title: CVTree: a phylogenetic tree reconstruction tool based on whole genomes.

text: Composition Vector Tree (CVTree) implements a systematic method of inferring evolutionary relatedness of microbial organisms from the oligopeptide content of their complete proteomes (http://cvtree.cbi.pku.edu.cn). Since the first bacterial genomes were sequenced in 1995 there have been several attempts to infer prokaryote phylogeny from complete genomes. Most of them depend on sequence alignment directly or indirectly and, in some cases, need fine-tuning and adjustment. The composition vector method circumvents the ambiguity of choosing the genes for phylogenetic reconstruction and avoids the necessity of aligning sequences of essentially different length and gene content. This new method does not contain 'free' parameter and 'fine-tuning'. A bootstrap test for a phylogenetic tree of 139 organisms has shown the stability of the branchings, which support the small subunit ribosomal RNA (SSU rRNA) tree of life in its overall structure and in many details. It may provide a quick reference in prokaryote phylogenetics whenever the proteome of an organism is available, a situation that will become commonplace in the near future.


10 years later...


Contagious acute gastrointestinal infections.


title: Clarification of Interaction Mechanism of Mouse Hepatitis Virus (MHV) N and nsp3 Protein with Homology Modeling and Protein-Protein Docking Analysis.

text: The coronavirus nucleocapsid (N) plays an important role in the virus structure, the replication, and the transcription of CoV. This protein, which has a helix and flexible structure, and capable of binding on to the viral genomic RNA, is a non-structural protein (nsp3). Many studies suggest that the N protein interaction with nsp3 plays a critical role in the virus replication early in infection. Therefore, it is necessary to know the definition of the interaction mechanism of N and nsp3 protein in terms of the CoV replication transcription mechanism. We report on the homology modeling, molecular dynamics simulation, and docking studies to explain the structure-function relationship and the interaction mechanism. In addition, the prototype MHV is preferred in the wet experiment, so we also based our study on the MHV N and nsp3 proteins that belong to the experimental study. The amino acid sequences of MHV N and nsp3 proteins have similarity between human and severe acute respiratory syndrome coronavirus. Therefore, the 3D structure models of these proteins were built with using the crystal structure of the CoV family members as a template. By following these models, molecular dynamics simulations were applied to attain the most stable conformation. Finally, protein-protein docking was performed to prove accuracy of model structures of the MHV N and to clarify the interaction with nsp3. As a result, Lys 113, Arg 125, Tyr 127, Glu 173, Tyr 190 residues that play an important role in virus replication were determined.


Detection of infectious bursal disease virus in digested formalin-fixed paraffin-embedded tissue sections by polymerase chain reaction.


title: Class orders now possible under Ontario's public health legislation.

text: In April 2003, the Ontario Legislature amended the province's public health legislation as part of a package of amendments related to the recent outbreak of Severe Acute Respiratory Syndrome (SARS). Although the amendments to the Health Protection and Promotion Act (HPPA) were clearly designed to address emergency situations like SARS, they may have unintended and negative consequences for people living with HIV/AIDS.


Scalable high-throughput micro-expression device for recombinant proteins.


title: Restriction of poliovirus RNA replication in persistently infected nerve cells.

text: The aetiology of post-polio syndrome may involve persistence of poliovirus (PV) in the CNS. PV persists in the CNS of infected paralysed mice for over a year after the acute phase of paralytic poliomyelitis. However, infectious PV particles cannot be recovered from homogenates of CNS from paralysed mice after the acute phase of disease, indicating that PV replication is restricted. To identify the molecular mechanism by which PV replication is limited, PV RNA synthesis was analysed by estimating the relative level of genomic (plus-strand) and complementary (minus-strand) PV RNA in the CNS of persistently infected mice. PV RNA replication decreased during the 6 months following onset of paralysis, due mainly to inhibition of plus-strand RNA synthesis. Thus, restriction of PV RNA synthesis may contribute to persistence by limiting virus replication in the mouse CNS. Interestingly, viral RNA replication was similarly inhibited in neuroblastoma IMR-32 cell cultures persistently infected with PV. This in vitro model thus shows that cellular factors play a role in the inhibition of viral RNA synthesis.


title: Measurement equivalence of the center for epidemiological studies depression scale for Latino and Anglo adolescents: a national study.

text: The cross-ethnic measurement equivalence of the Center for Epidemiologic Studies Depression Scale (CES-D; L. S. Radloff, 1977) was examined using a subsample of adolescents (N=10,691) from the National Longitudinal Study of Adolescent Health. Configural and metric invariance, as well as functional and scalar equivalence, were examined for Anglo American, Mexican American, Cuban American, and Puerto Rican American youths age 12-18 years. Confirmatory factor analysis (CFA) in each group provided evidence of configural invariance for European and Mexican American adolescents but not for Cuban and Puerto Rican youths. A 2-group CFA for Anglo and Mexican Americans demonstrated partial metric invariance for these groups. Multigroup structural equation modeling indicated similar relations between CES-D scores and self-esteem for all 4 groups, supporting cross-ethnic functional and scalar equivalence. The results have implications for using the CES-D in cross-ethnic research and, more broadly, for the assessment and treatment of depression in Latinos.


title: The History of Surgical Staplers: A Combination of Hungarian, Russian, and American Innovation.

text: Since their development in 1908, surgical staplers have been used as a method of "mechanical suturing" in efforts to divide hollow viscera and create anastomoses in an efficient and sterile manner. The concept for the surgical stapler was first developed by Humér Hultl, a Hungarian professor and surgeon, and designed by Victor Fischer, a Hungarian businessman and designer of surgical instruments. The design was highly acclaimed; however, it was bulky, cumbersome, and expensive to manufacture. In 1920, Aladár Petz, a student of Hultl, incorporated two innovations to the Fischer-Hultl stapler to create a more lightweight model, which was named the Petz clamp. In 1934, Friedrich of Ulm designed what would be the predecessor to the modern-day linear stapler. In the 1950s, Russian and American staplers began to emerge. Throughout the 1960s, a variety of stapling instruments were developed in the United States, manufactured by the United States Surgical Corporation. In the 1970s, Johnson & Johnson Ethicon brand joined the market. The United States Surgical Corporation was later bought by Tyco Healthcare and became Covidien in 2007. Through the collaboration of Felicien Steichen, Mark Ravitch, and Leon Hirsch, surgical staplers were further modified to incorporate interchangeable cartridges with various designs. With the advent of minimally invasive surgery began production of laparoscopic surgical staplers. Since its inception, the surgical stapler has provided a means to efficiently create safe and effective visceral and vascular anastomoses. The surgical stapler design continues to evolve while still maintaining the basic principles that were implemented in the original design.


Vitamin D, Covid-19 and Children.


title: Kunjin virus replicons: an RNA-based, non-cytopathic viral vector system for protein production, vaccine and gene therapy applications.

text: The application of viral vectors for gene expression and delivery is rapidly evolving, with several entering clinical trials. However, a number of issues, including safety, gene expression levels, cell selectivity and antivector immunity, are driving the search for new vector systems. A number of replicon-based vectors derived from positive-strand RNA viruses have recently been developed, and this paper reviews the current knowledge on the first flavivirus replicon system, which is based on the Australian flavivirus Kunjin (KUN). Like most replicon systems, KUN replicons can be delivered as DNA, RNA or virus-like particles, they replicate their RNA in the cytoplasm and direct prolonged high-level gene expression. However, unlike most alphavirus replicon systems, KUN replicons are non-cytopathic, with transfected cells able to divide, allowing the establishment of cell lines stably expressing replicon RNA and heterologous genes. As vaccine vectors KUN replicons can induce potent, long-lived, protective, immunogen-specific CD8+ T cell immunity, a feature potentially related to extended production of antigen and double-stranded RNA-induced 'danger signals'. The identification of KUN replicon mutants that induce increased levels of IFN-alpha/beta has also spawned investigation of KUN replicons for use in cancer gene therapy. The unique characteristics of KUN replicons may thus make them suitable for specific protein production, vaccine and gene therapy applications.


title: Self-sampling for analysis of respiratory viruses in a large-scale epidemiological study in Sweden.

text: Viral diagnosis of respiratory tract infections has so far required sampling by health professionals,hampering large-scale epidemiological studies of virus-specific disease outcomes. As part of a population-based, prospective study of work-related risk factors for transmission of viral infections (SWEDE-I), we developed a scheme for self-sampling with nasal swabs. Random selection from the gainfully employed population of a medium-sized town in central Sweden resulted in a study cohort of 2,237 men and women aged 25 to 63 years. From September 2011 through May 2012, the cohort reported all instances of respiratory tract infection or gastroenteritis and participants concomitantly sent self-sampled nasal swabs for analysis using regular mail. Diagnosis of 14 viruses was performed. A total of 1,843 samples were received. The week-wise average delay between disease on set and arrival of the specimens at the laboratory varied between four and six days, and the corresponding median delay was between 3.5 and six days. In line with previous community-based studies, picorna- and coronaviruses dominated in specimens obtained from the self-sampling scheme. The results of self-sampling were contrasted to those from contemporaneous routine clinical sampling, on the same age group, in the adjacent Stockholm county. Although higher proportions of positive samples for respiratory syncytial virus and influenza were observed in the clinical sampling scheme, estimations of seasonality for influenza A and picornaviruses derived from both schemes were similar. Our findings show that nasal self-sampling is feasible in large-scale surveillance of respiratory infections and opens new prospects for population based,virologically verified research on virus spread,burden of disease, and effects of environmental factors or interventions.


title: Identification of immunodominant sites on the spike protein of severe acute respiratory syndrome (SARS) coronavirus: implication for developing SARS diagnostics and vaccines.

text: The spike (S) protein of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is not only responsible for receptor binding and virus fusion, but also a major Ag among the SARS-CoV proteins that induces protective Ab responses. In this study, we showed that the S protein of SARS-CoV is highly immunogenic during infection and immunizations, and contains five linear immunodominant sites (sites I to V) as determined by Pepscan analysis with a set of synthetic peptides overlapping the entire S protein sequence against the convalescent sera from SARS patients and antisera from small animals immunized with inactivated SARS-CoV. Site IV located in the middle region of the S protein (residues 528-635) is a major immunodominant epitope. The synthetic peptide S(603-634), which overlaps the site IV sequence reacted with all the convalescent sera from 42 SARS patient, but none of the 30 serum samples from healthy blood donors, suggesting its potential application as an Ag for developing SARS diagnostics. This study also provides information useful for designing SARS vaccines and understanding the SARS pathogenesis.


title: Prevention of symptomatic pulmonary embolism in patients undergoing total hip or knee arthroplasty.

text: This clinical practice guideline is based on a systematic review of published studies on the management of adult patients undergoing total hip replacement (THR) or total knee replacement (TKR) aimed specifically at preventing symptomatic pulmonary embolism (PE). The guideline emphasizes the need to assess the patient's risk for both PE and postoperative bleeding. Mechanical prophylaxis and early mobilization are recommended for all patients. Chemoprophylactic agents were evaluated using a systematic literature review. Forty-two studies met eligibility criteria, of which 23 included patients who had TKR and 25 included patients who had THR. The following statements summarize the recommendations for chemoprophylaxis: Patients at standard risk of both PE and major bleeding should be considered for aspirin, low-molecular-weight heparin (LMWH), synthetic pentasaccharides, or warfarin with an international normalized ratio (INR) goal of < or =2.0. Patients at elevated (above standard) risk of PE and at standard risk of major bleeding should be considered for LMWH, synthetic pentasaccharides, or warfarin with an INR goal of < or =2.0. Patients at standard risk of PE and at elevated (above standard) risk of major bleeding should be considered for aspirin, warfarin with an INR goal of < or =2.0, or none. Patients at elevated (above standard) risk of both PE and major bleeding should be considered for aspirin, warfarin with an INR goal of < or =2.0, or none.


title: Risks from emerging animal diseases.

text: Emerging diseases of animals pose great threats to the health of the world and could potentially cripple financial wellbeing, food security or environmental vigour. Recent history has demonstrated that factors inherent in our globalised civilisation will ensure that new diseases will continue to occur in humans, as well as in animals. Focus has been on macroscopic factors underlying disease emergence, including trade, husbandry changes and environmental damage, any of which can facilitate the transfer of a microorganism from one host species to another, with possibly deadly results. However, the events that occur at the microscopic level deserve attention. The author presents the sequence of events that a microbe undertakes as it moves from one species to another and the hurdles faced as it negotiates a new environment to perhaps cause disease.


title: Patterns in Bacterial- and Viral-Induced Immunosuppression and Secondary Infections in the ICU.

text: Immunosuppression renders the host increased susceptible for secondary infections. It is becoming increasingly clear that not only bacterial sepsis, but also respiratory viruses with both severe and mild disease courses such as influenza, respiratory syncytial virus, and the human rhinovirus may induce immunosuppression. In this review, the current knowledge on (mechanisms of) bacterial- and virus-induced immunosuppression and the accompanying susceptibility toward various secondary infections is described. In addition, the frequently encountered secondary pathogens and their preferred localizations are presented. Finally, future perspectives in the context of the development of diagnostic markers and possibilities for personalized therapy to improve the diagnosis and treatment of immunocompromised patients are discussed.


title: [Techniques used for the diagnostic of upper and lower respiratory tract viral infections].

text: Techniques used for the diagnostic of upper and lower respiratory tract viral infections Techniques used for the diagnostic of upper and lower respiratory tract viral infections include conventional procedures and the new molecular tools. Serology has no interest for diagnosis. Antigen detection can be carried out by simple, easy and cheap tools. They are available at hospital and in community practice as well for the detection of influenza virus, RSV, hMPV, parainfluenza virus and adenovirus. To look for viruses which are non detectable by antigen detection assays (rhinovirus, coronavirus, bocavirus, polyomavirus...) or in severe or complicated respiratory lower infections, the use of molecular tools is highly indicated.


title: SJL/J mice are highly susceptible to infection by mouse adenovirus type 1.

text: Mouse adenovirus type 1 (MAV-1) targets endothelial and monocyte/macrophage cells throughout the mouse. Depending on the strain of mouse and dose or strain of virus, infected mice may survive, become persistently infected, or die. We surveyed inbred mouse strains and found that for the majority tested the 50% lethal doses (LD(50)s) were >10(4.4) PFU. However, SJL/J mice were highly susceptible to MAV-1, with a mean LD(50) of 10(-0.32) PFU. Infected C3H/HeJ (resistant) and SJL/J (susceptible) mice showed only modest differences in histopathology. Susceptible mice had significantly higher viral loads in the brain and spleen at 8 days postinfection than resistant mice. Infection of primary macrophages or mouse embryo fibroblasts from SJL/J and C3H/HeJ mice gave equivalent yields of virus, suggesting that a receptor difference between strains is not responsible for the susceptibility difference. When C3H/HeJ mice were subjected to sublethal doses of gamma irradiation, they became susceptible to MAV-1, with an LD(50) like that of SJL/J mice. Antiviral immunoglobulin G (IgG) levels were measured in susceptible and resistant mice infected by an early region 1A null mutant virus that is less virulent that wild-type virus. The antiviral IgG levels were high and similar in the two strains of mice. Taken together, these results suggest that immune response differences may in part account for differences in susceptibility to MAV-1 infection.


title: Will considerations of environmental sustainability revitalise the policy links between the urban environment and health?

text: This paper explores when and how considerations of population health have influenced the creation, planning and management of cities. Cities--now the dominant human habitat--must be planned and managed sustainably in a world that is manifestly experiencing increasing environmental and social strains. Early industrialisation entailed crowding, squalor and industrial environmental blight; the two great associated public health hazards were infectious diseases and air pollution. These hazards have been largely controlled in rich countries. Today's main urban health hazards are obesity (with its life-shortening health consequences) and the huge contribution of cities to climate change with the resultant risks to population health. These and other health issues in urban environments need to be understood and addressed at the community or population level. This is an ecological challenge, crucial to attaining real sustainability.


title: Extent and predictors of microbial hand contamination in a tertiary care ophthalmic outpatient practice.

text: PURPOSE To measure the extent of microbial hand contamination among ophthalmologists during routine clinic practice and examine its association with hand cleansing practices and beliefs, glove use, and patient load. METHODS This was a single-masked analysis of resident and transient flora of ophthalmologists before and after patient examination and after handwashing by agar imprints of the dominant hand. Standardized questionnaires were used to collect information concerning subjects' hand cleansing practices and patient load. RESULTS Of the 108 cultures, 107 (99.1%) were culture positive, yielding 15 separate organisms. Gram-negative bacilli were the most common transient flora, followed by Gram-positive cocci and fungi. Thirty-five (97.2%) ophthalmologists were culture positive for at least one resident and 8 (22.2%) ophthalmologists were culture positive for at least one transient organism, before patient contact. Regression models showed alcohol-based hand rub use, transient and resident floral load before patient contact, and patient load collectively accounted for 58.7% of the variance in resident floral load after patient contact. Use of alcohol-based hand rubs was associated with a mean resident floral reduction of 324.4 CFUs (95% confidence interval [CI] = 185.4 to 463.5; P < 0.01) and 31.6 CFUs (95% CI = 1.2 to 62.0; P < 0.05) after patient contact and handwashing, respectively. Handwashing with chlorhexidine was a significant predictor for transient floral load after handwashing (unstandardized beta = -17.2; 95% CI = -10.2 to -24.2; P < 0.01). CONCLUSIONS The extent of contamination with pathogenic organisms after contact with eye outpatients, who have traditionally been perceived as relatively "clean," was of concern. Previously identified risk factors for hand contamination in inpatient settings, such as patient load, only explained a small proportion of variance in microbial load in the ophthalmic outpatient setting.


title: Assessment of the effectiveness of the 2003-04 influenza vaccine among children and adults--Colorado, 2003.

text: The 2003-04 influenza season was characterized by the early onset of influenza activity, reports of severe illness, particularly in children, and predominant circulation of an influenza A (H3N2) virus strain that was antigenically different from the influenza A (H3N2) vaccine strain. In 2003, a retrospective cohort study among children and a case-control study among adults in Colorado were conducted to provide preliminary data on the effectiveness of the 2003-04 influenza vaccine. This report summarizes the results of those studies, which indicated vaccine effectiveness (VE) among both adults and children, differing from results of a previous study that did not indicate effectiveness among adults.


title: Viruses: overturning RNA turnover.

text: It is becoming clear that viruses interface with the mRNA decay machinery in a variety of ways during an infection. First, RNA viruses in particular must evade the mRNA decay machinery long enough to replicate and establish infection. Second, many viruses usurp or augment cellular mRNA decay pathways to regulate or selectively express their own genes, often inducing massive decay of the host transcripttome. Finally, temporal progression of a viral infection can depend on regulated decay of specific viral transcripts. Therefore, in order to fully understand viral biology, we must take into account the interactions between viruses and the mRNA decay machinery. This approach gives insights into regulatory mechanisms of cellular mRNA decay, as well as reveals novel ways to influence the outcome of viral infections.


A Case of COVID-19 Infection: Chief Symptom, Diarrhea.


[About public health communication strategies and campaigns: what do you know about 2019-nCoV?]


title: [New insight into bacterial zoonotic pathogens posing health hazards to humans].

text: This article presents the problem of evolutionary changes of zoonotic pathogens responsible for human diseases. Everyone is exposed to the risk of zoonotic infection, particularly employees having direct contact with animals, i.e. veterinarians, breeders, butchers and workers of animal products' processing industry. The article focuses on pathogens monitored by the European Centre for Disease Prevention and Control (ECDC), which has been collecting statistical data on zoonoses from all European Union countries for 19 years and publishing collected data in annual epidemiological reports. Currently, the most important 11 pathogens responsible for causing human zoonotic diseases are being monitored, of which seven are bacteria: Salmonella spp., Campylobacter spp., Listeria monocytogenes, Mycobacterium bovis, Brucella spp., Coxiella burnetti and Verotoxin-producing E. coli (VTEC)/Shiga-like toxin producing E. coli (STEC). As particularly important are considered foodborne pathogens. The article also includes new emerging zoonotic bacteria, which are not currently monitored by ECDC but might pose a serious epidemiological problem in a foreseeable future: Streptococcus iniae, S. suis, S. dysgalactiae and staphylococci: Staphylococcus intermedius, S. pseudintermedius. Those species have just crossed the animal-human interspecies barrier. The exact mechanism of this phenomenon remains unknown, it is connected, however, with genetic variability, capability to survive in changing environment. These abilities derive from DNA rearrangement and horizontal gene transfer between bacterial cells. Substantial increase in the number of scientific publications on this subject, observed over the last few years, illustrates the importance of the problem.


title: Infection with porcine respiratory coronavirus does not fully protect pigs against intestinal transmissible gastroenteritis virus.

text: Eight nine-week-old specific-pathogen-free pigs which had been infected with the transmissible gastroenteritis virus (TGEV)-related porcine respiratory coronavirus (PRCV) and four uninfected littermates were challenged with TGEV. The previous PRCV infection failed to protect them against the enteric TGEV infection. Virus excretion in faeces was detected by an ELISA in all the pigs for three to six consecutive days after inoculation. Although little diarrhoea was observed, the infection extended through much of the small intestine of one of the previously infected pigs four days after inoculation. Challenge with TGEV caused a secondary neutralising antibody response. By using a peroxidase conjugate of a monoclonal antibody which recognises a specific antigenic site on TGEV, antibodies against TGEV could be distinguished from antibodies against PRCV in an ELISA blocking test.


title: The United Nations and One Health: the International Health Regulations (2005) and global health security.

text: The One Health approach encompasses multiple themes and can be understood from many different perspectives. This paper expresses the viewpoint of those in charge of responding to public health events of international concern and, in particular, to outbreaks of zoonotic disease. Several international organisations are involved in responding to such outbreaks, including the United Nations (UN) and its technical agencies; principally, the Food and Agriculture Organization of the UN (FAO) and the World Health Organization (WHO); UN funds and programmes, such as the United Nations Development Programme, the World Food Programme, the United Nations Environment Programme, the United Nations Children's Fund; the UN-linked multilateral banking system (the World Bank and regional development banks); and partner organisations, such as the World Organisation for Animal Health (OIE). All of these organisations have benefited from the experiences gained during zoonotic disease outbreaks over the last decade, developing common approaches and mechanisms to foster good governance, promote policies that cut across different sectors, target investment more effectively and strengthen global and national capacities for dealing with emerging crises. Coordination among the various UN agencies and creating partnerships with related organisations have helped to improve disease surveillance in all countries, enabling more efficient detection of disease outbreaks and a faster response, greater transparency and stakeholder engagement and improved public health. The need to build more robust national public human and animal health systems, which are based on good governance and comply with the International Health Regulations (2005) and the international standards set by the OIE, prompted FAO, WHO and the OIE to join forces with the World Bank, to provide practical tools to help countries manage their zoonotic disease risks and develop adequate resources to prevent and control disease outbreaks, particularly at the animal source. All these efforts contribute to the One Health agenda.


Severe acute respiratory syndrome: numbers do not tell whole story.


title: Curcumin combined with glycyrrhetinic acid inhibits the development of hepatocellular carcinoma cells by down-regulating the PTEN/PI3K/AKT signalling pathway.

text: Curcumin is an active component of turmeric, which is derived from the rhizomes of Curcuma longa. Glycyrrhetinic acid (GA) is a natural compound extracted from liquorice. Both curcumin and GA are widely used as anticancer agents for treating many human cancers. In this study, curcumin and GA were used separately and in combination to treat human hepatocellular carcinoma (HCC) HepG2 cells. MTT assays were used to evaluate cell proliferation. Flow cytometry was carried out to measure cell apoptosis and determine cell cycle progression. Western blot analyses were applied to determine the expression levels of B-cell lymphoma-2 (Bcl-2), B-cell associated X protein (Bax), phosphatase and tensin homolog (PTEN), phosphorylated phosphoinositide 3-kinase (PI3K) and AKT serine/threonine kinase 1 (Akt). The results showed that combined treatment with curcumin and GA resulted in a significant reduction in proliferation and an increase in apoptosis and G1 cell cycle arrest in HepG-2 cells. A xenograft tumour model showed that curcumin and GA suppressed HCC development in vivo. Moreover, by knocking down the expression of PTEN, we confirmed that curcumin and GA exert their anticancer effects by inhibiting the PTEN/PI3K/Akt signalling pathway. Collectively, these results indicate that the combination of curcumin and GA could effectively inhibit the development of HepG2 cells by inhibiting PTEN/PI3K/Akt signalling and could be a promising treatment strategy for patients with HCC.


title: Clinical and pathological responses of weaned pigs to atmospheric ammonia and dust.

text: Nine hundred and sixty weaned pigs were exposed for five weeks to controlled concentrations of atmospheric ammonia and dust in a single, multifactorial experiment. The treatments were a mean dust concentration of either 1.2, 2.7, 5.1 or 9.9 mg/m3 (inhalable fraction) and a mean ammonia concentration of either 0.6, 10.0, 18.8 or 37.0 ppm, concentrations representative of commercial conditions. The experiment was carried out over two years and the pigs were used in eight batches, each consisting of five lots of 24 pigs. Each treatment combination was replicated once, and an additional control lot (nominally 0 mg/m3 dust and 0 ppm ammonia) was included in each batch. The dust concentration was the same in the other four lots in each batch in which the four concentrations of ammonia were used; thus, the split-plot design was more sensitive to the effects of ammonia than dust. The groups of pigs were kept separately in five rooms in a purpose-built facility, and the pollutants were injected continuously into the air supply. Ammonia was supplied from a pressurised cylinder, and the endogenous dust in each room was supplemented by an artificial dust manufactured from feed, barley straw and faeces, mixed by weight in the proportions 5:1:4; its ingredients were oven-dried, milled and mixed, and then resuspended in the air supply. The health of the pigs was assessed in terms of general pathology, respiratory tract pathology, and the microbiology of the nasal cavity, trachea and lung. In each batch, postmortem examinations were carried out on 40 pigs after five weeks' exposure to the pollutants and on 30 pigs two weeks later to test for carryover and recovery--a total of 560 pigs. These examinations revealed minimal gross pathology and widespread minor pathological changes of little significance. The pigs' turbinate and lung scores were low and unaffected by exposure to pollutants. All the putative bacterial pathogens, with the exception of toxigenic Pasteurella multocida type D, were isolated from the respiratory tract of the pigs of both ages, but there were no differences between the effects of the different concentrations of pollutants.


title: [Construction and identification of nanobody phage display library targeting Middle East respiratory syndrome coronavirus].

text: Objective To construct a phage display library of specific nano-antibodies against the Middle East respiratory syndrome coronavirus (MERS-CoV) and apply it to the screening of neutralizing nano-antibodies. Methods MERS-CoV receptor-binding domain (RBD) recombinant protein was used to immunize alpaca. After the last immunization, peripheral blood mononuclear cells (PBMCs) were isolated from the whole blood and total RNA was extracted. The VHH gene was amplified by PCR and used to construct recombinant phages. TG1 Escherichia coli was transformed by these recombinant phages. A phage display library of specific nano-antibodies against the MERS-CoV were obtained and used to screen and characterize the nano-antibodies. Results The volume of this library of nano-antibodies was 1.31×108 and its abundance rate was 5.65×1010/mL. The ratio of VHH insertion in the constructed library reached 96%. There was a rich diversity of nano-antibodies in this library. Nano-antibodies with neutralizing activity were identified and expressed from this library. Conclusion We successfully constructed a library of phages which could be effectively applied to the screening of nano-antibodies against MERS-CoV virus.


title: [Isolation and identification of the infective agent of severe acute respiratory syndrome (SARS) from a patient with atypical pneumonia].

text: The virological, morphological, molecular biological and immunochemical study of the infective agent isolated from the patient with the symptoms of atypical pneumonia, hospitalized in the infectious department of the clinical hospital in Blagoveshchensk, was carried out. Thus the fact of the appearance of SARS virus on the territory of Russia was proved. The isolated infective agent, identified as coronavirus strain CoD, was partly characterized and deposited to the virus collection of the Center of Special Laboratory Diagnostics and Treatment of Quarantine and Exotic Infectious Diseases.


title: Detection of turkey enteric coronavirus by enzyme-linked immunosorbent assay and differentiation from other coronaviruses.

text: A double-antibody ELISA for the detection of coronaviruses in intestinal contents from turkey poults with diarrhea was developed. Antibodies were raised in rabbits and guinea pigs against a Minnesota isolate of turkey enteric coronavirus (TCV) propagated in embryonating turkey eggs and were purified by density-gradient centrifugation. The specificity of antisera was confirmed by hemagglutination-inhibition and immunoelectron microscopy. Absorption of anti-TCV hyperimmune sera with egg extracts or egg ovalbumin and the use of different dilution and blocking buffers influenced the sensitivity and specificity of the ELISA. Reciprocal cross-reactivity was detected among turkey, chicken, bovine, and murine coronaviruses. Antisera to the transmissible gastroenteritis virus of swine, the rabbit enteric coronavirus, or the human coronavirus strain 299E failed to react with TCV. The TCV cross-reacted only moderately with the avian infectious bronchitis virus and the hemagglutinating encephalomyelitis virus of swine. Investigations with samples from 47 commercial turkey flocks in Quebec with episodes of transmissible enteritis revealed that the ELISA was more sensitive than was electron microscopy for detection of TCV.


title: [Isolation of a concentrated purified preparation of the transmissible gastroenteritis virus of swine and a study of its antigenic properties].

text: Pretreatment of the transmissible gastroenteritis virus of swine (TGE) (coronavirus) with trypsin increased the yield of the infectious virus approximately 100-fold when propagated in roller cultures of SPEV cells, the time required for the development of marked CPE being twice shorter than without treatment. The method of concentration and purification of TGE virus is described which yields a preparative amount of highly purified virions retaining their structure. Such preparations were used for immunization of guinea pigs. It is concluded that purified preparations of TGE virus possess marked antigenic potency and may be used for generation of highly active and specific hyperimmune sera.


title: The early warning and response system for communicable diseases in the EU: an overview from 1999 to 2005.

text: Under Decision 2119/98/EC of the European Parliament and of the Council, a network for epidemiological surveillance and control of communicable diseases in the Community was set up in 1998. One pillar of Decision 2119/98/EC is the early warning and response system (EWRS). The main objective of the network is to establish permanent communication between European Union (EU) Member States' public health authorities, which are responsible for determining the measures required to control communicable disease-related events. Since 1998, a web based informatics tool has been developed in order to allow information to be shared between the relevant public health authorities. Between 1998 and December 2005, a total of 583 messages were circulated through the EWRS, notifying 396 events. The information shared through the system helped to coordinate public health measures in the EU. However, only few events prompted specific measures at Community level and most of them were controlled with public health measures applied at national level. Major events (such as the Severe Acute Respiratory Syndrome) and the results of simulation exercises prompted the Commission to upgrade the informatics system on the basis of user needs. Since 1 May 2004 the 10 newest Member States have provided information under the current legislation and since April 2005 the European Centre for Disease Prevention and Control (ECDC) is part of the system. Future developments will include a link between the existing EWRS and the communication platform currently developed by the ECDC.


title: Effectiveness of treatment with lincomycin hydrochloride and/or vaccination against Mycoplasma hyopneumoniae for controlling chronic respiratory disease in a herd of pigs.

text: A herd of pigs infected with Mycoplasma hyopneumoniae was used in a double-blind randomised trial to assess the effectiveness of three control strategies against chronic respiratory disease in growing-finishing pigs. One group of 61 pigs received 220 ppm lincomycin hydrochloride in the feed from day 71 to day 91, a second group was vaccinated against M. hyopneumoniae at four and 28 days of age, and a third group received both treatments; a fourth group was left untreated as a control. Throughout the nursery-finishing period (day 29 to slaughter) the average daily weight gain and feed conversion rate of all the treated groups were slightly better than in the controls, but there were no significant differences between them. There were no significant differences between the treated groups in terms of clinical signs, serology, pathology or mortality, which was very low throughout the trial.


title: Immunohistochemical detection of Lawsonia intracellularis in tissue sections from pigs.

text: The aim of the present study was to develop an immunohistochemical method (IHC) for detection of Lawsonia intracellularis (L. intracellularis) in formalin-fixed, paraffin embedded sections of intestines from pigs and to implement this method in differential diagnosis of swine diseases with diarrhea in postweaning pigs. The study was conducted on 165 sections of intestines (ileum, caecum and colon) collected from 76 pigs, representing 42 Polish pig farms. The animals included in the analysis suffered from diarrhea, with bloody or grey to brown feces, and were suspected of porcine proliferative enteropathy (PPE). Sections of intestines were analyzed for the presence of L. intracellularis by polymerase chain reaction (PCR) and IHC. Among 165 intestinal samples from pigs with diarrhea, L. intracellularis DNA was detected by PCR in 33 (20.0%) samples. In this group, 30 samples (18.2% of all the samples tested) were also found positive in IHC, while only 3 (1.8%) were IHC-negative. One hundred thirty-two (80.0%) samples were negative in both tests. The PCR- and IHC-positive samples originated from 11 pigs, 4- to 20-week old, from 8 farms. L. intracellularis antigen was visualized by IHC mostly in intestinal crypts and/or in mononuclear cells of the lamina propria). The positive signal in epithelial cells was observed close to the luminal borders, creating typical specifically stained rims around the crypt lumina. The results of the present study further confirm the usefulness of IHC in the detection of L. intracellularis antigen in the intestinal tissues.


title: Anatomical and functional changes to the pelvic floor after robotic versus laparoscopic ventral rectopexy: a randomised study.

text: INTRODUCTION AND HYPOTHESIS To compare the effect of laparoscopic and robot-assisted ventral rectopexy for posterior compartment procidentia on the pelvic floor anatomy and function. METHODS A prospective randomised single-centre study was carried out of 29 female patients, who underwent robot-assisted or laparoscopic ventral mesh rectopexy for external or internal rectal prolapse with symptoms of obstructive defecation and/or faecal incontinence. Anatomical changes were measured by Pelvic Organ Prolapse Quantification (POP-Q) and magnetic resonance defecography. Functional changes were evaluated using symptom questionnaires before and 3 months after surgery. RESULTS After rectopexy, changes in POP-Q measurements were statistically significant for points Ap, Bp, C, D and Ba. The descent of the anorectum and cervix/vaginal cuff during straining were significantly reduced with regard to the reference line (mean, -10.4 ± 14.9 mm, p = 0.001) and (-13.3 ± 18.1 mm, p < 0.001) respectively. Pelvic organ mobility (POM) was reduced statistically significantly for the posterior (mean, -16.6 ± 20.8 mm, p < 0.001) and apical compartments (mean, -13.1 ± 14.8, p < 0.001). The PFDI-20, PFIQ-7 and PISQ-12 questionnaires showed statistically significant improvement of symptoms and sexual function. No significant differences were observed between the robot-assisted and laparoscopic techniques in terms of anatomical or functional parameters. CONCLUSION Ventral mesh recto-colpo-sacropexy effectively corrects the anatomy of the posterior compartment, elevates the vaginal apex and reduces pelvic organ mobility of the posterior and middle compartments. The robot-assisted and laparoscopic techniques had similar anatomical and functional outcomes.


title: Updated interim surveillance case definition for severe acute respiratory syndrome (SARS)--United States, April 29, 2003.

text: CDC's interim surveillance case definition for severe acute respiratory syndrome (SARS) has been updated to include laboratory criteria for evidence of infection with the SARS-associated coronavirus (SARS-CoV) (Figure, Box). In addition, clinical criteria have been revised to reflect the possible spectrum of respiratory illness associated with SARS-CoV. Epidemiologic criteria have been retained. The majority of U.S. cases of SARS continue to be associated with travel, with only limited secondary spread to household members or health-care providers.


Seasonal Influenza Vaccination and the Heightened Risk of Coronavirus and Other Pandemic Virus Infections: Fact or Fiction?


title: Laparoscopic repair of hiatal hernia after esophagectomy.

text: BACKGROUND Herniation of abdominal contents via the diaphragmatic hiatus is a potentially life-threatening complication of esophagectomy. Mounting evidence suggests that hiatal hernias are more common following minimally invasive esophagectomy. Therefore, post-esophagectomy hiatal hernia and its treatment bear increasing significance. METHODS We retrospectively reviewed the records of five patients with hiatal hernia following esophagectomy over a 5-year period. RESULTS Successful laparoscopic reduction of a post-esophagectomy hiatal hernia was done without mesh reinforcement in three patients. One patient underwent mesh reinforcement. One patient was found to have carcinomatosis upon laparoscopic inspection, and repair of the hiatal hernia was abandoned. There were no perioperative deaths or complications. One patient developed a recurrent hiatal hernia 14 months after repair of the initial hiatal hernia. Patients were discharged within a mean of 1.75 days after surgical repair. DISCUSSION We have successfully used laparoscopy to treat hiatal hernias after esophagectomy. The benefits conferred by laparoscopy, including better visualization of the right gastroepiploic artery supplying the gastric conduit, minimally invasive evaluation of the field for metastasis, and shorter recovery time, make it our favored approach. Here, we describe our experience with hiatal hernia following esophagectomy and our operative technique.


title: [Management of critical severe acute respiratory syndrome and risk factors for death].

text: OBJECTIVE To investigate the management of critical severe acute respiratory syndrome (SARS) and possible risk factors for death. METHODS Thirty-three patients with SARS referred to Guangzhou Institute of Respiratory Disease (GIRD) between December 2002 and March 2003 were studied retrospectively. Paired t-test using statistical software SPSS 10.0 was employed to compare the respiratory frequency and pulse O(2) saturation (SpO(2)) before and after noninvasive ventilation with continuous positive airway pressure (CPAP) on the 33 patients. Among them, 18 patients who presented with SpO(2) of 90% - 93% at rest under O(2) inhalation 5 L/min were further recorded for their SpO(2) during slight physical movement and CPAP. The possible death-related risk factors including age, underlying diseases, leucocytosis, thrombocytopenia, and lymphopenia were analyzed by the Mantel-Haenszel chi(2) test. RESULTS The respiratory frequencies were significantly decreased and SpO(2) was improved in the 33 patients after one hour of noninvasive ventilation. The SpO(2) in the latter 18 patients fell during slight physical movement and improved one hour after CPAP (p < 0.01). The RRs of the five death predictors concerning thrombocytopenia, age (> 50 yrs, underlying diseases, leucocytosis, and lymphopenia were 25.83, 8.57, 6.40, 1.64, and 1.17, respectively, with the 95% CI of 3.64 - 183.59, 1.94 - 37.83, 1.75 - 23.33, 0.38 - 7.05 and 0.16 - 8.48, respectively. Management with corticosteroids effectively ameliorated and suppressed the development of pulmonary fibrosis. CONCLUSIONS Noninvasive ventilation relieves dyspnea and SpO(2) in patients with critical SARS, and should also be employed in those with SpO(2) of 90% - 93% at rest under O(2) inhalation 5 L/min. Noninvasive as an add-on management may probably cut down on the dosage and duration of corticosteriod therapy. Among 5 possible risk factors, 3 were recognized as death-related, turning out to be thrombocytopenia, age (> 50 yrs) and underlying diseases.


Responding to new severe diseases--the case for routine hospital surveillance and clinical networks in Europe.


title: Reliability and psychometric properties of the Greek translation of the State-Trait Anxiety Inventory form Y: preliminary data.

text: BACKGROUND The State-Trait Anxiety Inventory form Y is a brief self-rating scale for the assessment of state and trait anxiety. The aim of the current preliminary study was to assess the psychometric properties of its Greek translation. MATERIALS AND METHODS 121 healthy volunteers 27.22 +/- 10.61 years old, and 22 depressed patients 29.48 +/- 9.28 years old entered the study. In 20 of them the instrument was re-applied 1-2 days later. Translation and Back Translation was made. The clinical diagnosis was reached with the SCAN v.2.0 and the IPDE. The Symptoms Rating Scale for Depression and Anxiety (SRSDA) and the EPQ were applied for cross-validation purposes. The Statistical Analysis included the Pearson Correlation Coefficient and the calculation of Cronbach's alpha. RESULTS The State score for healthy subjects was 34.30 +/- 10.79 and the Trait score was 36.07 +/- 10.47. The respected scores for the depressed patients were 56.22 +/- 8.86 and 53.83 +/- 10.87. Both State and Trait scores followed the normal distribution in control subjects. Cronbach's alpha was 0.93 for the State and 0.92 for the Trait subscale. The Pearson Correlation Coefficient between State and Trait subscales was 0.79. Both subscales correlated fairly with the anxiety subscale of the SRSDA. Test-retest reliability was excellent, with Pearson coefficient being between 0.75 and 0.98 for individual items and equal to 0.96 for State and 0.98 for Trait. CONCLUSION The current study provided preliminary evidence concerning the reliability and the validity of the Greek translation of the STAI-form Y. Its properties are generally similar to those reported in the international literature, but further research is necessary.


title: Newer respiratory virus infections: human metapneumovirus, avian influenza virus, and human coronaviruses.

text: PURPOSE OF REVIEW Recently, several previously unrecognized respiratory viral pathogens have been identified and several influenza A virus subtypes, previously known to infect poultry and wild birds, were transmitted to humans. Here we review the recent literature on these respiratory viruses. RECENT FINDINGS Human metapneumovirus has now been detected worldwide, causing severe respiratory tract illnesses primarily in very young, elderly and immunocompromised individuals. Animal models and reverse genetic techniques were designed for human metapneumovirus, and the first vaccine candidates have been developed. Considerable genetic and antigenic diversity was observed for human metapneumovirus, but the implication of this diversity for vaccine development and virus epidemiology requires further study. Two previously unrecognized human coronaviruses were discovered in 2004 in The Netherlands and Hong Kong. Their clinical impact and epidemiology are largely unknown and warrant further investigation. Several influenza A virus subtypes were transmitted from birds to humans, and these viruses continue to constitute a pandemic threat. The clinical symptoms associated with these zoonotic transmissions range from mild respiratory illnesses and conjunctivitis to pneumonia and acute respiratory distress syndrome, sometimes resulting in death. More basic research into virus ecology and evolution and development of effective vaccines and antiviral strategies are required to limit the impact of influenza A virus zoonoses and the threat of an influenza pandemic. SUMMARY Previously unknown and emerging respiratory viruses are an important threat to human health. Development of virus diagnostic tests, antiviral strategies, and vaccines for each of these pathogens is crucial to limit their impact.


Depression in patients with heart failure: prevalence, pathophysiological mechanisms, and treatment.


title: Superfamily 1 helicases .

text: Superfamily 1 helicases are nucleic acid motor proteins that couple ATP hydrolysis to translocation along, and concomitant unwinding of, DNA or RNA. This is central to many aspects of cellular DNA and RNA metabolism and, accordingly, they are implicated in a wide range of nucleic acid processing events including DNA replication, recombination and repair as well as many aspects of RNA metabolism. This review discusses our current understanding of the structure, function and mechanism of Superfamily 1 helicases.


title: Smallpox and bioterrorism.

text: Smallpox was declared to be eradicated on 8 May 1980, during the Thirty-third World Health Assembly. However, concerns about the possible use of the virus as a weapon of bioterrorism have increased in recent years. Governments have responded by initiating selective vaccination programmes and other public health measures. This review uses historical data from 20th century outbreaks to assess the risks to current populations (which have declining immunity) from a deliberate release of virus. The data presented supports the conclusion of a previous reviewer (Mack) that "smallpox cannot be said to live up to its reputation. Far from being a quick-footed menace, it has appeared as a plodding nuisance with more bark than bite." Its R value (the average number of secondary cases infected by a primary case) is lower than that for measles, human parvovirus, chickenpox, mumps, rubella, and poliomyelitis; only the value for severe acute respiratory syndrome (SARS) is lower. Like SARS, close person-to-person contact is required for effective spread of the disease, and exposure to the virus in hospitals has played an important role in transmission for both viruses. In the present paper the dangers of mass vaccination are emphasized, along with the importance of case isolation, contact tracing, and quarantine of close contacts for outbreak control. The need for rapid diagnosis and the continued importance of maintaining a network of electron microscopes for this purpose are also highlighted.


Vitamin E and respiratory tract infections in elderly persons.


title: Contact investigation of a case of human novel coronavirus infection treated in a German hospital, October-November 2012.

text: On 24 October 2012, a patient with acute respiratory distress syndrome of unknown origin and symptom onset on 5 October was transferred from Qatar to a specialist lung clinic in Germany. Late diagnosis on 20 November of an infection with the novel Coronavirus (NCoV) resulted in potential exposure of a considerable number of healthcare workers. Using a questionnaire we asked 123 identified contacts (120 hospital and three out-of-hospital contacts) about exposure to the patient. Eighty-five contacts provided blood for a serological test using a two-stage approach with an initial immunofluorescence assay as screening test, followed by recombinant immunofluorescence assays and a NCoV-specific serum neutralisation test. Of 123 identified contacts nine had performed aerosol-generating procedures within the third or fourth week of illness, using personal protective equipment rarely or never, and two of these developed acute respiratory illness. Serology was negative for all nine. Further 76 hospital contacts also tested negative, including two sera initially reactive in the screening test. The contact investigation ruled out transmission to contacts after illness day 20. Our two-stage approach for serological testing may be used as a template for similar situations.


title: Coronavirus inhibitor in human sera: age distribution and prevalence.

text: We studied the distribution, in human sera, of non antibody serum inhibitor active towards human OC43 and bovine NCDCV coronaviruses. Antibodies to coronaviruses, present with high prevalence in human sera, were filtered by Protein A Sepharose CL 4B column. In the present work we tested sera of newborns, infants, young children and adults. Inhibitory activity was revealed in all sera except these from newborns. This non antibody inhibitor was tested by a plaque-reduction assay.


title: [Left behind populations, COVID-19 and risks of health inequities : a guide of the local social-health network (Vaud, Switzerland)].

text: Since the emergence of the COVID-19 pandemic, the Confederation has referred to « vulnerable populations » over the age of 65 and/or with co-morbidities as potentially at risk. This group should not overshadow other highly vulnerable populations such as forced migrants, people deprived of their liberty, and the homeless. In the context of the current pandemic, there is a risk of increasing inequities in care among these populations. In this practical article, we list the marginalized and disadvantaged left behind populations in the canton of Vaud and the issues of inequities in care in the context of the pandemic; we also present the implementation of procedures sometimes original, always inter-professional and interdisciplinary, specifying who the partners are and what the resources are for front-line caregivers.


title: [Prokaryotic expression of SARS coronavirus spike protein and construction of its DNA vaccine].

text: OBJECTIVE To study the immunological characteristics of the spike (S) protein of SARS coronavirus (SARS-CoV) and analyze the feasibility of using this protein as the component for SARS vaccine development. METHODS The two truncated fragments of S gene were separately cloned into the prokaryotic expression vector pET-15b and expressed in E.coli. The resulting recombinant proteins, rS(a) and rS(b), were purified by affinity chromatography. The full-length S gene was cloned into the eukaryotic expression plasmid pSecTagB to prepare recombinant plasmid pSecS as the DNA vaccine to immunize BALB/c mice for inducing the secretion of anti-SARS-CoV protein. The immunological effect of anti-SARS-CoV antibody was tested with purified rS(a) and rS(b) proteins by enzyme-linked immunosorbent assay (ELISA). RESULTS Both the truncated recombinant proteins were expressed in soluble forms and reacted specifically with the sera from immunized pSecS mice and clinically diagnosed SARS patients. The prokaryotically expressed recombinant truncated S protein had similar antigenicity with SARS-CoV S protein. CONCLUSION The recombinant protein could be used as an antigen for detecting the serum of SARS CoV-infected patients. The SARS-CoV S gene vaccine could induce the production of specific antibody, which offers clues for the research of SARS DNA vaccine.


title: [Recommendations on the identification and transfer of children with critical diabetes during the COVID-19 outbreak].

text: Coronavirus disease 2019 (COVID-19) is the most serious public health problem in China. Children with diabetes are also among the population susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Traffic problems caused by epidemic prevention and control increase the difficulty in the management of children with severe diabetes. In order to control the spread of epidemic, children with mild diabetes are advised to be managed at home and in the community. However, how to treat children with severe diabetes effectively and safely during the outbreak of COVID-19 brings great challenges to primary doctors. The Subspecialty Group of Endocrinology and Metabolism, Society of Pediatrics, Chinese Medical Association and the Subspecialty Group of Endocrinology and Metabolism, Society of Pediatrics, Chinese Medical Doctor Association have developed the recommendations on the identification and transfer of children with critical diabetes during the COVID-19 outbreak, which provide a reference for primary doctors to quickly assess the severity of patient's condition and treat the illness accordingly, thus reducing the risk of referral infection and improving clinical prognosis.


title: Synthetic reconstruction of zoonotic and early human severe acute respiratory syndrome coronavirus isolates that produce fatal disease in aged mice.

text: The severe acute respiratory syndrome (SARS) epidemic was characterized by high mortality rates in the elderly. The molecular mechanisms that govern enhanced susceptibility of elderly populations are not known, and robust animal models are needed that recapitulate the increased pathogenic phenotype noted with increasing age. Using synthetic biology and reverse genetics, we describe the construction of a panel of isogenic SARS coronavirus (SARS-CoV) strains bearing variant spike glycoproteins that are representative of zoonotic strains found in palm civets and raccoon dogs, as well as isolates spanning the early, middle, and late phases of the SARS-CoV epidemic. The recombinant viruses replicated efficiently in cell culture and demonstrated variable sensitivities to neutralization with antibodies. The human but not the zoonotic variants replicated efficiently in human airway epithelial cultures, supporting earlier hypotheses that zoonotic isolates are less pathogenic in humans but can evolve into highly pathogenic strains. All viruses replicated efficiently, but none produced clinical disease or death in young animals. In contrast, severe clinical disease, diffuse alveolar damage, hyaline membrane formation, alveolitis, and death were noted in 12-month-old mice inoculated with the palm civet HC/SZ/61/03 strain or early-human-phase GZ02 variants but not with related middle- and late-phase epidemic or raccoon dog strains. This panel of SARS-CoV recombinants bearing zoonotic and human epidemic spike glycoproteins will provide heterologous challenge models for testing vaccine efficacy against zoonotic reintroductions as well as provide the appropriate model system for elucidating the complex virus-host interactions that contribute to more-severe and fatal SARS-CoV disease and acute respiratory distress in the elderly.


title: World Organisation for Animal Health: strengthening Veterinary Services for effective One Health collaboration.

text: To effectively reduce health risks at the animal-human-ecosystems interface, a One Health strategy is crucially important to create strong national and regional animal health systems that are well coordinated with strong public health systems. Animal diseases, particularly those caused by new and emerging zoonotic pathogens, must be effectively controlled at their source to reduce their potentially devastating impact upon both animal and human health. As the international organisation responsible for developing standards, guidelines and recommendations for animal health, the World Organisation for Animal Health (OIE) plays an important role in minimising animal and public health risks attributable to zoonoses and other animal diseases, which can have severe consequences for global food safety and security. National Veterinary Services, which implement OIE animal health and welfare standards and other measures, are the first line of defence against these diseases, and must have the capacity to meet the core requirements necessary for their diagnosis and control. The OIE works collaboratively with the World Health Organization and Food and Agriculture Organization of the United Nations to improve the ability of national animal and public health systems to respond to current and emerging animal health risks with public health consequences. In addition to improving and aligning national laboratory capacities in high-risk areas, the OIE collaborates on One Health-oriented projects for key diseases, establishing model frameworks which can be applied to manage other existing and emerging priority diseases. This article reviews the role and activities of the OIE in strengthening the national Veterinary Services of its Member Countries for a more effective and sustainable One Health collaboration.


title: Ease of intubation with the Parker Flex-Tip or a standard Mallinckrodt endotracheal tube using a video laryngoscope (GlideScope).

text: Two endotracheal tubes (ETTs) are available for use in operative suites for intubation: the Parker Flex-Tip (PFT, Parker Medical) and the standard Mallinckrodt (Covidien). To the authors' knowledge, no study has compared these 2 ETTs with each other when the anesthesia provider uses the GlideScope video laryngoscope (Verathon) for intubation. The purpose of the study was to determine if there are differences related to ease of intubation reported by anesthesia providers who use the PFT tube compared with the standard tube while using the GlideScope. The study was a randomized block intervention design. The sample consisted of 58 observed intubations in an operating room setting. Data analysis was completed with a 2-factor analysis of covariance using 2 covariates. The PFT tube in suboptimal conditions demonstrated a significantly greater ease of intubation, as measured by decreased time for ETT insertion and greater ease of ETT insertion score. The number of redirections at the glottis to intubate the trachea once the glottis was visualized was not statistically different. Based on the findings from this study, anesthesia providers may want to consider the use of the PFT tube when using the GlideScope to promote ease of intubation.


title: Frequency of detection of picornaviruses and seven other respiratory pathogens in infants.

text: BACKGROUND Previous studies in which molecular-based techniques have been used to identify the causative pathogens of respiratory tract infection have investigated hospitalized children only. We report a prospective study designed to determine the frequency and clinical presentation of community-acquired respiratory illness in infancy associated with 8 common respiratory pathogens. METHODS Eighty-eight infants were monitored through their first winter. With each respiratory illness, infants were examined, and a nasal lavage specimen was collected. Individual reverse transcription-polymerase chain reactions were performed to detect infection with picornaviruses (rhinoviruses and enteroviruses), coronaviruses (serotypes OC43 and 229E), adenoviruses, parainfluenza viruses 1-3, influenza viruses (types A and B), respiratory syncytial virus (RSV), Chlamydia pneumoniae and Mycoplasma pneumoniae. RESULTS Picornaviruses were the most frequently detected pathogen identified in 46% (56 of 123) of episodes, followed by RSV (27%), parainfluenza viruses (13%) and coronaviruses (9%). Dual pathogen infections were identified in 20% of episodes, predominantly caused by picornaviruses together with either RSV or parainfluenza viruses. RSV infection was significantly associated with a diagnosis of bronchiolitis. No other associations were found between pathogen and clinical diagnosis. Dual infection did not predispose infants to a more severe clinical course. CONCLUSIONS Picornaviruses are the predominant cause of community-acquired respiratory tract infection in the first year of life. Large prospective community-based studies will be needed to fully evaluate the contribution of picornaviruses, both in isolation and in combination with other respiratory pathogens, to the various clinical syndromes of respiratory infection observed during infancy.


title: Three outbreaks of salmonellosis associated with baby poultry from three hatcheries--United States, 2006.

text: During 2006, state health departments notified CDC of three outbreaks of Salmonella species infections in persons who had been in contact with chicks and other baby poultry (ducklings, goslings, and baby turkeys) purchased at agricultural feed stores. The feed stores received the poultry from hatcheries, and each of the three outbreaks was traced to a single hatchery. For decades, baby poultry, particularly chicks and ducklings, have been known to be a source of salmonellosis. More recently, the source of birds associated with salmonellosis outbreaks has been traced back to individual hatcheries. Many persons who purchase baby poultry remain unaware that contact with these birds puts them and others who are exposed to the birds, especially children and immunocompromised persons, at risk for salmonellosis. This report describes the three outbreaks and provides recommendations for preventing transmission of Salmonella infection from birds to humans.


title: A human cadaver model for laparoscopic kidney transplant.

text: OBJECTIVES To evaluate the technique of laparoscopic kidney transplant and demonstrate the feasibility of this procedure by an extraperitoneal approach. MATERIALS AND METHODS The procedure was performed on 2 human cadavers. Retroperitoneal endoscopic left nephrectomy was performed. An extraperitoneal space was established by inflation of a balloon dilator. The external iliac artery and vein were exposed. A Pfannenstiel incision (6 cm) was made and a hand-access device was used. The renal artery was anastomosed to the external iliac artery (end-to-side anastomosis); the renal vein was anastomosed to the external iliac vein (end-to-side anastomosis). The ureter was anastomosed to the bladder with an extravesical tunnelling technique. RESULTS The donor kidney grafts were obtained successfully. The preparation of the external iliac artery and vein was satisfactory. The entire procedure for the renal artery, renal vein, and ureteral anastomoses was performed with laparoscopic technique without any difficulty. CONCLUSIONS The present model on human cadavers may provide a feasible approach for training surgeons to perform human laparoscopic kidney transplant. The present technique may be applied to clinical human kidney transplant.


title: Importance of animal/human health interface in potential Public Health Emergencies of International Concern in the Americas.

text: This study analyzed the importance of zoonoses and communicable diseases common to man and animals as potential Public Health Emergencies of International Concern to build an evidence base for future efforts to reduce risk of infection at the animal/human health interface. The events recorded in the World Health Organization (WHO) Event Management System (EMS) database for the Americas during the 18 months since the implementation of the 2005 revised version of WHO's International Health Regulations (15 June 2007-31 December 2008) were the main source for this analysis. Of the 110 events recorded by the EMS for the Americas during the study period, 86 were classified as communicable diseases-77 (70.0%) "within the animal/human health interface," 9 (8.2%) "not common to man and animals," 16 (14.5%) "syndromes with unknown etiologies," and 8 (7.3%) "product-related/ other." Of the 77 events within the animal/human health interface, 48 were "substantiated" (the presence of hazard was confirmed and/or human cases occurred clearly in excess of normal expectancy). These results confirm previous research and underscore the importance of the animal/human health interface as well as inter-sectoral collaboration.


title: Role of picornaviruses in flu-like illnesses of adults enrolled in an oseltamivir treatment study who had no evidence of influenza virus infection.

text: The primary objective of this study was to determine the role of picornavirus in flu-like episodes (temperature of > or =38.0 degrees C plus one respiratory and one constitutional symptom) among otherwise healthy adults enrolled in a placebo-controlled, double-blind, randomized oseltamivir treatment study. Combined nasal and pharyngeal swabs were collected at baseline for influenza cultures and picornavirus reverse transcription (RT)-PCR. In addition, acute- and convalescent-serum samples were obtained for serological studies of common respiratory pathogens. From a total of 719 subjects enrolled in the clinical trial within 36 h of the onset of symptoms, 475 (66%) had evidence of recent influenza A or B virus infections by means of culture and/or serological testing. Of the 244 remaining patients, 36 (15%) presented a seroconversion for at least one of the common respiratory viruses or atypical pathogens. An RT-PCR assay for the picornavirus 5" noncoding region (NCR) was positive in a subset of 15 (19%) of 78 patients with flu-like illnesses of undetermined etiology. Sequence analysis of the picornavirus 5" NCR amplicons revealed that 14 (93%) of them had greater homology to rhinoviruses, whereas 1 (7%) was related to enteroviruses. Interestingly, median total symptom scores and oral temperatures of picornavirus-positive patients (n = 15) and placebo-treated influenza virus-positive patients (n = 161) were similar over a 3-week period. We conclude that, among the influenza virus-negative preselected cases of this study, rhinoviruses were relatively frequent pathogens associated with important respiratory and systemic symptoms.


title: [Cardiovascular disease in times of COVID-19].

text: There are increasing reports of a drastic drop in consultations and cardiovascular procedures (including urgencies and emergencies) in regions affected by the COVID-19 pandemic, with a consequent marked increase in total mortality that is not fully explained by COVID-19. Cardiovascular disease leads the ranking in deaths in adults in Argentina with 280 deaths per day, and in recent decades we have reduced its mortality by 20-30% through various evidence-based interventions. Herein we conducted predictive analyses to understand what could be the consequences of a worse implementation of those interventions. We estimate that less control of cardiovascular risk factors from April to October 2020 could cause up to 10 500 new preventable cases of cardiovascular disease. In terms of myocardial infarction, a drop from 40% to 60% of the reperfusion treatment could increase mortality by 3% to 5%. A marginal 10% to 15% increase in relative risk of cardiovascular death would be equivalent to an excess of 6000 to 9000 preventable deaths. In conclusion, given the high prevalence and fatality of cardiovascular disease, even a small negative impact on the efficacy of its care will translate into large numbers of people affected in Argentina. It is necessary to inform the authorities and educate the public so cardiovascular diseases and their risk factors remain a health priority, as long as resources exist and minimizing the risk of contagion and spread of the virus.


title: Sequence analysis of the nucleocapsid protein gene of porcine epidemic diarrhoea virus.

text: The nucleotide (nt) sequence of 1.7 kbp cDNA representing the 3' end of the PEDV genome has been determined. Viral RNA was reverse transcribed and the cDNA was amplified by polymerase chain reaction using degenerate primers. The sequences of the primers were based on conserved regions of coronaviral genomes. A 1323 nt open reading frame (ORF) showed good homology to the nucleocapsid (N) gene of other coronaviruses. The greatest homologies at the amino acid and the nt levels were observed with Human Coronavirus 229E. A second 336 nt ORF, which might encode a leucine-rich protein, was found within the N gene. Between the 3' end of the N gene and the poly(A) tail was a sequence of eleven nt, which is conserved among the other sequenced coronaviruses. Finally, a seven base sequence similar to the conserved intergenic sequences was present 5' to the N gene. These results confirm the classification of PEDV as a coronavirus.


title: Passive immunity to bovine rotavirus in newborn calves fed colostrum supplements from immunized or nonimmunized cows.

text: Colostrum was collected and pooled from each of five cows in three experimental groups: group I cows received intramuscular and intramammary inoculations of adjuvanted modified live Ohio Agricultural Research and Development Center rotavirus vaccine; group II cows were injected intramuscularly with a commercial modified-live rota-coronavirus vaccine; and group III cows were uninoculated controls. Pooled colostrum from group I cows had higher (P less than 0.05) enzyme-linked immunosorbent assay (ELISA) immunoglobulin G (IgG1) and virus neutralization (VN) rotavirus antibody titers (ELISA IgG1 = 2,413,682; VN = 360,205) than did colostrum from group II (ELISA IgG1 = 8,192; VN = 4,395) or group III cows (ELISA IgG1 = 5,916; VN = 2,865). The antibody titers of these last two colostrum pools did not differ (P greater than 0.05). Samples of these colostrum pools were fed as daily supplements (percent [vol/vol] in cow's milk infant formula) to 28 newborn, unsuckled, antibody-seronegative, male Holstein calves. Eight calves received no supplemental colostrum. The calves were orally challenged with virulent bovine rotavirus and monitored daily for diarrhea and fecal rotavirus shedding. Diarrhea and rotavirus shedding occurred in the eight calves fed no supplemental colostrum and persisted longest in this group. The pooled colostrum from group I cows protected eight of eight calves from both rotavirus diarrhea and shedding when fed as a 1% supplement. The pooled colostrum from neither group II nor group III cows protected 12 other calves against rotavirus diarrhea or shedding when fed at the same concentration (1%). Six rotavirus-challenged calves fed 0.1% supplemental colostrum from group I cows and two calves fed 10 and 50% supplemental colostrum from control cows displayed partial passive immunity, exemplified by delayed onset and shortened duration of rotavirus-associated diarrhea and virus shedding.


A novel coronavirus and SARS.


title: Intracellular transport of recombinant coronavirus spike proteins: implications for virus assembly.

text: Coronavirus spike protein genes were expressed in vitro by using the recombinant vaccinia virus expression system. Recombinant spike proteins were expressed at the cell surface and induced cell fusion in a host-cell-dependent fashion. The intracellular transport of recombinant spike proteins was studied. The half time of acquisition of resistance to endo-beta-N-acetylglucosaminidase H was approximately 3 h for the recombinant feline infectious peritonitis virus S protein. The S protein in feline infectious peritonitis virus-infected cells was found to have a half time of acquisition of resistance to endo-beta-N-acetylglucosaminidase H of approximately 1 h. This difference can be explained by the fact that coronavirus budding takes place at intracellular membranes and that the oligosaccharides of the spike protein are modified after budding. Apparently, spike protein incorporated into budded virions is transported faster through the Golgi apparatus than is spike protein alone. These findings provide new insights into the mechanism of coronavirus budding and are discussed in relation to current models of intracellular transport and sorting of proteins.


title: Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus.

text: Coronaviruses are a family of enveloped, single-stranded, positive-strand RNA viruses classified within the Nidovirales order. This coronavirus family consists of pathogens of many animal species and of humans, including the recently isolated severe acute respiratory syndrome coronavirus (SARS-CoV). This review is divided into two main parts; the first concerns the animal coronaviruses and their pathogenesis, with an emphasis on the functions of individual viral genes, and the second discusses the newly described human emerging pathogen, SARS-CoV. The coronavirus part covers (i) a description of a group of coronaviruses and the diseases they cause, including the prototype coronavirus, murine hepatitis virus, which is one of the recognized animal models for multiple sclerosis, as well as viruses of veterinary importance that infect the pig, chicken, and cat and a summary of the human viruses; (ii) a short summary of the replication cycle of coronaviruses in cell culture; (iii) the development and application of reverse genetics systems; and (iv) the roles of individual coronavirus proteins in replication and pathogenesis. The SARS-CoV part covers the pathogenesis of SARS, the developing animal models for infection, and the progress in vaccine development and antiviral therapies. The data gathered on the animal coronaviruses continue to be helpful in understanding SARS-CoV.


MHV neuropathogenesis: the study of chimeric S genes and mutations in the hypervariable region.


title: The 2019 Novel Coronavirus Outbreak - A Global Threat.

text: The 2019 Novel Corona virus infection (COVID 19) is an ongoing public health emergency of international significance. There are significant knowledge gaps in the epidemiology, transmission dynamics, investigation tools and management. In this article, we review the available evidence about this disease. Every decade has witnessed the evolution of a new coronavirus epidemic since the last three decades. The varying transmission patterns, namely, nosocomial transmission and spread through mildly symptomatic cases is an area of concern. There is a spectrum of clinical features from mild to severe life threatening disease with major complications like severe pneumonia, ARDS, acute cardiac injury and septic shock. Presence of bilateral ground glass opacity and consolidation on imaging in appropriate clinical background should raise a suspicion about COVID 19. Poor prognostic factors include Multilobular infiltration on chest imaging, Lymphopenia, Bacterial co-infection, Smoking history, Chronic medical conditions like Hypertension and age >60 years (MuLBSTA score). Diagnosis is confirmed with PCR based testing of appropriate respiratory samples. Management is primarily supportive, with newer antivirals (lopinavir ritonavir and Remdesivir) under investigation. Role of steroids is still inconclusive. Standard infection control and prevention techniques should be followed. Vigilant screening of suspected cases and their contacts is important. Isolation of symptomatic cases and home quarantine of asymptomatic contacts is recommended. To conclude, controlling this highly transmissible disease requires international co-ordination.


title: Mechanisms of zoonotic severe acute respiratory syndrome coronavirus host range expansion in human airway epithelium.

text: In 2003, severe acute respiratory syndrome coronavirus (SARS-CoV) emerged and caused over 8,000 human cases of infection and more than 700 deaths worldwide. Zoonotic SARS-CoV likely evolved to infect humans by a series of transmission events between humans and animals for sale in China. Using synthetic biology, we engineered the spike protein (S) from a civet strain, SZ16, into our epidemic strain infectious clone, creating the chimeric virus icSZ16-S, which was infectious but yielded progeny viruses incapable of propagating in vitro. After introducing a K479N mutation within the S receptor binding domain (RBD) of SZ16, the recombinant virus (icSZ16-S K479N) replicated in Vero cells but was severely debilitated in growth. The in vitro evolution of icSZ16-S K479N on human airway epithelial (HAE) cells produced two viruses (icSZ16-S K479N D8 and D22) with enhanced growth on HAE cells and on delayed brain tumor cells expressing the SARS-CoV receptor, human angiotensin I converting enzyme 2 (hACE2). The icSZ16-S K479N D8 and D22 virus RBDs contained mutations in ACE2 contact residues, Y442F and L472F, that remodeled S interactions with hACE2. Further, these viruses were neutralized by a human monoclonal antibody (MAb), S230.15, but the parent icSZ16-S K479N strain was eight times more resistant than the mutants. These data suggest that the human adaptation of zoonotic SARS-CoV strains may select for some variants that are highly susceptible to select MAbs that bind to RBDs. The epidemic, icSZ16-S K479N, and icSZ16-S K479N D22 viruses replicate similarly in the BALB/c mouse lung, highlighting the potential use of these zoonotic spike SARS-CoVs to assess vaccine or serotherapy efficacy in vivo.


title: [Modified molecular beacon-based dual real-time PCR for detection of SARS virus and its application].

text: OBJECTIVE To develop the modified molecular beacon-based dual fluorescent PCR assays for detection of SARS virus. The assay was applied to the early clinic diagnosis & animal tracking. METHODS On the basis of the obtained core sequence of open reading frame 1b of the coronavirus polymerase gene sequences, which was published in GenBank, using modified molecular beacon probe, artifical virus techinique and two different fragments amplification with different fluoresce, one set of primers and probe were designed. Then fluorescent PCR assays for specific and sensitive detection of the SARS virus was established, while the ELISA & the traditional method were used as control. 368 clinical specimens such as the throat swab, serum, feces, and urine from different cases, 52 cell cultures and 50 animal specimens were detected by the molecular beacon-based PCR. RESULTS The sensitivity of real -time PCR was 10 - 100 copies/ml, there was no cross reaction to other respiratory viruses such as influenza virus etc. Of 368 specimens, 20 were positive by using molecular beacon-based fluorescence PCR. The positive rate of SARS case (10/47) were 21.27%, the positive rate of the throat swab of SARS cases (10/23) were 43.87% . Among 52 SARS cell cultures, 29 were positive. The positive rate of SARS cell cultures was 55.77% . Of 50 animal specimens, 23 were positive. The positive rate was 46%. Furthermore, SARS virus RNA was detected in feces and in serum during the acute phase. CONCLUSION The molecular beacon-based PCR is sensitive and specific, it could be applied to the early diagnosis and animal tracking. This molecular beacon-based PCR kit is useful for the different units.


title: Medical problems encountered among travelers in Bahrain International Airport clinic.

text: BACKGROUND The Middle East is one of the most rapidly growing destination for travelers. Objective. The aim of this study was to determine the medical conditions affecting travelers needing medical assistance in Bahrain International Airport (BIA). METHOD Logbook documenting medical conditions of travelers presenting to the BIA clinic from January 1 till the end of December 2004 was reviewed. RESULTS A total of 3,350 travelers attended the clinic, constituting 0.12% of the disembarking and transit travelers. Most common conditions faced were respiratory problems (24.4%), followed by headaches (19.2%), trauma, musculoskeletal pains (12.9%), and gastrointestinal problems (11.0%). Only 2.1% of all complaints were referred to secondary care. The majority of cases were handled by the nurse. CONCLUSIONS Majority of the patients examined had acute minor medical problems. Ninety-eight percent of conditions affecting travelers were handled in the airport clinic by the nurse and the family physician. Airport clinic could serve as an efficient emergency triage system for filtering serious illnesses needing urgent management.


title: Molecular evidence for the role of mycobacteria in sarcoidosis: a meta-analysis.

text: The aetiology of sarcoidosis is currently unknown. Due to the clinical and histological similarities between sarcoidosis and tuberculosis, the role of mycobacteria has been repeatedly investigated as an aetiological agent for sarcoidosis. The current meta-analysis aimed to evaluate the available molecular evidence on the possible role of mycobacteria in the development of sarcoidosis. The MEDLINE, EMBASE, CINAHL, DARE and CENTRAL databases were searched for relevant studies published from 1980 to 2006, and studies evaluating the presence of mycobacteria using molecular techniques in biological samples of patients with sarcoidosis were included in the current analysis. The 95% confidence intervals (CI) were calculated for the expected proportion (of individual studies); the data was then pooled to obtain a summary success rate with 95% CI. The odds ratio (95% CI) was also calculated in order to assess the presence of mycobacteria in samples of patients with sarcoidosis versus those from nonsarcoidosis control samples. The database search yielded 31 studies. All studies used polymerase chain reaction for nucleic acid amplification followed by identification of nucleic acid sequences specific for different types of mycobacteria. Overall, 231 out of the 874 patients were positive for mycobacteria with a positive signal rate of 26.4 (23.6-29.5%), and the odds of finding mycobacteria in samples of patients with sarcoidosis versus controls were 9.67 (4.56-20.5%) using the random effects model and 19.49 (11.21-35.54%) using the exact method. There was methodological and statistical heterogeneity and evidence of publication bias. The results of the current study illustrate a demonstrable mycobacterial presence in sarcoidosis lesions suggesting an association between mycobacteria and some cases of sarcoidosis. To avoid methodological diversity, larger multicentre trials with a central laboratory for sample testing should be designed.


title: Shedding of enteric coronavirus in adult cattle.

text: Electron microscopic examination of fecal specimens from adult dairy cows indicated seasonal coronavirus shedding. Fifty-two cows from a 300 cow herd were monitored for shedding of coronavirus. Approximately 50% to 60% of the cows monitored shed coronavirus during the winter months (November to March) of the first year of the study. During 2 subsequent years of monitoring the same cows, 20% to 30% of the cows shed coronavirus during the winter months. Virus shedding was not detected during the summer months (July to September). Half of the cows monitored were vaccinated with a modified-live rotavirus-coronavirus-Escherichia coli combination vaccine; however, vaccination did not influence seasonal shedding of coronavirus, as compared with shedding in the nonvaccinated cows. In nonvaccinated cows that calved in the winter months, the incidence of coronavirus shedding increased from 20% to 30% during the last 2 months of gestation to 65% to 70% at parturition. In vaccinated cows, the incidence of shedding did not increase at parturition.


News Items.


title: Invasive pulmonary aspergillosis: high incidence of disseminated intravascular coagulation in fatal cases.

text: BACKGROUND AND PURPOSE Disseminated intravascular coagulation (DIC) is a rarely described finding in invasive pulmonary aspergillosis (IPA) with unclear impact on mortality. METHODS This study included patients with positive cultures of Aspergillus spp. from respiratory specimens, serological evidence of aspergillosis, or lung biopsy findings supporting aspergillosis treated at National Taiwan University Hospital from January 1999 to June 2005. IPA was defined based on the consensus of the European Organization for Research and Treatment of Cancer, and the Mycosis Study Group of the National Institute of Allergy and Infectious Diseases. Univariate logistic regression analysis was used to evaluate the factors associated with mortality. RESULTS Proven or probable IPA was diagnosed in 26 patients. Hematological malignancy was found in 11 patients (42%) and immunosuppressive agents had been administered to 17 patients (65%). Among 20 culture-proven infections (77%), the most frequently encountered fungi were Aspergillus fumigatus (46%) and Aspergillus flavus (23%). The overall mortality rate was 62%. Univariate and multivariate analyses revealed that DIC was the only factor that was significantly associated with death attributable to IPA (p<0.01). CONCLUSIONS IPA is associated with a high mortality rate, particularly for patients with DIC.


Education and disaster risk reduction.


title: Infection in social networks: using network analysis to identify high-risk individuals.

text: Simulation studies using susceptible-infectious-recovered models were conducted to estimate individuals' risk of infection and time to infection in small-world and randomly mixing networks. Infection transmitted more rapidly but ultimately resulted in fewer infected individuals in the small-world, compared with the random, network. The ability of measures of network centrality to identify high-risk individuals was also assessed. "Centrality" describes an individual's position in a population; numerous parameters are available to assess this attribute. Here, the authors use the centrality measures degree (number of contacts), random-walk betweenness (a measure of the proportion of times an individual lies on the path between other individuals), shortest-path betweenness (the proportion of times an individual lies on the shortest path between other individuals), and farness (the sum of the number of steps between an individual and all other individuals). Each was associated with time to infection and risk of infection in the simulated outbreaks. In the networks examined, degree (which is the most readily measured) was at least as good as other network parameters in predicting risk of infection. Identification of more central individuals in populations may be used to inform surveillance and infection control strategies.


title: Smallpox DNA vaccine protects nonhuman primates against lethal monkeypox.

text: Two decades after a worldwide vaccination campaign was used to successfully eradicate naturally occurring smallpox, the threat of bioterrorism has led to renewed vaccination programs. In addition, sporadic outbreaks of human monkeypox in Africa and a recent outbreak of human monkeypox in the U.S. have made it clear that naturally occurring zoonotic orthopoxvirus diseases remain a public health concern. Much of the threat posed by orthopoxviruses could be eliminated by vaccination; however, because the smallpox vaccine is a live orthopoxvirus vaccine (vaccinia virus) administered to the skin, the vaccine itself can pose a serious health risk. Here, we demonstrate that rhesus macaques vaccinated with a DNA vaccine consisting of four vaccinia virus genes (L1R, A27L, A33R, and B5R) were protected from severe disease after an otherwise lethal challenge with monkeypox virus. Animals vaccinated with a single gene (L1R) which encodes a target of neutralizing antibodies developed severe disease but survived. This is the first demonstration that a subunit vaccine approach to smallpox-monkeypox immunization is feasible.


title: Chronic rhinoviral infection in lung transplant recipients.

text: RATIONALE Lung transplant recipients are particularly at risk of complications from rhinovirus, the most frequent respiratory virus circulating in the community. OBJECTIVES To determine whether lung transplant recipients can be chronically infected by rhinovirus and the potential clinical impact. METHODS We first identified an index case, in which rhinovirus was isolated repeatedly, and conducted detailed molecular analysis to determine whether this was related to a unique strain or to re-infection episodes. Transbronchial biopsies were used to assess the presence of rhinovirus in the lung parenchyma. The incidence of chronic rhinoviral infections and potential clinical impact was assessed prospectively in a cohort of 68 lung transplant recipients during 19 mo by screening of bronchoalveolar lavages. MEASUREMENTS AND MAIN RESULTS We describe 3 lung transplant recipients with graft dysfunctions in whom rhinovirus was identified by reverse transcriptase-polymerase chain reaction in upper and lower respiratory specimens over a 12-mo period. In two cases, rhinovirus was repeatedly isolated in culture. The persistence of a unique strain in each case was confirmed by sequence analysis of the 5'NCR and VP1 gene. In the index case, rhinovirus was detected in the lower respiratory parenchyma. In the cohort of lung transplant recipients, rhinoviral infections were documented in bronchoalveolar lavage specimens of 10 recipients, and 2 presented with a persistent infection. CONCLUSIONS Rhinoviral infection can be persistent in lung transplant recipients with graft dysfunction, and the virus can be detected in the lung parenchyma. Given the potential clinical impact, chronic rhinoviral infection needs to be considered in lung transplant recipients.


Funding the global control of bird flu.


title: An Inexpensive Modified Primary Closure Technique for Class IV (Dirty) Wounds Significantly Decreases Superficial and Deep Surgical Site Infection.

text: Despite the creation of several programs to decrease the incidence of surgical site infection, it remains a common complication that has a significant impact on patient recovery and medical costs. The following is a description and brief outcome report of a modified primary closure technique used for dirty (Class IV) wounds. There were 14 consecutive patients who had a laparotomy with Class IV wounds treated by a single surgeon (TAA) from 2011 to 2015. All patients had a history of cancer and either showed signs suggestive for an acute abdomen and required an emergent exploratory laparotomy or were found to have purulent intraabdominal infection at the time of elective surgery. The operation and "modified primary closure" technique (subcutaneous wound wicks with stapled skin closure) were performed in every case. The modified primary closure technique was utilized in 14 patients with a Class IV wound. There were no 30-day mortalities or readmissions. Wound wicks were slowly advanced out over a 7-day period, and only one patient required subsequent wound packing of a single-wicked area. There were no superficial or deep surgical site infections, or wound dehiscence during the hospital course, or 30-day postoperative period. The modified primary closure technique is efficient and inexpensive and was effective in a series of 14 patients with wounds classified as dirty.