title: [Neutrophil to lymphocyte ratio as a prognostic marker in COVID-19].

text: In December 2019, a new coronavirus was identified as the cause of an outbreak of pneumonia and respiratory distress in Wuhan, China. It was declared pandemic in March 2020. It is important to know predictors of poor outcomes in order to optimize the strategies of care in newly diagnosed patients. The neutrophil to lymphocyte ratio (NLR) constitutes a novel prognostic marker for oncologic, cardiovascular and infectious diseases. We aimed to assess its prognostic value in COVID-19. We evaluated a retrospective cohort of 131 patients with COVID-19 from March to May 2020. We analyzed the association of an NLR = 3 with severe COVID-19, baseline characteristics of the population and the mortality rate. The median age was 52 years, and 54% were men. 21 patients presented criteria of severe disease, 9 of them required mechanical ventilation. NLR = 3 was found in 81% (18/21) of severe patients and in 33% (36/110) of mild patients (OR = 8.74. 95% CI 2.74-27.86; p < 0.001). Age and hypertension were associated with severe disease. A mortality rate of 7% (9) was obtained. Seven of the 9 patients who died presented NLR = 3, with a significant association between mortality and NLR = 3 (p = 0.03). NLR could be used in conjunction with other predictors, as an early prognostic marker in COVID-19 given its accessibility and low cost.


title: Impaired heart contractility in Apelin gene-deficient mice associated with aging and pressure overload.

text: Apelin constitutes a novel endogenous peptide system suggested to be involved in a broad range of physiological functions, including cardiovascular function, heart development, control of fluid homeostasis, and obesity. Apelin is also a catalytic substrate for angiotensin-converting enzyme 2, the key severe acute respiratory syndrome receptor. The in vivo physiological role of Apelin is still elusive. Here we report the generation of Apelin gene-targeted mice. Apelin mutant mice are viable and fertile, appear healthy, and exhibit normal body weight, water and food intake, heart rates, and heart morphology. Intriguingly, aged Apelin knockout mice developed progressive impairment of cardiac contractility associated with systolic dysfunction in the absence of histological abnormalities. We also report that pressure overload induces upregulation of Apelin expression in the heart. Importantly, in pressure overload-induced heart failure, loss of Apelin did not significantly affect the hypertrophy response, but Apelin mutant mice developed progressive heart failure. Global gene expression arrays and hierarchical clustering of differentially expressed genes in hearts of banded Apelin(-/y) and Apelin(+/y) mice showed concerted upregulation of genes involved in extracellular matrix remodeling and muscle contraction. These genetic data show that the endogenous peptide Apelin is crucial to maintain cardiac contractility in pressure overload and aging.


title: Medicine in the 21st century: towards a Darwinian medical epistemology.

text: In this review we reflect upon the new science of Darwinian medicine. It is a tenet of modern biology that evolutionary theory as proposed by Charles Darwin and further refined via the new synthesis is the common thread that ties all of biological inquiry into a coherent whole. This review aims at making clear how evolution by natural selection is relevant to medicine. A set of pertinent examples linking Homo sapiens sapiens' present disease conditions to its evolution during the Late Pleistocene and Holocene epochs are discussed. The review concludes with observations as to the epistemological value of evolutionary theory as a heuristic tool for articulating a medical paradigm in accord with modern biology.


title: Responding to the Potential of Ebola Virus Disease (EVD) Importation into Malaysia.

text: The current Ebola outbreak, which is the first to affect West African countries, has been declared to have met the conditions for a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO). Thus, the Ministry of Health (MOH) of Malaysia has taken steps to strengthen and enhanced the five core components of preparedness and response to mitigate the outbreak. The National Crisis Preparedness and Response Centre (CPRC) commands, controls and coordinates the preparedness and response plans for disasters, outbreaks, crises and emergencies (DOCE) related to health in a centralised way. Through standardised case definition and mandatory notification of Ebola by public and private practitioners, surveillance of Ebola is made possible. Government hospitals and laboratories have been identified to manage and diagnose Ebola virus infections, and medical staff members have been trained to handle an Ebola outbreak, with emphasis on strict infection prevention and control practices. Monitoring of the points of entry, focusing on travellers and students visiting or coming from West African countries is made possible by interagency collaborations. To alleviate the public's anxiety, effective risk communications are being delivered through various channels. With experience in past outbreak control, the MOH's preparedness and response plans are in place to abate an Ebola outbreak.


title: Daily Situation Report on Coronavirus disease (COVID-19) in Iran; March 14, 2020.

text: After detection of the first confirmed cases of COVID-19 in Iran, the National Committee on COVID-19 Epidemiology in Ministry of Health and Medical Education was established. This Committee is official source of gathering, analyzing, and reporting the COVID-19 data in Iran. The data of all sources in the country including, medical care monitoring center (MCMC), Hospitals' Information Systems (HIS), Laboratory portal, the data of the center for communicable disease control (MOH), as well as the data from community health centers are integrated and used in this regards. This factsheet contain daily situation report on coronavirus disease (covid-19) in Iran; March 14, 2020.


title: [When to ask a microbiological diagnostic test in pneumonia and how to interpret the results].

text: Pneumonia is a leading cause of death in adults in the industrialised countries and in the rest of the world in infants. Most of the time the pathogens stay unkown and the current recommendations for the treatment of pneumonia are mainly based on a severity score to adapt the treatement to the risk. Nonethless new pathogens have recently been identified, coronavirus for SRASS, H5N1 for avian Flu, N1N1 for pandemic Flu, 35 years after the identification of Legionella pneumophila. These exemples stress the necessity to do and continue to identify pathogens in these clinical situations. Those last years new diagnostic tests have been elaborated: antigen detection in urines or in nasopharyngeal samples, molecular methods allowing to look at one or several pathogens at the same time on a single sample (Multiplex) with an increased sensitivity with regard to the more classical methods. Indirect methods have been developed to quantify inflammation in correlation with a bacterial or not infection. All these tests contribute to a better understanding but can and/or could be used in new algorithms to treat patients with pneumonia.


title: Canine distemper in terrestrial carnivores: a review.

text: Canine distemper virus is a member of the genus Morbillivirus in the family Paramyxoviridae. Canine distemper has been recorded in domestic dogs for centuries. It is now recognized as a worldwide problem of carnivores and has the second highest fatality rate of any infectious disease, after rabies, in domestic dogs. The importance of this disease in nondomestic animals has become evident with vaccine-induced infections in a variety of species and large-scale epidemics in captive and free-ranging felids. To date, canine distemper has been reported in all families of terrestrial carnivores: Canidae, Felidae, Hyaenidae, Mustelidae, Procyonidae, Ursidae, and Viverridae. Veterinarians, including those working with nondomestic carnivores, should be familiar with the clinical signs, diagnosis, and clinical management of this disease.


China is still not open enough about SARS, says WHO.


title: Feline infectious peritonitis.

text: Feline infectious peritonitis (FIP) frequently results in death in cats. It is caused by a mutated, highly contagious coronavirus, and it is more common in indoor cats in multicat households. A complex interaction between the coronavirus and the feline immune system causes disseminated vasculitis, which is the hallmark of FIP. New tests are being developed, but the antemortem diagnosis of FIP continues to be difficult and frustrating. Current treatments are crude and involve supportive care and immunosuppression. Minimizing exposure is the best method of preventing infection.


title: Paediatric emergency department staff perceptions of infection control measures against severe acute respiratory syndrome.

text: OBJECTIVES To determine paediatric emergency department (ED) staff perceptions of the effectiveness and practice of infection control measures against a novel virulent pathogen. METHODS All medical staff of the paediatric ED in a tertiary medical centre completed a written questionnaire near the onset of the severe acute respiratory syndrome (SARS) outbreak. Level of concern regarding SARS, and perceptions of effectiveness and use of infection control measures were assessed on a 5 point scale. Statistical analysis was performed using chi2 test and one way analysis of variance with significance at p<0.05. RESULTS Response rate was 97% (116/120). All scores were given out of 5 possible points. Using isolation rooms (mean score 4.6), wearing a mask when examining patients (4.5), and handwashing (4.5) were considered most effective. Staff physicians reported handwashing more than nurses and trainees (4.9 v 4.5 and 4.5, respectively; p<0.05) while other measures were reported equally. Respondents considering SARS a high public health threat reported higher compliance with handwashing (4.8 v 4.4), always wearing a mask (3.9 vs 3.2) and gloves (3.6 v 2.9) in the ED (p<0.05), but not eye protection (3.4 v 3.0), gown use (4.9 v 4.7), or wearing a mask when examining patients (5.0 v 4.8). Staff who considered combined infection control measures effective in protecting patients and healthcare workers did not report increased compliance. CONCLUSIONS Eye protection was perceived as only moderately effective in protecting against the spread of SARS, and reported compliance was relatively poor among ED staff. Concern of SARS as a public health threat rather than perceived effectiveness of infection control measures appears to have a greater impact on compliance.


title: Genomic features of intertypic recombinant sabin poliovirus strains excreted by primary vaccinees.

text: The trivalent oral poliomyelitis vaccine (OPV) contains three different poliovirus serotypes. It use therefore creates particularly favorable conditions for mixed infection of gut cells, and indeed intertypic vaccine-derived recombinants (VdRec) have been frequently found in patients with vaccine-associated paralytic poliomyelitis. Nevertheless, there have not been extensive searches for VdRec in healthy vaccinees following immunization with OPV. To determine the incidence of VdRec and their excretion kinetics in primary vaccinees, and to establish the general genomic features of the corresponding recombinant genomes, we characterized poliovirus isolates excreted by vaccinees following primary immunization with OPV. Isolates were collected from 67 children 2 to 60 days following vaccination. Recombinant strains were identified by multiple restriction fragment length polymorphism assays. The localization of junction sites in recombinant genomes was also determined. VdRec excreted by vaccinees were first detected 2 to 4 days after vaccination. The highest rate of recombinants was on day 14. The frequency of VdRec depends strongly on the serotype of the analyzed isolates (2, 53, and 79% of recombinant strains in the last-excreted type 1, 2, and 3 isolates, respectively). Particular associations of genomic segments were preferred in the recombinant genomes, and recombination junctions were found in the genomic region encoding the nonstructural proteins. Recombination junctions generally clustered in particular subgenomic regions that were dependent on the serotype of the isolate and/or on the associations of genomic segments in recombinants. Thus, VdRec are frequently excreted by vaccinees, and the poliovirus replication machinery requirements or selection factors appear to act in vivo to shape the features of the recombinant genomes.


title: Efficacy of Polyhexamethylene Biguanide-containing Antimicrobial Foam Dressing Against MRSA Relative to Standard Foam Dressing.

text: Many modern foam wound dressings possess a variety of attributes that are designed to create a supportive wound-healing environment. These attributes include absorbing exudate, providing optimum moisture balance at the wound surface, and preventing maceration of surrounding tissue. However, studies suggest that controlling wound bioburden should also be targeted when developing wound therapeutics. Thus, traditional foam dressings may absorb a copious amount of fluid, but may also provide an environment where microbes can grow unchallenged, leading to an increase in wound bioburden. However, antimicrobial foam dressings may prevent or reduce microbial growth, increasing the potential for wound healing. Studies reported herein evaluated the efficacy of 0.5% polyhexamethylene biguanide (PHMB) treated dressings to prevent the growth of methicillin-resistant Staphylococcus aureus (MRSA). An antimicrobial foam (Kendall™ AMD, Covidien, Mansfield, MA), which contains PHMB and a standard foam dressing (Copa™, Covidien, Mansfield, MA), which contains no PHMB (control), were directly inoculated with clinical isolate of MRSA and placed on a growth medium for selected time intervals. The presence or absence of microbial growth was quantified using plate counts and was visually assessed using scanning electron microscopy. At all time points, the antimicrobial foam dressing significantly reduced the MRSA growth compared to the control dressing. Similar results were also obtained in the microscopic evaluations. .


Are intestinal mucins involved in the pathogenicity of transmissible gastroenteritis coronavirus?


title: Interventions for the interruption or reduction of the spread of respiratory viruses.

text: BACKGROUND Viral epidemics or pandemics such as of influenza or severe acute respiratory syndrome (SARS) pose a significant threat. Antiviral drugs and vaccination may not be adequate to prevent catastrophe in such an event. OBJECTIVES To systematically review the evidence of effectiveness of interventions to interrupt or reduce the spread of respiratory viruses (excluding vaccines and antiviral drugs, which have been previously reviewed). SEARCH STRATEGY We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2006, Issue 4); MEDLINE (1966 to November 2006); OLDMEDLINE (1950 to 1965); EMBASE (1990 to November 2006); and CINAHL (1982 to November 2006). SELECTION CRITERIA We scanned 2300 titles, excluded 2162 and retrieved the full papers of 138 trials, including 49 papers of 51 studies. The quality of three randomised controlled trials (RCTs) was poor; as were most cluster RCTs. The observational studies were of mixed quality. We were only able to meta-analyse case-control data. We searched for any interventions to prevent viral transmission of respiratory viruses (isolation, quarantine, social distancing, barriers, personal protection and hygiene). Study design included RCTs, cohort studies, case-control studies, cross-over studies, before-after, and time series studies. DATA COLLECTION AND ANALYSIS We scanned the titles, abstracts and full text articles using a standardised form to assess eligibility. RCTs were assessed according to randomisation method, allocation generation, concealment, blinding, and follow up. Non-RCTs were assessed for the presence of potential confounders and classified as low, medium, and high risk of bias. MAIN RESULTS The highest quality cluster RCTs suggest respiratory virus spread can be prevented by hygienic measures around younger children. Additional benefit from reduced transmission from children to other household members is broadly supported in results of other study designs, where the potential for confounding is greater. The six case-control studies suggested that implementing barriers to transmission, isolation, and hygienic measures are effective at containing respiratory virus epidemics. We found limited evidence that the more uncomfortable and expensive N95 masks were superior to simple surgical masks. The incremental effect of adding virucidals or antiseptics to normal handwashing to decrease respiratory disease remains uncertain. The lack of proper evaluation of global measures such as screening at entry ports and social distancing prevent firm conclusions about these measures. AUTHORS' CONCLUSIONS Many simple and probably low-cost interventions would be useful for reducing the transmission of epidemic respiratory viruses. Routine long-term implementation of some of the measures assessed might be difficult without the threat of a looming epidemic.


title: National Clinical Guidance for the Management of Cardiovascular Intervention in the COVID-19 Pandemic: From Bangladesh Society of Cardiovascular Interventions (BSCI).

text: Since the first recorded case of SARS-CoV-2 in Bangladesh on 8th March 2020, COVID-19 has spread widely through different regions of the country, resulting in a necessity to re-evaluate the delivery of cardiovascular services, particularly procedures pertaining to interventional cardiology in resource-limited settings. Given its robust capacity for human-to-human transmission and potential of being a nosocomial source of infection, the disease has specific implications on healthcare systems and health care professionals faced with performing essential cardiac procedures in patients with a suspected or confirmed diagnosis of COVID-19. The limited resources in terms of cardiac catheterization laboratories that can be designated to treat only COVID positive patients are further compounded by the additional challenges of unavailability of widespread rapid testing on-site at tertiary cardiac hospitals in Bangladesh. This document prepared for our nation by the Bangladesh Society of Cardiovascular Interventions (BSCI) is intended to serve as a clinical practice guideline for cardiovascular health care professionals, with a focus on modifying standard practice of care during the COVID-19 pandemic, in order to ensure continuation of adequate and timely treatment of cardiovascular emergencies avoiding hospital-based transmission of SARS-COV-2 among healthcare professionals and the patients. This is an evolving document based on currently available global data and is tailored to healthcare systems in Bangladesh with particular focus on, but not limited to, invasive cardiology facilities (cardiac catheterization, electrophysiology & pacing labs). This guideline is limited to the provision of cardiovascular care, and it is expected that specific targeted pharmaco-therapeutics against SARS-CoV-2 be prescribed as stipulated by the National Guidelines on Clinical Management of Corona virus Disease 2019 (COVID-19) published by the Director General of Health Services, Ministry of Health and Family Welfare of Bangladesh.


title: RNA meets chromatin.

text: In the universe of science, two worlds have recently collided-those of RNA and chromatin. The intersection of these two fields has been impending, but evidence for such a meaningful collision has only recently become apparent. In this review, we discuss the implications for noncoding RNAs and the formation of specialized chromatin domains in various epigenetic processes as diverse as dosage compensation, RNA interference-mediated heterochromatin assembly and gene silencing, and programmed DNA elimination. While mechanistic details as to how the RNA and chromatin worlds connect remain unclear, intriguing parallels exist in the overall design and machinery used in model organisms from all eukaryotic kingdoms. The role of potential RNA-binding chromatin-associated proteins will be discussed as one possible link between RNA and chromatin.


title: Severe acute respiratory syndrome coronavirus 3a protein is released in membranous structures from 3a protein-expressing cells and infected cells.

text: Severe acute respiratory syndrome coronavirus (SCoV) accessory protein 3a is a virus structural protein. We demonstrate here that 3a protein was released efficiently in membranous structures from various cell lines expressing 3a protein. A subpopulation of the released 3a protein is associated with detergent-resistant membranes. The presence of the YxxPhi and diacidic motifs, located within the cytoplasmic tail of the 3a protein, was not required for its efficient release. Analysis of supernatant from SCoV-infected cells with sucrose gradient sedimentation and virus capture assay indicated that the 3a protein was released from infected cells in two distinct populations, as a component of SCoV particles, and in membrane structures with a lower buoyant density. These data provide new insights into the biological properties of SCoV 3a protein.


title: Anisotropic patterns of liver cancer prevalence in Guangxi in Southwest China: is local climate a contributing factor?

text: Geographic information system (GIS) technology has useful applications for epidemiology, enabling the detection of spatial patterns of disease dispersion and locating geographic areas at increased risk. In this study, we applied GIS technology to characterize the spatial pattern of mortality due to liver cancer in the autonomous region of Guangxi Zhuang in southwest China. A database with liver cancer mortality data for 1971-1973, 1990-1992, and 2004-2005, including geographic locations and climate conditions, was constructed, and the appropriate associations were investigated. It was found that the regions with the highest mortality rates were central Guangxi with Guigang City at the center, and southwest Guangxi centered in Fusui County. Regions with the lowest mortality rates were eastern Guangxi with Pingnan County at the center, and northern Guangxi centered in Sanjiang and Rongshui counties. Regarding climate conditions, in the 1990s the mortality rate of liver cancer positively correlated with average temperature and average minimum temperature, and negatively correlated with average precipitation. In 2004 through 2005, mortality due to liver cancer positively correlated with the average minimum temperature. Regions of high mortality had lower average humidity and higher average barometric pressure than did regions of low mortality. Our results provide information to benefit development of a regional liver cancer prevention program in Guangxi, and provide important information and a reference for exploring causes of liver cancer.


title: Neutralizing antibodies against vesicular stomatitis viruses (serotypes New Jersey and Indiana) in horses in Costa Rica.

text: Serum samples were collected from domestic horses in 4 different regions of Costa Rica to detect antibodies against vesicular stomatitis viruses, serotypes New Jersey (VSV-NJ) and Indiana (VSV-IN). A total of 214 samples were tested by the virus neutralization test. The sampling regions were identified as low North Pacific dry area (1), low Middle Atlantic humid area (2), low South Pacific humid area (3), and the highlands (4). In region 1, 97.1% of horses were positive for VSV-NJ and 16.5% were positive for VSV-IN. The mean antibody titer and its standard deviation after logarithmic transformation were 5.86 +/- 0.9 for VSV-NJ and 3.55 +/- 1.66 for VSV-IN for region 1. In region 2, 40.7% of horses were positive for VSV-NJ and 32.2% were positive for VSV-IN. The mean antibody titer in region 2 was 4.33 +/- 1.82 for VSV-NJ and 3.47 +/- 1.73 for VSV-IN. In region 3, 20.79% of horses were positive for VSV-NJ and 27.6% were positive for VSV-IN. The mean antibody titer in region 3 was 4.39 +/- 1.89 for VSV-NJ and 3.47 +/- 1.82 for VSV-IN. In region 4, 91.3% of horses were positive for VSV-NJ and 73.9% were positive for VSV-IN. The mean antibody titer in region 4 was 5.77 +/- 1.10 for VSV-NJ and 4.85 +/- 1.63 for VSV-IN. This is the first published report of the detection of virus-neutralizing antibodies against VSV-NJ and VSV-IN in horses in Costa Rica.


title: Totally Transanal Laparo-Endoscopic Single-Site ProctoColectomy-Ileoanal J-Pouch (TLPC-J): An Experimental Study of a Novel Approach.

text: BACKGROUND The natural orifice transluminal endoscopic surgery (NOTES) has become a commonly considered novel approach in the surgical field. The NOTES provide possibility of operation through the natural orifice and decreases the intentional puncture of the systemic organ and subsequent complications. Totally transanal laparo-endoscopic single-site proctoColectomy-Ileoanal J-Pouch (TLPC-J) is a novel method in minimally invasive surgery for total colectomy. The main goal of this study is to perform this new method on an animal model, to assess probable complication and to resolve probable issues by using patients that are candidate for total colectomy. METHOD Five dogs were prepared in lithotomy position. The TLPC-I procedure consists of endorectal technique with full thickness rectal dissection starting 1 cm orally from the dentate line above the peritoneal reflection and the proximal bowel was replaced into the abdominal cavity. Afterwards, the TriPort system was inserted in the anal canal and mesentrial resection of the total colon, mobilization of a distal ileal segment and intracorporeal suture of an ileal J-loop was accomplished by this system. An incision in the J-loop was conducted transanally. The J-pouch was created with an Endo-GIA® and sutured to the rectal wall. RESULTS All animals survived and passed stool with clear post operation situation. There was no infection in site of anastomosis. CONCLUSION The TLPC-I provides the possibility of surgery without abdominal wall incision and decreases post operation complication such as pain, abdominal wound infection and wound dehiscence. This technique increases the quality of life and surgeons can discharge the patients early.


title: Longitudinal study of viruses associated with canine infectious respiratory disease.

text: In this investigation a population of dogs at a rehoming center was monitored over a period of 2 years. Despite regular vaccination of incoming dogs against distemper, canine adenovirus type 2 (CAV-2), and canine parainfluenza virus (CPIV), respiratory disease was endemic. Tissue samples from the respiratory tract as well as paired serum samples were collected for analysis. The development of PCR assays for the detection of CPIV, canine adenovirus types 1 and 2, and canine herpesvirus (CHV) is described. Surprisingly, canine adenovirus was not detected in samples from this population, whereas 19.4% of tracheal and 10.4% of lung samples were positive for CPIV and 12.8% of tracheal and 9.6% of lung samples were positive for CHV. As reported previously, a novel canine respiratory coronavirus (CRCoV) was detected in this population (K. Erles, C. Toomey, H. W. Brooks, and J. Brownlie, Virology 310:216-223, 2003). Infections with CRCoV occurred mostly during the first week of a dog's stay at the kennel, whereas CPIV and CHV were detected at later time points. Furthermore, the evaluation of an enzyme-linked immunosorbent assay for detection of antibodies to CPIV and an immunofluorescence assay for detection of antibodies to CHV is described. This study shows that CPIV is present at kennels despite vaccination. In addition, other agents such as CHV and CRCoV may play a role in the pathogenesis of canine respiratory disease, whereas CAV-2 and canine distemper virus were not present in this population, indicating that their prevalence in the United Kingdom is low due to widespread vaccination of dogs.


title: Mouse hepatitis virus S RNA sequence reveals that nonstructural proteins ns4 and ns5a are not essential for murine coronavirus replication.

text: Genes 4 and 5 of mouse hepatitis virus (MHV) are known to encode nonstructural proteins ns4, ns5a, and ns5b, whose function is unknown. In this study, we demonstrated that one of the MHV strains, MHV-S, did not synthesize mRNA 4 and made a smaller mRNA 5. Sequence analysis showed that the transcription initiation site for gene 4 of MHV-S was mutated from the consensus UCUAAAC to UUUAAAC, consistent with the idea that mutations in this region abolish mRNA synthesis. Furthermore, within gene 5 there were deletions totaling 307 nucleotides which deleted almost all of open reading frame 5a, but preserved open reading frame 5b of gene 5. Comparison of the growth of MHV-S with other MHV strains in DBT cells revealed no significant growth defect in MHV-S. These results suggest that ns4 and ns5a are not essential for viral replication in tissue culture cells, and thus join gene 2 and the hemagglutinin-esterase (HE) gene as nonessential viral genes in MHV.


title: Cross-protective immune responses elicited by a Korean variant of infectious bronchitis virus.

text: Infectious bronchitis virus (IBV) infections cause great economic losses to the poultry industry worldwide. IBVs continuously evolve by developing mutations in antigenic sites; therefore, an IBV vaccine that provides broad cross-protection can be a highly relevant and practical method in IBV control strategies. Although some IBV vaccine strains are known to provide protection against multiple IBV serotypes, in general commercially available IBV vaccine strains provide protection against antigenically related viruses but not distinct heterologous viruses. In the present study we characterized the Korean variant IBV K40/09 strain with regard to its immunogenicity and protective efficacy against seven currently circulating IBV serotypes. Three-week-old specific-pathogen-free chickens were intraocularly immunized with the IBV K40/09 strain at 10(3.5) 50% egg infective dose (EID50). Three weeks after immunization all the birds were challenged with seven different strains at 10(4.5) EID50. Chickens immunized with the IBV K40/09 strain showed significantly high levels of protection against all challenge viruses at the trachea and kidney levels. Our results suggest that IBV K40/09 could be useful to ensure IBV vaccine effectiveness owing to its cross-protective ability. Therefore, the IBV K40/09 strain merits consideration as a vaccine candidate to prevent infection as well as the spread of new IBV strains and many IBV variants that have been reported worldwide.


title: The pneumoplex assays, a multiplex PCR-enzyme hybridization assay that allows simultaneous detection of five organisms, Mycoplasma pneumoniae, Chlamydia (Chlamydophila) pneumoniae, Legionella pneumophila, Legionella micdadei, and Bordetella pertussis, and its real-time counterpart.

text: Respiratory disease caused by atypical bacteria remains an important cause of morbidity and mortality for adults and children, despite the widespread use of effective antimicrobials agents. Culture remains the "gold standard" for the detection of these agents. However, culture is labor-intensive, takes several days to weeks for growth, and can be very insensitive for the detection of some of these organisms. Newer singleplex PCR diagnostic tests are sensitive and specific, but multiple assays would be needed to detect all of the common pathogens. Therefore, we developed the Pneumoplex assays, a multiplex PCR-enzyme hybridization assay (the standard assay) and a multiplex real-time assay to detect the most common atypical pathogens in a single test. Primer and probe sequences were designed from conserved regions of specific genes for each of these organisms. The limits of detection were as follows: for Bordetella pertussis, 2 CFU/ml; for Legionella pneumophila (serotypes 1 to 15) and Legionella micdadei, 9 and 80 CFU/ml, respectively; for Mycoplasma pneumoniae, 5 CFU/ml; and for Chlamydia (Chlamydophila) pneumoniae, 0.01 50% tissue culture infective doses. Recombinant DNA controls for each of these organisms were constructed, and the number of copies for each DNA control was calculated. The Pneumoplex could detect each DNA control down to 10 copies/ml. The analytical specificity demonstrated no cross-reactivity between 23 common respiratory pathogens. One hundred twenty-five clinical bronchoalveolar lavage fluid samples tested by the standard assay demonstrated that the Pneumoplex yielded a sensitivity and a specificity of 100 and 98.5%, respectively. This test has the potential to assist clinicians in establishing a specific etiologic diagnosis before initiating therapy, to decrease hospital costs, and to prevent inappropriate antimicrobial therapy.


A preoperative chest radiograph is needed during an outbreak of SARS.


title: Phylogenetic analysis and seroprevalence of influenza C virus in Mie Prefecture, Japan in 2012.

text: Reverse transcription polymerase chain reaction (RT-PCR) and real-time RT-PCR were used to detect 14 (6.6%) influenza C virus (InfC) among 213 clinical samples collected from children with respiratory symptoms in Mie Prefecture, Japan, between January 2012 and December 2012. Virus isolation using Madin-Darby canine kidney cells and/or embryonated chicken eggs was also successful for 3 of the 14 PCR-positive samples. Eleven patients (78.6%) were aged <3 years. Phylogenetic analysis of the hemagglutinin-esterase gene showed that the InfC detected in Mie Prefecture belonged to the C/Sao Paulo/82-related lineage. To determine the seroprevalence of InfC, a total of 575 serum samples from patients aged 1 month to 69 years in Mie Prefecture were screened by hemagglutination inhibition test using the C/Mie/199/2012 (C/Sao Paulo/82-related lineage) strain as the antigen. The samples with an antibody titer of ≥1:16 were designated as antibody-positive. The results showed that 53.7% of the 296 serum samples collected in 2011 and 85.3% of the 279 samples collected in 2012 were positive for antibodies against InfC, suggesting that an outbreak of InfC infection occurred in Mie Prefecture in 2012. Therefore, continuous and proactive monitoring is important to determine the number of InfC-infections and to better understand the epidemiology.


title: Medical Education During the COVID-19 Pandemic: A Single Institution Experience.

text: Social distancing to curb the COVID-19 pandemic has caused suspension of classroom teaching in all educational institutions. We implemented a novel online classroom platform at our institute to continue medical education. The program attracted encouraging feedback from the students. It may serve as a model for uninterrupted teaching and training during times of crisis.


title: The 3' cis-acting genomic replication element of the severe acute respiratory syndrome coronavirus can function in the murine coronavirus genome.

text: The 3' untranslated region (3' UTR) of the genome of the severe acute respiratory syndrome coronavirus can functionally replace its counterpart in the prototype group 2 coronavirus mouse hepatitis virus (MHV). By contrast, the 3' UTRs of representative group 1 or group 3 coronaviruses cannot operate as substitutes for the MHV 3' UTR.


title: Respiratory syncytial virus infection results in airway hyperresponsiveness and enhanced airway sensitization to allergen.

text: Viral respiratory infections can predispose to the development of asthma by mechanisms that are presently undetermined. Using a murine model of respiratory syncytial virus (RSV) infection, acute infection is associated with airway hyperresponsiveness as well as enhanced responses to subsequent sensitization to allergen. We demonstrate that acute viral infection results in increased airway responsiveness to inhaled methacholine and pulmonary neutrophilic and eosinophilic inflammation. This response is associated with predominant production of Th-1-type cytokines in peribronchial lymph node cells in vitro. Mice sensitized to ovalbumin via the airways after RSV infection developed increased airway responsiveness to methacholine and pulmonary eosinophilic and neutrophilic inflammation, associated with the predominant production of Th-2-type cytokines. Treatment of the mice with anti-IL-5 antibody abolished airway hyperresponsiveness and eosinophilic but not neutrophilic inflammation in both acutely infected mice and mice sensitized after infection. We conclude that RSV infection results in airway hyperresponsiveness in the acute phase and leads to changes in immune function that can enhance the effects of airway sensitization to antigen after infection. In both situations, airway hyperresponsiveness is closely associated with pulmonary eosinophilic inflammation. This model provides a means for further analyzing the influence of viral respiratory infections on airway sensitization and the development of altered airway responsiveness.


title: Are Belgian senior medical students ready to deliver basic medical care in case of a H5N1 pandemic?

text: Medical care systems will be overwhelmed if a human H5N1 pandemic should occur. Several national disaster plans, including that of Belgium, focus on maximal treatment at home with senior medical students supporting frontline care. To evaluate the knowledge and preparedness of Belgian senior medical students, an e-mail survey of senior medical students (last two years of education) attending Flemish universities was conducted. A total of 243 students (30%) replied. Only 21.8% of them were aware of the possibility of being involved in this planning. A total of 77.4% estimated H5N1 to be a possible threat to national health. Seventy percent of respondents reacted positively towards the idea of being involved in implementing primary care, and only 9.5% were absolutely opposed to the idea. A total of 82.3% would care for pandemic patients if necessary, but only 41.2% would do so if these patients were children. Only 18.9% estimated themselves to be sufficiently educated regarding H5N1. Ninety-one percent were convinced that care for H5N1-influenza patients should be incorporated into their regular curriculum. Several antiviral products were reported by the students to be efficient for treating H5N1, but only 34.6% correctly chose oseltamavir and/or zanamavir and 35.4% replied "I don't know". A total of 95.5% correctly answered that the regular influenza vaccination doesn't protect against H5N1. The risk for human-to-human transmission was rated to be small by 50.6% (none 21%, high 27.6%). The human infection risk was rated to be small by 74.1% (none 1.6%, high 23%). There is a high level of willingness to participate among senior medical students. However, in the case of pediatric patients they're more reserved. It would be useful to incorporate a focused session on preparedness in the regular teaching program. A legal base for their actions should also be provided. Ethical guidelines on rights and duties in case of a pandemic should be prepared by an international, multidisciplinary group of experts.


title: Proventricular dilatation disease associated with Avian bornavirus in a scarlet macaw (Ara macao).

text: A case of proventricular dilatation disease is described in a scarlet macaw (Ara macao) from clinical presentation to diagnosis with molecular methods. The initial clinical signs were depression progressing to head pressing over several days. A leukocytosis with toxic heterophil changes, hypoalbuminemia, and increased serum activity of aspartate aminotransferase and creatine kinase were present. Lead and zinc assays were within reference ranges, and results from Chlamydophila and polyomavirus testing were negative. Contrast-enhanced fluoroscopy revealed normal gastrointestinal transit times and motility as well as the presence of 2 small metallic foreign bodies in the ventriculus. The macaw was treated with antimicrobials, analgesics, vitamins E and B complex, force-feeding, and fluid administration with little improvement. Euthanasia was elected, and histologic examination of brain tissue revealed a perivascular lymphoplasmacytic infiltration, while the lungs had evidence of a fungal pneumonia. Tissue samples from the brain and proventriculus tested positive for the presence of Avian bornavirus genotype 2, while serology confirmed Avian bornavirus infection.


title: Undesirable evolutionary consequences of trophy hunting.

text: Phenotype-based selective harvests, including trophy hunting, can have important implications for sustainable wildlife management if they target heritable traits. Here we show that in an evolutionary response to sport hunting of bighorn trophy rams (Ovis canadensis) body weight and horn size have declined significantly over time. We used quantitative genetic analyses, based on a partly genetically reconstructed pedigree from a 30-year study of a wild population in which trophy hunting targeted rams with rapidly growing horns, to explore the evolutionary response to hunter selection on ram weight and horn size. Both traits were highly heritable, and trophy-harvested rams were of significantly higher genetic 'breeding value' for weight and horn size than rams that were not harvested. Rams of high breeding value were also shot at an early age, and thus did not achieve high reproductive success. Declines in mean breeding values for weight and horn size therefore occurred in response to unrestricted trophy hunting, resulting in the production of smaller-horned, lighter rams, and fewer trophies.


title: [Dynamic changes and the meanings of blood cytokines in severe acute respiratory syndrome].

text: OBJECTIVE To investigate the dynamic changes observed in serum levels of interleukins (ILs), tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) in severe acute respiratory syndrome (SARS). METHODS Sixty-one cases of SARS were classified into the following categories according to the duration from the onset of illness to the time blood was drawn: 3-7 day group, 8-14 day group and over 14 day group. Forty-four healthy individuals served as the control. Serum levels of ILs, TNF-alpha and TGF-beta1 were measured in all cases. Serum antibodies to SARS-coronavirus (SARS-CoV) were measured only in SARS cases. RESULTS The mean concentration of serum IL-6 in SARS patients did not differ from the control group in 3-7 day group and 8-14 day group, but became significantly higher in over 14 day group as compared to the control group, 3-7 day group and 8-14 day group (P < 0.01). The mean concentration of serum IL-8 in SARS patients did not differ from the control group in 3-7 day group, were significantly higher than the control group in 8-14 days group and in over 14 day group (P < 0.05) and significantly higher in over 14 day group than in 3-7 day group and 8-14 day group (P < 0.01). The mean concentration of IL-16 and TNF-alpha in all groups of SARS was higher than that of the control group, but it was the highest in over 14 day group (P < 0.01). SARS patients experienced higher concentration of serum IL-13 as compared to controls in 3-7 day group (P < 0.01), but it returned to normal levels in 8-14 day group and the over 14 day group. The mean concentration of serum IL-18 in SARS patients was significantly lower than that of the control group during all groups of SARS patients (P < 0.05); The mean concentration of TGF-beta1 in all groups of SARS patients was higher than that of the control group. Although TGF-beta1 in sera decreased in over 14 day group, the average was still higher than that of the control group (P < 0.01). CONCLUSIONS Proinflammatory cytokines and TGF-beta1 were elevated during the early phase of SARS, a phenomenon which may be associated with lung infiltration and proliferation. Concurrently, the mean concentration of serum IL-13 decreased gradually and the mean concentration of serum IL-18 level in SARS patients was lower than that of the control group during the whole disease course. It suggested that the immune state of SARS was obviously abnormal. Observing the dynamic changes in blood cytokine levels can provide us with a scientific basis to assess pathogenesis and efficacy of clinical treatment of SARS.


title: Effectiveness of the LigaSure Small Jaw Vessel-Sealing System in Hepatic Resection.

text: BACKGROUND In hepatic resection for liver tumors, reducing operation time and blood loss are important for postsurgical complication prevention. This study aimed to compare the safety and efficacy of the LigaSure Small Jaw (Covidien, Boulder, CO) with those of the Cavitation Ultrasonic Surgical Aspirator (CUSA) system (Integra Life Sciences, Plainsboro, NJ) in hepatic surgery. METHODS We enrolled 102 patients with liver tumors, of whom 51 underwent liver resection with the CUSA (CUSA group) between March 2004 and April 2011. Another 51 underwent resection with the LigaSure Small Jaw (LS group) between June 2011 and July 2012. We stratified patients by time period depending on the instrument used, and compared operative duration; intraoperative bleeding; and postoperative liver function and complication rate. RESULTS Total operation time (mean ± SD) was significantly shorter in the LS group than in the CUSA group (358.8 ± 91.7 versus 460.6 ± 146.1 min, P < 0.001). Blood loss was not significantly different between the 2 groups. Frequency of postoperative complications was lower, but not significantly, in the LS group. CONCLUSION The LigaSure Small Jaw may allow a shorter total operative duration than the CUSA device.


title: Discovery of potent anilide inhibitors against the severe acute respiratory syndrome 3CL protease.

text: A diversified library of peptide anilides was prepared, and their inhibition activities against the SARS-CoV 3CL protease were examined by a fluorogenic tetradecapeptide substrate. The most potent inhibitor is an anilide derived from 2-chloro-4-nitroaniline, l-phenylalanine and 4-(dimethylamino)benzoic acid. This anilide is a competitive inhibitor of the SARS-CoV 3CL protease with K(i) = 0.03 muM. The molecular docking experiment indicates that the P1 residue of this anilide inhibitor is distant from the nucleophilic SH of Cys145 in the active site.


title: SARS: caring for patients in Hong Kong.

text: AIM AND OBJECTIVE To explore in depth the experiences of nurses' caring for SARS patients in Hong Kong. BACKGROUND Severe Acute Respiratory Syndrome (SARS) dramatically demonstrates the global havoc that can be wreaked by a newly emerging infectious disease. The current literature either has a predominantly biomedical focus or deals with the psychological impact on healthcare workers. Published studies on the lived experience of nurses caring for SARS patients are currently lacking. DESIGN A phenomenological design. METHODS Using methods consistent with Husserl's philosophy, eight Registered Nurses working in three regional hospitals in Hong Kong were invited to participate in sharing their lived experience of caring for SARS patients and data were analysed using Colaizzi's approach. RESULTS The three major themes explicated were: the various emotions experienced in caring for SARS patients, the concept of uncertainty and revisiting the 'taken for granted' features of nursing. CONCLUSION These themes, when taken together, describe the essence of the voyage undertaken by nurses who cared for SARS patients during the outbreak. The findings of this study indicate that extensive and ongoing support is needed to prepare and enable nurses to care for SARS patients during a crisis and make it easier for nurses to deal with the various uncertainties. RELEVANCE TO CLINICAL PRACTICE The essence of caring for SARS patients is highlighted in this study. The experience of caring for SARS patients prompts nurses to find meaning in their experience(s), and to develop knowledge and attitudes on how best to care for patients and prepare for a new crisis in the future. This paper considers a more in-depth understanding of the lived experience of nurses during the crisis and the relevance of this perspective for education and support of nurses.


title: Avian influenza and pandemic influenza preparedness in Hong Kong.

text: Avian influenza A H5N1 continues to be a major threat to global public health as it is a likely candidate for the next influenza pandemic. To protect public health and avert potential disruption to the economy, the Hong Kong Special Administrative Region Government has committed substantial effort in preparedness for avian and pandemic influenza. Public health infrastructures for emerging infectious diseases have been developed to enhance command, control and coordination of emergency response. Strategies against avian and pandemic influenza are formulated to reduce opportunities for human infection, detect pandemic influenza timely, and enhance emergency preparedness and response capacity. Key components of the pandemic response include strengthening disease surveillance systems, updating legislation on infectious disease prevention and control, enhancing traveller health measures, building surge capacity, maintaining adequate pharmaceutical stockpiles, and ensuring business continuity during crisis. Challenges from avian and pandemic influenza are not to be underestimated. Implementing quarantine and social distancing measures to contain or mitigate the spread of pandemic influenza is problematic in a highly urbanised city like Hong Kong as they involved complex operational and ethical issues. Sustaining effective risk communication campaigns during interpandemic times is another challenge. Being a member of the global village, Hong Kong is committed to contributing its share of efforts and collaborating with health authorities internationally in combating our common public health enemy.


title: Palmitoylations on murine coronavirus spike proteins are essential for virion assembly and infectivity.

text: Coronavirus spike (S) proteins are palmitoylated at several cysteine residues clustered near their transmembrane-spanning domains. This is achieved by cellular palmitoyl acyltransferases (PATs), which can modify newly synthesized S proteins before they are assembled into virion envelopes at the intermediate compartment of the exocytic pathway. To address the importance of these fatty acylations to coronavirus infection, we exposed infected cells to 2-bromopalmitate (2-BP), a specific PAT inhibitor. 2-BP profoundly reduced the specific infectivities of murine coronaviruses at very low, nontoxic doses that were inert to alphavirus and rhabdovirus infections. 2-BP effected only two- to fivefold reductions in S palmitoylation, yet this correlated with reduced S complexing with virion membrane (M) proteins and consequent exclusion of S from virions. At defined 2-BP doses, underpalmitoylated S proteins instead trafficked to infected cell surfaces and elicited cell-cell membrane fusions, suggesting that the acyl chain adducts are more critical to virion assembly than to S-induced syncytial developments. These studies involving pharmacologic inhibition of S protein palmitoylation were complemented with molecular genetic analyses in which cysteine acylation substrates were mutated. Notably, some mutations (C1347F and C1348S) did not interfere with S incorporation into virions, indicating that only a subset of the cysteine-rich region provides the essential S-assembly functions. However, the C1347F/C1348S mutant viruses exhibited relatively low specific infectivities, similar to virions secreted from 2-BP-treated cultures. Our collective results indicate that the palmitate adducts on coronavirus S proteins are necessary in assembly and also in positioning the assembled envelope proteins for maximal infectivity.


Optimisation of Vitamin D Status for Enhanced Immuno-protection Against Covid-19.


title: [Clinical features and management of recurrence of severe acute respiratory syndrome].

text: OBJECTIVE To investigate the clinical features of recurrence of severe acute respiratory syndrome (SARS) and therapeutic response. METHODS Recurrence was analyzed retrospectively in SARS patients referred to our hospital from April to May this year to understand the clinical features, the recurrent related factors, the response of treatment and the outcomes. RESULTS One hundred and twenty three patients with SARS were referred to the First Hospital of Peking University from 8, April to 14, May this year and of whom 51 were the critical. Twenty-five patients experienced recurrence, account for 20.3% of total patients (25/123) and 31.4% of critical patients. The clinical features included recurrent fever, worsened breathlessness, exacerbation in radiological lesions and elevated LDH, etc.. These patients were treated with glucocorticoids. Eleven of them were mechanical ventilated. Twenty-one patients recovered. Pulmonary fibrosis were left in 2 patients and another 2 patients died. CONCLUSION The recurrence of symptoms in SARS patients is one of the common clinical feature of critical patients with SARS. Mechanism of recurrence in SARS patient is unknown. Management with glucocorticoids and noninvasive ventilation can control the progression in these patients effectively.


Esophagostomy feeding tube placement in the dog and cat.


Management of severe acute respiratory syndrome: the Hong Kong University experience.


title: Structural characterization of the fusion-active complex of severe acute respiratory syndrome (SARS) coronavirus.

text: The causative agent of a recent outbreak of an atypical pneumonia, known as severe acute respiratory syndrome (SARS), has been identified as a coronavirus (CoV) not belonging to any of the previously identified groups. Fusion of coronaviruses with the host cell is mediated by the envelope spike protein. Two regions within the spike protein of SARS-CoV have been identified, showing a high degree of sequence conservation with the other CoV, which are characterized by the presence of heptad repeats (HR1 and HR2). By using synthetic and recombinant peptides corresponding to the HR1 and HR2 regions, we were able to characterize the fusion-active complex formed by this novel CoV by CD, native PAGE, proteolysis protection analysis, and size-exclusion chromatography. HR1 and HR2 of SARS-CoV associate into an antiparallel six-helix bundle, with structural features typical of the other known class I fusion proteins. We have also mapped the specific boundaries of the region, within the longer HR1 domain, making contact with the shorter HR2 domain. Notably, the inner HR1 coiled coil is a stable alpha-helical domain even in the absence of interaction with the HR2 region. Inhibitors binding to HR regions of fusion proteins have been shown to be efficacious against many viruses, notably HIV. Our results may help in the design of anti-SARS therapeutics.


title: [Almost two-thirds of the elderly with covid-19 surviving in nursing homes].

text: A large proportion of deaths worldwide have occurred among elderly living in nursing homes. Sweden is no exception with a comparable proportion making up around half of all deaths. The elderly, frail individuals living in nursing homes are among the most vulnerable and with the highest risk to die of covid-19. In spite of that we see almost two-thirds of the infected are still alive with a majority recovering fully after receiving treatment at the nursing home. Of 8 057 residents living in nursing homes in Stockholm, 1 464 (18 %) individuals have so far been diagnosed with covid-19 and 532 have died (6 % of all residents). Importantly, this means that a great majority of the residents are still alive including almost two-thirds (932/1 464) of the infected individuals.


title: Construction and characterization of a fluorescent sendai virus carrying the gene for envelope fusion protein fused with enhanced green fluorescent protein.

text: Sendai virus (SeV) is an enveloped virus with a non-segmented negative-strand RNA genome. SeV envelope fusion (F) glycoproteins play crucial roles in the viral life cycle in processes such as viral binding, assembly, and budding. In this study, we developed a viable recombinant SeV designated F-EGFP SeV/ΔF, in which the F protein was replaced by an F protein fused to EGFP at the carboxyl terminus. Living infected cells of the recombinant virus were directly visualized by green fluorescence. The addition of EGFP to the F protein maintained the activities of the F protein in terms of intracellular transport to the plasma membrane via the ER and the Golgi apparatus and fusion activity in the infected cells. These results suggest that this fluorescent SeV is a useful tool for studying the viral binding, assembly, and budding mechanisms of F proteins and the SeV life cycle in living infected cells.


title: Does the motor unit synchronization induced by vibration enhance maximal voluntary isometric contraction force? A randomized controlled double-blind trial.

text: OBJECTIVES Motor unit synchronization has been proposed as a potential mechanism underlying muscle strength gains for vibration training, but it has yet to be definitely demonstrated. Aim of this study was to determine whether motor unit synchronization induced by vibration has an effect on isometric muscle strength. METHODS Thirty-six healthy volunteers were randomized into two groups: the vibration and the control (sham vibration) groups. Two sets of test measurements and vibration resistance training between the two sets were applied to the right wrist flexors. The maximal voluntary isometric contraction force, and flexor carpi radialis EMG activity were recorded in the first (without vibratory stimulation) and the second (with vibratory stimulation) set. RESULTS There was no difference in the normalized peak force between the first and the second set in the vibration group (p=0.554). Motor units fired with maximal voluntary isometric contraction synchronized at the vibration frequency (25 Hz) during vibration in all participants of the vibration group. CONCLUSION The present study indicates that vibration-induced motor unit synchronization does not have a significant effect on the maximal voluntary isometric contraction force..


title: [Clinical manifestation, treatment, and outcome of severe acute respiratory syndrome: analysis of 108 cases in Beijing].

text: OBJECTIVE To investigate the clinical manifestations, treatment, and outcome of severe acute respiratory syndrome (SARS). METHODS The clinical data of 108 SARS in-patients were analyzed. RESULTS Among the 108 cases, 35 males (32.4%) and 73 females (67.6%), aged 37 +/- 9 (range 13 approximately 83 years), most were white-collar workers, medical workers accounting for 28.7%. 87.0% had a definite contact history. 20.4% were complicated by other internal diseases. The main clinical manifestations included fever, cough, pectoralgia, chest distress, headache, etc. Involvement of multiple organs was often. The incubation period was 2 approximately 14 days. The course included early stage, progressive stage, climax, and convalescence. Mild type accounted for 4.6%, common type 39.8%, severe type 20.4%, and extremely severe type 35.2%. At the early stage, white blood cell count, lymphocyte count and ratio of lymphocyte, proalbumin, transferring, CD(3)(+), CD(4)(+), CD(8)(+) cell count were remarkably decreased, and C-reactive protein, alpha-acid glycoprotein, and alpha(2)-globulin were remarkably increased. X-ray chest film showed solitary or multiple local exudative changes, mostly in pulmonary lower field. During the progressive stage the hyaline or consolidation images were enlarged. High solution CT showed solitary or multiple cotton wadding like images and ground glass-like or consolidation images. Hypoxemia was common. At the progressive stage application of adrenocortical hormones and non-invasive mechanical ventilation helped stop the progress of disease. Ninety-four cases were discharged, 14 cases died. Traditional Chinese medicine (TCM) regards SARS as one of epidemic febrile diseases. Treatment by combination of TCM and Western medicine was effective. CONCLUSION SARS mainly affects youth and people in their prime of life. It has its own characteristic clinical manifestations. The classification system of 5 types and 4 stages helps judge the condition. Treatment by combination of TCM and Western medicine is encouraged.


title: Minimum costs to manufacture new treatments for COVID-19.

text: Introduction 'Repurposing' existing drugs to treat COVID-19 is vital to reducing mortality and controlling the pandemic. Several promising drugs have been identified and are in various stages of clinical trials globally. If efficacy of these drugs is demonstrated, rapid, mass availability at an affordable cost would be essential to ensuring equity and access especially amongst low- and middle-income economies. Methods Minimum costs of production were estimated from the costs of active pharmaceutical ingredients using established methodology, which had good predictive accuracy for medicines for hepatitis C and HIV amongst others. Data were extracted from global export shipment records or analysis of the route of chemical synthesis. The estimated costs were compared with list prices from a range of countries where pricing data were available. Results Minimum estimated costs of production were US $0.93/day for remdesivir, $1.45/day for favipiravir, $0.08/day for hydroxychloroquine, $0.02/day for chloroquine, $0.10/day for azithromycin, $0.28/day for lopinavir/ritonavir, $0.39/day for sofosbuvir/daclatasvir and $1.09/day for pirfenidone. Costs of production ranged between $0.30 and $31 per treatment course (10-28 days). Current prices of these drugs were far higher than the costs of production, particularly in the US. Conclusions Should repurposed drugs demonstrate efficacy against COVID-19, they could be manufactured profitably at very low costs, for much less than current list prices. Estimations for the minimum production costs can strengthen price negotiations and help ensure affordable access to vital treatment for COVID-19 at low prices globally.


title: [Clinical symptoms and diagnosis of feline infectious peritonitis].

text: Body effusions from 197 cats and blood serum samples from 252 cats, where Feline Infectious Peritonitis (FIP) was part of the differential diagnosis, were analysed. The diagnoses were confirmed by clinical follow up or histopathology. The final diagnosis FIP was always confirmed by histopathology. The median age of cats with FIP was 1.6 years. FIP was responsible for 41% of the body effusions, whereas malignomas caused 24%, cardial insufficiencies 14% and purulent serositis 12% of the body effusions. The rivalta test was highly sensitive for FIP. Predictive value of a negative result was 100%, predictive value of a positive result was 84%. In half of the cases with purulent serositis and in 20% of malignomas rivalta reacted positive. The cardial insufficiencies were negative for rivalta. Coronavirus antigen could be demonstrated by immunofluorescence in 34 of 49 body effusions caused by FIP, whereas in the 50 body effusions caused by other diseases no coronavirus antigen was detected. An albumin globulin ratio of < 0.6 was highly diagnostic for an inflammatory process, nearly exclusively for FIP. An albumin globulin ratio of > or = 0.8 almost excluded FIP. Only a negative or very high (1:1600) FIP titer could contribute to confirm diagnosis. Low and medium titers, however, should not be interpreted.


Endoproteolysis in health and diseases--implications of proprotein convertases (PCs).


title: Targeted disruption of the mouse Stat1 gene results in compromised innate immunity to viral disease.

text: The STAT1 transcription factor is activated in response to many cytokines and growth factors. To study the requirement for STAT1 in vivo, we disrupted the Stat1 gene in embryonic stem (ES) cells and in mice. Stat1(-1-)ES cells were unresponsive to interferon (IFN), but retained responsiveness to leukemia inhibitory factor (LIF) and remained LIF dependent for undifferentiated growth. Stat1(-1-1) animals were born at normal frequencies and displayed no gross developmental defects. However, these animals failed to thrive and were extremely susceptible to viral disease. Cells and tissues from Stat1(-1-) mice were unresponsive to IFN, but remained responsive to all other cytokines tested. Thus, STAT1 appears to be specific for IFN pathways that are essential for viability in the face of otherwise innocuous pathogens.


title: The use of pancreas biopsy scoring provides reliable porcine islet yields while encapsulation permits the determination of microbiological safety.

text: For clinical xenogenic islet transplantation to be successful, several requirements must be met. Among them is a sizeable and reliable source of fully functional and microbiologically safe islets. The inherent variability among porcine pancreases, with respect to islet yield, prompted us to develop a Biopsy Score technique to determine the suitability of each pancreas for islet isolation processing. The Biopsy Score consists of an assessment of five variables: warm ischemia time, pancreas color, fat content, islet size, and islet demarcation, each of which is assigned a value of -1 or +1, depending on whether or not the established criteria is met. For determination of islet size and demarcation, fresh biopsies of porcine pancreases are stained with dithizone (DTZ) solution and examined under a dissecting microscope. Based on the scoring of such biopsies in pancreases from 26-56-month-old sows, we report here that the presence of large (>100 microm diameter), well-demarcated islets in the pancreas biopsy is a reliable predictor of isolation success. Encapsulation of the isolated porcine islets within the inner layer of a 1.5% agarose and an outer layer of 5.0% agarose macrobead, containing 500 equivalent islet number (EIN), provides for extended in vitro functional viability (>6 months of insulin production in response to glucose), as well as for comprehensive microbiological testing and at least partial isolation of the xenogeneic islets from the host immune system. All microbiological testing to date has been negative, except for the presence of porcine endogenous retrovirus (PERV). Taken together, we believe that the Biopsy Score enhancement of our islet isolation technique and our agarose-agarose macroencapsulation methodology bring us significantly closer to realizing clinical porcine islet xenotransplantation for the treatment of insulin-dependent diabetic patients.


title: Statistical monitoring-based alarming systems in modeling the AIDS epidemic in the United States, 1985-2011.

text: BACKGROUND Better decisions for the control of HIV/AIDS and other infectious diseases require better information. The large amount of available public health data makes it possible to extract such information to monitor and predict significant disease events in disease epidemic. The detection of unusual events often involves a combination of a forecasting and a decision mechanism assessing the extent to which an observed event differs significantly from a forecast event. A number of methods and models have been proposed to monitor the trend of infectious disease and to detect unusual events. Although these existing methods and models are useful, many new issues remain to be addressed, including the complicated data structure and the infectious disease dynamics. To overcome these issues, we introduced the statistical tool using statistical process control, and proposed a new method under that framework. METHODS In this paper, we first reviewed the most commonly used methods and models, including the historical limit method, the time series analysis, the hidden Markov models, and the process control charts. Then, we further discussed issues with the current available methods. We proposed a new method using statistical process control. A major feature of the new method is that it prospectively monitors the disease incidence using sequentially collected data over time. It also takes into account a wide variety of longitudinal patterns and possible autocorrelation in the data. RESULTS We test this novel method with the recorded data of the number of AIDS cases in different states of US from 1985 to 2011. The results show that our new method is effective in detecting and predicting the time trends of AIDS epidemic for individual states and for US as a whole. Although AIDS data are used in our demonstration, this method can be used for monitoring other infectious diseases.


Hospital doctors will get below inflation pay increase, while GPs get nothing.


title: The Greek translation of the symptoms rating scale for depression and anxiety: preliminary results of the validation study.

text: BACKGROUND The aim of the current study was to assess the reliability, validity and the psychometric properties of the Greek translation of the Symptoms Rating Scale For Depression and Anxiety. The scale consists of 42 items and permits the calculation of the scores of the Beck Depression Inventory (BDI)-21, the BDI 13, the Melancholia Subscale, the Asthenia Subscale, the Anxiety Subscale and the Mania Subscale METHODS 29 depressed patients 30.48 +/- 9.83 years old, and 120 normal controls 27.45 +/- 10.85 years old entered the study. In 20 of them (8 patients and 12 controls) the instrument was re-applied 1-2 days later. Translation and Back Translation was made. Clinical Diagnosis was reached by consensus of two examiners with the use of the SCAN v.2.0 and the IPDE. CES-D and ZDRS were used for cross-validation purposes. The Statistical Analysis included ANOVA, the Spearman Correlation Coefficient, Principal Components Analysis and the calculation of Cronbach's alpha. RESULTS The optimal cut-off points were: BDI-21: 14/15, BDI-13: 7/8, Melancholia: 8/9, Asthenia: 9/10, Anxiety: 10/11. Chronbach's alpha ranged between 0.86 and 0.92 for individual scales. Only the Mania subscale had very low alpha (0.12). The test-retest reliability was excellent for all scales with Spearman's Rho between 0.79 and 0.91. CONCLUSIONS The Greek translation of the SRSDA and the scales that consist it are both reliable and valid and are suitable for clinical and research use with satisfactory properties. Their properties are close to those reported in the international literature. However one should always have in mind the limitations inherent in the use of self-report scales.


title: Comparison of clinical course of patients with severe acute respiratory syndrome among the multiple generations of nosocomial transmission.

text: BACKGROUND Severe acute respiratory syndrome (SARS) is characterized by both an atypical pneumonia and efficient nosocomial transmission. However, it remains unknown whether the infectivity and the virulence of the pathogen will change throughout the successive transmission. This study was conducted to compare the clinical features and management regimens of patients with SARS among the multiple generations from nosocomial transmission initiated by a super-spreader. METHODS The clinical data of 84 epidemiologically-linked SARS patients from a hospital outbreak were retrospectively studied. All patients, in whom a clear-cut transmission generation could be noted, had a direct or indirect exposure to the index patient and the epidemic successively propagated through the multiple generations of cases within a short period of time. RESULTS There were 66 women and 18 men with mean age of (29.2 +/- 10.3) years in this cluster; and 96.4% of whom were health care workers. Detailed contact tracing identified 35 (41.7%) first-generation cases, 34 (40.5%) second-generation cases, and 15 (17.8%) third-generation cases. No statistical differences among the multiple generations of transmission were found in terms of age, gender, incubation period and length of hospital stay. With the advanced transmission generations, the initial temperature lowered, the number of cases with dry cough decreased. There were no statistical differences in the peak temperature and duration of fever, other accompanying symptoms, leucopenia; however, the time from initial pulmonary infiltrates to radiographic recovery shortened (P < 0.05). No differences were found in maximum number of lung fields involved, duration from the onset of fever to the occurrence of pulmonary infiltrates and time from the initial pulmonary infiltrate to its peak among the multiple transmission generations (P > 0.05). No statistical differences were found in modes of oxygen therapy and sorts of antibiotics prescribed among the various transmission generations (P > 0.05); however, as with the advanced transmission generations, the number of cases prescribed with methylprednisolone, human gamma-globulin, interferon-alpha, antiviral drugs (oral ribavirin or oseltamivir) increased (P < 0.05) and time from admission to starting these medication shortened (P < 0.05). CONCLUSIONS There is no evidence that SARS infection will evolve or transmit within a fashion that permits it to become less powerful throughout the successive transmission within a short time.


title: [Syndromic surveillance for the detection of outbreaks of unusual infectious diseases].

text: Syndromic surveillance has been developed in order to detect outbreaks of unusual infectious diseases such as severe acute respiratory syndrome (SARS) or anthrax at an early stage. Whereas the usual surveillance systems are based on established diagnoses and emergency department discharge data, syndromic surveillance uses preliminary outcomes and derived data such as absenteeism, prescription medication and requests for laboratory tests. Investigations abroad have indicated the potential ofsyndromic surveillance. In the Netherlands, the National Institute of Public Health and Environment (RIVM) is examining the feasibility of implementing syndromic surveillance.


title: Dengue virus (DENV) antibody-dependent enhancement of infection upregulates the production of anti-inflammatory cytokines, but suppresses anti-DENV free radical and pro-inflammatory cytokine production, in THP-1 cells.

text: The immunopathogenesis of dengue haemorrhagic fever and dengue shock syndrome is thought to be mediated by a variety of host factors. Enhancing antibodies are one of the key regulating molecules. These antibodies, via antibody-dependent enhancement (ADE) of infection, are able to facilitate dengue virus (DENV) growth in Fc-bearing host cells. The mechanism of ADE-enhanced DENV production is believed to be mediated through increasing the infected-cell mass. In the present work, the effect of ADE infection was explored further, focusing on the post-entry events of ADE infection. It was hypothesized that the higher virus production in ADE infection compared with DENV infection may be due to the ability of this infection pathway to suppress key antiviral molecules. Therefore, the influence of ADE infection on pro- and anti-inflammatory cytokines, including interleukin-12 (IL-12), gamma interferon (IFN-gamma), tumour necrosis factor alpha (TNF-alpha), IL-6 and IL-10, was investigated and it was found that DENV infection via the Fc receptor-mediated pathway was able to suppress the transcription and translation of IL-12, IFN-gamma and TNF-alpha. In contrast, infection via this route facilitated expression and synthesis of the anti-inflammatory cytokines IL-6 and IL-10. Moreover, this study demonstrates that the ADE infection pathway also suppresses an innate anti-DENV mediator, nitric oxide radicals, by disrupting the transcription of the iNOS gene transcription factor, IRF-1, and blocking the activation of STAT-1. In conclusion, ADE infection not only facilitates the entry process, but also modifies innate and adaptive intracellular antiviral mechanisms, resulting in unrestricted DENV replication in THP-1 cells.


title: Foundations of the severe acute respiratory syndrome preparedness and response plan for healthcare facilities.

text: OBJECTIVE To help facilities prepare for potential future cases of severe acute respiratory syndrome (SARS). DESIGN AND PARTICIPANTS The Centers for Disease Control and Prevention (CDC), assisted by members of professional societies representing public health, healthcare workers, and healthcare administrators, developed guidance to help facilities both prepare for and respond to cases of SARS. INTERVENTIONS The recommendations in the CDC document were based on some of the important lessons learned in healthcare settings around the world during the SARS outbreak of 2003, including that (1) a SARS outbreak requires a coordinated and dynamic response by multiple groups; (2) unrecognized cases of SARS-associated coronavirus are a significant source of transmission; (3) restricting access to the healthcare facility can minimize transmission; (4) airborne infection isolation is recommended, but facilities and equipment may not be available; and (5) staffing needs and support will pose a significant challenge. CONCLUSIONS Healthcare facilities were at the center of the SARS outbreak of 2003 and played a key role in controlling the epidemic. Recommendations in the CDC's SARS preparedness and response guidance for healthcare facilities will help facilities prepare for possible future outbreaks of SARS.


title: Heterologous protein production using the Pichia pastoris expression system.

text: The Pichia pastoris expression system is being used successfully for the production of various recombinant heterologous proteins. Recent developments with respect to the Pichia expression system have had an impact on not only the expression levels that can be achieved, but also the bioactivity of various heterologous proteins. We review here some of these recent developments, as well as strategies for reducing proteolytic degradation of the expressed recombinant protein at cultivation, cellular and protein levels. The problems associated with post-translational modifications performed on recombinant proteins by P. pastoris are discussed, including the effects on bioactivity and function of these proteins, and some engineering strategies for minimizing unwanted glycosylations. We pay particular attention to the importance of optimizing the physicochemical environment for efficient and maximal recombinant protein production in bioreactors and the role of process control in optimizing protein production is reviewed. Finally, future aspects of the use of the P. pastoris expression system are discussed with regard to the production of complex membrane proteins, such as G protein-coupled receptors, and the industrial and clinical importance of these proteins.


All India Institute of Medical Sciences, New Delhi.


title: [Potential harms associated with 4-aminoquinoline treatment].

text: Hydroxychloroquine and chloroquine are currently being evaluated as treatment against COVID-19. These drugs are associated with some potential harms, including QTc-interval prolongation, hypoglycaemia, severe skin reactions and psychiatric effects. Use of hydroxychloroquine or chloroquine should be reserved to current indications or clinical trials, as recommended by several governmental medical products agencies.


title: Multiple sclerosis and viruses: an overview.

text: The evidence for a viral etiology of MS has been reviewed. The strongest evidence favoring a virus is based primarily on epidemiologic considerations. Less convincing evidence comes from pathologic studies, serology, lymphocyte reactivity to viral antigens, and reports of identification of virus in MS tissues. Animal models of viral demyelination exist, which may provide insight into possible etiologic agents and pathogenetic mechanisms. Considering all the data, it is clear that no agent can be convincingly linked to MS at the present time. If a single virus causes the majority of cases of MS, then a morbilliform virus--canine distemper--is a leading contender, because this agent is consistent with the epidemiologic and serologic findings and is highly neurovirulent for animals ranging from mice to primates. Since no virus fulfills the usual criteria for linking an infectious agent to a disease, other possibilities must be considered. If MS is caused by a single virus, it may be a common virus not presently considered as being associated with MS, or an agent as yet unidentified. It is also conceivable that multiple agents, acting alone or in concert, initiate the MS process, perhaps through a common immune-mediated pathway. In this regard, another human demyelinating disease--the Guillain-Barré syndrome--which may in some instances become a chronic remitting and relapsing disorder, is thought to be initiated by multiple infectious agents but to have an immunologic pathogenesis.


title: Current Controversies in Transanal Surgery for Rectal Cancer.

text: Local surgery for rectal tumors has been traditionally limited due to technical issues for lower risk lesions. In the 1980s, Buess described the transanal endoscopic microsurgery (TEM) technique that enabled excision of lesions that were larger and in a higher location. TEM in a short time became the gold standard for the excision of large adenomas and early rectal carcinomas. Since the advent of TEM, and due to advances in minimal invasive technology, new devices and procedures have come to the surgical armamentarium, in many cases with only very slight differences between them. However, local surgery for rectal cancer still remains a challenge. An overview of the current status of minimal transanal invasive techniques is presented here and sheds some light on the controversies that the local management of rectal cancer still raises.


title: Identification of nonessential regions of the nsp2 replicase protein of porcine reproductive and respiratory syndrome virus strain VR-2332 for replication in cell culture.

text: The nonstructural protein 2 (nsp2) of porcine reproductive and respiratory syndrome virus (PRRSV) is a multidomain protein and has been shown to undergo remarkable genetic variation, primarily in its middle region, while exhibiting high conservation in the N-terminal putative protease domain and the C-terminal predicted transmembrane region. A reverse genetics system of PRRSV North American prototype VR-2332 was developed to explore the importance of different regions of nsp2 for viral replication. A series of mutants with in-frame deletions in the nsp2 coding region were engineered, and infectious viruses were subsequently recovered from transfected cells and further characterized. The results demonstrated that the cysteine protease domain (PL2), the PL2 downstream flanking sequence (amino acids [aa] 181 to 323), and the putative transmembrane domain were critical for replication. In contrast, the segment of nsp2 preceding the PL2 domain (aa 13 to 35) was dispensable for viral replication, and the nsp2 middle hypervariable region (aa 324 to 813) tolerated 100-aa or 200-aa deletions but could not be removed as a whole; the largest deletion was about 400 aa (nsp2Delta324-726). Characterization of the mutants demonstrated that those with small deletions possessed growth kinetics and RNA expression profiles similar to those of the parental virus, while the nsp2Delta324-726 mutant displayed decreased cytolytic activity on MARC-145 cells and did not develop visible plaques. Finally, the utilization of the genetic flexibility of nsp2 to express foreign genes was examined by inserting the gene encoding green fluorescent protein (GFP) in frame into one nsp2 deletion mutant construct. The recombinant virus was viable but impaired and unstable and gradually gained parental growth kinetics by the loss of most of the GFP gene.


Listening to SARS: lessons for infection control.


title: Design, synthesis, testing, and quantitative structure-activity relationship analysis of substituted salicylaldehyde Schiff bases of 1-amino-3-hydroxyguanidine tosylate as new antiviral agents against coronavirus.

text: Further modifications of the structural features of Schiff bases of hydroxyaminoguanidines (SB-HAG) led to nine substituted salicylaldehyde Schiff bases of HAG (SSB-HAG) derivatives and three other SB-HAG derivatives. These new compounds were tested for the first time against infection by a coronavirus, mouse hepatitis virus (MHV). The most active compound, 2 [1-[(3'-allyl-2'-hydroxybenzylidene)amino]- 3-hydroxyguanidine], against the growth of MHV is about 376 times more active than hydroxyguanidine and about 564 times more active than HAG itself when the TCID50 values are compared. Plaque assays of MHV released from cells treated with these compounds suggest that SSB-HAG tosylate may inhibit the transcription of viral RNAs in virus-infected cells. Quantitative structure-activity relationship (QSAR) analyses of two subsets show that the inhibitory activities correlate well with the electronic and the lipophilic parameters. The structural requirements for the antiviral activity of substituted SSB-HAG tosylate against coronaviral infection are stringent according to the inhibitory activities and QSAR analysis of these new compounds.


title: The many important facets of T-cell repertoire diversity.

text: In the thymus, a diverse and polymorphic T-cell repertoire is generated by random recombination of discrete T-cell receptor (TCR)-alphabeta gene segments. This repertoire is then shaped by intrathymic selection events to generate a peripheral T-cell pool of self-MHC restricted, non-autoaggressive T cells. It has long been postulated that some optimal level of TCR diversity allows efficient protection against pathogens. This article focuses on several recent advances that address the required diversity for the generation of an optimal immune response.


title: Toll-like receptors and the eye.

text: PURPOSE OF REVIEW This review will describe the structure, expression/distribution and functional activity of Toll-like receptors, in particular in the ocular structures. It will also discuss innate and adaptive immune responses, by exploring the possible modulation/regulation of innate and adaptive immunity by Toll-like receptors, in view of recent findings observed in the ocular surface. RECENT FINDINGS Current knowledge indicates that Toll-like receptors represent essential elements in host defence against pathogens, a prerequisite to the induction of adaptive immune responses. The expression/distribution of Toll-like receptors in the healthy eye highlights the possible function of Toll-like receptors in both innate and adaptive responses during pathological conditions of the ocular surface. SUMMARY Recent findings have greatly increased the knowledge of the possible role of Toll-like receptors in innate and adaptive immune responses. Toll-like receptors seem to play different roles in a wide range of activities of the immune system, and might represent an exclusive link between innate and adaptive responses under pathological conditions. Recent studies in ophthalmology have highlighted the role of Toll-like receptors in infections (keratitis) as well as in allergic states of the ocular surface. This review thus describes the relationship between Toll-like receptors and the main immune/structural cells taking part in inflammatory disorders. Understanding the complex mechanisms underlying Toll-like receptor localization and function will provide additional data that might help devise novel therapeutic approaches involving Toll-like receptors and their agonists, in an attempt to modulate the biased immune system.


title: Emergency management and infection control in a radiology department during an outbreak of severe acute respiratory syndrome.

text: The World Health Organization classified Taiwan as a serious epidemic-stricken area when the extent of severe acute respiratory syndrome (SARS) in Taiwan became clear. As of 11 July 2003, 671 probable SARS cases had been identified in Taiwan and 7 healthcare workers had died from the disease. Radiographers were easily infected by SARS because they had close contact with suspected or probable cases while conducting chest X-ray examinations. Three radiographers had been infected by the end of May 2003. Because of the impact of SARS on the Radiology Department, the department established a SARS emergency infection control team and re-designed the department's infection-control and emergency-management procedures based on the concept of risk-grade protection. This effort included installing a radiographic room at the fever-screening station, re-allocating human resources in the Radiology Department, training the department staff in infection control, and drafting new operational procedures for radiographers conducting X-ray examinations on SARS patients. The goal of this program was to reduce the infection rate and distribute materials efficiently in the department. This article introduces the emergency-management procedure of the Radiology Department during the SARS outbreak and the infection-protection experience of the department staff.


title: Viral respiratory tract infection and exacerbations of asthma in adult patients.

text: The role of viral respiratory tract infections in acute exacerbations of asthma was studied prospectively in 31 patients with atopic asthma aged 15-56 years. Patients recorded symptom scores for asthma and peak expiratory flow rate daily for 11 months. In addition, they reported for detailed clinical, functional, and virological study every four weeks and as soon as possible after the onset of worsening asthma or symptoms suggesting a respiratory tract infection. Thirty viral identifications were made, of which 18 (60%) were associated with an exacerbation of asthma. Viral respiratory tract infection was identified in 18 (10%) of the 178 exacerbations of asthma, and in 10 (36%) of the 28 severe exacerbations. The frequency of viral identifications in 16 non-asthmatic, control subjects during the same period was similar. It is concluded that viral respiratory tract infections may cause or be associated with exacerbations of asthma in adults, and that they are an important factor in severe exacerbations.


title: Head and neck manifestations of lymphogranuloma venereum.

text: Lymphogranuloma venereum (LGV)--caused by Chlamydia trachomatis serovars L1, L2, or L3--rarely occurs in the United States. The disease clinically manifests in three stages: primary, secondary, and tertiary. The primary manifestation, a self-limited genital ulcer at the site of inoculation, often is absent by the time the patient seeks medical attention. The most common clinical manifestation of LGV is evident in its secondary stage: unilateral tender inguinal and/or femoral lymphadenopathy. However, proctocolitis or inflammatory involvement of perirectal or perianal lymphatic tissues resulting in fistulas and strictures may also occur. The diagnosis of LGV is usually made serologically and by exclusion of other causes of inguinal lymphadenopathy or genital ulcers. Doxycycline is the preferred treatment; it cures the infection and prevents ongoing tissue damage. This case highlights an unusual manifestation of LGV infection--cervical lymphadenopathy following suspected oropharyngeal infection with C trachomatis. Head and neck manifestations of LGV may become an increasing problem in the future if sexual practices such as orogenital contact become more widespread.


title: Replication of rat coronaviruses in intestinal cell line, RCN-9, derived from F344 rats.

text: To examine the susceptibility of the epithelial cell line to rat coronavirus (RCV), we inoculated sialodacryoadenitis virus and Parker's RCV into five cell lines; JTC-19, rat L2, LLC, RCN-9 and LBC cells originating in the lungs, intestines and mammary tumors of rodents. Both RCVs were replicated in LBC and RCN-9 cells, but not in the others. The infectivity titers of both RCVs grown in RCN-9 cells were significantly higher than those in LBC cells in every passage (2.5-3.9 log rate). Both RCVs replicated in LBC cells showed higher tropism to RCN-9 cells than to LBC cells, suggesting that RCN-9 cells are more suitable for the replication of RCVs than LBC cells. The RCN-9 cell line would be useful for the investigation of RCV infection in rodents.


title: [Epidemiology, diagnosis and treatment of Middle East respiratory syndrome].

text: Middle East respiratory syndrome (MERS) has raised global public health concerns. The recent outbreak of MERS coronavirus (MERS-CoV) infection has led to 1 338 laboratory-confirmed cases in 26 countries worldwide as reported till 19 June, 2015. MERS-CoV may be considered a zoonotic virus that has crossed the species barrier to humans, but the pathogenesis and the routes of transmission are not completely understood. Most MERS-CoV cases reported thus far have a history of residence in or travel to the Middle East. Human-to-human transmission though was observed on some occasions in Korea, it is documented as non-sustainable event. The envelope spike glycoprotein on the surface of MERS-CoV which mediates receptor binding, membrane fusion and viral entry is thought to be involved in the mechanism of MERS-CoV.No specific and effective treatment for MERS-CoV is currently recommended, although supportive treatment has played an important role. Prophylactic strategies are necessary to prevent MERS-CoV infection.


title: Intracellular localization of the severe acute respiratory syndrome coronavirus nucleocapsid protein: absence of nucleolar accumulation during infection and after expression as a recombinant protein in vero cells.

text: The nucleocapsid (N) protein of several members within the order Nidovirales localizes to the nucleolus during infection and after transfection of cells with N genes. However, confocal microscopy of N protein localization in Vero cells infected with the severe acute respiratory syndrome coronavirus (SARS-CoV) or transfected with the SARS-CoV N gene failed to show the presence of N in the nucleoplasm or nucleolus. Amino acids 369 to 389, which contain putative nuclear localization signal (NLS) and nucleolar localization signal motifs, failed to restore nuclear localization to an NLS-minus mutant Rev protein. These data indicate that nuclear localization is not a conserved property among all nidoviruses.


title: Detection of 12 respiratory viruses with two-set multiplex reverse transcriptase-PCR assay using a dual priming oligonucleotide system.

text: BACKGROUND We intended to evaluate the diagnostic usefulness of a multiplex reverse transcriptase- PCR (mRT-PCR) assay kit under dual priming oligonucleotide system (DPO) for the childhood acute respiratory tract infections. METHODS Two hundred nasopharyngeal aspirates were taken from children < or =5 yr old admitted due to acute respiratory infections in 2004. Direct fluorescent antibody (FA) assays were performed with fresh specimens; then, mRT-PCRs for the detection of 12 respiratory viruses (Seeplex RV detection kit, SeeGene, Seoul, Korea) were tested with frozen specimens. RESULTS FA assays for five common respiratory viruses showed positive results in 66 patients (33.0%), while mRT-PCR detected causative viruses in 112 patients (56.0%), including 16 co-infected cases (8.0%). A total of 129 viruses were identified: respiratory syncytial virus A/B (38.0%/7.8%), influenza virus A/B (10.1%/5.4%), parainfluenza virus 1/2/3 (7.0%/3.1%/7.8%), coronavirus 229E or NL63 (6.2%), human metapneumovirus (4.7%), adenovirus (4.7%), rhinovirus (3.9%), and coronavirus OC43 (1.6%). CONCLUSIONS DPO-based mRT-PCR was found as a sensitive tool for the detection of the viruses that cause childhood respiratory infections. Clinical significances of the agents detected by mRTPCR need further evaluations.


title: A 5'-proximal RNA sequence of murine coronavirus as a potential initiation site for genomic-length mRNA transcription.

text: Coronavirus transcription is a discontinuous process, involving interactions between a trans-acting leader and the intergenic transcription initiation sequences. A 9-nucleotide (nt) sequence (UUUAUAAAC), which is located immediately downstream of the leader at the 5' terminus of the mouse hepatitis virus (MHV) genomic RNA, contains a sequence resembling the consensus intergenic sequence (UCUAAAC). It has been shown previously that the presence of the 9-nt sequence facilitates leader RNA switching and may enhance subgenomic mRNA transcription. It is unclear how the 9-nt sequence exerts these functions. In this study, we inserted the 9-nt sequence into a defective interfering (DI) RNA reporter system and demonstrated that mRNA transcription could be initiated from the 9-nt sequence almost as efficiently as from the intergenic sequence between genes 6 and 7. Sequence analysis of the mRNAs showed that the 9-nt sequence served as a site of fusion between the leaders and mRNA. The transcription initiation function of the 9-nt sequence could not be substituted by other 5'-terminal sequences. When the entire 5'-terminal sequence, including four copies of the UCUAA sequence plus the 9-nt sequence, was present, transcription could be initiated from any of the UCUAA copies or the 9-nt sequence, resulting in different copy numbers of the UCUAA sequence and the deletion of the 9-nt sequence in some mRNAs. All of these heterogeneous RNA species were also detected from the 5'-terminal region of the viral genomic-length RNA in MHV-infected cells. These results thus suggest tha the heterogeneity of the copy number of UCUAA sequences at the 5' end, the deletion of the 9-nt sequence in viral and DI RNAs, and the leader RNA switching are the results of transcriptional initiation from the 9-nt site. They also show that an mRNA species (mRNA 1) that lacks the 9-nt sequence can be synthesized during MHV infection. Therefore, MHV genomic RNA replication and mRNA 1 transcription may be distinguishable.


title: SARS-CoV-2 invades the West. How to face a COVID-19 epidemic in Lombardy, Northern Italy?

text: Not available.


Early neuroschistosomiasis complicating Katayama syndrome.


title: Design and synthesis of cinanserin analogs as severe acute respiratory syndrome coronavirus 3CL protease inhibitors.

text: The severe acute respiratory syndrome (SARS) coronavirus 3CL protease is an attractive target for the development of anti-SARS drugs. In this paper, cinanserin (1) analogs were synthesized and tested for the inhibitory activities against SARS-coronavirus (CoV) 3CL protease by fluorescence resonance energy transfer (FRET) assay. Four analogs show significant activities, especially compound 26 with an IC(50) of 1.06 microM.