Coronavirus disease 2019 (COVID‐19): not one epidemic but four


title: Cluster of Middle East Respiratory Syndrome Coronavirus Infections in Iran, 2014

text: During January 2013–August 2014, a total of 1,800 patients in Iran who had respiratory illness were tested for Middle East respiratory syndrome coronavirus. A cluster of 5 cases occurred in Kerman Province during May–July 2014, but virus transmission routes for some infections were unclear.


title: Chemical evolution for taming the ‘pathogenic kinase’ PAK1

text: To celebrate the 25th anniversary of the cloning of the first mammalian p21-activated kinases (PAKs) (RAC/CDC42-activated kinases) by Ed Manser, the first international PAK symposium was held in NYC in October 2019. Among six distinct PAKs in mammals, PAK1 is the major ‘pathogenic kinase’, the abnormal activation of which is responsible for a wide variety of diseases and disorders including cancers, ageing processes and infectious and inflammatory diseases such as pandemic coronaviral infection. Recently, for a clinical application, a few potent (highly cell-permeable and water-soluble) PAK1 blockers have been developed from natural or synthetic PAK1 blockers (triptolide, vitamin D3 and ketorolac) via a series of ‘chemical evolutions’ that boost pharmacological activities >500 times.


title: Coronavirus membrane-associated papain-like proteases induce autophagy through interacting with Beclin1 to negatively regulate antiviral innate immunity

text: Autophagy plays important roles in modulating viral replication and antiviral immune response. Coronavirus infection is associated with the autophagic process, however, little is known about the mechanisms of autophagy induction and its contribution to coronavirus regulation of host innate responses. Here, we show that the membrane-associated papain-like protease PLP2 (PLP2-TM) of coronaviruses acts as a novel autophagy-inducing protein. Intriguingly, PLP2-TM induces incomplete autophagy process by increasing the accumulation of autophagosomes but blocking the fusion of autophagosomes with lysosomes. Furthermore, PLP2-TM interacts with the key autophagy regulators, LC3 and Beclin1, and promotes Beclin1 interaction with STING, the key regulator for antiviral IFN signaling. Finally, knockdown of Beclin1 partially reverses PLP2-TM’s inhibitory effect on innate immunity which resulting in decreased coronavirus replication. These results suggested that coronavirus papain-like protease induces incomplete autophagy by interacting with Beclin1, which in turn modulates coronavirus replication and antiviral innate immunity.


title: Advanced electrocatalytic properties of nano-CoWO4 and CoWO4/nitrogen-doped graphene oxide as the anode materials of water electrolysis

text: Abstract The electrocatalytic performance of tungsten-based compounds was significantly enhanced via the crystal facets engineering, defect tuning, and combination with conductive 2D materials. Stating from Na2WO4·2H2O and CoCl2·6H2O we synthesized two types of nano-CoWO4 with different morphologies. The products were characterized by XRD, FE-SEM, HRTEM, XPS and EDS in details. The electrochemical performance of CoWO4 nanorods was obviously superior to CoWO4 nanodots due to the enhanced electrochemical active areas. Furthermore, CoWO4 and nitrogen-doped graphene oxides (NGO) composites were obtained under the similar synthetic conditions. As expected, the CoWO4/NGO composites showed significant improvement on electrochemical properties.


title: Imaging Proteolytic Activities in Mouse Models of Cancer

text: Proteases are “protein-cleaving” enzymes, which, in addition to their non-specific degrading function, also catalyze the highly specific and regulated process of proteolytic processing, thus regulating multiple biological functions. Alterations in proteolytic activity occur during pathological conditions such as cancer. One of the major deregulated classes of proteases in cancer is caspases, the proteolytic initiators and mediators of the apoptotic machinery. The ability to image apoptosis noninvasively in living cells and animal models of cancer can not only provide new insight into the biological basis of the disease but can also be used as a quantitative tool to screen and evaluate novel therapeutic strategies. Optical molecular imaging such as bioluminescence-based genetically engineered biosensors has been developed in our laboratory and exploited to study protease activity in animal models with a high signal to noise. Using the circularly permuted form of firefly luciferase, we have developed a reporter for Caspase 3/7, referred to as Caspase 3/7 GloSensor. Here, we discuss the use of the Caspase 3/7 GloSensor for imaging apoptotic activity in mouse xenografts and genetically engineered mouse models of cancer and present the potential of this powerful platform technology to image the proteolytic activity of numerous other proteases.


Severe acute respiratory syndrome (SARS): An old virus jumping into a new host or a new creation?


title: Influencia de la pandemia por coronavirus 2(sars-cov-2) en la apendicitis aguda. Sars-cov-2 en la apendicitis aguda

text: Abstract Introduction: Acute appendicitis (AA) is the most common abdominal surgical emergency. No specific studies have been found that evaluate the impact of the coronavirus 2 (SARS-Cov-2) pandemic on AA and its surgical management. An analysis was made on the influence of this new pathology on the clinical course of AA. Material and methods: Retrospective observational study was conducted on patients operated on for AA from January to April 2020. They were classified according to the time of the appendectomy, before the declaration of the state of alarm (Pre-COVID-19), and after its declaration (Post-COVID-19) in Spain, one the most affected countries in the world. An evaluation was made of demographic variables, duration of symptoms, type of appendicitis, surgical time, hospital stay, and postoperative complications. Results: The study included 66 patients (41 Pre-COVID-19; 25 Post-COVID-19) with mean age of 10.7±3 and 9.3±3.1; p=.073, respectively. Fever was found in a higher number of post-COVID-19 patients (52 vs 19.5%; p=.013), as well as a higher CRP (72.7±96.2 vs 31.3±36.2 mg/dL; p=.042). This group presented with a higher proportion of complicated appendicitis when compared to Pre-COVID-19 (32 vs 7.3%; p=.015). The mean hospital stay was longer in the Post-COVID-19 group (5.6±5.9 vs 3.2±4.3 days; p=.041). No differences were found in the time of onset of symptoms or surgical time. Conclusions: The SARS-Cov-2 pandemic influenced the time of diagnosis of appendicitis, as well as its course, and mean hospital stay. Peritonitis was more frequently seen. As a result of the significant circumstances, delaying diagnosis and treatment of AA during SARS-Cov-2 pandemic, inappropriate management of this common surgical disorder has been noticed.


title: Canine distemper virus may affect European wild cat populations in Central Spain

text: The main objective of this brief communication is to inform about the exposure to certain pathogens of interest for mesocarnivores in wildcats (Felis silvestris silvestris) that inhabit a human-domestic-wild ecotone located in a Natural Park (Serranía de Cuenca, Central Spain). Blood and mucosal swabs (nasal, conjunctival and rectal) samples were collected from nine alive animals to detect canine distemper virus (CDV), parvovirus (CPV/FPV), feline leukaemia virus (FeLV), feline coronavirus (FCoV), feline immunodeficiency virus (FIV), Leptospira interrogans, Chlamydia felis, Ehrlichia canis, Toxoplasma gondii, and Neospora caninum. ELISA, immunochromatograpy, microscopy agglutination test and PCR assays were used. The results show the first worldwide detection of exposure of wildcats to L. interrogans (3 positive/9 analysed) and the first detection of exposure to CVD (7/9), of carriers ofC felis (2/9) and of fecal spreading of CPV-FPV (2/9) in wildcats in Spain. Exposure to T. gondii and CPV-FPV was detected in 5 of the 9 wildcats analysed, and to FelV in 4 of 9. No FIV, FCoV, Ehrlichia canis and Neospora caninum were detected. The results reveal the circulation of pathogens among the wildcat population studied, but more vigilance is needed for an accurate assessment of the impact of these pathogens on the health status of this population.


title: Lyssavirus surveillance in bats of southern China’s Guangxi Province

text: Although rabies virus is widely distributed in the world, and has been the subject of extensive investigations with the objective of its ultimate prevention, control, and management, there is much less knowledge of the characteristics, distribution, and infectivity of other lyssaviruses. Since bats are known animal vectors for all but one of the known lyssavirus genotypes, we have performed an extensive survey of bats in the Guangxi Province to provide information on lyssavirus distribution in southern China. The lyssavirus nucleoprotein gene was detected in brains of 2.86 % of 2,969 bats. Nucleotide sequence homologies among isolates were 86.9–99.6 %, but only 70.0–85.0 % for lyssaviruses in GenBank. These infected bats were detected from a wide area, essentially forming a band running from the south-west to the north-east of Guangxi, and it appears that infection by new lyssaviruses is widespread in this region.


title: Low-Dose Serotherapy Improves Early Immune Reconstitution after Cord Blood Transplantation for Primary Immunodeficiencies

text: Abstract Cord blood transplantation (CBT) is curative for many primary immunodeficiencies (PIDs) but is associated with risks of viral infection and graft-versus-host disease (GvHD). Serotherapy reduces GvHD but potentially increases the risk of viral infection by delaying immune reconstitution. Because many PID patients have pre-existing viral infections, the optimal dose of serotherapy is unclear. We performed a retrospective analysis in 34 consecutive PID patients undergoing CBT and compared immune reconstitution, viral infection, GvHD, mortality, and long-term immune function between high-dose (n = 11) and low-dose (n = 9) serotherapy. Serotherapy dose had no effect on neutrophil engraftment. Median CD3+ engraftment occurred at 92.5 and 97 days for high- and low-dose serotherapy, respectively. The low-dose serotherapy group had higher CD3+, CD4+, and early thymic emigrant counts at 4 months compared with the high-dose group. GvHD severity and number of viral infections did not differ between serotherapy doses. Survival from the transplantation process was 90.9% for high-dose and 100% for low-dose groups. In conclusion, low-dose serotherapy enhanced T cell reconstitution and thymopoiesis during the first year after CBT with no increase in GvHD.


title: Characteristics and Outcomes of Patients with Pulmonary Acute Respiratory Distress Syndrome Infected with Influenza versus Other Respiratory Viruses

text: BACKGROUND: Although the frequency of respiratory viral infection in patients with pulmonary acute respiratory distress syndrome (ARDS) is not uncommon, clinical significance of the condition remains to be further elucidated. The purpose of this study was to compare characteristics and outcomes of patients with pulmonary ARDS infected with influenza and other respiratory viruses. METHODS: Clinical data of patients with pulmonary ARDS infected with respiratory viruses January 2014–June 2018 were reviewed. Respiratory viral infection was identified by multiplex reverse transcription–polymerase chain reaction (RT-PCR). RESULTS: Among 126 patients who underwent multiplex RT-PCR, respiratory viral infection was identified in 46% (58/126): 28 patients with influenza and 30 patients with other respiratory viruses. There was no significant difference in baseline and clinical characteristics between patients with influenza and those with other respiratory viruses. The use of extracorporeal membrane oxygenation (ECMO) was more frequent in patients with influenza than in those with other respiratory viruses (32.1% vs 3.3%, p=0.006). Co-bacterial pathogens were more frequently isolated from respiratory samples of patients with pulmonary ARDS infected with influenza virus than those with other respiratory viruses. (53.6% vs 26.7%, p=0.036). There were no significant differences regarding clinical outcomes. In multivariate analysis, acute physiology and chronic health evaluation II was associated with 30-mortality (odds ratio, 1.158; 95% confidence interval, 1.022–1.312; p=0.022). CONCLUSION: Respiratory viral infection was not uncommon in patients with pulmonary ARDS. Influenza virus was most commonly identified and was associated with more co-bacterial infection and ECMO therapy.


Role of telehealth in outbreaks—Where the classical healthcare systems fail


title: The Landscape of Human Cancer Proteins Targeted by SARS-CoV-2

text: The mapping of SARS-CoV-2 human protein–protein interactions by Gordon and colleagues revealed druggable targets that are hijacked by the virus. Here, we highlight several oncogenic pathways identified at the host–virus interface of SARS-CoV-2 to enable cancer biologists to apply their knowledge for rapid drug repurposing to treat COVID-19, and help inform the response to potential long-term complications of the disease.


Offline: CoHERE—a call for a post-pandemic health strategy


title: Respiratory Viral Antigens in Autopsy Lung Tissue Specimens from Patients with Cancer or Myocardial Infarction

text: Using immunoenzyme histochemical analysis, we retrospectively examined lung tissue specimens obtained at autopsy from 118 patients with cancer who had received chemotherapy and 20 patients who had died after myocardial infarction. Respiratory viral antigens were demonstrated in lung tissue specimens from eight of 118 cancer patients and two of 20 myocardial infarction patients. Most of the patients with demonstrable viral antigens were febrile and had signs of pulmonary infection, but in no case was pulmonary viral infection considered clinically. The following viral antigens were demonstrated: influenza A virus (6 patients), respiratory syncytial virus (2), influenza B virus (1), and parainfluenza virus type 1 (1).


title: The day after COVID-19 in IBD: how to go back to ‘normal’

text: During the coronavirus disease 2019 (COVID-19) pandemic, inflammatory bowel disease (IBD) practices have been disrupted. This Comment summarizes the key strategies that should be implemented for both patients and IBD specialists to provide optimal care while avoiding new outbreaks for the first 6–12 months after the peak of the COVID-19 pandemic.


title: Experimental inoculation of equine coronavirus into Japanese draft horses

text: Recently, outbreaks associated with equine coronavirus (ECoV) have occurred in Japan and the United States. While ECoV is likely to be pathogenic to horses, it has not been shown that experimental inoculation of horses with ECoV produces clinical signs of disease. In this study, we inoculated three Japanese draft horses with an ECoV-positive diarrheic fecal sample to confirm infection after inoculation and to investigate the clinical course and virus shedding patterns of ECoV. Virus neutralization tests showed that all three horses became infected with ECoV. Two of the three horses developed clinical signs similar to those observed during ECoV outbreaks, including fever, anorexia, and gastrointestinal dysfunction. All horses excreted a large amount of virus into their feces for more than 9 days after inoculation regardless of the presence or absence of clinical signs, which suggests that feces are an important source of ECoV infection. ECoV was also detected in nasal swabs from all horses, suggesting that respiratory transmission of ECoV may occur. Both symptomatic horses developed viremia, while the asymptomatic horse did not. White blood cell counts and serum amyloid A concentrations changed relative to the clinical condition of the inoculated horses; these may be useful markers for monitoring the clinical status of horses infected with ECoV. This is the first report of induction of clinical signs of ECoV infection in horses by experimental inoculation. These clinical and virological findings should aid further investigation of the pathogenesis of ECoV.


title: FluMob: Enabling Surveillance of Acute Respiratory Infections in Health-care Workers via Mobile Phones

text: Singapore is a hotspot for emerging infectious diseases and faces a constant risk of pandemic outbreaks as a major travel and health hub for Southeast Asia. With an increasing penetration of smart phone usage in this region, Singapore’s pandemic preparedness framework can be strengthened by applying a mobile-based approach to health surveillance and control, and improving upon existing ideas by addressing gaps, such as a lack of health communication. FluMob is a digitally integrated syndromic surveillance system designed to assist health authorities in obtaining real-time epidemiological and surveillance data from health-care workers (HCWs) within Singapore, by allowing them to report influenza incidence using smartphones. The system, integrating a fully responsive web-based interface and a mobile interface, is made available to HCW using various types of mobile devices and web browsers. Real-time data generated from FluMob will be complementary to current health-care- and laboratory-based systems. This paper describes the development of FluMob, as well as challenges faced in the creation of the system.


title: Atypical presentation of human bocavirus: Severe respiratory tract infection complicated with encephalopathy

text: Human bocavirus (HBOV) has been reported as a worldwide distributed respiratory pathogen. It has also been associated with encephalitis recently by detection of the virus in cerebrospinal fluid (CSF) of patients presented with encephalitis. This retrospective study aimed to present clinical features of HBOV infections in children with respiratory symptoms and describe unexplained encephalopathy in a subgroup of these patients. Results of 1,143 pediatric nasal samples from mid‐December 2013 to July 2014 were reviewed for detection of HBOV. A multiplex real time polymerase chain reaction assay was used for viral detection. Medical records of the patients were retrospectively analyzed. HBOV was detected in 30 patients (2.6%). Median age was 14 months (5–80). Clinical diagnoses were upper respiratory tract infection (n = 10), bronchopneumonia (n = 9), acute bronchiolitis (n = 5), pneumonia (n = 4), acute bronchitis (n = 1), and asthma execarbation (n = 1). Hospitalization was required in 16 (53.3%) patients and 10 (62.5%) of them admitted to pediatric intensive care unit (PICU). Noninvasive mechanical ventilation modalities was applied to four patients and mechanical ventilation to four patients. Intractable seizures developed in four patients while mechanically ventilated on the 2nd–3rd days of PICU admission. No specific reason for encephalopathy was found after a thorough investigation. No mortality was observed, but two patients were discharged with neurological sequela. HBOV may lead to respiratory infections in a wide spectrum of severity. This report indicates its potential to cause severe respiratory infections requiring PICU admission and highlights possible clinical association of HBOV and encephalopathy, which developed during severe respiratory infection. J. Med. Virol. 87:1831–1838, 2015. © 2015 Wiley Periodicals, Inc.


Civil society’s response to emerging public health events in China


title: Legacy and social media respectively influence risk perceptions and protective behaviors during emerging health threats: A multi-wave analysis of communications on Zika virus cases

text: Abstract Objective Both legacy media, such as television and newspapers, and online social media are potentially important but incompletely understood sources of information in the face of emerging public health risks. This research aimed to understand media effects on risk perceptions and behaviors concerning the Zika virus in the United States. Methods We analyzed a multi-wave nationally representative survey (N = 29,062) and the volume of communications in social and legacy media (i.e., legacy media data from news sources and databases, N = 2,660 and social media data from Twitter, N = 1,605,752) in the United States between April and October 2016, dates coinciding with the early cases of local transmission of Zika in the United States (i.e., 25 weeks). The present study conducted econometric analyses (i.e., Granger causality tests) to assess the associations of legacy and social media coverage with risk perceptions and protective behaviors in the total sample and specific groups separated by pregnancy status/intent, geographic region, income, education level, age, and ethnicity. Results The results from the overall sample suggested that changes in the volume of information in legacy and social media (i.e., Twitter) were followed by different changes in community risk perceptions and protective behaviors. Specifically, social media coverage correlated with the level of risk perceptions, whereas the legacy media coverage correlated with the level of protective behaviors. Analyses across different subpopulations, including those of different pregnancy status/intent, geographic Zika risk, income, education level, age, and ethnicity, replicated the social media associations with risk perceptions in most cases. However, legacy media and protective behaviors were linked only in some vulnerable subpopulations (e.g., the less-educated populations). Conclusion Understanding how media coverage relates to Zika risk perceptions and protective behaviors will help to facilitate effective risk communications by healthcare professionals and providers, particularly when a health risk emerges.


Hypothetical unfolding of a global conjoint epidemic


title: Importance of Pediatric Inclusion in COVID-19 Therapeutic Trials

text: Pediatric patients are excluded from most coronavirus disease 2019 (COVID-19) therapeutic trials. We outline a rationale for the inclusion of children in COVID-19 therapeutic trials, which enabled us to include children of all ages in a therapeutic COVID-19 trial at our institution.


title: The red half‐moon nail sign: a novel manifestation of coronavirus infection

text: The novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19). The pandemic condition was declared by the WHO on March 11, 2020. The main clinical symptoms are fever, dry cough and dyspnea, although new symptoms are emerging, such as diarrhea, anosmia and ageusia. The virus enters cells, likely including those lining blood vessels, by binding to angiotensin converting enzyme 2 (ACE2) receptors on the cell surface. Infection can also promote blood clots, heart attacks and cardiac inflammation.


The psychological challenges for oncological patients in times of COVID-19 pandemic: telemedicine, a solution?


title: Enterovirus D68 respiratory infection in a children's hospital in Japan in 2015

text: BACKGROUND: Outbreaks of enterovirus D68 (EV‐D68) respiratory infections in children were reported globally in 2014. In Japan, there was an EV‐D68 outbreak in the autumn of 2015 (September–October). The aim of this study was to compare EV‐D68‐specific polymerase chain reaction (PCR)‐positive and EV‐D68‐specific PCR‐negative patients. METHODS: Pediatric patients admitted for any respiratory symptoms between September and October 2015 were enrolled. Nasopharyngeal swabs were tested for multiplex respiratory virus PCR and EV‐D68‐specific reverse transcription‐PCR. EV‐D68‐specific PCR‐positive and ‐negative patients were compared regarding demographic data and clinical information. RESULTS: A nasopharyngeal swab was obtained from 76 of 165 patients admitted with respiratory symptoms during the study period. EV‐D68 was detected in 40 samples (52.6%). Median age in the EV‐D68‐specific PCR‐positive and ‐negative groups was 3.0 years (IQR, 5.5 years) and 3.0 years (IQR, 4.0 years), respectively. The rates of coinfection in the two groups were 32.5% and 47.2%, respectively. There was no significant difference in the history of asthma or recurrent wheezing, length of hospitalization, or pediatric intensive care unit admission rate between the groups. The median days between symptom onset and admission was significantly lower for the EV‐D68‐positive group (3.0 days vs 5.0 days, P = 0.001). EV‐D68 was identified as clade B on phylogenetic analysis. No cases of acute flaccid myelitis were encountered. CONCLUSIONS: More than half of the samples from the children admitted with respiratory symptoms were positive for EV‐D68‐specific PCR during the outbreak. Asthma history was not associated with the risk of developing severe respiratory infection.


title: Impact of respiratory viruses in the neonatal intensive care unit

text: OBJECTIVE: To describe the epidemiology and clinical impact of respiratory viruses in a neonatal intensive care unit (NICU). STUDY DESIGN: We conducted a retrospective observational study of infants with respiratory viruses detected by multiplex reverse-transcriptase PCR from May 2012 to May 2017. The proportion of symptomatic vs. asymptomatic infants and associated morbidity were assessed. The association of infection prevention and control (IP&C) strategies and transmission was ascertained. RESULTS: Respiratory viruses were detected in 83 infants representing 86 unique episodes during which infants remained asymptomatic in 15 (17%). Of the 71 symptomatic episodes, only 45% were associated with increased respiratory and/or nutritional support. Rhinovirus/enteroviruses were most common (69%) and involved nine of 12 transmission events. IP&C strategies including restricting visitors <12 years of age and screening exposed infants were associated with decreased transmission rates. CONCLUSIONS: NICU patients can be asymptomatic carriers of respiratory viruses. Identification of such infants is important to prevent transmission in the NICU.


title: CFD investigation on the effects of wind and thermal wall-flow on pollutant transmission in a high-rise building

text: Abstract The solar radiation can heat the building outer surface, and then cause the upward natural convection flows adjacent to the wall. This phenomenon is especially obvious on a windless sunny day. The near wall thermal plume can drive gaseous pollutants released from lower floors to upper floors. Combined with the effect of ambient approaching wind, the transmission routes will be very complicated. The paper aims to investigate the airflow patterns and pollutant transmission within a building under the effects of wind and thermal forces. A hypothetical twenty-storey slab-shape high-rise building in Shanghai with single-sided natural ventilation is set as the research object in the present study. The intensity of solar radiation on a typical day during transition season is theoretically analysed. The temperature difference between the heated building envelope and the ambient air is calculated by a simplified heat balance model. Finally, the tracer gas method is employed in the numerical simulation to analyse the influence of the wind and wall thermal plume flow on the inter-flat pollutant transmission characteristics. The results show that, the temperature difference between sunward and shady side wall is about 10 K at noon on the designate day. When the source is set as a point with steady intensity and the buoyancy is stronger than or approximately equivalent to the wind, the reentry ratio of the flat immediately above the source can be around 25%.


title: Toxoplasmosis in Sand cats (Felis margarita) and other animals in the Breeding Centre for Endangered Arabian Wildlife in the United Arab Emirates and Al Wabra Wildlife Preservation, the State of Qatar

text: Abstract The Sand cat (Felis margarita) is a small-sized felid found in sand and stone deserts ranging from the north of Africa to Asia, with the Arabian Peninsula as its centre of distribution. The Sand cat captive breeding program at the Breeding Centre for Endangered Arabian Wildlife (BCEAW), Sharjah, UAE, has experienced high newborn mortality rates, and congenital toxoplasmosis was recently recognized as one of the causes of this mortality. In the present study, one 18-month-old Sand cat (FM019) died of acute toxoplasmosis-associated hepatitis and pneumonitis acquired after birth; Toxoplasma gondii was demonstrated in histological sections which reacted with T. gondii polyclonal antibodies by immunohistochemistry (IHC). T. gondii DNA was found by PCR of extracted DNA from liver and lung tissues of this cat. Antibodies to T. gondii were found in serum examined in 1:1600 dilution in the modified agglutination test (MAT); its 2-year-old cage mate seroconverted (MAT titer 1:3200) at the same time. Another Sand cat (FM017) was euthanized because of ill health when 3 years old; its MAT titer was >1:3200, and T. gondii tissue cysts were found in brain, heart, ocular muscles and skeletal muscle, confirmed by IHC. Viable T. gondii was isolated by bioassays in mice inoculated with tissues of another chronically infected Sand cat (FM002); T. gondii was not found in histological sections of this cat. T. gondii antibodies were found in several species of animals tested, notably in 49 of 57 wild felids at BCEAW. A 7-year-old Sand cat (3657) from Al Wabra Wildlife Preservation (AWWP), Doha, State of Qatar died of acute visceral toxoplasmosis with demonstrable T. gondii tachyzoites by IHC, and T. gondii DNA by PCR, and a MAT titer of >3200. T. gondii antibodies were found in 21 of 27 of wild felids at AWWP. PCR-RFLP genotyping at 10 genetic loci revealed that these T. gondii isolates from Sand cat (FM002 and FM019) at BCEAW have an atypical genotype, which was previously reported in T. gondii isolates of dogs from Sri Lanka. The genotype from the cat from AWWP (3657) is a genetic Type II strain with a Type I allele at locus Apico. This is the first report of genetic characterization of T. gondii isolates from Middle East.


title: Spectrum of COVID‐19 in Children

text: The prevalence of coronavirus disease 2019 (COVID‐19) is lower in children compared to adults. Children contribute to 1‐5% of all COVID‐19 cases (1) . A recent study from China reported that 171(12.3%) of 1391 children with suspected disease had confirmed COVID‐19 infection (2) . As of May 15, 2020, there are 33,241 children with COVID‐19 in the United States (3) . The most common symptoms in children with confirmed and suspected COVID‐19 include fever and cough followed by diarrhea, and abdominal pain.


title: Promoting influenza prevention for elderly people in Hong Kong using health action process approach: study protocol

text: BACKGROUND: People 65 years or older are at greater risk of serious complications from the seasonal influenza compared with young. To promote elderly people’s behavioral compliance toward influenza prevention, the aim of the current project is to develop, implement, and evaluate a theory-based low-administration-cost intervention building on a leading psychological theory, the Health Action Process Approach (HAPA). METHODS: The target group is Hong Kong Chinese elderly people aged 65 or older who rarely or never adopt any preventive actions. This project will be conducted in three phases over 24 months. In phase 1, intervention program will be developed building on the HAPA theoretical framework which comprises both the initiation and maintenance of influenza prevention behaviors. In phase 2, intervention will be implemented and evaluated using a randomized controlled trial, including: (a) behavior initiation only, (b) behavior initiation + behavior maintenance, and (c) control group. Both the initiation and maintenance components will comprise weekly-delivered telephone-based individual intervention sessions in 3 months. In phase 3, outcome evaluation of behavioral and psychological variables and process evaluation will be conducted. The effectiveness of the intervention will be analyzed using a series of linear mixed models on each behavioral and psychological outcome variable. Structural equation modelling will be used to test the hypothesized theoretical sequence in the HAPA model. DISCUSSION: The proposed project is expected to design theory-based intervention materials to promote the influenza prevention behaviors in Hong Kong elderly people and provide information on its effectiveness and the potential changing mechanism of behavior initiation and maintenance. TRIAL REGISTRATION: This randomized controlled trial was funded by the Health and Medical Research Fund (HMRF), Food and Health Bureau of the Government of the Hong Kong Special Administrative Region (Ref: 16151222) and was registered on 13/10/2017 at CCRB Clinical Trials Registry of the Chinese University of Hong Kong, a Partner Registry of a WHO Primary Registry (Ref: CUHK_CCRB00567).


title: On the origin and continuing evolution of SARS-CoV-2

text: The SARS-CoV-2 epidemic started in late December 2019 in Wuhan, China, and has since impacted a large portion of China and raised major global concern. Herein, we investigated the extent of molecular divergence between SARS-CoV-2 and other related coronaviruses. Although we found only 4% variability in genomic nucleotides between SARS-CoV-2 and a bat SARS-related coronavirus (SARSr-CoV; RaTG13), the difference at neutral sites was 17%, suggesting the divergence between the two viruses is much larger than previously estimated. Our results suggest that the development of new variations in functional sites in the receptor-binding domain (RBD) of the spike seen in SARS-CoV-2 and viruses from pangolin SARSr-CoVs are likely caused by mutations and natural selection besides recombination. Population genetic analyses of 103 SARS-CoV-2 genomes indicated that these viruses evolved into two major types (designated L and S), that are well defined by two different SNPs that show nearly complete linkage across the viral strains sequenced to date. Although the L type (∼70%) is more prevalent than the S type (∼30%), the S type was found to be the ancestral version. Whereas the L type was more prevalent in the early stages of the outbreak in Wuhan, the frequency of the L type decreased after early January 2020. Human intervention may have placed more severe selective pressure on the L type, which might be more aggressive and spread more quickly. On the other hand, the S type, which is evolutionarily older and less aggressive, might have increased in relative frequency due to relatively weaker selective pressure. These findings strongly support an urgent need for further immediate, comprehensive studies that combine genomic data, epidemiological data, and chart records of the clinical symptoms of patients with coronavirus disease 2019 (COVID-19).


title: Viral fitness: definitions, measurement, and current insights

text: Viral fitness is an active area of research, with recent work involving an expanded number of human, non-human vertebrate, invertebrate, plant, and bacterial viruses. Many publications deal with RNA viruses associated with major disease emergence events, such as HIV-1, influenza virus, and Dengue virus. Study topics include drug resistance, immune escape, viral emergence, host jumps, mutation effects, quasispecies diversity, and mathematical models of viral fitness. Important recent trends include increasing use of in vivo systems to assess vertebrate virus fitness, and a broadening of research beyond replicative fitness to also investigate transmission fitness and epidemiologic fitness. This is essential for a more integrated understanding of overall viral fitness, with implications for disease management in the future.


title: Avian infectious bronchitis virus genomic RNA contains sequence homologies at the intergenic boundaries

text: Abstract cDNAs derived from the 3'-terminus of IBV Beaudette genomic RNA by oligo(dT)-primed reverse transcription were cloned in PAT153/HB101. 25 clones were characterised and two of these were found to cover 3.3 kb extending from the poly(A) tail. The relationships of the two smallest IBV mRNAs, A and B, to the cloned sequences were established by restriction fragment hybridisation to Northern blots. The 5'-termini of mRNAs A and B were located on the clones by S1 mapping. DNA sequencing of cloned sequences corresponding to the intergenic boundaries of mRNAs A and B was carried out. Homologies between the sequences at these boundaries were observed.


title: Feline bocavirus-1 associated with outbreaks of hemorrhagic enteritis in household cats: potential first evidence of a pathological role, viral tropism and natural genetic recombination

text: Feline bocavirus-1 (FBoV-1) was identified in cats from different households with hemorrhagic enteritis during outbreaks of an unusual clinical presentation of feline panleukopenia virus (FPLV) in Thailand. Use of polymerase chain reaction revealed the presence of the FBoV-1 DNA in several tissues, suggesting hematogenous viremia, with the viral nucleic acid, detected by in situ hybridization (ISH), was localized in intestinal cells and vascular endothelium of intestinal mucosa and serosa, and in necrosis areas primarily in various lymph nodes while FPLV-immunohistochemical analysis revealed viral localization only in cryptal cells, neurons, and limited to leukocytes in the mesenteric lymph node. Full-length coding genome analysis of the Thai FBoV-1 strains isolated from moribund cats revealed three distinct strains with a high between-strain genetic diversity, while genetic recombination in one of the three FBoV-1 strains within the NS1 gene. This is the first report identifying natural genetic recombination of the FBoV-1 and describing the pathology and viral tropism of FBoV-1 infection in cats. Although the role of FBoV-1 associated with systemic infection of these cats remained undetermined, a contributory role of enteric infection of FBoV-1 is possible. Synergistic effects of dual infection with FPLV and FBoV-1 are hypothesized, suggesting more likely severe clinical presentations.


title: Pathogenetic mechanisms of severe acute respiratory syndrome

text: Abstract Severe acute respiratory syndrome (SARS) is an acute respiratory disease with significant morbidity and mortality. While its clinical manifestations have been extensively studied, its pathogenesis is not yet fully understood. A limited number of autopsy studies have revealed that the lungs and the immune system are the organs that sustain the most severe damage. Other organs affected include the kidneys, brain, digestive tract, heart, liver, thyroid gland and urogenital tract. The primary target cells are pneumocytes and enterocytes, both cell types abundantly expressing angiotensin-converting enzyme 2 which is the main SARS-CoV receptor. Other cell types infected include the epithelial cells of renal tubules, cerebral neurons, and immune cells. The pathology of this disease results from both direct and indirect injury. Direct injury is caused by infection of the target cells by the virus. Indirect injury mainly results from immune responses, circulatory dysfunction, and hypoxia. In this review, we summarize the major pathological findings at the gross, cellular and molecular levels and discuss the various possible mechanisms that may contribute to the pathogenesis of SARS. The implications of the proposed pathogenesis for prevention, diagnosis and therapy of the disease are discussed.


title: RIEMS: a software pipeline for sensitive and comprehensive taxonomic classification of reads from metagenomics datasets

text: BACKGROUND: Fuelled by the advent and subsequent development of next generation sequencing technologies, metagenomics became a powerful tool for the analysis of microbial communities both scientifically and diagnostically. The biggest challenge is the extraction of relevant information from the huge sequence datasets generated for metagenomics studies. Although a plethora of tools are available, data analysis is still a bottleneck. RESULTS: To overcome the bottleneck of data analysis, we developed an automated computational workflow called RIEMS – Reliable Information Extraction from Metagenomic Sequence datasets. RIEMS assigns every individual read sequence within a dataset taxonomically by cascading different sequence analyses with decreasing stringency of the assignments using various software applications. After completion of the analyses, the results are summarised in a clearly structured result protocol organised taxonomically. The high accuracy and performance of RIEMS analyses were proven in comparison with other tools for metagenomics data analysis using simulated sequencing read datasets. CONCLUSIONS: RIEMS has the potential to fill the gap that still exists with regard to data analysis for metagenomics studies. The usefulness and power of RIEMS for the analysis of genuine sequencing datasets was demonstrated with an early version of RIEMS in 2011 when it was used to detect the orthobunyavirus sequences leading to the discovery of Schmallenberg virus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-015-0503-6) contains supplementary material, which is available to authorized users.


title: Different computed tomography patterns of Coronavirus Disease 2019 (COVID-19) between survivors and non-survivors

text: This study aimed to compare the chest computed tomography (CT) findings between survivors and non-survivors with Coronavirus Disease 2019 (COVID-19). Between 12 January 2020 and 20 February 2020, the records of 124 consecutive patients diagnosed with COVID-19 were retrospectively reviewed and divided into survivor (83/124) and non-survivor (41/124) groups. Chest CT findings were qualitatively compared on admission and serial chest CT scans were semi-quantitively evaluated between two groups using curve estimations. On admission, significantly more bilateral (97.6% vs. 73.5%, p = 0.001) and diffuse lesions (39.0% vs. 8.4%, p < 0.001) with higher total CT score (median 10 vs. 4, p < 0.001) were observed in non-survivor group compared with survivor group. Besides, crazy-paving pattern was more predominant in non-survivor group than survivor group (39.0% vs. 12.0%, p < 0.001). From the prediction of curve estimation, in survivor group total CT score increased in the first 20 days reaching a peak of 6 points and then gradually decreased for more than other 40 days (R(2) = 0.545, p < 0.001). In non-survivor group, total CT score rapidly increased over 10 points in the first 10 days and gradually increased afterwards until ARDS occurred with following death events (R(2) = 0.711, p < 0.001). In conclusion, persistent progression with predominant crazy-paving pattern was the major manifestation of COVID-19 in non-survivors. Understanding this CT feature could help the clinical physician to predict the prognosis of the patients.


title: Specific Aptamer-Based Probe for Analyzing Biomarker MCP Entry Into Singapore Grouper Iridovirus-Infected Host Cells via Clathrin-Mediated Endocytosis

text: Biomarkers have important roles in various physiological functions and disease pathogenesis. As a nucleocytoplasmic DNA virus, Singapore grouper iridovirus (SGIV) causes high economic losses in the mariculture industry. Aptamer-Q5-complexed major capsid protein (MCP) in the membrane of SGIV-infected cells can be used as a specific molecular probe to investigate the crucial events of MCP endocytosis into SGIV-infected host cells during viral infection. Chlorpromazine blocks clathrin-mediated endocytosis, and MCP endocytosis into SGIV-infected cells decreased significantly when the cells were pretreated with chlorpromazine. The disruption of cellular cholesterol by methyl-β-cyclodextrin also significantly reduced MCP endocytosis. In contrast, inhibitors of key regulators of caveolae/raft-dependent endocytosis and macropinocytosis, including genistein, Na(+)/H(+) exchanger, p21-activated kinase 1 (PAK1), myosin II, Rac1 GTPase, and protein kinase C (PKC), had no effect on MCP endocytosis. The endocytosis of the biomarker MCP is dependent on low pH and cytoskeletal actin filaments, as shown with various inhibitors (chloroquine, ammonia chloride, cytochalasin D). Therefore, MCP enters SGIV-infected host cells via clathrin-mediated endocytosis, which is dependent on dynamin, cholesterol, low pH, and cytoskeletal actin filaments. This is the first report of a specific aptamer-based probe used to analyze MCP endocytosis into SGIV-infected host cells during viral infection. This method provides a convenient strategy for exploring viral pathogenesis and facilitates the development of diagnostic tools for and therapeutic approaches to viral infection.


title: Herbal Medicine for the management of COVID-19 during the medical observation period: A review of guidelines

text: BACKGROUND: Medical observation period is a period of 14 days after any exposure to coronavirus disease 2019 (COVID-19) occurred. This review aimed to summarize and analyze the herbs and herbal formulae recommended by available guidelines. METHODS: A total of 14 sources were searched for potential guidelines that provide herbal medicine treatment for the medical observation period of COVID-19. We summarized and analyzed the recommended herbal formulae and performed a network analysis to identify the relationship between herbs. RESULTS: We found 9 guidelines that provide herbal formula for medical observation based on clinical manifestation. There are 12 herbal formulae with a total of 53 herbs recommended by the guidelines. The result of our network analysis showed that the herb Citri Reticulatae Pericarpium (Chen Pi) strongly paired with the herb Glycyrrhizae Radix et Rhizoma (Gan Cao). CONCLUSION: This review briefly summarized the usage of herbal medicine for the medical observation period of COVID-19 and may serve as a reference for future studies. More research is needed in the future to provide evidence on the usage of herbal medicine in various phases of COVID-10.


title: A phylogenetically distinct Middle East respiratory syndrome coronavirus detected in a dromedary calf from a closed dairy herd in Dubai with rising seroprevalence with age

text: Middle East respiratory syndrome coronavirus (MERS-CoV) was detected by monoclonal antibody-based nucleocapsid protein-capture enzyme-linked immunosorbent assay (ELISA), RNA detection, and viral culture from the nasal sample of a 1-month-old dromedary calf in Dubai with sudden death. Whole genome phylogeny showed that this MERS-CoV strain did not cluster with the other MERS-CoV strains from Dubai that we reported recently. Instead, it formed a unique branch more closely related to other MERS-CoV strains from patients in Qatar and Hafr-Al-Batin in Saudi Arabia, as well as the MERS-CoV strains from patients in the recent Korean outbreak, in which the index patient acquired the infection during travel in the eastern part of the Arabian Peninsula. Non-synonymous mutations, resulting in 11 unique amino acid differences, were observed between the MERS-CoV genome from the present study and all the other available MERS-CoV genomes. Among these 11 unique amino acid differences, four were found in ORF1ab, three were found in the S1 domain of the spike protein, and one each was found in the proteins encoded by ORF4b, ORF5, envelope gene, and ORF8. MERS-CoV detection for all other 254 dromedaries in this closed dairy herd was negative by nucleocapsid protein-capture ELISA and RNA detection. MERS-CoV IgG sero-positivity gradually increased in dromedary calves with increasing age, with positivity rates of 75% at zero to three months, 79% at four months, 89% at five to six months, and 90% at seven to twelve months. The development of a rapid antigen detection kit for instantaneous diagnosis is warranted.


title: Picornavirus etiology of acute infections among hospitalized infants

text: Abstract Background Enteroviruses (EV) and parechoviruses (PeV) are ubiquitous viruses that cause a range of illness, including acute illness in children aged <1 year. Objectives We describe EV and PeV infections among children from 2 US study sites aged <1 year and hospitalized with acute infections. For EV- and PeV-negative case-patients, we explored other viral etiologies. Methods Participants were aged <1 year, hospitalized during 2016, and had cerebrospinal fluid (CSF) collected for routine diagnostic testing. Demographic and clinical data were abstracted from medical charts, and residual specimens were sent to CDC for confirmatory testing and typing. Results Of 472 eligible case-patients, CSF specimen was available for 319 (67.6%). Among those, 13 (4.1%) were positive for EV and 11 (3.4%) for PeV. Most case-patients (86.8%, n = 277) were aged <2 months, as were all EV- or PeV-positive case-patients. None of the positive case-patients had underlying conditions, and the chief complaint for 91.7% (n = 22) was fever. Twelve positive case-patients were admitted to intensive care (ICU) and had brief hospital stays (median 2 days). Sequencing revealed a variety of EV types and the predominance of PeV-A3 among the PeV-positive case-patients. Conclusions A range of EV and PeV types were associated with acute febrile illnesses leading to hospitalization in children aged <2 months. Approximately half of EV and PeV case-patients were admitted to ICU, but length of hospital stay was brief and illnesses were generally self-limiting. Clinicians should consider EV and PeV infections in infants presenting with febrile illness.


title: MHC class II alleles associated with Th1 rather than Th17 type immunity drive the onset of early arthritis in a rat model of rheumatoid arthritis

text: Polymorphisms in the MHC class II (MHCII) genes are strongly associated with rheumatoid arthritis, supporting the importance of autoreactive T helper (Th) cells for the development of this disease. Here, we used pristane‐induced arthritis (PIA), induced by the non‐antigenic hydrocarbon pristane, to study the impact of different MHCII alleles on T‐cell activation and differentiation. In MHCII‐congenic rats with disease‐promoting MHCII alleles, pristane primarily induced activation of Th1 cells, whereas activated T cells were Th17 biased in rats with protective MHCII alleles. Neutralization of IFN‐γ during T‐cell activation abrogated the development of disease, suggesting that Th1 immunity is important for disease induction. Neutralization of IL‐17, by contrast, suppressed arthritis only when performed in rats with established disease. Adoptive T‐cell transfers showed that T cells acquired arthritogenic capacity earlier in strains with a prevailing Th1 response. Moreover, upon pristane injection, these strains exhibited more Ag‐primed OX40+ and proliferating T cells of polyclonal origin. These data show that T cells are polarized upon the first encounter with peptide‐MHCII complexes in an allele‐dependent fashion. In PIA, the polyclonal expansion of autoreactive Th1 cells was necessary for the onset of arthritis, while IL‐17 mediated immunity contributed to the progression to chronic disease.


title: (+)-Catechin inhibition of transmissible gastroenteritis coronavirus in swine testicular cells is involved its antioxidation

text: ABSTRACT Transmissible gastroenteritis virus (TGEV) causes transmissible gastroenteritis (TGE), especially in newborn piglets, which severely threatens the worldwide pig industry. In this study, (+)-catechin was evaluated for its antiviral effect against TGEV in vitro. Viability assays revealed that (+)-catechin treatment exerted a dose-dependent rescue effect in TGEV-infected ST cells, and this result was only obtained with the post-treatment application of (+)-catechin. The viral yields in (+)-catechin-treated cultures were reduced by almost three log10 units. Quantitative real-time PCR analysis of the TGEV genome revealed that TGEV RNA replication was restricted after (+)-catechin treatment. Intracellular reactive oxygen species (ROS) detection showed that (+)-catechin alleviated ROS conditions induced by TGEV infection. Our results showed that (+)-catechin exerts an inhibitory effect on TGEV proliferation in vitro and is involved its antioxidation.


title: Can routine laboratory tests discriminate SARS‐CoV‐2‐infected pneumonia from other causes of community‐acquired pneumonia?

text: BACKGROUND: The clinical presentation of SARS‐CoV‐2‐infected pneumonia (COVID‐19) resembles that of other etiologies of community‐acquired pneumonia (CAP). We aimed to identify clinical laboratory features to distinguish COVID‐19 from CAP. METHODS: We compared the hematological and biochemical features of 84 patients with COVID‐19 at hospital admission and 221 patients with CAP. Parameters independently predictive of COVID‐19 were calculated by multivariate logistic regression. The receiver operating characteristic (ROC) curves were generated and the area under the ROC curve (AUC) was measured to evaluate the discriminative ability. RESULTS: Most hematological and biochemical indexes of patients with COVID‐19 were significantly different from patients with CAP. Nine laboratory parameters were identified to be predictive of a diagnosis of COVID‐19. The AUCs demonstrated good discriminatory ability for red cell distribution width (RDW) with an AUC of 0.87 and hemoglobin with an AUC of 0.81. Red blood cell, albumin, eosinophil, hematocrit, alkaline phosphatase, and mean platelet volume had fair discriminatory ability. Combinations of any two parameters performed better than did the RDW alone. CONCLUSIONS: Routine laboratory examinations may be helpful for the diagnosis of COVID‐19. Application of laboratory tests may help to optimize the use of isolation rooms for patients when they present with unexplained febrile respiratory illnesses.


title: A 55‐year‐old COVID‐19‐positive man managed with self‐regulation of high‐flow oxygen by high‐velocity nasal insufflation therapy

text: Management of critically ill coronavirus disease 2019 (COVID‐19) patients remains both risky and technically challenging. A 55‐year‐old male COVID‐19‐positive patient with obstructive sleep apnoea (OSA), diabetes, and obesity presented with cough and shortness of breath, escalating to requiring high‐flow oxygen therapy by high‐velocity nasal insufflation. The patient's flow rate and oxygen fraction remained labile throughout much of the hospitalization. This lability required frequent clinician interactions and use of personal protective equipment. The patient was alert and oriented and was instructed on the operation of the high‐flow system, specifically the adjustment of both flow rate and oxygen percentage. The patient was instructed to modify oxygen to maintain an SpO(2) (peripheral capillary oxygen saturation) target range, and flow rate to address dyspnoea as well as reduction of flow as tolerated when other staff entered the room. The patient was successfully self‐regulated for 10 days and was discharged on 2 L/min nasal cannula on day 14 of his illness.


title: Artrópodos vectores en España y sus enfermedades transmisibles

text: Resumen Diferentes aspectos relacionados con la globalización junto a la gran capacidad de los artrópodos vectores para adaptarse a un mundo cambiante propician la emergencia y reemergencia de numerosos procesos infecciosos transmitidos por los mismos. Dípteros (culícidos y flebótomos), garrapatas, pulgas y piojos, entre otros, provocan un variado espectro de enfermedades con gran importancia en Salud Pública. En esta revisión se repasan las diferentes afecciones transmitidas por artrópodos vectores, haciendo un especial hincapié en el riesgo existente para contraerlas en España en función de diferentes parámetros, como la presencia del artrópodo y la circulación o posible circulación de los agentes causales. Abstract Different aspects related to globalization together with the great capacity of the arthropod vectors to adapt to a changing world favour the emergence and reemergence of numerous infectious diseases transmitted by them. Diptera (mosquitoes and sandflies), ticks, fleas and lice, among others, cause a wide spectrum of diseases with relevance in public health. Herein, arthropod-borne disease are reviewed, with special emphasis on the existing risk to contract them in Spain according to different parameters, such as the presence of arthropod and the circulation or the possible circulation of the causative agents.


Response letter to COIVD-19 Disease: Tackling a pandemic in 21(st) Century


title: Hospital wastewater treatment scenario around the globe

text: Wastewaters generated from hospitals contain pharmaceuticals residues, pathogens, chemical reagents, radionuclide, and other harmful matter. The wastewater characteristics, quantity, and handling methods have not only variations among countries but also within a country. Some hazardous substances of hospital wastewaters (HWWs) may have a regulatory status and should be treated accordingly while others have characteristics similar to that of domestic sewage. At a global level, guidelines do exist for treatment of these HWWs. But literatures have shown that legislation has various loopholes in implementation. This chapter outlines the current status of management and handling of HWWs around the major industrial hubs of worlds in two categories of developed (the United States, United Kingdom, and Europe) and developing (India, China, Iran, and Bangladesh) countries. Various literatures and guidelines of these countries have been referred which mainly highlight different treatment scenarios and status of coverage of HWW management guidelines.


title: Zoonotic Disease Programs for Enhancing Global Health Security

text: Most infectious diseases that recently emerged in humans originated in animals. Besides close contact between animals and humans, other factors probably contribute to the cross-species transmission of infectious diseases. It is critical to establish effective mechanisms for coordination and collaboration between the animal, human, and environmental health sectors before new threats emerge by bringing the different sectors together to tackle endemic zoonotic diseases of greatest concern. Such multisectoral partnerships should begin by identifying priority zoonotic diseases for national engagement with equal input from the different sectors. Improvements in surveillance and data sharing for prioritized zoonotic diseases and enhancements of laboratory testing and joint outbreak response capacities in the human and animal health sectors will create and strengthen the mechanisms necessary to effectively detect and respond to emerging health threats, and thereby enhance global health security.


title: Avascular osteonecrosis after treatment of SARS: a 3‐year longitudinal study

text: Objective To investigate the relationship between avascular osteonecrosis (AVN) and corticosteroid treatment given to patients with severe acute respiratory syndrome (SARS). Methods Longitudinal study of 71 former SARS patients (mainly health care workers) who had been treated with corticosteroids, with an observation time of 36 months. Magnetic resonance images (MRI) and X‐rays of hips, knees, shoulders, ankles and wrists were taken as part of the post‐SARS follow‐up assessments. Results Thirty‐nine per cent developed AVN of the hips within 3–4 months after starting treatment. Two more cases of hip necrosis were seen after 1 year and another 11 cases of AVN were diagnosed after 3 years, one with hip necrosis and 10 with necrosis in other joints. In total, 58% of the cohort had developed AVN after 3 years of observation. The sole factor explaining AVN in the hip was the total dose of corticosteroids received. Conclusion The use of corticosteroids in SARS has been debated; opinions conflict about whether the immediate benefits in terms of saving lives compensate for the adverse effects, including AVN.


title: Heterogeneous pathological outcomes after experimental pH1N1 influenza infection in ferrets correlate with viral replication and host immune responses in the lung

text: The swine-origin pandemic (p) H1N1 influenza A virus causes mild upper-respiratory tract disease in most human patients. However, some patients developed severe lower-respiratory tract infections with fatal consequences, and the cause of these infections remain unknown. Recently, it has been suggested that different populations have different degrees of susceptibility to pH1N1 strains due to host genetic variations that are associated with inappropriate immune responses against viral genetic characteristics. Here, we tested whether the pathologic patterns of influenza strains that produce different disease outcomes in humans could be reproduced in a ferret model. Our results revealed that the severities of infection did not correspond to particular viral isolate and were not associated with the clinical phenotypes of the corresponding patients. Severe pathological outcomes were associated with higher viral replication, especially in alveolar areas, and with an exacerbated innate cellular immune response that was characterised by substantial phagocytic and cytotoxic cell migration into the lungs. Moreover, detrimental innate cellular responses were linked to the up-regulation of several proinflammatory cytokines and chemokines and the down-regulation of IFNα in the lungs. Additionally, severe lung lesions were associated with greater up-regulations of pro-apoptotic markers and higher levels of apoptotic neutrophils and macrophages. In conclusion, this study confirmed that the clinicopathological outcomes of pH1N1 infection in ferrets were not only due to viral replication abilities but also depended on the hosts’ capacities to mount efficient immune responses to control viral infection of the lung. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-014-0085-8) contains supplementary material, which is available to authorized users.


title: Overview of Infectious Disease Surveillance System in Japan, 1999-2005

text: BACKGROUND: In 1999 the Communicable Disease Prevention Law of Japan was completely revised into the "New" Infectious Disease Control Law, which reiterated the importance of surveillance and information dissemination and re-organized the surveillance system. This paper is an attempt to illustrate the potential impact of the new surveillance system through a description of the existing surveillance system and data before and after the revision. METHODS: After a historical review of surveillance system in Japan, the current surveillance system is described. Data sets of actual case numbers reported and incidence rate per 1,000,000 population are compared before and after the revision. RESULTS: Comparison of the data between the 2 periods revealed that most of the diseases have had declining trends after the new law was enacted with several exceptions. However, although no major break in continuity is observed in seriously perceived disease, in milder diseases there are striking gaps between the numbers reported in the mandatory and sentinel reporting framework. Sentinel reporting framework maintained the continuity of data without major gaps. CONCLUSIONS: From this perspective, the new surveillance system with two different frameworks of mandatory reporting for severe diseases and sentinel reporting for milder diseases seems to be working well. But continuous efforts should be made for evaluation and improvement of surveillance system and risk communication through the research on data analysis and effective communication method.


title: Proteomic analyser with applications to diagnostics and vaccines

text: Abstract This paper describes a method for proteomic analysis with applications to diagnostics and vaccines. A panel of N (⪢1) reagents called X(j), with j=1 to N, is used. The binding strength of each of the X(j) reagents to each other is measured, for example by an ELISA assay, giving an N×N matrix K . The matrix K is used to define another set of N reagents called Y(j), with j=1 to N, each of which is a linear combination of the X(j) reagents and each of which is tailored to be complementary to one of the X(j) reagents. Each of the N pairs of reagents X(j) and Y(j) defines an axis in an N-dimensional shape space. The definition of these axes facilitates proteomic analysis of diverse biological samples, for example, mixtures of proteins such as serum samples or T cell extracts. A method for defining and measuring similarity between pairs of biological samples and between sets of biological samples in the context of the set of N reagent pairs is described. This leads to methods for using the N reagent pairs in the diagnosis of diseases and in the formulation of preventive and therapeutic vaccines. The relationship of this work to previous research on shape space is discussed.


title: Bovine adenovirus-3 as a vaccine delivery vehicle

text: Abstract The use of vaccines is an effective and relatively inexpensive means of controlling infectious diseases, which cause heavy economic losses to the livestock industry through animal loss, decreased productivity, treatment expenses and decreased carcass quality. However, some vaccines produced by conventional means are imperfect in many respects including virulence, safety and efficacy. Moreover, there are no vaccines for some animal diseases. Although genetic engineering has provided new ways of producing effective vaccines, the cost of production for veterinary use is a critical criterion for selecting the method of production and delivery of vaccines. The cost effective production and intrinsic ability to enter cells has made adenovirus vectors a highly efficient tool for delivery of vaccine antigens. Moreover, adenoviruses induce both humoral and cellular immune responses to expressed vaccine antigens. Since nonhuman adenoviruses are species specific, the development of animal specific adenoviruses as vaccine delivery vectors is being evaluated. This review summarizes the work related to the development of bovine adenovirus-3 as a vaccine delivery vehicle in animals, particularly cattle.


title: Gene regulation: translational initiation by internal ribosome binding

text: Abstract During the past year, several examples of cellular mRNAs have been described in which translational initiation occurs by internal ribosome binding, a mechanism hitherto thought to be restricted to picornaviral RNAs. New insights into the molecular mechanism of internal ribosome entry have been provided by the structural and functional analyses of both the internal ribosome entry sites and the protein factors that stimulate translation mediated by these elements.


title: Porcine Epidemic Diarrhea Virus and the Host Innate Immune Response

text: Porcine epidemic diarrhea virus (PEDV), a swine enteropathogenic coronavirus (CoV), is the causative agent of porcine epidemic diarrhea (PED). PED causes lethal watery diarrhea in piglets, which has led to substantial economic losses in many countries and is a great threat to the global swine industry. Interferons (IFNs) are major cytokines involved in host innate immune defense, which induce the expression of a broad range of antiviral effectors that help host to control and antagonize viral infections. PEDV infection does not elicit a robust IFN response, and some of the mechanisms used by the virus to counteract the host innate immune response have been unraveled. PEDV evades the host innate immune response by two main strategies including: 1) encoding IFN antagonists to disrupt innate immune pathway, and 2) hiding its viral RNA to avoid the exposure of viral RNA to immune sensors. This review highlights the immune evasion mechanisms employed by PEDV, which provides insights for the better understanding of PEDV-host interactions and developing effective vaccines and antivirals against CoVs.


title: Chapter 3 Measuring, Monitoring, and Evaluating the Health of a Population

text: Abstract Public health depends on information derived from monitoring population health status to identify community health problems, and to diagnose and investigate health problems and hazards in the community. These depend on vital statistics and disease reporting systems, including for non-communicable diseases, injuries, risk factors, health care resources, utilization of resources, and special disease registries such as for cancer, birth defects, and many others. Information technology and computerization allow data systems to be linked to assess the impact of health conditions and utilization of services providing vital information for epidemiological and economic analyses for policy development. Epidemiology and its associated quantitative disciplines of biostatistics and demography are augmented by social and behavioral qualitative research methods. The disciplines of health systems research provide evidence from population health monitoring crucial to policy and priority determination. This introductory chapter is augmented in subsequent chapters, and by specialized courses in public health education programs.


Ventilating multiple patients on a single ventilator: Statement from the French Society of Anaesthesia and Intensive Care Medicine (SFAR)


title: Complete Genome Characterization of Korean Porcine Deltacoronavirus Strain KOR/KNU14-04/2014

text: In April 2014, porcine deltacoronavirus (PDCoV) was first identified in feces from diarrheic piglets in South Korea and found to be closely related to other PDCoV strains. The complete genome of the Korean PDCoV strain, KOR/KNU14-04/2014, was sequenced and analyzed to characterize PDCoV circulating in South Korea.


Recent patent applications in antiviral vaccines


title: Competitive Fitness in Coronaviruses Is Not Correlated with Size or Number of Double-Membrane Vesicles under Reduced-Temperature Growth Conditions

text: Positive-stranded viruses synthesize their RNA in membrane-bound organelles, but it is not clear how this benefits the virus or the host. For coronaviruses, these organelles take the form of double-membrane vesicles (DMVs) interconnected by a convoluted membrane network. We used electron microscopy to identify murine coronaviruses with mutations in nsp3 and nsp14 that replicated normally while producing only half the normal amount of DMVs under low-temperature growth conditions. Viruses with mutations in nsp5 and nsp16 produced small DMVs but also replicated normally. Quantitative reverse transcriptase PCR (RT-PCR) confirmed that the most strongly affected of these, the nsp3 mutant, produced more viral RNA than wild-type virus. Competitive growth assays were carried out in both continuous and primary cells to better understand the contribution of DMVs to viral fitness. Surprisingly, several viruses that produced fewer or smaller DMVs showed a higher fitness than wild-type virus at the reduced temperature, suggesting that larger and more numerous DMVs do not necessarily confer a competitive advantage in primary or continuous cell culture. For the first time, this directly demonstrates that replication and organelle formation may be, at least in part, studied separately during infection with positive-stranded RNA virus.


title: Dangerous state of denial

text: Despite the warning shots of SARS and last year's Asian outbreak of avian flu, governments are still not doing enough to monitor and prepare for the next viral pandemic. This inaction is scandalous.


Viral Genomics and Bioinformatics


title: Detection of Coronaviruses in Bats of Various Species in Italy

text: Bats are natural reservoirs for many mammalian coronaviruses, which have received renewed interest after the discovery of the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) CoV in humans. This study describes the identification and molecular characterization of alphacoronaviruses and betacoronaviruses in bats in Italy, from 2010 to 2012. Sixty-nine faecal samples and 126 carcasses were tested using pan-coronavirus RT-PCR. Coronavirus RNAs were detected in seven faecal samples and nine carcasses. A phylogenetic analysis of RNA-dependent RNA polymerase sequence fragments aided in identifying two alphacoronaviruses from Kuhl’s pipistrelle (Pipistrellus kuhlii), three clade 2b betacoronaviruses from lesser horseshoe bats (Rhinolophus hipposideros), and 10 clade 2c betacoronaviruses from Kuhl’s pipistrelle, common noctule (Nyctalus noctula), and Savi’s pipistrelle (Hypsugo savii). This study fills a substantive gap in the knowledge on bat-CoV ecology in Italy, and extends the current knowledge on clade 2c betacoronaviruses with new sequences obtained from bats that have not been previously described as hosts of these viruses.


title: The Impact of COVID-19 related Measures on the Solar Resource in Areas with High Levels of Air Pollution

text: Abstract: Restrictions enacted to reduce the spreading of COVID-19 have resulted in notably clearer skies around the world. In this study, we confirm that reduced levels of air pollution correlate with unusually high levels of clear sky insolation in Delhi, India. Restrictions here were announced on March 19th, with the Nation going into lockdown on March 24th. Comparing insolation data before and after these dates with insolation from previous years (2017 to 2019) we observe an 8.3±1.7 % higher irradiance than usual in late March and a 5.9±1.6 % higher one in April, while we find no significant differences to values from previous years in February or early March. Using results from a previous study, we calculated the expected increase in insolation based on measured PM2.5 concentration levels. Measurements and calculations agree within confidence intervals, suggesting that reduced pollution levels are a major cause for the observed increase in insolation.


title: Ocular abnormalities associated with hypovitaminosis A in Hanwoo calves: a report of two cases

text: This study reports on two Hanwoo (a native Korean breed of cattle) calves, a 3- and 6-month-old presenting with diarrhea, anorexia and blindness. Ophthalmoscopic examination revealed bilateral papilledema in both calves. Reverse-transcription polymerase chain reaction tests for bovine viral diarrhea virus, rotavirus and coronavirus were all negative. The levels of serum vitamin A in the two affected calves were 0.317 µg/dl and 0.481 µg/dl, respectively. These values are much lower than the normal vitamin A levels; therefore, the calves were diagnosed with hypovitaminosis A.


title: Molecular Pathogenesis of Secondary Bacterial Infection Associated to Viral Infections Including SARS-CoV-2

text: Secondary bacterial infections are commonly associated with prior or concomitant respiratory viral infections. Viral infections damage respiratory airways and simultaneously defects both innate and acquired immune response that provides a favorable environment for bacterial growth, adherence, and facilitates invasion into healthy sites of the respiratory tract. Understanding the molecular mechanism of viral-induced secondary bacterial infections will provide us a chance to develop novel and effective therapeutic approaches for disease prevention. The present study describes details about the secondary bacterial infection during viral infections and their immunological changes.The outcome of discussion avails an opportunity to understand possible secondary bacterial infections associated with novel SARS-CoV-2, presently causing pandemic outbreak COVID-19.


title: Genomic and antigenic characterization of bovine parainfluenza-3 viruses in the United States including modified live virus vaccine (MLV) strains and field strains from cattle

text: Abstract This study investigated the genetic and antigenic characterization of parainfluenza-3 virus (PI3V) of cattle. Using molecular tests including real time PCR and viral genome sequencing, PI3V strains could be separated into PI3V types, including PI3V A, PI3V B, and PI3V C. Isolates from cattle with bovine respiratory disease clinical signs and commercial vaccines in the U.S. with MLV PI3V were typed using these molecular tests. All the MLV vaccine strains tested were PI3V A. In most cases PI3V field strains from calves receiving MLV vaccines were types heterologous to the vaccine type A. Also antigenic differences were noted as PI3V C strains had lower antibody levels than PI3V A in serums from cattle receiving MLV PI3V A vaccines. This study further demonstrates there is genetic variability of U.S. PI3V strains and also antigenic variability. In addition, isolates from cattle with BRD signs and receiving MLV vaccines may have heterologous types to the vaccines, and molecular tests should be performed to differentiate field from vaccine strains. Potentially the efficacy of current PI3V A vaccines should be evaluated with other types such a PI3V B and PI3V C.


title: WHO led the digital transformation of your company? A reflection of IT related challenges during the pandemic

text: In this paper we reflect on a number of IT related challenges during the COVID19 pandemic, primarily from a CIO and IT professionals perspective. We consider three time periods, namely the period before the pandemic, the response to the pandemic and the period after it. For each period we discuss the key challenges that practitioners faced and outline important areas to consider for the future. Hopefully, the lessons learnt and the experiences gained will positively inform future academic research and practice.


title: A Methodology for Determining Which Diseases Warrant Care in a High-Level Containment Care Unit †

text: Although the concept of high-level containment care (HLCC or ‘biocontainment’), dates back to 1969, the 2014–2016 outbreak of Ebola virus disease (EVD) brought with it a renewed emphasis on the use of specialized HLCC units in the care of patients with EVD. Employment of these units in the United States and Western Europe resulted in a significant decrease in mortality compared to traditional management in field settings. Moreover, this employment appeared to significantly lessen the risk of nosocomial transmission of disease; no secondary cases occurred among healthcare workers in these units. While many now accept the wisdom of utilizing HLCC units and principles in the management of EVD (and, presumably, of other transmissible and highly hazardous viral hemorrhagic fevers, such as those caused by Marburg and Lassa viruses), no consensus exists regarding additional diseases that might warrant HLCC. We propose here a construct designed to make such determinations for existing and newly discovered diseases. The construct examines infectivity (as measured by the infectious dose needed to infect 50% of a given population (ID(50))), communicability (as measured by the reproductive number (R(0))), and hazard (as measured by morbidity and mortality). Diseases fulfilling all three criteria (i.e., those that are highly infectious, communicable, and highly hazardous) are considered candidates for HLCC management if they also meet a fourth criterion, namely that they lack effective and available licensed countermeasures.


title: High Viral Load of Human Bocavirus Correlates with Duration of Wheezing in Children with Severe Lower Respiratory Tract Infection

text: BACKGROUND: Human bocavirus (HBoV) is a newly discovered parvovirus and increasing evidences are available to support its role as an etiologic agent in lower respiratory tract infection (LRTI). The objective of this study is to assess the impact of HBoV viral load on clinical characteristics in children who were HBoV positive and suffered severe LRTI. METHODS: Lower respiratory tract aspirates from 186 hospitalized children with severe LRTI were obtained by bronchoscopy. HBoVs were detected by real-time PCR and other 10 infectious agents were examined using PCR and/or direct fluorescent assay. RESULTS: Thirty-one patients (24.6%) were tested positive for HBoV in the respiratory tract aspirates. Fifteen samples had a high viral load (>10(4) copies/mL) and the other sixteen samples had a low viral load (<10(4) copies/mL). The duration of presented wheezing and hospitalization was longer in children with high viral load of HBoV than that in children with low viral load. The days of wheezing showed a correlation with viral load of HBoV. CONCLUSION: We confirmed that HBoV was frequently detected in patients with severe LRTI. Wheezing was one of the most common symptoms presented by patients with positive HBoV. A high HBoV viral load could be an etiologic agent for LRTI, which led to more severe lower respiratory tract symptom, longer duration of wheezing and hospitalization.


title: Frequent detection of human rhinoviruses, paramyxoviruses, coronaviruses, and bocavirus during acute respiratory tract infections

text: Viruses are the major cause of pediatric acute respiratory tract infection (ARTI) and yet many suspected cases of infection remain uncharacterized. We employed 17 PCR assays and retrospectively screened 315 specimens selected by season from a predominantly pediatric hospital‐based population. Before the Brisbane respiratory virus research study commenced, one or more predominantly viral pathogens had been detected in 15.2% (n = 48) of all specimens. The Brisbane study made an additional 206 viral detections, resulting in the identification of a microbe in 67.0% of specimens. After our study, the majority of microbes detected were RNA viruses (89.9%). Overall, human rhinoviruses (HRVs) were the most frequently identified target (n = 140) followed by human adenoviruses (HAdVs; n = 25), human metapneumovirus (HMPV; n = 18), human bocavirus (HBoV; n = 15), human respiratory syncytial virus (HRSV; n = 12), human coronaviruses (HCoVs; n = 11), and human herpesvirus‐6 (n = 11). HRVs were the sole microbe detected in 37.8% (n = 31) of patients with suspected lower respiratory tract infection (LRTI). Genotyping of the HRV VP4/VP2 region resulted in a proposed subdivision of HRV type A into sublineages A1 and A2. Most of the genotyped HAdV strains were found to be type C. This study describes the high microbial burden imposed by HRVs, HMPV, HRSV, HCoVs, and the newly identified virus, HBoV on a predominantly paediatric hospital population with suspected acute respiratory tract infections and proposes a new formulation of viral targets for future diagnostic research studies. J. Med. Virol. 78:1232–1240, 2006. © 2006 Wiley‐Liss, Inc.


title: Rheum australe, an endangered high-value medicinal herb of North Western Himalayas: a review of its botany, ethnomedical uses, phytochemistry and pharmacology

text: Rheum australe (Himalayan Rhubarb) is a multipurpose, endemic and endangered medicinal herb of North Western Himalayas. It finds extensive use as a medicinal herb since antiquity in different traditional systems of medicine to cure a wide range of ailments related to the circulatory, digestive, endocrine, respiratory and skeletal systems as well as to treat various infectious diseases. The remedying properties of this plant species are ascribed to a set of diverse bioactive secondary metabolite constituents, particularly anthraquinones (emodin, chrysophanol, physcion, aloe-emodin and rhein) and stilbenoids (piceatannol, resveratrol), besides dietary flavonoids known for their putative health benefits. Recent studies demonstrate the pharmacological efficacy of some of these metabolites and/or their derivatives as lead molecules for the treatment of various human diseases. Present review comprehensively covers the literature available on R. australe from 1980 to early 2018. The review provides up-to-date information available on its botany for easy identification of the plant, and origin and historical perspective detailing its trade and commerce. Distribution, therapeutic potential in relation to traditional uses and pharmacology, phytochemistry and general biosynthesis of major chemical constituents are also discussed. Additionally, efficient and reproducible in vitro propagation studies holding vital significance in preserving the natural germplasm of the plant and for its industrial exploitation have also been highlighted. The review presents a detailed perspective for future studies to conserve and sustainably make use of this endangered plant species at a commercial scale.


title: Anaesthetic Considerations for Rationalizing Drug Use in the Operating Theatre: Strategies in a Singapore Hospital During COVID-19

text: COVID-19 patients in the critical care unit tend to have prolonged hospital stay requiring high doses of sedation and paralysis to treat acute respiratory distress syndrome, resulting in a shortage of these drugs. In our hospital, we have instituted strategies to rationalise drug and oxygen usage. This includes prioritising time-sensitive elective cases, reducing overall elective case load, favouring opioid-reduction strategies and usage of alternative anaesthetic agents not commonly used in ICU. Both intensive care physicians and anaesthesiologists have to cooperate on drug conservation as similar drugs are used in elective operating lists as in the ICU. Patient safety is of utmost importance and we should keep in mind some pitfalls and ethical concerns of these alternative strategies.


title: On the Treatment of Airline Travelers in Mathematical Models

text: The global spread of infectious diseases is facilitated by the ability of infected humans to travel thousands of miles in short time spans, rapidly transporting pathogens to distant locations. Mathematical models of the actual and potential spread of specific pathogens can assist public health planning in the case of such an event. Models should generally be parsimonious, but must consider all potentially important components of the system to the greatest extent possible. We demonstrate and discuss important assumptions relative to the parameterization and structural treatment of airline travel in mathematical models. Among other findings, we show that the most common structural treatment of travelers leads to underestimation of the speed of spread and that connecting travel is critical to a realistic spread pattern. Models involving travelers can be improved significantly by relatively simple structural changes but also may require further attention to details of parameterization.


title: Why Italian ENT physicians should be aware of SARS-CoV-2

text: Perchè gli specialisti ORL italiani devono stare in guardia contro SARS-CoV-2.


title: ELISA for human serum leucine-rich alpha-2-glycoprotein-1 employing cytochrome c as the capturing ligand

text: Abstract Leucine-rich alpha-2-glycoprotein-1 (LRG) is a serum glycoprotein of unknown function that has shown promise based on qualitative assessments as a biomarker for certain diseases including microbial infections and cancer. However, the lack of a quantitative assay for LRG has limited its application. Here an indirect enzyme-linked immunosorbent assay (ELISA) for quantifying LRG in human serum is described in which cytochrome c is employed as the capturing ligand and a monoclonal antibody specific for LRG is used to detect the captured glycoprotein. Application of this assay in quantifying LRG in various patients' sera is demonstrated. The concentration of LRG in sera of control subjects as determined by this assay is approximately 50 μg/ml. Consistent with expectations from published reports, LRG was found to be significantly elevated in the sera of some patients with a bacterial infection (toxic shock syndrome, TSS). LRG was only slightly elevated in patients infected with the human immunodeficiency virus as compared to uninfected control subjects, while normal levels of LRG were observed in patients with non-infectious diseases (inflammatory arthritis and neurological disorders, primarily Parkinson's disease). Although LRG and C-reactive protein (CRP) are both produced by the liver and are classified as acute-phase proteins, there was no significant correlation between the levels of LRG and CRP in the sera of the patients. Thus, LRG and CRP measurements are non-redundant and indicate different physiological contexts. The ELISA described in this report should be useful to further assess serum LRG as a biomarker for clinical diagnostics.


title: Carbohydrate Antigen Microarrays

text: This chapter describes one of my laboratory’s working protocols for carbohydrate-based microarrays. Using a standard microarray spotter, we print carbohydrate antigens directly on the nitrocellulose-coated bioarray substrates. Because these substrates support noncovalent immobilization of many spotted antigens, in general no chemical modification of the antigen is needed for microarray production. Thus, this bioarray platform is technically simple and applicable for high-throughput construction of carbohydrate antigen microarrays. A number of nitrocellulose-coated glass slides with different technical characteristics are commercially available. Given the structural diversity of carbohydrate antigens, examining each antigen preparation to determine the efficacy of its immobilization in a given type of substrate and the surface display of the desired glycoepitopes in a microarray assay is essential.


title: Prevalence and risk factors of feline leukaemia virus and feline immunodeficiency virus in peninsular Malaysia

text: BACKGROUND: Feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) are major causes of morbidity and mortality in domestic and wild felids. Despite the clinical importance of feline retroviruses and the growing interest in cats as pets, information about FeLV and FIV in Malaysia is presently insufficient to properly advise veterinarians and pet owners. A cross-sectional study was carried out from January 2010 to December 2010 to determine the prevalence and risk factors associated with FeLV and FIV among domestic cats in peninsular Malaysia. Plasma samples were harvested from the blood of 368 domestic cats and screened for evidence of FeLV p27 antigen and FIV antibodies, using an immunochromatographic kit. Additionally, data on cat demographics and health were collected using a structured questionnaire, and were evaluated as potential risk factors for FeLV or FIV status. RESULTS: Of the 368 cats that were evaluated in this study, 12.2% (45/368; 95% CI = 8.88 - 15.58) were positive for FeLV p27 antigen, 31.3%, (115/368; 95% CI = 26.51 - 35.99) were seropositive to FIV antibodies, and 4.3% (16/368; 95% CI = 2.27 - 6.43) had evidence of both viruses. Factors found to significantly increase the risk for FeLV seropositivity include sex, age, behaviour, sickness, and living in a multi-cat household. Seropositive response to FIV was significantly associated with sex, neuter status, age, behaviour, and health status. CONCLUSIONS: The present study indicates that FeLV and FIV are common among domestic cats in peninsular Malaysia, and that factors related to cat demographics and health such as age, sex, behaviour, health status and type of household are important predictors for seropositive status to FeLV or FIV in peninsular Malaysia. High prevalence of FeLV or FIV observed in our study is of concern, in view of the immunosuppressive potentials of the two pathogens. Specific measures for control and prevention such as screening and routine vaccination are needed to ensure that FeLV and FIV are controlled in the cat population of peninsular Malaysia.


title: Nucleic acid-based diagnostics for infectious diseases in public health affairs

text: Infectious diseases, mostly caused by bacteria and viruses but also a result of fungal and parasitic infection, have been one of the most important public health concerns throughout human history. The first step in combating these pathogens is to get a timely and accurate diagnosis at an affordable cost. Many kinds of diagnostics have been developed, such as pathogen culture, biochemical tests and serological tests, to help detect and fight against the causative agents of diseases. However, these diagnostic tests are generally unsatisfactory because they are not particularly sensitive and specific and are unable to deliver speedy results. Nucleic acid-based diagnostics, detecting pathogens through the identification of their genomic sequences, have shown promise to overcome the above limitations and become more widely adopted in clinical tests. Here we review some of the most popular nucleic acid-based diagnostics and focus on their adaptability and applicability to routine clinical usage. We also compare and contrast the characteristics of different types of nucleic acid-based diagnostics.


The effect of Severe Acute Respiratory Syndrome on a hospital obstetrics and gynaecology service


title: Numerical investigation of airborne contaminant transport under different vortex structures in the aircraft cabin

text: Abstract Airborne contaminants such as pathogens, odors and CO2 released from an individual passenger could spread via air flow in an aircraft cabin and make other passengers unhealthy and uncomfortable. In this study, we introduced the airflow vortex structure to analyze how airflow patterns affected contaminant transport in an aircraft cabin. Experimental data regarding airflow patterns were used to validate a computational fluid dynamics (CFD) model. Using the validated CFD model, we investigated the effects of the airflow vortex structure on contaminant transmission based on quantitative analysis. It was found that the contaminant source located in a vorticity-dominated region was more likely to be “locked” in the vortex, resulting in higher 62% higher average concentration and 14% longer residual time than that when the source was on a deformation dominated location. The contaminant concentrations also differed between the front and rear parts of the cabin because of different airflow structures. Contaminant released close to the heated manikin face was likely to be transported backward according to its distribution mean position. Based on these results, the air flow patterns inside aircraft cabins can potentially be improved to better control the spread of airborne contaminant.


title: The murine coronavirus as a model of trafficking and assembly of viral proteins in neural tissue

text: Abstract The replication of JHM, a murine coronavirus, provides a useful model of the assembly and dissemination of viral components in neuronal cells. Involvement of microtubules in virus trafficking is an important feature which may explain dissemination of the infection from primary cell targets at olfactory, hippocampal and cerebellar sites within the central nervous system, resulting in severe neuropathies.


title: MAp19, the alternative splice product of the MASP2 gene

text: Abstract The lectin pathway of complement is a central part of innate immunity, but as a powerful inducer of inflammation it needs to be tightly controlled. The MASP2 gene encodes two proteins, MASP-2 and MAp19. MASP-2 is the serine protease responsible for lectin pathway activation. The smaller alternative splice product, MAp19, lacks a catalytic domain but retains two of three domains involved in association with the pattern-recognition molecules (PRMs): mannan-binding lectin (MBL), H-ficolin, L-ficolin and M-ficolin. MAp19 reportedly acts as a competitive inhibitor of MASP-2-mediated complement activation. In light of a ten times lower affinity of MAp19, versus MASP-2, for association with the PRMs, much higher serum concentrations of MAp19 than MASP-2 would be required for MAp19 to exert such an inhibitory activity. Just four amino acid residues distinguish MAp19 from MASP-2, and these are conserved between man, mouse and rat. Nonetheless we generated monoclonal rat anti-MAp19 antibodies and established a quantitative assay. We found the concentration of MAp19 in serum to be 217ng/ml, i.e., 11nM, comparable to the 7nM of MASP-2. In serum all MASP-2, but only a minor fraction of MAp19, was associated with PRMs. In contrast to previous reports we found that MAp19 could not compete with MASP-2 for binding to MBL, nor could it inhibit MASP-2-mediated complement activation. Immunohistochemical analyses combined with qRT-PCR revealed that both MAp19 and MASP-2 were mainly expressed in hepatocytes. High levels of MAp19 were found in urine, where MASP-2 was absent.


Family‐centred care during a pandemic: The hidden impact of restricting family visits


title: Developing and testing a measure of COVID-19 Organizational Support of Healthcare Workers – Results from Peru, Ecuador, and Bolivia

text: During the COVID-19 pandemic, healthcare workers are facing high workloads with resource constraints and risk of virus exposure, and healthcare organizations need to support their healthcare workers to reduce their anxiety. Based on a recent 8-point framework of COVID-19 specific organization support, we devised a measure of COVID-19 Organizational Support (COVID-OS). We tested the new measure with 712 healthcare workers in Bolivia, Ecuador, and Peru and found the new measure formed three factors to predict healthcare workers’ anxiety and life satisfaction during the COVID-19 pandemic. We call for further studies to test COVID-OS in other countries and settings.