich, allerdings kommen auch atypische Bakterien infrage. Die Therapie mit Antibiotika wird daher nur bei klarem Erregernachweis empfohlen.


title: Anti-pandemic influenza A (H1N1) virus potential of catechin and gallic acid

text: Abstract Background The pandemic influenza A (H1N1) virus has spread worldwide and infected a large proportion of the human population. Discovery of new and effective drugs for the treatment of influenza is a crucial issue for the global medical community. According to our previous study, TSL-1, a fraction of the aqueous extract from the tender leaf of Toonasinensis, has demonstrated antiviral activities against pandemic influenza A (H1N1) through the down-regulation of adhesion molecules and chemokine to prevent viral attachment. Methods The aim of the present study was to identify the active compounds in TSL-1 which exert anti-influenza A (H1N1) virus effects. XTT assay was used to detect the cell viability. Meanwhile, the inhibitory effect on the pandemic influenza A (H1N1) virus was analyzed by observing plaque formation, qRT-PCR, neuraminidase activity, and immunofluorescence staining of influenza A-specific glycoprotein. Results Both catechin and gallic acid were found to be potent inhibitors in terms of influenza virus mRNA replication and MDCK plaque formation. Additionally, both compounds inhibited neuraminidase activities and viral glycoprotein. The 50% effective inhibition concentration (EC50) of catechin and gallic acid for the influenza A (H1N1) virus were 18.4 μg/mL and 2.6 μg/mL, respectively; whereas the 50% cytotoxic concentrations (CC50) of catechin and gallic acid were >100 μg/mL and 22.1 μg/mL, respectively. Thus, the selectivity indexes (SI) of catechin and gallic acid were >5.6 and 22.1, respectively. Conclusion The present study demonstrates that catechin might be a safe reagent for long-term use to prevent influenza A (H1N1) virus infection; whereas gallic acid might be a sensitive reagent to inhibit influenza virus infection. We conclude that these two phyto-chemicals in TSL-1 are responsible for exerting anti-pandemic influenza A (H1N1) virus effects.


title: An exploration of social and economic outcome and associated health-related quality of life after critical illness in general intensive care unit survivors: a 12-month follow-up study

text: INTRODUCTION: The socio-economic impact of critical illnesses on patients and their families in Europe has yet to be determined. The aim of this exploratory study was to estimate changes in family circumstances, social and economic stability, care requirements and access to health services for patients during their first 12 months after ICU discharge. METHODS: Multi-center questionnaire-based study of survivors of critical illness at 6 and 12 months after ICU discharge. RESULTS: Data for 293 consenting patients who spent greater than 48 hours in one of 22 UK ICUs were obtained at 6 and 12 months post-ICU discharge. There was little evidence of a change in accommodation or relationship status between pre-admission and 12 months following discharge from an ICU. A negative impact on family income was reported by 33% of all patients at 6 months and 28% at 12 months. There was nearly a 50% reduction in the number of patients who reported employment as their sole source of income at 12 months (19% to 11%) compared with pre-admission. One quarter of patients reported themselves in need of care assistance at 6 months and 22% at 12 months. The majority of care was provided by family members (80% and 78%, respectively), for half of whom there was a negative impact on employment. Amongst all patients receiving care, 26% reported requiring greater than 50 hours a week. Following discharge, 79% of patients reported attending their primary care physician and 44% had seen a community nurse. Mobility problems nearly doubled between pre-admission and 6 months (32% to 64%). Furthermore, 73% reported moderate or severe pain at 12 months and 44% remained significantly anxious or depressed. CONCLUSIONS: Survivors of critical illness in the UK face a negative impact on employment and commonly have a care requirement after discharge from hospital. This has a corresponding negative impact on family income. The majority of the care required is provided by family members. This effect was apparent by 6 months and had not materially improved by 12 months. This exploratory study has identified the potential for a significant socio-economic burden following critical illness.


COVID-19: Radiology Department Financial Impact and Planning for Post-COVID Recovery


Emerging outbreaks associated with equine coronavirus in adult horses


title: Interactions of SARS Coronavirus Nucleocapsid Protein with the host cell proteasome subunit p42

text: BACKGROUND: Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spreads rapidly and has a high case-mortality rate. The nucleocapsid protein (NP) of SARS-CoV may be critical for pathogenicity. This study sought to discover the host proteins that interact with SARS-CoV NP. RESULTS: Using surface plasmon resonance biomolecular interaction analysis (SPR/BIA) and matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry, we found that only the proteasome subunit p42 from human fetal lung diploid fibroblast (2BS) cells bound to SARS-CoV NP. This interaction was confirmed by the glutathione S-transferase (GST) fusion protein pulldown technique. The co-localization signal of SARS-CoV NP and proteasome subunit p42 in 2BS cells was detected using indirect immunofluorescence and confocal microscopy. p42 is a subunit of the 26S proteasome; this large, multi-protein complex is a component of the ubiquitin-proteasome pathway, which is involved in a variety of basic cellular processes and inflammatory responses. CONCLUSION: To our knowledge, this is the first report that SARS-CoV NP interacts with the proteasome subunit p42 within host cells. These data enhance our understanding of the molecular mechanisms of SARS-CoV pathogenicity and the means by which SARS-CoV interacts with host cells.


title: Critically ill patients with COVID-19 with ECMO and artificial liver plasma exchange: A retrospective study

text: COVID-19 is an emerging infectious disease capable of causing severe pneumonia. We aimed to characterize a group of critically ill patients in a single-center study. This was a retrospective case series of 23 patients with confirmed COVID-19-related critical illness in the intensive care unit (ICU) of a hospital in Hangzhou Zhejiang Province between January 22 and March 20, 2020. Of the 23 critically ill patients, the median age was 66 years (interquartile range [IQR] 59–80 years). The median time from disease onset to ICU admission was 10 days (IQR 6–11 days), to mechanical ventilation (MV) was 11 days (IQR 7.75–13 days), to artificial liver plasma exchange was 12 days (IQR 9.75–14.75 days), and to extracorporeal membrane oxygenation (ECMO) was 22 days (IQR 17.5–30 days). Nine patients required high flow oxygen. Fourteen patients received MV. Six required ECMO. Nine received artificial liver plasma exchange. Mortality was 0 at day 28. Mortality was 0 at day 28 in our single-center study. Extracorporeal membrane oxygenation reduced the requirements for ventilator support. Artificial liver plasma exchange significantly reduced inflammatory cytokine levels. These supportive therapies helped to extend the patients’ survival times and increase the chance of follow-up treatments.


title: Membrane interaction and structure of the transmembrane domain of influenza hemagglutinin and its fusion peptide complex

text: BACKGROUND: To study the organization and interaction with the fusion domain (or fusion peptide, FP) of the transmembrane domain (TMD) of influenza virus envelope glycoprotein for its role in membrane fusion which is also essential in the cellular trafficking of biomolecules and sperm-egg fusion. RESULTS: The fluorescence and gel electrophoresis experiments revealed a tight self-assembly of TMD in the model membrane. A weak but non-random interaction between TMD and FP in the membrane was found. In the complex, the central TMD oligomer was packed by FP in an antiparallel fashion. FP insertion into the membrane was altered by binding to TMD. An infrared study exhibited an enhanced membrane perturbation by the complex formation. A model was built to illustrate the role of TMD in the late stages of influenza virus-mediated membrane fusion reaction. CONCLUSION: The TMD oligomer anchors the fusion protein in the membrane with minimal destabilization to the membrane. Upon associating with FP, the complex exerts a synergistic effect on the membrane perturbation. This effect is likely to contribute to the complete membrane fusion during the late phase of fusion protein-induced fusion cascade. The results presented in the work characterize the nature of the interaction of TMD with the membrane and TMD in a complex with FP in the steps leading to pore initiation and dilation during virus-induced fusion. Our data and proposed fusion model highlight the key role of TMD-FP interaction and have implications on the fusion reaction mediated by other type I viral fusion proteins. Understanding the molecular mechanism of membrane fusion may assist in the design of anti-viral drugs.


Fuse me IFITM can!


title: Inhibition of infection caused by severe acute respiratory syndrome-associated coronavirus by equine neutralizing antibody in aged mice

text: Abstract The high susceptibility of elderly to severe acute respiratory syndrome-associated coronavirus (SARS-CoV) indicates how crucial it is to protect the elderly by various strategies. Aged BALB/c mice displayed a high susceptibility to SARS-CoV and have been a valuable platform for evaluation of strategies against SARS-CoV infection. In this study, we confirmed the validity of this model using various methods, and verified that equine anti-SARS-CoV F(ab')2 can prevent aged animals from SARS-CoV infection. In a therapeutic setting, treatment with anti-SARS-CoV F(ab')2 decreased viral load more than several thousand folds in the lungs. Thus, this antibody should be a potential candidate for treatment of elderly patients suffering from SARS.


title: The Structure Analysis and Antigenicity Study of the N Protein of SARS-CoV

text: The Coronaviridae family is characterized by a nucleocapsid that is composed of the genome RNA molecule in combination with the nucleoprotein (N protein) within a virion. The most striking physiochemical feature of the N protein of SARS-CoV is that it is a typical basic protein with a high predicted pI and high hydrophilicity, which is consistent with its function of binding to the ribophosphate backbone of the RNA molecule. The predicted high extent of phosphorylation of the N protein on multiple candidate phosphorylation sites demonstrates that it would be related to important functions, such as RNA-binding and localization to the nucleolus of host cells. Subsequent study shows that there is an SR-rich region in the N protein and this region might be involved in the protein-protein interaction. The abundant antigenic sites predicted in the N protein, as well as experimental evidence with synthesized polypeptides, indicate that the N protein is one of the major antigens of the SARS-CoV. Compared with other viral structural proteins, the low variation rate of the N protein with regards to its size suggests its importance to the survival of the virus.


title: Using simple artificial intelligence methods for predicting amyloidogenesis in antibodies

text: BACKGROUND: All polypeptide backbones have the potential to form amyloid fibrils, which are associated with a number of degenerative disorders. However, the likelihood that amyloidosis would actually occur under physiological conditions depends largely on the amino acid composition of a protein. We explore using a naive Bayesian classifier and a weighted decision tree for predicting the amyloidogenicity of immunoglobulin sequences. RESULTS: The average accuracy based on leave-one-out (LOO) cross validation of a Bayesian classifier generated from 143 amyloidogenic sequences is 60.84%. This is consistent with the average accuracy of 61.15% for a holdout test set comprised of 103 AM and 28 non-amyloidogenic sequences. The LOO cross validation accuracy increases to 81.08% when the training set is augmented by the holdout test set. In comparison, the average classification accuracy for the holdout test set obtained using a decision tree is 78.64%. Non-amyloidogenic sequences are predicted with average LOO cross validation accuracies between 74.05% and 77.24% using the Bayesian classifier, depending on the training set size. The accuracy for the holdout test set was 89%. For the decision tree, the non-amyloidogenic prediction accuracy is 75.00%. CONCLUSIONS: This exploratory study indicates that both classification methods may be promising in providing straightforward predictions on the amyloidogenicity of a sequence. Nevertheless, the number of available sequences that satisfy the premises of this study are limited, and are consequently smaller than the ideal training set size. Increasing the size of the training set clearly increases the accuracy, and the expansion of the training set to include not only more derivatives, but more alignments, would make the method more sound. The accuracy of the classifiers may also be improved when additional factors, such as structural and physico-chemical data, are considered. The development of this type of classifier has significant applications in evaluating engineered antibodies, and may be adapted for evaluating engineered proteins in general.


title: Chapter 2 Recent Advances in Hantavirus Molecular Biology and Disease

text: Abstract Hantaviruses are emerging zoonotic pathogens that belong to the Bunyaviridae family. They have been classified as category A pathogens by CDC (centers for disease control and prevention). Hantaviruses pose a serious threat to human health because their infection causes two highly fatal diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). These pathogens are transmitted to humans through aerosolized excreta of their infected rodent hosts. Hantaviruses have a tripartite-segmented negative-sense RNA genome. The three genomic RNA segments, S, M, and L, encode a nucleocapsid protein (N), a precursor glycoprotein that is processed into two envelope glycoproteins (Gn and Gc) and the viral RNA-dependent RNA polymerase (RdRp), respectively. N protein is the major structural component of the virus, its main function is to protect and encapsidate the three genomic RNAs forming three viral ribonucleocapsids. Recent studies have proposed that N in conjunction with RdRp plays important roles in the transcription and replication of viral genome. In addition, N preferentially facilitates the translation of viral mRNA in cells. Glycoproteins, Gn and Gc, play major roles in viral attachment and entry to the host cells, virulence, and assembly and packaging of new virions in infected cells. RdRp functions as RNA replicase and transcriptase to replicate and transcribe the viral RNA and is also thought to have endonuclease activity. Currently, no antiviral therapy or vaccine is available for the treatment of hantavirus-associated diseases. Understanding the molecular details of hantavirus life cycle will help in the identification of targets for antiviral therapeutics and in the design of potential antiviral drug for the treatment of HFRS and HCPS. Due to the alarming fatality of hantavirus diseases, development of an effective vaccine against hantaviruses is a necessity.


title: Meningitis, Viral

text: Abstract This article provides an overview of the pathogenesis, epidemiology, causes, clinical presentation, laboratory diagnosis, and treatment of the most common causes of viral meningitis in the United States. It also summarizes other infectious and noninfectious causes of lymphocytic or aseptic meningitis.


title: Where to buy face masks? Survey of applications using Taiwan’s open data in the time of coronavirus disease 2019

text: The coronavirus disease 2019 (COVID-19) had spread rapidly since late December 2019. Personal protective equipment was essential to prevent transmission. Owing to shortage of face masks, Taiwan government began to implement quasi rationing on February 6, 2020, by allowing each resident to purchase two masks in seven days. Taiwan National Health Insurance Administration offered online data with real-time updates on face mask availability in all contracted pharmacies and selected local health centers. Based on the open data, numerous software applications quickly emerged to assist the public in finding sales locations efficiently. METHODS: Up until March 15, 2020, the Public Digital Innovation Space of Taiwan government had recorded 134 software applications of face mask availability, and 24 software applications were excluded due to defect, duplicate, and unavailability. These applications were analyzed according to platform, developer type, and display mode. RESULTS: Of the 110 valid software applications, 67 (60.9%) applications were deployed on websites, followed by 21 (19.1%) on social networking sites, 19 (17.3%) as mobile applications, and 3 (2.7%) in other modes. Nearly two thirds (n = 70) of applications were developed by individuals, one third (n = 37) by commercial companies, only two applications by central and local governments, and one by a nongovernmental organization. With respect to the display mode, 47 (42.7%) applications adopted map-view only, 41 (37.3%) adopted table-view only, and 19 (17.3%) adopted both modes. Of the remaining three applications, two offered voice user interfaces and one used augmented reality. CONCLUSION: Taiwan’s open data strategy facilitated rapid development of software applications for information dissemination to the public during the COVID-19 crisis. The transparency of real-time data could help alleviate the panic of the public. The collaborative contributions from the grassroots in disasters were priceless treasures.


title: Has COVID-19 played an unexpected “stroke” on the chain of survival?

text: Abstract Background The COVID-19 pandemics required several changes in stroke management and it may have influenced some clinical or functional characteristics. We aimed to evaluate the effects of the COVID-19 pandemics on stroke management during the first month of Italy lockdown. In addition, we described the emergency structured pathway adopted by an Italian University Hub Stroke Unit in the cross-border Italy-Slovenia area. Methods We analyzed admitted patients' clinical features and outcomes between 9th March 2020 and 9th April 2020 (first month of lockdown), and compared them with patients admitted during the same period in 2019. Results Total admissions experienced a reduction of 45% during the lockdown compared to the same period in 2019 (16 vs 29, respectively), as well as a higher prevalence of severe stroke (NIHSS>10) at admission (n = 8, 50% vs n = 8, 28%). A dramatic prevalence of stroke of unknown symptom onset was observed in 2020 (n = 8, 50% vs n = 3, 10%). During lockdown, worse functional and independence outcomes were found, despite the similar proportion of reperfused patients. Similar ‘symptoms alert-to-admission’ and ‘door-to-treatment’ times were observed. During lockdown hospitalization was shorter and fewer patients completed the stroke work-up. Conclusion In conclusion, the adopted strategies for stroke management during the COVID-19 emergency have suggested being effective, while suffering a reduced and delayed reporting of symptoms. Therefore, we recommend raising awareness among the population against possible stroke symptoms onset. Thus, think F.A.S.T. and do not stay-at-home at all costs.


title: Response of UK interventional radiologists to the COVID-19 pandemic – survey findings

text: BACKGROUND: The COVID-19 pandemic has had an unprecedented effect upon the National Health Service (NHS). Like other specialties, Interventional Radiology (IR) rapidly adapted to the evolving situation. Members of BSIR were surveyed to obtain a snapshot of the experiences of UK IRs in response to COVID-19. An electronic survey was compiled using Google Forms, approved by the BSIR Council Officers and distributed to BSIR members by email on 18 (th) April 2020. A total of 228 responses were received. The survey was open for a 14-day period and the data analysed in Microsoft Excel 365. The response rate was 29% (228/800). RESULTS: Two thirds of respondents work in a Tertiary unit and 33% deliver IR in a District Hospital. 84% have a day-case facility. After the COVID-19 crisis, 81% of respondents were able to maintain 24–7 On-call service. 59% of respondents had been required change their day to day practice to allow the on-call service to continue. 55% of respondents were involved in providing a central line service. Of those questioned, 91% continued to offer endovascular services, 98% genitourinary and 92% hepatobiliary services, although a degree of service reduction was described. 38% have provided IR trainees with additional training material during this pandemic. CONCLUSIONS: This survey has confirmed that the responses of UK IR departments to the COVID-19 crisis have ensured vital on-call and urgent services have continued, including ongoing availability of most IR sub-specialties. Availability of a day case facility has possibly influenced the positive response.


title: Research in epidemic and emergency situations: A model for collaboration and expediting ethics review in two Caribbean countries

text: Various forms of research are essential in emergency, disaster and disease outbreak situations, but challenges exist including the long length of time it takes to get research proposals approved. Consequently, it would be very advantageous to have an acceptable model for efficient coordination and communication between and among research ethics committees/IRBs and ministries of health, and templates for expediting (done with speed and efficiency) ethical review of research proposals in emergency and epidemic situations to be used across the Caribbean and in other low and middle income countries. This project involved a literature search and the interviewing of ministry of health officials, public health practitioners, and research ethics committee/IRB members in Jamaica and St. Lucia, to obtain suggestions for the best model for efficient coordination and communication between research ethics committees (RECs), and developed a template for expediting review of research protocols in epidemic and emergency conditions.


title: On being the right size

text: The first replicating molecules were probably composed of RNA and undoubtedly small, limited in size by a self-destructing error rate. A new study shows that a relatively minor increase in replication fidelity may have had a large effect on the size, and hence complexity, of early replicators.


title: Dairy Calf Pneumonia The Disease and Its Impact

text: The author discusses the syndrome of respiratory disease in dairy calves, reviewing the disease and the causative agents. Attention is given to the epidemiology of the disease with discussion of morbidity, mortality, proportionate mortality and risk factors associated with dairy calf pneumonia. The economic impact of dairy calf pneumonia is discussed in detail and management options for calf rearing are suggested.


title: Can Nanotechnology and Materials Science Help the Fight against SARS-CoV-2?

text: Since 2004, we have been developing nanomaterials with antimicrobial properties, the so-called nanoantimicrobials. When the coronavirus disease 2019 (COVID-19) emerged, we started investigating new and challenging routes to nanoantivirals. The two fields have some important points of contact. We would like to share with the readership our vision of the role a (nano)materials scientist can play in the fight against the COVID-19 pandemic. As researchers specifically working on surfaces and nanomaterials, in this letter we underline the importance of nanomaterial-based technological solutions in several aspects of the fight against the virus. While great resources are understandably being dedicated to treatment and diagnosis, more efforts could be dedicated to limit the virus spread. Increasing the efficacy of personal protection equipment, developing synergistic antiviral coatings, are only two of the cases discussed. This is not the first nor the last pandemic: our nanomaterials community may offer several technological solutions to challenge the ongoing and future global health emergencies. Readers’ feedback and suggestions are warmly encouraged.


Corrigendum to “The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China” [J. Autoimmun. 109C (2020) 102434]


title: Que doivent savoir les chirurgiens à propos des troubles digestifs et des anomalies paracliniques induits par le COVID 19?

text: Resume Les symptômes liés au COVID-19 sont principalement caractérisés par la triade fièvre, toux sèche et dyspnée. Toutefois, des symptômes digestifs ont également été rapportés dont la fréquence initialement considérée comme faible semble toucher plus de la moitié des patients à des degrés divers. Ceux-ci se manifestent principalement par une anorexie, une diarrhée, des nausées et ou vomissements et des douleurs abdominales. Bien que le pronostic soit lié à l’atteinte pulmonaire, les troubles digestifs semblent significativement plus fréquents chez les patients ayant une infection sévère à COVID-19. Des formes digestives isolées ou pouvant précéder les symptômes pulmonaires sont désormais bien décrites avec de la diarrhée au premier plan clinique. Les principales anomalies biologiques pouvant orienter précocement vers une infection à COVID-19 sont la lymphopénie, une CRP augmentée et une augmentation des transaminases prédominant sur les ASAT. Le scanner thoraco-abdominal semble utile dans ce cas pour éliminer une pathologie digestive non liée au coronavirus et pour rechercher des images pulmonaires compatibles avec une infection à COVID-19. Il n’existe pas de données sur l’intérêt de l’endoscopie digestive en cas de symptômes digestifs persistants. Le risque de contamination de l’endoscopiste semble par ailleurs significatif. Un mode de transmission oro-fécale de l’infection est possible ce d’autant que l’excrétion virale dans les selles semblent fréquente et durer plus longtemps qu’au niveau ORL, y compris chez des patients avec prélèvement pharyngé négatif ou sans symptômes digestifs. Ainsi, dans certains cas douteux, une analyse virologique des selles peut permettre de porter un diagnostic de certitude. La contagiosité persistante d’un patient en cas d’excrétion virale prolongée dans les selles est possible mais pas parfaitement établi. L’avènement proche de la sérologie devrait permettre d’identifier les malades ayant été infectés par l’épidémie de COVID-19 notamment les sujets pauci-symptomatiques non détectés au sein du personnel de santé. La reprise de l’activité médico-chirurgicale devra faire l’objet d’une stratégie dédiée en amont du déconfinement. Abstract The symptoms associated with COVID-19 are mainly characterized by a triad composed of fever, dry cough and dyspnea. However, digestive symptoms have also been reported; at first considered as infrequent, they in fact seem to affect (to some extent) more than half of patients. The symptoms are mainly manifested by anorexia, diarrhea, nausea and/or vomiting and abdominal pain. Even though prognosis is associated with lung injury, digestive symptoms seem significantly more frequent in patients presenting with severe COVID-19 infection. Digestive forms, which may be isolated or which can precede pulmonary symptoms, have indeed been reported, with diarrhea as a leading clinical sign. The main biological abnormalities that can suggest COVID-19 infection at an early stage are lymphopenia, elevated CRP and heightened ASAT transaminases. Thoraco-abdominal scan seems useful as a means of on the one hand ruling out digestive pathology not connected with coronavirus and on the other hand searching for pulmonary images compatible with COVID-19 infection. No data exist on the interest of digestive endoscopy in cases of persistent digestive symptoms. Moreover, the endoscopic surgeons may themselves be at significant risk of contamination. Fecal-oral transmission of the infection is possible, especially insofar as viral shedding in stools seems frequent and of longer duration than at the ENT level, including in patients with negative throat swab and without digestive symptoms. In some doubtful cases, virologic assessment of stool samples can yield definitive diagnosis. In the event of prolonged viral shedding in stools, a patient’s persistent contagiousness is conceivable but not conclusively established. Upcoming serology should enable identification of the patients having been infected by the COVID-19 epidemic, particularly among previously undetected pauci-symptomatic members of a health care staff. Resumption of medico-surgical activity should be the object of a dedicated strategy preceding deconfinement.


title: Interplay between Intrinsic and Innate Immunity during HIV Infection

text: Restriction factors are antiviral components of intrinsic immunity which constitute a first line of defense by blocking different steps of the human immunodeficiency virus (HIV) replication cycle. In immune cells, HIV infection is also sensed by several pattern recognition receptors (PRRs), leading to type I interferon (IFN-I) and inflammatory cytokines production that upregulate antiviral interferon-stimulated genes (ISGs). Several studies suggest a link between these two types of immunity. Indeed, restriction factors, that are generally interferon-inducible, are able to modulate immune responses. This review highlights recent knowledge of the interplay between restriction factors and immunity inducing antiviral defenses. Counteraction of this intrinsic and innate immunity by HIV viral proteins will also be discussed.


title: SARS‐CoV‐2 pandemic and repercussions for male infertility patients: A proposal for the individualized provision of andrological services

text: The prolonged lockdown of health facilities providing non‐urgent gamete cryopreservation—as currently recommended by many reproductive medicine entities and regulatory authorities due to the SARS‐CoV‐2 pandemic will be detrimental for subgroups of male infertility patients. We believe the existing recommendations should be promptly modified and propose that the same permissive approach for sperm banking granted for men with cancer is expanded to other groups of vulnerable patients. These groups include infertility patients (eg, azoospermic and cryptozoospermic) undergoing medical or surgical treatment to improve sperm quantity and quality, as well as males of reproductive age affected by inflammatory and systemic auto‐immune diseases who are about to start treatment with gonadotoxic drugs or who are under remission. In both scenarios, the “fertility window” may be transitory; postponing diagnostic semen analysis and sperm banking in these men could compromise the prospects of biological parenthood. Moreover, we provide recommendations on how to continue the provision of andrological services in a considered manner and a safe environment. Our opinion is timely and relevant given the fact that fertility services are currently rated as of low priority in most countries.


title: Forecasting herd-level porcine epidemic diarrhea (PED) frequency trends in Ontario (Canada)

text: Abstract Porcine Epidemic Diarrhea Virus (PEDV) emerged in North America in 2013. The first case of PEDV in Canada was identified on an Ontario farm in January 2014. Surveillance was instrumental in identifying the initial case and in minimizing the spread of the virus to other farms. With recent advances in predictive analytics showing promise for health and disease forecasting, the primary objective of this study was to apply machine learning predictive methods (random forest, artificial neural networks, and classification and regression trees) to provincial PEDV incidence data, and in so doing determine their accuracy for predicting future PEDV trends. Trend was defined as the cumulative number of new cases over a four-week interval, and consisted of four levels (zero, low, medium and high). Provincial PEDV incidence and prevalence estimates from an industry database, as well as temperature, humidity, and precipitation data, were combined to create the forecast dataset. With 10-fold cross validation performed on the entire dataset, the overall accuracy was 0.68 (95% CI: 0.60 – 0.75), 0.57 (95% CI: 0.49 – 0.64), and 0.55 (0.47 – 0.63) for the random forest, artificial neural network, and classification and regression tree models, respectively. Based on the cross-validation approach to evaluating predictive accuracy, the random forest model provided the best prediction.


title: Probable causes and risk factors for positive SARS‐CoV‐2 test in recovered patients: Evidence from Brunei Darussalam

text: Case reports of COVID‐19 patients who have been discharged and subsequently report positive RT‐PCR again (hereafter referred as ‘re‐positive’) do not fully describe the magnitude and significance of this issue. In order to determine the re‐positive rate (proportion) and review probable causes and outcomes, we conduct a retrospective study of all 119 discharged patients in Brunei Darussalam up till April 23. Patients who were discharged are required to self‐isolate at home for 14 days and undergo NP specimen collection post‐discharge. Discharged patients found to be re‐positive were readmitted. We reviewed the clinical and epidemiological records of all discharged patients and apply log‐binomial models to obtain risk ratios for re‐positive status. One in five recovered patients subsequently test positive again for SARS‐CoV‐2 – this risk is more than six times higher in persons aged 60 years and above. The average Ct value of re‐positive patients was lower pre‐discharge compared to their readmission Ct value. Out of 111 close contacts tested, none were found to be positive as a result of exposure to a re‐positive patient. Our findings support prolonged but intermittent viral shedding as the probable cause for this phenomenon. We did not observe infectivity potential in these patients. This article is protected by copyright. All rights reserved.


title: Characterization of the cytokine and maturation responses of pure populations of porcine plasmacytoid dendritic cells to porcine viruses and toll-like receptor agonists

text: Abstract Plausible representatives of plasmacytoid dendritic cells (pDCs) in pigs have been characterized as being CD4hiCD172lo. Due to their paucity in blood, we utilized novel fluorescent-activated cell sorting procedures to isolate them from PBMC. The resultant subset was greater than 98% homogeneous in regards to the selected phenotype and contained the preponderance of individuals secreting IFN-α after exposure to a known stimulant, transmissible gastroenteritis virus (TGEV). In addition to being a potent source of IFN-α, other properties of these porcine CD4hiCD172lo cells including their morphological transition from a plasma cell-like shape during quiescence to one resembling a dendritic cell (DC) after activation by TGEV and their relatively strong constitutive expression of interferon regulatory factor-7 (IRF-7) conformed to the expectations of genuine pDCs. While a substantial IFN-α response was also elicited from the porcine pDCs by pseudorabies virus (PrV), swine influenza virus (SIV), and TLR7 and 9 agonists, there was an agent-dependent induction of varying amounts of IL-2, IL-6, IL-8, IL-12, IFN-γ, and TNF-α. Notably, porcine reproductive and respiratory syndrome virus (PRRSV) failed to provoke the pDCs to secrete any of the measured cytokines except IL-2. Moreover, whereas pDCs exposed to TGEV or the TLR9 agonist rapidly increased IRF-7 production and morphed into DCs with enhanced CD80/86 expression, similar alterations were not observed during incubation with PRRSV. This atypical response of pDCs to PRRSV may contribute to its pathogenesis, which unlike that associated with PrV, SIV or TGEV includes persistent infection and limited development of protective immunity.


title: Efficacy and safety of tocilizumab in critically ill adults with COVID-19 infection in Bahrain: A report of 5 cases

text: Tocilizumab has been recognized as one of the few existing biologic useful for combating COVID-19 infections especially in critically ill patient. We had experience in treating five critically ill patients with severe lung injury who were COVID-19 positive with tocilizumab. In the present case series, we have attempted to summarize their clinical profile, changes in laboratory biomarkers and outcomes.


title: The role of economic structural factors in determining pandemic mortality rates: Evidence from the COVID-19 outbreak in France

text: Abstract Among the majority of research on individual factors leading to coronavirus mortality, age has been identified as a dominant factor. Health and other individual factors including gender, comorbidity, ethnicity and obesity have also been identified by other studies. In contrast, we examine the role of economic structural factors on COVID-19 mortality rates. Particularly, focusing on a densely populated region of France, we document evidence that higher economic “precariousness indicators” such as unemployment and poverty rates, lack of formal education and housing are important factors in determining COVID-19 mortality rates. Our study will help inform policy makers regarding the role of economic factors in managing pandemics.


title: Differential effects of triptolide and tetrandrine on activation of COX-2, NF-κB, and AP-1 and virus production in dengue virus-infected human lung cells

text: Abstract Most virus infections induce cycloxygenase-2 (COX-2) expression and subsequent prostaglandin E2 (PGE2) production in cells, an inflammatory response that might be detrimental to virus replication and pathogenesis. This response in dengue virus infection remains to be elucidated. Triptolide and tetrandrine, compounds derived from two commonly used Chinese herbs, both demonstrate anti-inflammatory and immunosuppressive effects partly through modulation of COX-2 expression and, hence, may have antiviral effects. In this study, we examined, firstly, the immune response to dengue virus infection with respect to COX-2 expression and PGE2 production in human lung cells (A549), liver cells (HepG2) and dendritic cells. Secondly, we assessed the potential antiviral effects of triptolide and tetrandrine on dengue virus infection vis-à-vis expression of COX-2, PGE2, transcription factors, as well as virus production. We found that dengue virus infection enhanced COX-2 expression and PGE2 production in A549 cells, similarly to the response in dendritic cells, but not in HepG2 cells. In dengue virus-infected A549 cells, nuclear factor κB (NF-κB) and activator protein 1 (AP-1) were also activated, and both were dose-dependently inhibited by triptolide (0.5–4 ng/ml). Tetrandrine (1–10 μM) had no similar immunosuppressive effects and, moreover, at higher concentrations, enhanced NF-κB and AP-1 activity, COX-2 expression and PGE2 production. However, unexpectedly, tetrandrine, but not triptolide, dose-dependently suppressed dengue virus production in A549 cells, independent of PGE2 level. Our findings imply that triptolide and tetrandrine may attenuate dengue virus infection in human lung cells, but through distinct pathways.


Identification of Ferret ACE2 and its Receptor Function for Sars-Coronavirus


title: Evidence of human bocavirus circulating in children and adults, Cleveland, Ohio

text: Abstract Background Viral respiratory illness is a major cause of morbidity and mortality. The human bocavirus (HBoV) is a recently recognized parvovirus isolated from human respiratory secretions. Objectives To define the clinical and epidemiologic characteristics in adult and pediatric patients with evidence of HBoV. Study design From October 2005 through October 2006, we screened respiratory samples from children and adults negative for common respiratory pathogens for HBoV by PCR. Demographic and clinical characteristics were obtained from medical records of HBoV positive individuals. Results Of 2075 samples screened, 1826 (88.0%) represented distinct respiratory events: 1539 (84.3%) were pediatric (<18 years), and 273 (15.0%) adult (≥18 years). Forty (2.2%) patients had HBoV: 36 (2.3%) children and 4 (1.5%) adults. HBoV positive children had history of prematurity (31.3%) and cardiac disease (18.8%). Adults had underlying pulmonary (100%) and cardiac (50%) disease. Twenty-seven children (84.4%) were hospitalized; 9 (28.1%) required intensive care. All adults were hospitalized; none required intensive care. Nosocomial acquisition likely occurred in 3 patients. Conclusions HBoV circulates in Cleveland, OH, in children and adults with similar frequencies, and can warrant hospitalization and intensive care. Further study would clarify our understanding of this newly recognized human pathogen.


title: Solutions of a disease model with fractional white noise

text: Abstract We consider an epidemic disease system by an additive fractional white noise to show that epidemic diseases may be more competently modeled in the fractional-stochastic settings than the ones modeled by deterministic differential equations. We generate a new SIRS model and perturb it to the fractional-stochastic systems. We study chaotic behavior at disease-free and endemic steady-state points on these systems. We also numerically solve the fractional-stochastic systems by an trapezoidal rule and an Euler type numerical method. We also associate the SIRS model with fractional Brownian motion by Wick product and determine numerical and explicit solutions of the resulting system. There is no SIRS-type model which considers fractional epidemic disease models with fractional white noise or Wick product settings which makes the paper totally a new contribution to the related science.


title: The effects of delayed access to feed and water on the physical and functional development of the digestive system of young turkeys

text: Abstract Three experiments were conducted with turkeys to determine the influence of delayed access to feed and water on the development of the digestive system. In all experiments, poults were randomly assigned to three placement times, 6, 30, and 54 h posthatch. Experiments 1, 2, and 3 were terminated when poults were 10, 28, and 14 d old, respectively. In Experiment 1, six poults per treatment were sampled on Days 1, 2, 3, 4, 5, 6, 8, and 10. In Experiment 2, 12 poults per treatment were sampled on Days 1, 2, 3, 4, 5, 10, 15, and 28. The objective of Experiment 3 was to determine the effect of delayed placement on dietary MEn. Delaying access to feed and water for 54 h adversely affected BW through 10, 28, and 14 d of age in Experiments 1, 2, and 3, respectively (P < or = 0.01). Delayed access to feed and water for 54 h decreased the absolute weights of the small intestine and pancreas and reduced lengths of the small intestine through 5 d posthatch (P < or = 0.05). The relative weights of the small intestine and proventriculus were reduced by delayed access to nourishment through 4 d posthatch. Poults placed on feed at 54 h posthatch had decreased pancreatic amylase activity (P < or = 0.05) at 3 and 4 d, and trypsin activities were depressed at 3 d posthatch (P < or = 0.05). In Experiment 3, dietary MEn value determined at 4 d of age with poults placed 54 h posthatch was less (P < or = 0.07) than the MEn value obtained with poults placed at 6 h posthatch. A 54-h delay in access to feed and water generally delayed development of the digestive system, impaired nutrient utilization, and reduced BW.


title: Site-specific analysis of the SARS-CoV-2 glycan shield

text: The emergence of the betacoronavirus, SARS-CoV-2 that causes COVID-19, represents a significant threat to global human health. Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, that mediates cell entry and membrane fusion. SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in immune evasion and occluding immunogenic protein epitopes. Here, using a site-specific mass spectrometric approach, we reveal the glycan structures on a recombinant SARS-CoV-2 S immunogen. This analysis enables mapping of the glycan-processing states across the trimeric viral spike. We show how SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiology and vaccine design.


title: Solvent/Detergent Virally Inactivated Serum Eye Drops Restore Healthy Ocular Epithelium in a Rabbit Model of Dry-Eye Syndrome

text: Application of autologous serum eye drops (SEDs) is a recognized means to treat severe dry-eye syndrome (DES). Due to the inconvenience and difficulty of preparing SEDs from some patients, producing SEDs from allogeneic blood donations is gaining popularity. A major safety concern associated with allogeneic blood is virus transmission. We therefore herein evaluated the possibility of applying a solvent/detergent (S/D) treatment to inactivate viruses and studied the impacts of such treatment of SEDs to resolve DES in a rabbit model. Sera prepared from the blood of five rabbits were pooled and divided into two sub-pools. One was untreated (SEDs), while the other was virally-inactivated with 1% Tri-n-butyl phosphate/1% Triton X-45 at 31°C for 1 h (S/D-SEDs). DES was induced in rabbits using 0.1% benzalkonium chloride (BAC). Rabbits were divided into five groups of two rabbits each. One group was untreated (control), three were treated twice daily for 3 weeks using PBS, SEDs, or S/D-SEDs, and the last received an additional 0.1% BAC (as the negative control). The DES condition was determined by measuring aqueous tear secretion (Schirmer’s test), corneal fluorescein staining, a corneal histologic examination, TUNEL stain apoptosis, and corneal inflammatory marker (tumor necrosis factor-α, interleukin (IL)-1β, IL-8, and IL-6) expressions. We first confirmed that SEDs and S/D-SEDs had similar protein profiles and transforming growth factor (TGF)-β contents. Animal experiments showed that tear secretion did not significantly differ between the SED and S/D-SED groups but was significantly higher than in the PBS group. Eye fluorescein staining revealed dramatic improvements in epithelial defects in groups treated with SEDs or S/D-SEDs, and hematoxylin/eosin staining revealed microscopic epithelial layers similar to those of the untreated controls. Inflammatory markers and TUNEL studies showed that healthy epithelium had been restored in groups treated with SEDs or S/D-SEDs. In conclusion, this preclinical study supports the possibility of using S/D virally inactivated SEDs to treat DES and restore a normal epithelium.


title: An effective inactivant based on singlet oxygen-mediated lipid oxidation implicates a new paradigm for broad-spectrum antivirals

text: Emerging viral pathogens cause substantial morbidity and pose a severe threat to health worldwide. However, a universal antiviral strategy for producing safe and immunogenic inactivated vaccines is lacking. Here, we report an antiviral strategy using the novel singlet oxygen ((1)O(2))-generating agent LJ002 to inactivate enveloped viruses and provide effective protection against viral infection. Our results demonstrated that LJ002 efficiently generated (1)O(2) in solution and living cells. Nevertheless, LJ002 exhibited no signs of acute toxicity in vitro or in vivo. The (1)O(2) produced by LJ002 oxidized lipids in the viral envelope and consequently destroyed the viral membrane structure, thus inhibiting the viral and cell membrane fusion necessary for infection. Moreover, the (1)O(2)-based inactivated pseudorabies virus (PRV) vaccine had no effect on the content of the viral surface proteins. Immunization of mice with LJ002-inactiviated PRV vaccine harboring comparable antigen induced more neutralizing antibody responses and efficient protection against PRV infection than conventional formalin-inactivated vaccine. Additionally, LJ002 inactivated a broad spectrum of enveloped viruses. Together, our results may provide a new paradigm of using broad-spectrum, highly effective inactivants functioning through (1)O(2)-mediated lipid oxidation for developing antivirals that target the viral membrane fusion process.


Airway management for postoperative respiratory failure: Use of the laryngeal mask airway


title: Pandemic Influenza: Are We Ready?

text: An influenza pandemic is inevitable, and the H5N1 avian influenza outbreak in Southeast Asia has heightened concern that a disaster is imminent. Pandemic preparations are beginning around the world, and it is important for first responders, particularly disaster management personnel, to understand the difference between pandemic and epidemic influenza preparedness. This article will focus on distinguishing between an influenza epidemic and an influenza pandemic and, in light of these distinctions, how to manage the next pandemic with limited resources, particularly the absence of vaccine.


title: Diastereoselective synthesis of 2-fluoroaziridine-2-carboxylates by Reformatsky-type aza-Darzens reaction

text: Abstract The reaction of ethyl dibromofluoroacetate with imines using zinc metal gave 2-fluoroaziridine-2-carboxylates via aza-Darzens reaction of the primary product of the Reformatsky reaction with high diastereoselectivity in excellent yields (quantitative yield and Dr=85:15). This chemoselective formation of 2-fluoroaziridines was achieved by using CH3CN as a solvent. Interestingly, the reaction proceeded without activation of zinc metal, which was necessary for the Reformatsky reaction of bromodifluoroacetate. None of α-bromo-α-fluoro-β-lactams, four-membered cyclization products, and noncyclized 3-amino-2-bromo-2-fluorocarboxylic esters, usual Reformatsky adducts, were formed.


title: Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January 2020

text: Since December 2019, China has been experiencing a large outbreak of a novel coronavirus (2019-nCoV) which can cause respiratory disease and severe pneumonia. We estimated the basic reproduction number R(0) of 2019-nCoV to be around 2.2 (90% high density interval: 1.4–3.8), indicating the potential for sustained human-to-human transmission. Transmission characteristics appear to be of similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and pandemic influenza, indicating a risk of global spread.


title: Acute Viral Infections with Combined Involvement of the Respiratory and Gastrointestinal Tracts in Children. Therapy with Interferon

text: We evaluated the percent of acute respiratory viral infections with gastrointestinal syndrome in the structure of morbidity in babies aging 6 months and elder. Therapeutic efficiency and safety of anaferon (pediatric formuation) as a component of complex therapy of acute respiratory viral infections with involvement of the gastrointestinal tract were proven; more rapid disappearance of all symptoms and improvement of the immune status parameters were demonstrated.


title: Modelling the effective reproduction number of vector-borne diseases: the yellow fever outbreak in Luanda, Angola 2015–2016 as an example

text: The burden of vector-borne diseases (Dengue, Zika virus, yellow fever, etc.) gradually increased in the past decade across the globe. Mathematical modelling on infectious diseases helps to study the transmission dynamics of the pathogens. Theoretically, the diseases can be controlled and eventually eradicated by maintaining the effective reproduction number, ([Image: see text] ), strictly less than 1. We established a vector-host compartmental model, and derived ([Image: see text] ) for vector-borne diseases. The analytic form of the ([Image: see text] ) was found to be the product of the basic reproduction number and the geometric average of the susceptibilities of the host and vector populations. The ([Image: see text] ) formula was demonstrated to be consistent with the estimates of the 2015–2016 yellow fever outbreak in Luanda, and distinguished the second minor epidemic wave. For those using the compartmental model to study the vector-borne infectious disease epidemics, we further remark that it is important to be aware of whether one or two generations is considered for the transition “from host to vector to host” in reproduction number calculation.


title: Associations between body mass index, physical activity and the built environment in disadvantaged, minority neighborhoods: Predictive validity of GigaPan® imagery

text: Abstract Background The built environment has been shown to influence health in studies of disadvantaged populations using different measurement methods. This study determined whether environmental exposures derived from GigaPan® images could serve as valid predictors of body mass index (BMI), walking and moderate to vigorous physical activity (MVPA) in a longitudinal study of low-income adults living in two primarily African American neighborhoods in Pittsburgh, Pennsylvania, USA. GigaPan® is a robotic system used to obtain high-resolution, panoramic images of environments. Methods Microscale environmental features along 481 streets were audited in 2015–2016 using an audit form. Environmental exposures were estimated for 731 adult participants, using a sample of street segments within a 0.4 km (0.25 mile) network distance from each participant's residential address. Summary environmental exposures were constructed using factor analysis. We tested associations between participant-level environmental exposures and objectively measured BMI, self-reported walking and objectively measured MVPA in regression models controlling for baseline health and demographic variables. Results Three factors representing participants’ environmental exposures were constructed: pedestrian bicycle-amenities; hilly-vacant-boarded; physical activity-recreation/low housing density. Environments with infrastructure and amenities supportive of walking and bicycling were associated with lower BMI (Coef. = ‒0.47, p = 0.02). Frequent walking was less likely in environments with more physical activity and recreation venues/low housing density (OR = 0.81, 95% CI [0.67, 0.96]). MVPA was not associated with any of the environmental measures and the hilly-vacant-boarded factor was not associated with any of the outcomes. Conclusions Predictive validity was demonstrated for an environmental exposure factor that captured features supportive of walking and cycling in a model predicting BMI, using built environment audit data from GigaPan® imagery. A complementary analysis found lower odds of frequent walking in the neighborhood among participants with exposure to more physical activity and recreational features, but fewer types and lower density of housing.


title: Higher prevalence of asymptomatic or mild COVID‐19 in children, claims and clues

text: The current pandemic of COVID-19 has generated many challenging questions for the scientific community, ranging from queries about the origin of the virus to its pathogenesis and clinical management. This article is protected by copyright. All rights reserved.


title: Viral shedding patterns of coronavirus in patients with probable severe acute respiratory syndrome

text: Severe acute respiratory syndrome (SARS) is thought to be caused by a novel coronavirus, SARS-associated coronavirus. We studied viral shedding of SARS coronavirus to improve diagnosis and infection control. Reverse-transcriptase PCR was done on 2134 specimens of different types. 355 (45%) specimens of nasopharyngeal aspirates and 150 (28%) of faeces were positive for SARS coronavirus RNA. Positive rates peaked at 6–11 days after onset of illness for nasopharyngeal aspirates (87 of 149 [58%], to 37 of 62 [60%]), and 9–14 days for faeces (15 of 22 [68%], to 26 of 37 [70%]). Overall, peak viral loads were reached at 12–14 days of illness when patients were probably in hospital care, which would explain why hospital workers were prone to infection. Low rate of viral shedding in the first few days of illness meant that early isolation measures would probably be effective.


title: Virus-Receptor Interactions and Receptor-Mediated Virus Entry into Host Cells

text: The virus particles described in previous chapters are vehicles that transmit the viral genome and the infection from cell to cell. To initiate the infective cycle, the viral genome must therefore translocate from the viral particle to the cytoplasm. Via distinct proteins or motifs in their outermost shell, the particles attach initially to specific molecules on the host cell surface. These virus receptors thus mediate penetration of the viral genome inside the cell, where the intracellular infective cycle starts. The presence of these receptors on the cell surface is a principal determinant of virus host tropism. Viruses can use diverse types of molecules to attach to and enter into cells. In addition, virus-receptor recognition can evolve over the course of an infection, and virus variants with distinct receptor-binding specificities and tropism can appear. The identification of virus receptors and the characterization of virus-receptor interactions have been major research goals in virology for the last two decades. In this chapter, we will describe, from a structural perspective, several virus-receptor interactions and the active role of receptor molecules in virus entry.


title: Flattening the Mental Health Curve: COVID-19 Stay-at-Home Orders Are Associated With Alterations in Mental Health Search Behavior in the United States

text: BACKGROUND: The coronavirus disease (COVID-19) has led to dramatic changes worldwide in people’s everyday lives. To combat the pandemic, many governments have implemented social distancing, quarantine, and stay-at-home orders. There is limited research on the impact of such extreme measures on mental health. OBJECTIVE: The goal of this study was to examine whether stay-at-home orders produced differential changes in mental health symptoms using internet search queries on a national scale. METHODS: In the United States, individual states vary in their adoption of measures to reduce the spread of COVID-19; as of March 23, 2020, 11 of the 50 states had issued stay-at-home orders. The staggered rollout of stay-at-home measures across the United States allows us to investigate whether these measures impact mental health by exploring variations in mental health search queries across the states. This paper examines the changes in mental health search queries on Google between March 16-23, 2020, across each state and Washington, DC. Specifically, this paper examines differential changes in mental health searches based on patterns of search activity following issuance of stay-at-home orders in these states compared to all other states. The participants were all the people who searched mental health terms in Google between March 16-23. Between March 16-23, 11 states underwent stay-at-home orders to prevent the transmission of COVID-19. Outcomes included search terms measuring anxiety, depression, obsessive-compulsive, negative thoughts, irritability, fatigue, anhedonia, concentration, insomnia, and suicidal ideation. RESULTS: Analyzing over 10 million search queries using generalized additive mixed models, the results suggested that the implementation of stay-at-home orders are associated with a significant flattening of the curve for searches for suicidal ideation, anxiety, negative thoughts, and sleep disturbances, with the most prominent flattening associated with suicidal ideation and anxiety. CONCLUSIONS: These results suggest that, despite decreased social contact, mental health search queries increased rapidly prior to the issuance of stay-at-home orders, and these changes dissipated following the announcement and enactment of these orders. Although more research is needed to examine sustained effects, these results suggest mental health symptoms were associated with an immediate leveling off following the issuance of stay-at-home orders.


title: Viral Profile of COPD Exacerbations According to Patients§

text: BACKGROUND : To compare the differences between elderly and non-elderly patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) due to viral infections. METHODS : Patients with chronic obstructive pulmonary disease (COPD) exacerbation were recruited and classified as elderly (>65 years) and non-elderly (≤ 65 years). Sputum and oropharyngeal samples were assessed, PCR for respiratory viruses and cultures for common pathogens were performed. RESULTS : 247 patients (median age: 69.3±9.5 years) were recruited and categorized into group A: non-elderly patients [n=81 (32.8%), median age 58±5.99] and group B: elderly patients [n=166 (67.2%), median age 74.8±4.8] years. In 133 (53.8%) patients a viral infection was identified and in 34 (13.8%) a bacterial pathogen was isolated from cultures. In 18 (7.3%) patients a double infection (bacterial+viral) was identified. In group B, the presence of cardiac failure (46.6% vs 28.3%, p<0.001), renal failure (10.5% vs 4%, p=0.03), bacterial co-infection (13.8% vs 7.4%, p=0.04), influenza vaccination rates (45.5% vs 215, p<0.001), and longer hospital stay (8.4±4.4 vs 7.5±3.2 days, p=0.02) were higher than group A. The overall rate of viral infections did not differ according to age. A trend to higher rates of infection with parainfluenza 3 [19 (20%) patients in group B vs3 (7.5%) patients in group A, p=0.04] was observed in older patients. CONCLUSION : No differences on the rate and type of viral infections were noted for elderly vs non elderly patients. However, they tended to have more bacterial co-infections that led to AECOPD and longer hospitalization stays compared to non-elderly patients.


title: Cytoplasmic Translocation of Polypyrimidine Tract-Binding Protein and Its Binding to Viral RNA during Japanese Encephalitis Virus Infection Inhibits Virus Replication

text: Japanese encephalitis virus (JEV) has a single-stranded, positive-sense RNA genome containing a single open reading frame flanked by the 5′- and 3′-non-coding regions (NCRs). The virus genome replicates via a negative-sense RNA intermediate. The NCRs and their complementary sequences in the negative-sense RNA are the sites for assembly of the RNA replicase complex thereby regulating the RNA synthesis and virus replication. In this study, we show that the 55-kDa polypyrimidine tract-binding protein (PTB) interacts in vitro with both the 5′-NCR of the positive-sense genomic RNA - 5NCR(+), and its complementary sequence in the negative-sense replication intermediate RNA - 3NCR(-). The interaction of viral RNA with PTB was validated in infected cells by JEV RNA co-immunoprecipitation and JEV RNA-PTB colocalization experiments. Interestingly, we observed phosphorylation-coupled translocation of nuclear PTB to cytoplasmic foci that co-localized with JEV RNA early during JEV infection. Our studies employing the PTB silencing and over-expression in cultured cells established an inhibitory role of PTB in JEV replication. Using RNA-protein binding assay we show that PTB competitively inhibits association of JEV 3NCR(-) RNA with viral RNA-dependent RNA polymerase (NS5 protein), an event required for the synthesis of the plus-sense genomic RNA. cAMP is known to promote the Protein kinase A (PKA)-mediated PTB phosphorylation. We show that cells treated with a cAMP analogue had an enhanced level of phosphorylated PTB in the cytoplasm and a significantly suppressed JEV replication. Data presented here show a novel, cAMP-induced, PTB-mediated, innate host response that could effectively suppress JEV replication in mammalian cells.


title: Cough and the Common Cold ACCP Evidence-Based Clinical Practice Guidelines

text: Objective: To review the literature on cough and the common cold. Methods: MEDLINE was searched through May 2004 for studies published in the English language since 1980 on human subjects using the medical subject heading terms “cough” and “common cold.” Selected case series and prospective descriptive clinical trials were reviewed. Additional references from these studies that were pertinent to the topic were also reviewed. Results: Based on extrapolation from epidemiologic data, the common cold is believed to be the single most common cause of acute cough. The most likely mechanism is the direct irritation of upper airway structures. It is also clear that viral infections of the upper respiratory tract that produce the common cold syndrome frequently produce a rhinosinusitis. In the setting of a cold, the presence of abnormalities seen on sinus roentgenograms or sinus CT scans are frequently due to the viral infection and are not diagnostic of bacterial sinus infection. Conclusion: Cough due to the common cold is probably the most common cause of acute cough. In a significant subset of patients with “postinfectious” cough, the etiology is probably an inflammatory response triggered by a viral upper respiratory infection (ie, the common cold). The resultant subacute or chronic cough can be considered to be due to an upper airway cough syndrome, previously referred to as postnasal drip syndrome. This process can be self-perpetuating unless interrupted with active treatment.


title: Detecting a trend change in cross-border epidemic transmission

text: Abstract A method for a system of Langevin equations is developed for detecting a trend change in cross-border epidemic transmission. The equations represent a standard epidemiological SIR compartment model and a meta-population network model. The method analyzes a time series of the number of new cases reported in multiple geographical regions. The method is applicable to investigating the efficacy of the implemented public health intervention in managing infectious travelers across borders. It is found that the change point of the probability of travel movements was one week after the WHO worldwide alert on the SARS outbreak in 2003. The alert was effective in managing infectious travelers. On the other hand, it is found that the probability of travel movements did not change at all for the flu pandemic in 2009. The pandemic did not affect potential travelers despite the WHO alert.


Contamination and infection: what the coronavirus pandemic could reveal about the evolutionary origins of obsessive-compulsive disorder


Will Colombian intensive care units collapse due to the COVID-19 pandemic?


title: Prevalence and factors associated with social avoidance of recovered SARS patients in the Hong Kong general population

text: The study investigated the general population's perceived infectivity of asymptomatic and recovered severe acute respiratory syndrome (SARS) patients and factors associated with avoidance and discriminatory attitudes, including demographic background, SARS-related perceptions and emotional response to the SARS epidemic. A population-based survey was conducted in Hong Kong during 3 December 2003 through 4 January 2004; 475 Hong Kong Chinese adults participated in the survey. Perceptions of the infectivity and health conditions of recovered SARS patients and avoidance and discrimination towards them were measured. Of the respondents, 75.7% and 16.2%, respectively, believed that SARS could be transmitted via asymptomatic SARS patients and those patients who have recovered from SARS for 18 months; 72.7% of the respondents believed that the health of SARS patients would severely and permanently be damaged; 16.6% showed some tendency of avoiding recovered SARS patients and 35.7% expressed some sort of job-related discriminatory attitudes. Perceived infectivity of asymptomatic and recovered SARS patients, health sequelae and emotional distress from SARS were independently associated with avoidance and discriminatory attitudes. The study showed that misconceptions about the infectivity of asymptomatic and recovered SARS patients were common. Recovered SARS patients may also be facing avoidance and discrimination.


title: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the Central Nervous System

text: Emerging evidence indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of COVID-19, can cause neurological complications. We provide a brief overview of these recent observations and discuss some of their possible implications. In particular, given the global dimension of the current pandemic, we highlight the need to consider the possible long-term impact of COVID-19, potentially including neurological and neurodegenerative disorders.


title: Weaning management of newly received beef calves with or without continuous exposure to a persistently infected bovine viral diarrhea virus pen mate: Effects on health, performance, bovine viral diarrhea virus titers, and peripheral blood leukocytes

text: Exposure to animals persistently infected (PI) with bovine viral diarrhea virus (BVDV) results in immunomodulation of cohorts that may have health and growth consequences; however, effects may differ in low-risk, preconditioned (PC) vs. high-risk, auction market (AM) beef cattle. Our objective was to compare health and performance of PC or AM management systems with (PI) or without (CON) presence of a PI-BVDV pen mate using a 2 × 2 factorial arrangement. Four shipment blocks of crossbred PC steers (n = 236) from 3 ranch-origins were weaned, dewormed, vaccinated, tested for PI-BVDV, and kept on the ranch for ≥42 d. Subsequently, PC steers were transported to a stocker receiving unit (RU), weighed (251 ± 2 kg), blood sampled, stratified by d −1 BW, and assigned randomly to treatment (PCPI or PCCON) with no additional processing. Simultaneously, 4 blocks of crossbred AM calves (n = 292) were assembled from regional auction markets and transported to the RU ± 36 h from PC arrival. The AM calves were weighed (245 ± 1.3 kg), stratified by gender and d −1 BW, processed under the same regimen used for PC steers at their origin ranch except bull calves were castrated, and then assigned randomly to treatment (AMPI or AMCON). Treatment pens (0.45 ha) were arranged spatially such that PI did not have fence-line or water source contact with CON. Calves were fed identically and followed the same antibiotic treatment protocol. Daily BW gain for the entire 42-d receiving trial was greater (P < 0.001) for PC (1.2 kg) compared with AM (0.85 kg). There was an exposure effect (P = 0.002) on ADG from d 28 to 42; CON gained 1.12 kg vs. 0.90 kg BW for PI cohort. Morbidity was markedly greater (P < 0.001) in AM (70%) vs. PC (7%), resulting in (P < 0.001) an antibiotic treatment cost of $20.52 and $2.48/animal, respectively. Treatment with a third antibiotic occurred more often (P = 0.04) for PI cohort, and the percentage of chronically ill cattle was greatest (P = 0.06) for AMPI. Upon arrival, BVDV type 1a, 1b, and 2a titers were greater for PC (treatment × day, P < 0.001), and the percentage seropositive to BVDV type 1a on d 0 was 100% for PC vs. 23% in AM. Platelets increased transiently (P < 0.001) with greater platelets observed in AM (P < 0.001). Results indicate that PC calves gain faster and require fewer antibiotic treatments during the receiving period. Exposure to PI reduced BW gain from d 28 to 42, increased the number of calves treated thrice, and increased chronically ill cattle for AM.


title: Photocatalytic activity of Cu(2+)/TiO(2)-coated cordierite foam inactivates bacteriophages and Legionella pneumophila

text: We investigated the antiviral activity of TiO(2)-coated cordierite foam used in air cleaners, as well as the evaluation methodology. Furthermore, we developed Cu(2+)/TiO(2)-coated cordierite foam and investigated the reduction in viral infection ratio. The method for evaluation of antibacterial activity of TiO(2)-coated cordierite foam could also be applied to evaluation of antiviral activity. We showed that Cu(2+)/TiO(2)-coated cordierite foam reduced the viral infection ratio to a greater extent than TiO(2)-coated cordierite foam. Our findings suggest that the infection risk by polluted air could be decreased using Cu(2+)/TiO(2)-coated cordierite foam in air cleaners.