title: [Coronaviruses in pathology].

text: The crown-like projections on the surface of the particles permits differentiation of coronaviruses from other riboviruses and their individualization as a distinct family. Recognition of their role in the aetiology of respiratory, enteral and encephalitic infections has promoted investigations for the finding of preventive vaccines. Selection of the strains showed that their immunogenicity depends upon the density and salience of the crown-like projections, the antigenic relationship of the projections determining cross serologic reactions between different species. At present experiments are being carried out on animals with vaccines prepared with antigenically related heterologous cornavirus species, not pathogenic for the host, and with subunitary vaccines prepared from the projections of the homologous species. The Coronaviridae family established on morphologic criteria is thus confirmed by the immunologic relationship and specificity of its members.


When isn't the cause of acute respiratory distress syndrome important?


title: Functional analysis of cell surface-expressed hepatitis C virus E2 glycoprotein.

text: Hepatitis C virus (HCV) glycoproteins E1 and E2, when expressed in eukaryotic cells, are retained in the endoplasmic reticulum (ER). C-terminal truncation of E2 at residue 661 or 715 (position on the polyprotein) leads to secretion, consistent with deletion of a proposed hydrophobic transmembrane anchor sequence. We demonstrate cell surface expression of a chimeric glycoprotein consisting of E2 residues 384 to 661 fused to the transmembrane and cytoplasmic domains of influenza A virus hemagglutinin (HA), termed E2661-HATMCT. The E2661-HATMCT chimeric glycoprotein was able to bind a number of conformation-dependent monoclonal antibodies and a recombinant soluble form of CD81, suggesting that it was folded in a manner comparable to "native" E2. Furthermore, cell surface-expressed E2661-HATMCT demonstrated pH-dependent changes in antigen conformation, consistent with an acid-mediated fusion mechanism. However, E2661-HATMCT was unable to induce cell fusion of CD81-positive HEK cells after neutral- or low-pH treatment. We propose that a stretch of conserved, hydrophobic amino acids within the E1 glycoprotein, displaying similarities to flavivirus and paramyxovirus fusion peptides, may constitute the HCV fusion peptide. We demonstrate that influenza virus can incorporate E2661-HATMCT into particles and discuss experiments to address the relevance of the E2-CD81 interaction for HCV attachment and entry.


title: [Diagnosis of bovine coronaviruses using mouse erythrocyte suspensions stabilized with formalin].

text: Bovine coronavirus isolated from calf faeces diseased with gastroenteritis and passaged to colostrum-free calves agglutinated mouse and rat erythrocytes. The agglutination reaction depended on temperature and took place only at a temperature of 4 degrees C. At a temperature of 37 degrees C the agglutinate broke down within 15 minutes. The coronavirus could be detected by the haemagglutination test in the contents of the small and large intestines and in the faeces of experimentally and naturally infected calves. The agglutination capacity of mouse erythrocytes was not affected by careful fixation of these erythrocytes with formalin and subsequent lyophilization and remained unchanged for as long as 52 weeks of storage at a temperature of 4 degrees C. It was demonstrated by a comparative examination of 182 samples of the faeces of calves suffering from diarrhoea that haemagglutination test was as sensitive as electron microscopy.


title: The silent revolution: RNA interference as basic biology, research tool, and therapeutic.

text: RNA interference (RNAi) is an evolutionarily conserved mechanism for silencing gene expression. In primitive organisms, RNAi protects the genome from viruses and other insertable genetic elements and regulates gene expression during development. The antisense (guide) strand of short double-stranded RNAs is incorporated into an RNA-induced silencing complex that can either suppress protein expression or direct degradation of messenger RNAs that contain homologous sequence(s). The discovery that RNAi works in mammalian cells has sparked intense investigation into its role in normal mammalian cell function, its use as a tool to understand or screen for genes functioning in cellular pathways in healthy and diseased cells and animals, and its potential for therapeutic gene silencing. RNAi may provide an important new therapeutic modality for treating infection, cancer, neurodegenerative disease, and other illnesses, although in vivo delivery of small interfering RNAs into cells remains a significant obstacle.


title: Human coronavirus 229E nonstructural protein 13: characterization of duplex-unwinding, nucleoside triphosphatase, and RNA 5'-triphosphatase activities.

text: The human coronavirus 229E (HCoV-229E) replicase gene-encoded nonstructural protein 13 (nsp13) contains an N-terminal zinc-binding domain and a C-terminal superfamily 1 helicase domain. A histidine-tagged form of nsp13, which was expressed in insect cells and purified, is reported to unwind efficiently both partial-duplex RNA and DNA of up to several hundred base pairs. Characterization of the nsp13-associated nucleoside triphosphatase (NTPase) activities revealed that all natural ribonucleotides and nucleotides are substrates of nsp13, with ATP, dATP, and GTP being hydrolyzed most efficiently. Using the NTPase active site, HCoV-229E nsp13 also mediates RNA 5'-triphosphatase activity, which may be involved in the capping of viral RNAs.


title: A serosurvey of viral infections in lions (Panthera leo), from Queen Elizabeth National Park, Uganda.

text: Serum samples from 14 lions (Panthera leo) from Queen Elizabeth National Park, Uganda, were collected during 1998 and 1999 to determine infectious disease exposure in this threatened population. Sera were analyzed for antibodies against feline immunodeficiency virus (FIV), feline calicivirus (FCV), feline herpesvirus 1 (feline rhinotracheitis: FHV1), feline/canine parvovirus (FPV/CPV), feline infectious peritonitis virus (feline coronavirus: FIPV), and canine distemper virus (CDV) or for the presence of feline leukemia virus (FeLV) antigens. Ten lions (71%) had antibodies against FIV, 11 (79%) had antibodies against CDV, 11 (79%) had antibodies against FCV, nine (64%) had antibodies against FHV1, and five (36%) had antibodies against FPV. Two of the 11 CDV-seropositive lions were subadults, indicating recent exposure of this population to CDV or a CDV-like virus. No lions had evidence of exposure to FeLV or FIPV. These results indicate that this endangered population has extensive exposure to common feline and canine viruses.


Inhaled Nebulized Sodium Pyruvate Use in COVID-19 Patients.


title: Influenza-associated pediatric deaths--United States, September 2010-August 2011.

text: Influenza-associated pediatric mortality has been a nationally notifiable condition since October 2004. This report summarizes the 115 cases of influenza-associated pediatric mortality reported to CDC that occurred from September 1, 2010, through August 31, 2011. Deaths occurred in 33 states. Nearly half of the deaths (46%) occurred in children aged <5 years. Of the children who died, 49% had no known Advisory Committee on Immunization Practices (ACIP)-defined high-risk medical conditions, and 35% died at home or in the emergency department. Of the 74 children aged ≥6 months for whom vaccination data were available, 17 (23%) had been fully vaccinated. ACIP recommends that all children aged ≥6 months receive vaccination against influenza annually. These findings underscore the importance of vaccinating children to prevent influenza virus infection and its potentially severe complications. Health-care providers should develop a comprehensive strategy to increase vaccination coverage among children.


title: A randomized controlled study of botulinum toxin A in the treatment of hemiplegic shoulder pain associated with spasticity.

text: OBJECTIVES To assess the effects of botulinum toxin A (BT-A) on hemiplegic shoulder pain associated with spasticity. DESIGN Randomized, double-blind, placebo-controlled study. SETTING Outpatient clinic of a rehabilitation department. PARTICIPANTS Patients, more than three months post stroke, with hemiplegic shoulder pain associated with shoulder adductor and elbow flexor spasticity, randomly assigned to BT-A or placebo. INTERVENTION One-time injection of BT-A (500 units) into the pectoralis major and biceps brachii on the hemiplegic side. MAIN MEASURES Visual analogue scale of shoulder pain (0 -10), shoulder adductor and elbow flexor tone using the Ashworth Scale and passive range of shoulder abduction. These were assessed at baseline, four weeks, eight weeks and 12 weeks post injection. RESULTS Seventeen patients were enrolled, eight in the BT-A group and nine in the placebo group. At baseline, the median visual analogue scale score for shoulder pain was 6, the median Ashworth Scale shoulder adductor and elbow flexor spasticity score was 2 and the median range of shoulder abduction 76 degrees. Subjects who received BT-A showed significantly greater improvements in median shoulder adductor and elbow flexor Ashworth Scale scores than placebo at week 4 (P B / 0.01) but not at week 8 and 12. For shoulder pain and passive shoulder abduction range, all subjects showed postinjection improvements and no difference could be demonstrated between the two groups. DISCUSSION Possible reasons for the negative finding in this study include the small sample size and the presence of causes of shoulder pain not related to spasticity which could have confounded outcome.


title: Bluetongue in the United Kingdom and northern Europe in 2007 and key issues for 2008.

text: As predicted, bluetongue arrived in the UK in 2007. Here, John Gloster and colleagues investigate the meteorological parameters that allowed this incursion into the UK and discuss key issues related to the disease's possible re-establishment in 2008.


Erratum to: Alphacoronavirus in urban Molossidae and Phyllostomidae bats, Brazil.


title: Cannabinoid receptors and endocannabinoids: role in neuroinflammatory and neurodegenerative disorders.

text: The G-protein coupled receptors for Δ⁹-tetrahydrocannabinol, the major psychoactive principle of marijuana, are known as cannabinoid receptors of type 1 (CB₁) and 2 (CB₂) and play important functions in degenerative and inflammatory disorders of the central nervous system. Whilst CB₁ receptors are mostly expressed in neurons, where they regulate neurotransmitter release and synaptic strength, CB₂ receptors are found mostly in glial cells and microglia, which become activated and over-express these receptors during disorders such as Alzheimer's disease, multiple sclerosis, amyotropic lateral sclerosis, Parkinson's disease, and Huntington's chorea. The neuromodulatory actions at CB₁ receptors by endogenous agonists ('endocannabinoids'), of which anandamide and 2-arachidonoylglycerol are the two most studied representatives, allows them to counteract the neurochemical unbalances arising during these disorders. In contrast, the immunomodulatory effects of these lipophilic mediators at CB₂ receptors regulate the activity and function of glia and microglia. Indeed, the level of expression of CB₁ and CB₂ receptors or of enzymes controlling endocannabinoid levels, and hence the concentrations of endocannabinoids, undergo time- and brain region-specific changes during neurodegenerative and neuroinflammatory disorders, with the initial attempt to counteract excitotoxicity and inflammation. Here we discuss this plasticity of the endocannabinoid system during the aforementioned central nervous system disorders, as well as its dysregulation, both of which have opened the way to the use of either direct and indirect activators or blockers of CB₁ and CB₂ receptors for the treatment of the symptoms or progression of these diseases.


title: Quasispecies development by high frequency RNA recombination during MHV persistence.

text: Recent studies suggest that infectious viruses and particularly persisting viral RNAs often exist as diverse populations or "quasispecies". We have developed an approach to characterize populations of the murine coronavirus mouse hepatitis virus (MHV) generated during persistent infection which has allowed us to begin to address the role of the viral quasispecies in MHV pathogenesis. We analyzed the population of persisting viral RNAs using reverse-transcription polymerase chain reaction amplification (RT-PCR) of the S1 "hypervariable" region of the spike gene followed by differential colony hybridization to identify spike deletion variants (SDVs) from acute and persistently infected mice. Sequence analysis revealed that mice with the most severe chronic paralysis harbored the most complex quasispecies. Mapping of the SDVs to the predicted RNA secondary structure of the spike RNA revealed that an isolated stem loop structure is frequently deleted. Overall, these results are consistent with high frequency recombination at sites of RNA secondary structure contributing to expansion of the viral quasispecies and persisting viral pathogenesis.


title: [Detection of RNA of SARS coronavirus in hospital sewage].

text: OBJECTIVE In order to explore the existence of SARS coronavirus (Co-V) and/or its RNA in sewage of hospitals administered SARS patients. METHODS A novel electropositive filter was used to concentrate the SARS-CoV from the sewage of two hospitals administered SARS patients in Beijing, including twelve 2,500 ml sewage samples from the hospitals before disinfection, and ten 25,000 ml samples after disinfection; as well as cell culture, RT-PCR and sequencing of gene to detect and identify the viruses from sewage. RESULTS There was no live SARS-CoV detected in the sewage in this study. The nucleic acid of SARS-CoV had been found in the 12 sewage samples before disinfection from both hospitals by semi-nested PCR. After disinfection, SARS-CoV RNA could only be detected from the samples from the 309th Hospital, and the others were negative. CONCLUSION It provides evidence that there is no live SARS-Cov in the sewage from hospitals with SARS patients though SARS-CoV RNA can be detected.


title: [Digital surveillance tools for contact tracking of infected persons by SARS-CoV-2.]

text: BACKGROUND In times of pandemic, case management and tracking people with contact can be differential elements for controlling the spread. The objective of this review was to evaluate the digital tools used to track contacts of people infected with SARS-CoV-2. METHODS A systematic exploratory review was conducted in the electronic databases Pubmed, Scopus and Web of Science on May 29, 2020 through the descriptors: coronavirus, digital surveillance and contact tracing. A total of 11 studies were finally selected. RESULTS The results showed that some countries are implementing digital tools for contact tracking through mobile apps that allow user data to be shared via the device's GPS and/or Bluetooth. The terms on the privacy and confidentiality of the population data are, in some cases, questionable. CONCLUSIONS The use of digital surveillance tools to track contacts of people infected with an infectious disease, such as SARS-CoV-2, can be key to reducing the number of people infected and reducing the spread of the virus.


title: Veterinary geographic information systems applications in Nigeria: limitations, challenges and needs.

text: In developed countries, the application of geographic information systems (GIS) and other geo-information technologies in facilitating epizootiological studies of animal disease outbreaks, disease reporting, monitoring, surveillance, prediction and intervention (prevention, treatment and control) programmes, has been in vogue for decades. Although not yet in the curricula of any of Nigeria's five veterinary schools, Veterinary geo-information technologies have been promoted and applied at the Faculty of Veterinary Medicine, University of Ibadan, Nigeria, since 2001. Limitations encountered in the course of its application include poor, rudimentary and inconsistent disease reporting procedures, non-computerised (manual) disease recording techniques, raw unanalysed data, poor information networking and poor awareness of the role of geo-informatics in veterinary medicine. The major challenge is the development of sufficient and relevant veterinary databases. Major needs include the training and retraining of personnel involved in the use of GIS for veterinary medicine, the acquisition of relevant hardware and software and the funding of a Nigerian unit/centre devoted to GIS application to veterinary medicine. While Nigeria necessarily develops a national (veterinary) spatial data infrastructure, multilateral training and funding assistance is needed for a developing country like Nigeria to use developed country geo-information technologies to reduce the impact of animal diseases on animal and human populations.


title: Emerging respiratory and novel coronavirus 2012 infections and mass gatherings.

text: Mass gatherings are attended by an increasingly global audience and thus raise the concern of possible acute public health risks not normally encountered by the host population. The potential acute risks to individual and population health include communicable diseases. The communicable disease risks include emerging and re-emerging diseases in host and visiting populations. In this review, we provide an overview ofthe literature on respiratory infections at mass gatherings, then describe the impact of novel coronavirus 2012 (nCoV), an emerging respiratory disease virus, on the preparations for mass gathering. Although, nCoV emerged prior to the 2012 Hajj pilgrimage season, Muslims completed their religious duty without acquiring infections by nCoV. Clearly, the global nature of mass gatherings and their potential risks to international health make it imperative that research on such events and guidelines produced for their management are relevant to diverse contexts and are a collaborative effort between global experts.


title: [Study on the psychosocial status and related factors in three universities during severe acute respiratory syndrome epidemic in Beijing].

text: OBJECTIVE To investigate the psychosocial status and related factors among university students during severe acute respiratory syndrome (SARS) epidemic in Beijing. METHODS By means of stratified cluster sampling, symptom checklist-90 (SCL-90) and questionnaire on general information were applied among 6800 students in three universities in Beijing. RESULTS There were 6280 valid questionnaires gathered. In order to control and prevent SARS, strict management was conducted in three universities which providing various social supports. Out of the 6280 students, 460 had SCL-90 positive symptoms with a rate of 7.3%. Risk factors of SCL-90 positive symptom were found as follows: major in arts (OR = 2.00), misconception on the control and prevention of SARS (OR = 1.91), considering measures non-effective (OR = 2.25), and do not believe that SARS can be under control (OR = 3.57). Protective factors of SCL-90 positive symptom would include as: being female (OR = 0.77), being graduate students (OR = 0.38), and being not much influenced on study and daily life during the period of strict management (OR = 0.54). CONCLUSION Psychosocial status of students was influenced by their knowledge and attitude on SARS. Various social supports might keep the university students to having a healthy psychosocial status.


Electron microscopic studies of coronavirus.


title: Structural basis for 2'-5'-oligoadenylate binding and enzyme activity of a viral RNase L antagonist.

text: UNLABELLED Synthesis of 2'-5'-oligoadenylates (2-5A) by oligoadenylate synthetase (OAS) is an important innate cellular response that limits viral replication by activating the latent cellular RNase, RNase L, to degrade single-stranded RNA. Some rotaviruses and coronaviruses antagonize the OAS/RNase L pathway through the activity of an encoded 2H phosphoesterase domain that cleaves 2-5A. These viral 2H phosphoesterases are phylogenetically related to the cellular A kinase anchoring protein 7 (AKAP7) and share a core structure and an active site that contains two well-defined HΦ(S/T)Φ (where Φ is a hydrophobic residue) motifs, but their mechanism of substrate binding is unknown. Here, we report the structures of a viral 2H phosphoesterase, the C-terminal domain (CTD) of the group A rotavirus (RVA) VP3 protein, both alone and in complex with 2-5A. The domain forms a compact fold, with a concave β-sheet that contains the catalytic cleft, but it lacks two α-helical regions and two β-strands observed in AKAP7 and other 2H phosphoesterases. The cocrystal structure shows significant conformational changes in the R loop upon ligand binding. Bioinformatics and biochemical analyses reveal that conserved residues and residues required for catalytic activity and substrate binding comprise the catalytic motifs and a region on one side of the binding cleft. We demonstrate that the VP3 CTD of group B rotavirus, but not that of group G, cleaves 2-5A. These findings suggest that the VP3 CTD is a streamlined version of a 2H phosphoesterase with a ligand-binding mechanism that is shared among 2H phosphodiesterases that cleave 2-5A. IMPORTANCE The C-terminal domain (CTD) of rotavirus VP3 is a 2H phosphoesterase that cleaves 2'-5'-oligoadenylates (2-5A), potent activators of an important innate cellular antiviral pathway. 2H phosphoesterase superfamily proteins contain two conserved catalytic motifs and a proposed core structure. Here, we present structures of a viral 2H phosphoesterase, the rotavirus VP3 CTD, alone and in complex with its substrate, 2-5A. The domain lacks two α-helical regions and β-strands present in other 2H phosphoesterases. A loop of the protein undergoes significant structural changes upon substrate binding. Together with our bioinformatics and biochemical findings, the crystal structures suggest that the RVA VP3 CTD domain is a streamlined version of a cellular enzyme that shares a ligand-binding mechanism with other 2H phosphodiesterases that cleave 2-5A but differs from those of 2H phosphodiesterases that cleave other substrates. These findings may aid in the future design of antivirals targeting viral phosphodiesterases with cleavage specificity for 2-5A.


title: Counting Coronavirus Disease 2019 (COVID-19) Cases: Case Definitions, Screened Populations and Testing Techniques Matter.

text: While counting cases of disease appears straightforward, there are issues to consider when enumerating disease counts during an epidemic. For example, for Coronavirus Disease-2019 (COVID-19), how is a case defined? Hubei province in China changed its case definition twice in a fortnight-from laboratory-confirmed cases to clinically-confirmed cases without laboratory tests, and back to laboratory-confirmed cases. This caused confusion in the reported number of cases. If a confirmed case requires laboratory testing, what is the population who are laboratory-tested? Due to limited laboratory testing capacity in the early phase of an emerging epidemic, only "suspected cases" are laboratory-tested in most countries. This will result in underdiagnosis of confirmed cases and also raises the question: how is a "suspect case" defined? With the passage of time and increased capability to perform laboratory tests, more people can be screened and the number of confirmed cases will increase. What are the technical considerations of laboratory testing? This includes specimen collection (variable collection methods), samples collected (upper or lower respiratory tract biospecimens), time of collection in relation to course of disease, different laboratory test methods and kits (not all of which may be standardised or approved by authorities such as the Food and Drug Administration). Are approved laboratory facilities and trained manpower available, and how are test results interpreted and false-negatives excluded? These issues will affect the accuracy of disease counts, which in turn will have implications on how we mount an appropriate response to the outbreak.


title: Processing of the human coronavirus 229E replicase polyproteins by the virus-encoded 3C-like proteinase: identification of proteolytic products and cleavage sites common to pp1a and pp1ab.

text: Replicase gene expression by the human coronavirus 229E involves the synthesis of two large polyproteins, pp1a and pp1ab. Experimental evidence suggests that these precursor molecules are subject to extensive proteolytic processing. In this study, we show that a chymotrypsin-like enzyme, the virus-encoded 3C-like proteinase (3CLpro), cleaves within a common region of pp1a and pp1ab (amino acids 3490 to 4068) at four sites. trans-cleavage assays revealed that polypeptides of 5, 23, 12, and 16 kDa are processed from pp1a/pp1ab by proteolysis of the peptide bonds Q3546/S3547, Q3629/S3630, Q3824/N3825, and Q3933/A3934. Relative rate constants for the 3CLpro-mediated cleavages Q2965/A2966, Q3267/S3268, Q3824/N3825, and Q3933/A3934 were derived by competition experiments using synthetic peptides and recombinant 3CLpro. The results indicate that coronavirus cleavage sites differ significantly with regard to their susceptibilities to proteolysis by 3CLpro. Finally, immunoprecipitation with specific rabbit antisera was used to detect the pp1a/pp1ab processing end products in virus-infected cells, and immunofluorescence data that suggest an association of these polypeptides with intracellular membranes were obtained.


title: Persistent excretion of rotavirus by pregnant cows.

text: In a study of the epizootiology and prevalence of enteropathogens which may be involved in neonatal calf diarrhoea, 10 in-calf cows from a herd with a history of rotavirus-induced calf diarrhoea were monitored over a period of six to seven months. All the cows excreted rotavirus intermittently without showing any clinical signs, and 21.8 per cent of faecal samples contained rotavirus. Reoviruses were isolated from 87 per cent of the samples from the cows, and from all the 10 calves born to them. However, rotavirus was detected in only one calf, and diarrhoea developed only in this calf even though the calves were housed in communal pens. Campylobacter jejuni was isolated from six of the 10 dams and from five of the 10 calves, not including the calf with diarrhoea. Other potential enteropathogens such as cryptosporidium, salmonella, Clostridium difficile, coronavirus and other viruses were not found, but two cows and two calves shed enterotoxigenic Escherichia coli.


title: Quality of life in patients with chronic kidney disease: focus on end-stage renal disease treated with hemodialysis.

text: The proper measures for assessing quality of life (QOL) in patients with chronic kidney disease (CKD) remain unclear. QOL measures are subjective or objective, functional or satisfaction-based, and generic or disease-specific. Treatment of end-stage renal disease with transplantation and treatment of anemia with erythropoietin in patients with CKD have been associated with dramatic improvements of QOL. Other factors such as age, ethnic or national background, stage of CKD, modality of dialytic therapy, exercise interventions, sleep disturbances, pain, erectile dysfunction, patient satisfaction with care, depressive affect, symptom burden, and perception of intrusiveness of illness may be associated with differential perception of QOL. Recent studies showed an association between assessment of QOL and morbidity and mortality in end-stage renal disease patients, suggesting the measures do matter. Further studies are necessary in patients with early stages of CKD and in children. QOL measures should include validated psychosocial measures of depressive affect, perception of burden of illness, and social support. The challenge for the next decade will be to continue to devise interventions that meaningfully increase the QOL of patients with CKD at all stages.


title: Alphavirus M1 induces apoptosis of malignant glioma cells via downregulation and nucleolar translocation of p21WAF1/CIP1 protein.

text: Alphavirus, a genus of arthropod-borne togavirus, is well-known for its pro-apoptotic capability. However, the underlying mechanism remains to be further clarified. Here, we have identified that M1, an alphavirus isolated in 1960s, targeted C6 malignant glioma cells for apoptosis. Flow cytometry analysis showed that more cells enter S-phase post M1 infection, and subsequently undergo a classic apoptosis. To elucidate the mechanism of S-phase arrest and its relationship to apoptosis, we tested the expression of several critical cell cycle regulatory proteins and found elevated phosphorylation of cyclin-dependent kinase 2 (CDK2), decreased expression of cyclin A and proliferating cell nuclear antigen (PCNA). Notably, the protein level of p21(WAF1/CIP1) was downregulated earliest and most effectively among all tested changes of cell cycle regulators, though its mRNA level was strongly upregulated. To evaluate the role of p21(WAF1/CIP1) in S-phase accumulation and subsequent apoptosis, we confirmed that exogenous p21(WAF1/CIP1) overexpression or treatment with roscovitine (a selective chemical inhibitor of CDK2) efficiently protected against apoptosis with a reduced S-phase accumulation. Thus, it is indicated that the downregulation of p21(WAF1/CIP1) mediated C6 apoptosis via overactivation of CDK2. In addition, confocal microscopy showed that p21(WAF1/CIP1) totally translocated to nucleolus during M1-induced C6 apoptosis. Altogether, downregulation and nucleolar translocation of the p21(WAF1/CIP1) protein played an active role in M1-induced C6 apoptosis.


title: Small molecules targeting severe acute respiratory syndrome human coronavirus.

text: Severe acute respiratory syndrome (SARS) is an infectious disease caused by a novel human coronavirus. Currently, no effective antiviral agents exist against this type of virus. A cell-based assay, with SARS virus and Vero E6 cells, was developed to screen existing drugs, natural products, and synthetic compounds to identify effective anti-SARS agents. Of >10,000 agents tested, approximately 50 compounds were found active at 10 microM; among these compounds, two are existing drugs (Reserpine 13 and Aescin 5) and several are in clinical development. These 50 active compounds were tested again, and compounds 2-6, 10, and 13 showed active at 3 microM. The 50% inhibitory concentrations for the inhibition of viral replication (EC(50)) and host growth (CC(50)) were then measured and the selectivity index (SI = CC(50)/EC(50)) was determined. The EC(50), based on ELISA, and SI for Reserpine, Aescim, and Valinomycin are 3.4 microM (SI = 7.3), 6.0 microM (SI = 2.5), and 0.85 microM (SI = 80), respectively. Additional studies were carried out to further understand the mode of action of some active compounds, including ELISA, Western blot analysis, immunofluorescence and flow cytometry assays, and inhibition against the 3CL protease and viral entry. Of particular interest are the two anti-HIV agents, one as an entry blocker and the other as a 3CL protease inhibitor (K(i) = 0.6 microM).


title: Nephrogenic systemic fibrosis (NSF): a late adverse reaction to some of the gadolinium based contrast agents.

text: Until recently it was believed that extracellular gadolinium based contrast agents were safe for both the kidneys and all other organs within the dose range up to 0.3 mmol/kg body weight. However, in 2006, it was demonstrated that some gadolinium based contrast agents may trigger the development of nephrogenic systemic fibrosis, a generalised fibrotic disorder, in renal failure patients. Accordingly, the use of gadodiamide and gadopentate dimeglumine for renal failure patients was banned in Europe in spring 2007. The same two compounds should only be used cautiously in patients with moderate renal dysfunction. The current paper reviews the situation (July 2007) regarding gadolinium based contrast agent and the severe delayed reaction to some of these agents. The fear of nephrogenic systemic fibrosis should not lead to a denial of a well indicated enhanced magnetic resonance imaging examination.


title: Cytokine production in the nervous system of mice during acute and latent infection with herpes simplex virus type 1.

text: Immunocytochemistry on serial paraffin sections was used to monitor the production dynamics of cytokines (IL-2, IL-4, IL-6, IL-10, IFN-gamma and TNF-alpha) and viral antigens in the trigeminal ganglion (TG) and the central side of the dorsal root entry zone (DRE) of mice, following infection of the cornea with herpes simplex virus type 1. In normal TG, scattered satellite cells were TNF-alpha+ and in the DRE, TNF-alpha+ and/or low numbers of IL-6+ cells were detected. On day 3 after infection, foci of TG neurons with viral antigens were surrounded by large numbers of TNF-alpha+ and/or IL-6+ cells and low numbers of IFN-gamma+ cells. IL-2+ and/or IL-4+ cells appeared later, when viral antigens had almost cleared. In the TG, the most striking changes occurred with TNF-alpha, with respect to its source (satellite cells, Schwann cells and infiltrating cells) and the extent and long duration of its production. TNF-alpha was the predominant cytokine throughout acute and latent infection and even by day 30, numbers of satellite cells expressing this cytokine were three times higher than those in normal ganglia. Moreover, in the DRE, TNF-alpha was the only cytokine detected during virus clearance and again, its production continued, along with that of IL-6, on days 20 to 30, in both infiltrating cells and astrocytes. Thus, cytokines, particularly TNF-alpha and perhaps IL-6, from infiltrating cells and resident glial cells may have a role both in virus clearance and in normal homeostatic mechanisms in the nervous system such as repair and protection of neurons from damage.


title: Rhinovirus infection in hospitalized children in Hong Kong: a prospective study.

text: OBJECTIVES To analyze the clinical features and estimate the hospitalization disease burden of rhinovirus infection in children in Hong Kong. METHODS In this prospective study, nasopharyngeal aspirates were taken from children aged <18 years with symptoms of acute respiratory infection admitted to Queen Mary Hospital on one fixed day of the week during August 2001-July 2002 for detection of common respiratory viruses by immunofluorescence, viral culture, and for rhinovirus, human metapneumovirus, and coronaviruses by reverse transcription polymerase chain reaction. The clinical features of rhinovirus infections were analyzed and hospitalization disease burden was estimated. RESULTS Altogether 239 of the 426 nasopharyngeal aspirates (56.1%) were positive for respiratory viruses, including 151 patients with rhinovirus (35.4%). The median age was 2.34 years. Upper respiratory infection, asthma exacerbation, pneumonia, and acute bronchiolitis were diagnosed in 44.4%, 19.9%, 11.3%, and 7.9%, respectively. The most common symptoms were cough (81.5%), runny nose (76.8%), and fever (68.9%). Shortness of breath, wheezes, and crepitation were present in 25.8%, 29.1%, and 18.5%, respectively. Fifty-five of 99 patients (55.6%) had chest radiographic abnormalities, most commonly perihilar streakiness. Children with chronic diseases were more likely to have lower respiratory tract infection and these children required longer hospitalization (mean 0.6 days longer). Coinfection with other respiratory pathogens was common (33.1%). CONCLUSION Rhinovirus is frequently associated with asthmatic exacerbations and lower respiratory tract infection, especially in children with chronic diseases and is potentially an important contributor to hospitalization in children in Hong Kong.


title: [MERS-CoV: a new virus from Saudi Arabia].

text: Since about a year, a new pulmonary pathology occurred in Saudi Arabia and some cases are imported in Europa. This disease is due to a coronavirus named MERS-CoV (Middle East Respiratory Syndome Coronavirus). The main symptoms are fever, pulmonary and digestive troubles, with a risk of nosocomial transmission and a mortality of about 42%. The reservoir is probably the dromedary camel and the bat is the vector. There is no specific treatment or vaccine.


Rapid review of COVID-19.


title: Complete genome characterization and phylogenetic analysis of WU polyomavirus in Thai pediatric patients with respiratory tract infections in 2013.

text: BACKGROUND The WU polyomavirus (WUPyV) is a small DNA virus (family Polyomaviridae) that contains a circular double-stranded DNA genome, approximately 5 kb in length. WUPyV was first discovered in the respiratory tract of children with acute respiratory symptoms. OBJECTIVE This study focuses on the complete genome characterization and phylogenetic analysis of WUPyV obtained from Thai patients with respiratory diseases in 2013. MATERIAL AND METHOD DNA was extracted from nasopharyngeal (NP) suction specimens (n = 614) from patients with respiratory tract infections. WUPyV was detected by using semi-nested PCR and then characterized by whole genome sequencing. The nucleotides and deduced amino acid sequences were analyzed by multiple sequences alignment and phylogenetic tree. RESULTS Analysis revealed that 0.16% (1/614) of the sample was positive for WUPyV. Phylogenetic trees demonstrated that WUPyV(isolate CU_Chonburi 3) was closely related to previously described WUPyV. Moreover, whole genome sequences alignment of WUPyV showed several nucleotide variations within non-coding regions and amino acid changes in VP1 (position S347T); VP2 (positions L40V, G120R, Y121I, P123R, G127S, L137F, Q287R, and A327V); LTAg (positions Q357P, V369E, E377K, D378V, A381T, R382E, R383G, and D389G); and, STAg (positions R139S, K141E, R148K, and W153C). CONCLUSION Nucleotide variations within non-coding regions and critical amino acid substitutions in viral proteins may affect the rate of viral replication and viral adaptation; factors that may be linked to the susceptibility and severity of viral infection. Data obtained from this study may be useful in better understanding the genetic characterization and mutation patterns of WUPyV.


Outbreak of diarrhoea and milk drop in cows infected with bovine group B rotavirus.


title: Respiratory viral threats.

text: PURPOSE OF REVIEW To assess new information from peer-reviewed publications in 2005 regarding emerging respiratory viral threats. RECENT FINDINGS The expanding epizootic of avian A/H5N1 influenza and increasing number of human cases heighten concern regarding the threat of pandemic influenza. Studies of the 1918 pandemic virus have shown the potential for direct interspecies transmission from an avian host. In the absence of an effective vaccine, antiviral agents could provide an important response measure. Inadequate supplies and potential antiviral resistance are limiting factors. Seasonal influenza heavily affects infants and young children, who also serve to foster transmission at the community level, findings that indicate the need for broader immunization strategies in pediatric populations. Like avian influenza, the severe acute respiratory syndrome coronavirus was a zoonotic infection, perhaps derived from related coronaviruses in bats. Molecular diagnostic techniques have led to the recent identification of several new coronaviruses and a respiratory parvovirus. It has also helped to define the impact of previously described ones such as human metapneumovirus and rhinoviruses, which account for the majority of asthma exacerbations and frequent lower respiratory tract illnesses. SUMMARY Progress has been made in development of possible specific interventions for influenza and possibly severe acute respiratory syndrome coronavirus, but effective antivirals and vaccines for most other respiratory viruses are currently lacking.


title: Typing infectious bronchitis virus strains using reverse transcription-polymerase chain reaction and restriction fragment length polymorphism analysis to compare the 3' 7.5 kb of their genomes.

text: Typing infectious bronchitis virus (IBV) strains is useful for implementation of control measures and for understanding the epidemiology and evolution of IBV. The aim of the work reported here was to develop a rapid and sensitive method for typing isolates of IBV, if possible directly from tissues of infected birds. A procedure was developed for differentiation of IBV strains by restriction endonuclease fragment length polymorphism (RFLP) analysis of a 7.5 kb DNA fragment amplified from their genome by reverse transcription-polymerase chain reaction (RT-PCR). This fragment encompassed all of the genes encoding the structural proteins of the virus. Viral RNA was extracted either directly from tissues of diseased birds or from virus propagated in embryonated eggs, and was subjected to RT-PCR. Three different restriction endonucleases, AluI, Sau3AI and MnlI, were used to digest the 7.5 kb PCR product from different IBV strains and the resultant RFLP patterns were compared. Patterns obtained with all three enzymes grouped IBV strains belonging to the same serotype in the same cluster. These results show that the RT-PCR-RFLP system described here can be used as a quick and inexpensive tool for differentiating IBV strains.


title: Idiopathic CD4 lymphocytopenia.

text: PURPOSE OF REVIEW A severe decrease of CD4 T cells predisposes humans to opportunistic infections. In adults, HIV is certainly the most common cause of CD4 lymphocytopenia, but other causes, such as infections, autoimmune diseases, immunosuppressive therapy, lymphoma and idiopathic forms need to be considered. This review summarizes the current knowledge of the poorly understood syndrome of idiopathic CD4 lymphocytopenia. RECENT FINDINGS Little research has tried to systematically dissect this probably heterogeneic syndrome after its initial description in 1992. Numerous cases presenting with opportunistic infections have been reported. Disturbed differentiation of stem cell precursors may contribute to CD4 lymphocytopenia. Because infections and lymphoma may also cause CD4 lymphocytopenia, the distinction between cause and effect may evolve only during follow-up. SUMMARY The manifestation of opportunistic infections calls for the evaluation of the immune system for CD4 lymphocytopenia. The differential diagnosis of this condition in adults comprises primarily HIV infection and less often other diseases or drugs. Idiopathic CD4 lymphocytopenia is very rare. The clinical significance of low CD4 cell counts in HIV negative patients still awaits its systematic analysis. Prophylaxis of opportunistic infections is oriented at the recommendations of HIV-infected individuals and causal treatment remains experimental.


title: Localization of astrovirus in experimentally infected turkeys as determined by in situ hybridization.

text: Twenty-one 3-day-old turkey poults from British United Turkeys of America were orally inoculated with a recently characterized astrovirus, TAstV-2, isolated from turkeys with poult enteritis and mortality syndrome. At 1, 2, 3, 4, 5, 7, and 9 days postinfection (dpi), three inoculated birds were euthanatized, and tissues (intestines, spleen, bursa, and thymus) were collected immediately into 10% neutral buffered formalin. Inoculated birds were diarrheic by 3 dpi, and frothy feces persisted throughout the experimental period. Histologically, there was only slight evidence of enteric damage, which was characterized by mild epithelial necrosis, lamina propria infiltrates, minimal villus atrophy, and mild crypt hyperplasia. In situ hybridization, using a negative sense digoxigenin-labeled riboprobe to the capsid gene of TAstV-2, revealed viral RNA in intestinal epithelial cells at the basal margins of the villi, in distal small intestine, and in cecum at 2 dpi, with subsequent extension to epithelium of the large intestine and proximal small intestine (3-5 dpi). Minimal virus remained by 9 dpi.


title: Inhalational induction with "vasoparalytic" sevoflurane: are we "hyperoxygenating" while anesthetizing developing brains? A case series discussion.

text: BACKGROUND The concerns for hyperoxia-related brain tissue injury are well known to the medical community. The cerebro-vasodilatory properties of sevoflurane may create relative cerebral tissue "hyperoxia" during inhalational induction as compared to a propofol-based intravenous induction of anesthesia. STUDY OBJECTIVES The objective for this case series discussion was to identify any differences in cerebral tissue oxygenation secondary to induction of anesthesia with sevoflurane versus propofol. METHODS/STUDY PROCEDURES: After institutional review board approval, the computer data of tissue cerebral oximetry of pediatric patients (1-18 years age group) undergoing non-cardiac surgeries was comparatively analyzed for changes over time between the groups of children who received sevoflurane induction versus propofol induction of anesthesia. "Hyperoxia" ("hyperoxygenation") was defined as significant percent changes from the baseline values as recorded in tissue cerebral oximetry. RESULTS In this case series, seven patients underwent inhalational (INH) induction with high concentrations (8%) sevoflurane with nitrous oxide in 33% oxygen and four patients underwent intravenous (i.v.) induction with 2 mg/kg propofol and nitrous oxide in 33% oxygen. As compared to propofol, significant cerebral tissue "hyperoxia" occurred with sevoflurane induction (p = 0.003). This did not resolve over time. CONCLUSION As compared to intravenous induction with propofol, inhalational induction with "vasoparalytic" sevoflurane "hyperoxygenates" developing brains. This observation requires validation in larger trials to conclude appropriate effect on our practice of pediatric anesthesia and pediatric patient safety under anesthesia.


title: Efficacy and safety of psychostimulants for amphetamine and methamphetamine use disorders: a systematic review and meta-analysis.

text: BACKGROUND Amphetamine and methamphetamine use disorders are associated with severe health and social consequences. No pharmacological therapy has been approved for the treatment of these disorders. Psychostimulants can act as maintenance-like therapies for managing substance use among these patients. The aim of this study is to evaluate the literature examining the efficacy and safety of psychostimulant agents for increasing abstinence and treatment retention among patients with amphetamine and methamphetamine use disorders. METHODS We searched MEDLINE, EMBASE, PsycInfo, Cochrane Central, and CINAHL from inception to August 2016. Selection of studies, data extraction, and risk of bias assessment were conducted independently by two reviewers. We conducted meta-analyses to provide a pooled summary estimate for included trials and report the review according to PRISMA guidelines. RESULTS We identified and selected 17 studies with 1387 participants. Outcome reporting across trials was inconsistent, and the overall quality of evidence was very low due to high risk of bias and indirectness. A meta-analysis of five trials (642 participants) found no effect of psychostimulants for end-of-study abstinence (odds ratio = 0.97, 95% confidence interval 0.65 to 1.45). Additionally, the pooled estimate from 14 studies (1184 participants) showed no effect of psychostimulants for treatment retention (odds ratio = 1.20, 95% confidence interval = 0.91 to 1.58). The incidence of serious adverse events did not differ between intervention and placebo groups based on qualitative reports from trials. CONCLUSIONS Quantitative analyses showed no effect of psychostimulants for sustained abstinence or treatment retention. We also identified the need for more rigorous studies in this research area with clinician and patient important outcomes.


title: 'Primer alignment-and-extension': a novel mechanism of viral RNA recombination responsible for the rescue of inactivated poliovirus cDNA clones.

text: In the course of experiments designed to assess the potential role of alternative open reading frames (ORF) present in the 5'-terminal untranslated region (5'-UTR) of poliovirus type 1 (Mahoney strain) genomic RNA, we came across a double mutation that completely abrogated the infectivity of full-length cDNA clones. The infectivity was rescued in trans by cotransfecting COS-1 cells with short RNA transcripts of the wild-type 5'-UTR of poliovirus type 2 Lansing, provided a free 3'-OH was available. Direct sequencing of the viral RNA revealed that the infectious viruses recovered were recombinants Lansing/Mahoney, with variable points of 'crossing-over'. A novel mechanism of RNA-RNA recombination, which we propose to call 'primer alignment-and-extension', is described that would explain the high rate of recombination of RNA viruses observed in natural conditions.


title: The safety and usefulness of the single incision, transabdominal pre-peritoneal (TAPP) laparoscopic technique for inguinal hernia.

text: BACKGROUND The safety and usefulness of the SILS-TAPP (transabdominal pre-peritoneal) procedure remain unclear. The aim of this study was to clarify the safety and usefulness of the SILS-TAPP procedure compared with standard laparoscopic TAPP and TEPP (totally extra-peritoneal pre-peritoneal) procedures. PATIENTS AND METHODS 85 patients underwent laparoscopic inguinal hernia repairs (TEPP, 30 patients; TAPP, 20 patients; SILS-TAPP, 35 patients) from 2007 to 2011. The operative outcomes of the three groups were compared. RESULTS There was no difference in the patients' characteristics among the three groups. The TEPP Group had a longer operation time. One patient in the SILS-TAPP group had an intraoperative complication. One patient in the TAPP group had a postoperative complication, and one patient had ileus and one had an umbilical hernia in the SILS-TAPP group. The postoperative hospital stay was not significantly different among the three groups. There were no recurrences in the TEPP group, 1 case of recurrence (5.0%) in the TAPP group, and 1 case (2.9%) in the SILS-TAPP group. CONCLUSIONS The present findings show that the SILS-TAPP repair is safe and feasible for the repair of adult inguinal hernia.


title: [COVID-19 in the intensive care unit. Analysis of the experience during the first month of pandemic].

text: This is an analysis of clinical characteristics, images findings, laboratory variables and respiratory mechanics in patients with coronavirus disease 2019 (COVID-19) during the first month of the pandemic outbreak in Buenos Aires. In this descriptive case study of a single-centre, we included all confirmed cases of COVID-19 hospitalized in intensive care unit (ICU). All cases were confirmed by reverse transcription polymerase chain reaction. A total of 7 patients with confirmed COVID-19 were referred to out ICU. The median age was 71 years (interquartile range 52-75), including 4 men and 3 women. Patients most common clinical manifestations were fever (7), cough (5), asthenia (4) and shortness of breath (3). Among the radiological findings, five of them showed interstitial opacities and one patient had bilateral pulmonary consolidation. Five required invasive mechanical ventilation and multiple prone sessions. None died during hospitalization, although three still remain in the ICU. According to imaging examination, 71.4% showed interstitial opacities and one patient bilateral consolidation. Five patients required invasive mechanical ventilation and multiple prone sessions. None of them died during hospitalization, although three still remain in the ICU.


title: Sensitivity of Tru-cut and fine needle aspiration biopsies of liver and kidney for diagnosis of feline infectious peritonitis.

text: BACKGROUND The detection of typical lesions and feline coronavirus (FCoV) antigen in tissues is the only conclusive method for making a diagnosis of feline infectious peritonitis (FIP). A positive result using Tru-cut biopsy (TCB) and fine-needle aspiration biopsy (FNAB) has high diagnostic specificity, but information about the capacity of these techniques to correctly identify cats with FIP lesions is not available. OBJECTIVES The diagnostic sensitivity of TCB and FNAB for detecting liver and kidney histologic lesions caused by FIP was evaluated. METHODS TCB and FNAB specimens collected mainly at necropsy from 25 cats with FIP were analyzed. Diagnostic sensitivity was calculated on the basis of the number of false-negative and true-positive specimens, compared with the number of organs bearing histologic lesions of FIP. RESULTS Diagnostic sensitivity was higher for hepatic TCB (64%) and FNAB (82%) than for renal (39% and 42%, respectively) procedures. A high percentage of renal cytologic and TCB specimens were inadequate. Combined analysis of TCB and FNAB specimens collected from the same organ increased the diagnostic sensitivity for liver (86%) and kidney (48%). The sensitivity of immunohistochemical/cytochemical analysis was low (11-38% depending on the technique), probably due to variable distribution of feline coronavirus in the lesions. CONCLUSION Biopsy of liver and kidney can correctly identify FIP lesions. However, false-negative results or inadequate samples occur with moderate frequency, especially for immunochemical analysis. Diagnostic sensitivity may be increased when both TCB and FNAB specimens from the same organ are examined.


title: Inhibition, escape, and attenuated growth of severe acute respiratory syndrome coronavirus treated with antisense morpholino oligomers.

text: The recently emerged severe acute respiratory syndrome coronavirus (SARS-CoV) is a potent pathogen of humans and is capable of rapid global spread. Peptide-conjugated antisense morpholino oligomers (P-PMO) were designed to bind by base pairing to specific sequences in the SARS-CoV (Tor2 strain) genome. The P-PMO were tested for their capacity to inhibit production of infectious virus as well as to probe the function of conserved viral RNA motifs and secondary structures. Several virus-targeted P-PMO and a random-sequence control P-PMO showed low inhibitory activity against SARS coronavirus. Certain other virus-targeted P-PMO reduced virus-induced cytopathology and cell-to-cell spread as a consequence of decreasing viral amplification. Active P-PMO were effective when administered at any time prior to peak viral synthesis and exerted sustained antiviral effects while present in culture medium. P-PMO showed low nonspecific inhibitory activity against translation of nontargeted RNA or growth of the arenavirus lymphocytic choriomeningitis virus. Two P-PMO targeting the viral transcription-regulatory sequence (TRS) region in the 5' untranslated region were the most effective inhibitors tested. After several viral passages in the presence of a TRS-targeted P-PMO, partially drug-resistant SARS-CoV mutants arose which contained three contiguous base point mutations at the binding site of a TRS-targeted P-PMO. Those partially resistant viruses grew more slowly and formed smaller plaques than wild-type SARS-CoV. These results suggest PMO compounds have powerful therapeutic and investigative potential toward coronavirus infection.


title: Host cell cathepsins potentiate Moloney murine leukemia virus infection.

text: The roles of cellular proteases in Moloney murine leukemia virus (MLV) infection were investigated using MLV particles pseudotyped with vesicular stomatitis virus (VSV) G glycoprotein as a control for effects on core MLV particles versus effects specific to Moloney MLV envelope protein (Env). The broad-spectrum inhibitors cathepsin inhibitor III and E-64d gave comparable dose-dependent inhibition of Moloney MLV Env and VSV G pseudotypes, suggesting that the decrease did not involve the envelope protein. Whereas, CA-074 Me gave a biphasic response that differentiated between Moloney MLV Env and VSV G at low concentrations, at which the drug is highly selective for cathepsin B, but was similar for both glycoproteins at higher concentrations, at which CA-074 Me inhibits other cathepsins. Moloney MLV infection was lower on cathepsin B knockout fibroblasts than wild-type cells, whereas VSV G infection was not reduced on the B-/- cells. Taken together, these results support the notion that cathepsin B acts at an envelope-dependent step while another cathepsin acts at an envelope-independent step, such as uncoating or viral-DNA synthesis. Virus binding was not affected by CA-074 Me, whereas syncytium induction was inhibited in a dose-dependent manner, consistent with cathepsin B involvement in membrane fusion. Western blot analysis revealed specific cathepsin B cleavage of SU in vitro, while TM and CA remained intact. Infection could be enhanced by preincubation of Moloney MLV with cathepsin B, consistent with SU cleavage potentiating infection. These data suggested that during infection of NIH 3T3 cells, endocytosis brings Moloney MLV to early lysosomes, where the virus encounters cellular proteases, including cathepsin B, that cleave SU.


title: Viral gastroenteritis and diversity of Rotavirus strains in Colombian children: a systematic review.

text: BACKGROUND To determine the epidemiological profile of viruses associated with acute gastroenteritis in children younger than 5 years of age and the distribution of rotavirus genotypes circulating in Colombia. METHODOLOGY We conducted a review of 23 studies published in Spanish and English, plus an analysis of the detection rates of rotavirus as well as other viruses associated with acute gastroenteritis in young children from 1984 to 2006 in the three Colombian regions. This review also included the only two studies conducted to date (published between 2004 and 2006) reporting G-P rotavirus strains using RT-PCR. RESULTS The median detection rate of group A Rotavirus was 35.2% (range, 2.2%-57.4%) and those for Calicivirus, Astrovirus and Adenovirus 40/41 were 10.4%, 2.7% and 1.35%, respectively. The more commonly reported rotavirus GP combination, G3P [8] (32.7%) was more frequently documented than both G1P [8] (24.7%) and G2P [4] (22.9%). The G9 genotype, which is considered emergent, was also reported. CONCLUSIONS Group A Rotavirus was frequently associated with diarrhoea in children from the three regions. There was regional variation in rotavirus detection rates. Continual surveillance is needed to inform diarrhoea prevention programs as well as to provide information about the occurrence of native rotavirus strains.


title: Heterogeneous shedding of Escherichia coli O157 in cattle and its implications for control.

text: Identification of the relative importance of within- and between-host variability in infectiousness and the impact of these heterogeneities on the transmission dynamics of infectious agents can enable efficient targeting of control measures. Cattle, a major reservoir host for the zoonotic pathogen Escherichia coli O157, are known to exhibit a high degree of heterogeneity in bacterial shedding densities. By relating bacterial count to infectiousness and fitting dynamic epidemiological models to prevalence data from a cross-sectional survey of cattle farms in Scotland, we identify a robust pattern: approximately 80% of the transmission arises from the 20% most infectious individuals. We examine potential control options under a range of assumptions about within- and between-host variability in infection dynamics. Our results show that the within-herd basic reproduction ratio, R(0), could be reduced to <1 with targeted measures aimed at preventing infection in the 5% of individuals with the highest overall infectiousness. Alternatively, interventions such as vaccination or the use of probiotics that aim to reduce bacterial carriage could produce dramatic reductions in R(0) by preventing carriage at concentrations corresponding to the top few percent of the observed range of counts. We conclude that a greater understanding of the cause of the heterogeneity in bacterial carriage could lead to highly efficient control measures to reduce the prevalence of E. coli O157.


Immunization in Canada 2007.


Successful sequencing of the first SARS-CoV-2 genomes from Croatian patients.


title: [Analysis of Symptoms Relieved in Addition to Pain after Administration of Oxycodone or Morphine to Patients with Advanced Cancer Living at Home].

text: Cancer pain was observed in 131 of 160 patients with advanced cancer living at home. Oxycodone or morphine was administered to patients suffering from cancer pain or fentanyl transdermal patch was switched to morphine. Subsequently, 70 patients were found to have alleviation of symptoms such as nausea/vomiting, dyspnea, abdominal fullness, general fatigue, cough, and urinary urgency in addition to pain. Pain was defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage by the International Association for the Study of Pain. This definition of pain is cited in a lot of books. However, the author was unable to intervene with detailed reports of unpleasant sensations associated with tissue damage. Therefore, here the author reports about an unpleasant sensation caused by tissue damage of cancer that was alleviated by oxycodone or morphine.


title: Rice-based mucosal vaccine as a global strategy for cold-chain- and needle-free vaccination.

text: Capable of inducing antigen-specific immune responses in both systemic and mucosal compartments without the use of syringe and needle, mucosal vaccination is considered ideal for the global control of infectious diseases. In this study, we developed a rice-based oral vaccine expressing cholera toxin B subunit (CTB) under the control of the endosperm-specific expression promoter 2.3-kb glutelin GluB-1 with codon usage optimization for expression in rice seed. An average of 30 mug of CTB per seed was stored in the protein bodies, which are storage organelles in rice. When mucosally fed, rice seeds expressing CTB were taken up by the M cells covering the Peyer's patches and induced CTB-specific serum IgG and mucosal IgA antibodies with neutralizing activity. When expressed in rice, CTB was protected from pepsin digestion in vitro. Rice-expressed CTB also remained stable and thus maintained immunogenicity at room temperature for >1.5 years, meaning that antigen-specific mucosal immune responses were induced at much lower doses than were necessary with purified recombinant CTB. Because they require neither refrigeration (cold-chain management) nor a needle, these rice-based mucosal vaccines offer a highly practical and cost-effective strategy for orally vaccinating large populations against mucosal infections, including those that may result from an act of bioterrorism.


title: Complications and Failure of Endovenous Laser Ablation and Radiofrequency Ablation Procedures in Patients With Lower Extremity Varicose Veins in a 5-Year Follow-Up.

text: INTRODUCTION Thermal ablation techniques have gradually replaced Babcock procedure in varicose vein treatment. AIM A comparative quantitative-qualitative analysis of complications and failure of endovenous laser ablation (EVLA) and radiofrequency ablation (RFA) in a 5-year follow-up. MATERIALS AND METHODS One hundred ten adult participants with varicose veins clinical grade C2 to C6, treated for isolated great saphenous vein (GSV) or small saphenous vein (SSV) insufficiency in a single lower extremity in 2009 to 2010, were enrolled and subdivided into EVLA (n = 56) and RFA (n = 54) groups. Both groups were compared for demography, disease stage, affected veins, perioperative, and postoperative complications as well as treatment efficacy. RESULTS The perioperative and postoperative complications were statistically insignificant. Treatment efficacy, expressed as the number of participants with recurrent varicosity and recanalization, was comparable in both groups. The clinically significant recanalization rate was 3.6% and 5.6% in EVLA and RFA groups, respectively. CONCLUSION Endovenous laser ablation and RFA for the management of lower extremity varicose vein offer comparable efficacy and safety in a 5-year follow-up.


title: Toxicology and carcinogenesis studies of methylene blue trihydrate (Cas No. 7220-79-3) in F344/N rats and B6C3F1 mice (gavage studies).

text: UNLABELLED Methylene blue trihydrate has a variety of biomedical and biologically therapeutic applications. Methylene blue trihydrate was nominated by the National Cancer Institute (NCI) for carcinogenicity testing based on the numerous uses of this compound and the lack of long-term toxicity data, including epidemiological studies of methylene blue trihydrate, as well as the inadequate animal data on this compound. Male and female F344/N rats and B6C3F1 mice were administered methylene blue trihydrate in 0.5% aqueous methylcellulose by gavage for 1 month, 3 months, or 2 years. Genetic toxicology studies were conducted using Salmonella typhimurium, Escherichia coli, cultured Chinese hamster ovary cells, mouse bone marrow cells, and mouse peripheral blood erythrocytes. 1-MONTH STUDY IN RATS: Groups of 10 male and 10 female core study rats and groups of 10 male and 10 female clinical pathology study rats were administered methylene blue trihydrate in 0.5% aqueous methylcellulose solution by gavage at doses of 0, 125, 250, 500, 1,000, or 2,000 mg/kg, 5 days per week for 5 weeks. In the 500 mg/kg groups, one male died the first week of the study and one male and four females died the second week of the study. All rats in the 1,000 mg/kg group died by study day 10, and all rats in the 2,000 mg/kg group died by study day 6. Final mean body weights of male and female rats in the 250 and 500 mg/kg groups were significantly less than those of the vehicle controls. Dosed rats developed methemoglobinemia and a regenerative Heinz body anemia. Significant increases in spleen weights occurred in all surviving dosed groups. There were also significant decreases in the thymus weights of 250 and 500 mg/kg males and 125 and 250 mg/kg females. Spleen lesions associated with methylene blue trihydrate administration included hematopoietic cell proliferation, pigmentation, lymphoid depletion of the lymphoid follicles, and capsular fibrosis. Hyperplasia of the bone marrow occurred in all dosed groups of rats. Liver lesions associated with methylene blue exposure included centrilobular necrosis in rats dying early, hematopoietic cell proliferation, and Kupffer cell pigmentation with erythrophagocytosis. 1-MONTH STUDY IN MICE: Groups of 10 male and 10 female core study mice were administered methylene blue trihydrate in 0.5% aqueous methylcellulose solution by gavage at doses of 0, 125, 250, 500, 1,000, or 2,000 mg/kg, 5 days per week for 5 weeks. None of the mice in the 500, 1,000, and 2,000 mg/kg groups survived to the end of the study. In the 250 mg/kg groups, two females died on days 16 and 18 and two males died on days 6 and 13. Mean body weights of surviving dosed mice were similar to those of the vehicle controls. Thinness, abnormal respiration, hypothermia, lethargy, ataxia, and ruffled fur were observed in a few surviving animals in the 250 mg/kg groups. Hypothermia and abnormal posture were observed in mice in the 500, 1,000, and 2,000 mg/kg groups. Dosed mice developed methemoglobinemia and a regenerative Heinz body anemia. Significant increases in spleen weights occurred in all surviving dosed groups of mice compared to vehicle controls. Significant decreases occurred in the thymus weights of 250 mg/kg males and females. The heart weights of 125 and 250 mg/kg females were significantly increased. Lesions in the spleen associated with methylene blue trihydrate administration included hematopoietic cell proliferation, pigmentation, and congestion. Liver lesions associated with methylene blue trihydrate administration included periportal degeneration, hematopoietic cell proliferation, and Kupffer cell pigmentation with erythrophagocytosis. The incidences of bone marrow pigmentation were significantly increased in all dosed groups of mice. Forestomach lesions that were related to methylene blue trihydrate administration included focal ulcer, inflammation, and squamous hyperplasia. 3-MONTH STUDY IN RATS: Groups of 10 male and 10 female core study rats and groups of 20 male and 20 female clinical pathology study rats were administered methylene blue trihydrate in 0.5% aqueous methylcellulose solution by gavage at doses of 0, 25, 50, 100 or 200 mg/kg, 5 days per week for 14 weeks. Mean body weights of males in the 200 mg/kg group were significantly less than those of the vehicle controls. Dosed rats developed methemoglobinemia and a regenerative Heinz body anemia. Significant increases in spleen weights occurred in males and females administered 50 mg/kg or greater. Thymus and lung weights of 50, 100, and 200 mg/kg males (except relative lung weight at 100 mg/kg) were significantly less than those of the vehicle controls. Spleen lesions in dosed rats included hematopoietic cell proliferation, congestion, lymphoid depletion of the lymphoid follicles, and capsular fibrosis. The incidences of bone marrow hyperplasia were significantly increased in groups administered 50 mg/kg or greater. There were no consistent effects of methylene blue trihydrate administration on reproductive system measures in male or female rats. 3-MONTH STUDY IN MICE: Groups of 10 male and 10 female core study mice and groups of 20 male and 20 female clinical pathology study mice were administered methylene blue trihydrate in 0.5% aqueous methylcellulose solution by gavage at doses of 0, 25, 50, 100, or 200 mg/kg, 5 days per week for 14 weeks. Mean body weights of all dosed groups were similar to or only slightly less than those of the vehicle control groups. Dosed mice developed methemoglobinemia and a regenerative Heinz body anemia. Spleen weights of 100 and 200 mg/kg males and 50 mg/kg or greater females were significantly greater than those of the vehicle control groups. Heart weights were significantly increased in 200 mg/kg males. In females, there were significant decreases in thymus weights at 50 mg/kg or greater. Males had decreased sperm motility and increased epididymal sperm counts at 200 mg/kg. In all dosed groups, the incidences of hematopoietic cell proliferation and pigmentation in the spleen were significantly greater than those in the vehicle controls. In the liver, the incidences of hematopoietic cell proliferation were significantly increased in males and females in the 100 and 200 mg/kg groups, and the incidences of Kupffer cell pigmentation were significantly increased in groups administered 50 mg/kg or greater. The incidences of bone marrow pigmentation were significantly increased in all dosed groups of mice except 25 mg/kg females. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were administered methylene blue trihydrate in 0.5% aqueous methylcellulose solution by gavage at doses of 0, 5, 25, or 50 mg/kg, 5 days per week for 2 years. Additional groups of 10 male and 10 female rats were administered the same doses for up to 18 months and were evaluated at 2 weeks and 3, 12, and 18 months for hematology. Survival of all dosed groups of rats was similar to that of the vehicle controls. Mean body weights of 25 and 50 mg/kg male rats were less than those of the vehicle controls after weeks 29 and 21, respectively. In the 25 and 50 mg/kg females, mean body weights were less after weeks 73 and 53. Dosed male and female rats developed methemoglobinemia, and females developed a regenerative Heinz body anemia. The incidences of pancreatic islet cell adenoma and adenoma or carcinoma (combined) were increased in all dosed groups of males, were significantly increased in 25 mg/kg males, and exceeded the historical range in controls (all routes). The incidence of pancreatic islet cell hyperplasia was significantly increased in the 50 mg/kg males. In the spleen, the incidence of hematopoietic cell proliferation in 50 mg/kg males was significantly increased; the incidences of capsular fibrosis were significantly increased in all dosed groups of males and in 5 and 50 mg/kg females. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were administered methylene blue trihydrate in a 0.5% aqueous methylcellulose solution by gavage at doses of 0, 2.5, 12.5, or 25 mg/kg, 5 days per week for 2 years. Additional groups of 30 male and 30 female mice were administered the same doses for up to 18 months and were evaluated at 2 weeks and 3, 12, or 18 months for hematology. Survival of dosed male and female groups exceeded that of the vehicle controls in a generally dose-related manner. Mean body weights of dosed female mice began to increase after weeks 29, 61, and 85, reaching final values that were 113%, 111%, and 106% of vehicle controls for the 2.5, 12.5, and 25 mg/kg groups, respectively. Dosed mice developed methemoglobinemia and a regenerative Heinz body anemia. The incidences of carcinoma and of adenoma or carcinoma (combined) of the small intestine occurred with a positive trend in males. The incidences of malignant lymphoma occurred with a positive trend in females, and the incidence in 25 mg/kg males exceeded the historical control range. The incidences of hematopoietic cell proliferation of the spleen were significantly increased in 12.5 and 25 mg/kg males and in 25 mg/kg females. The incidences of inflammation of the nose were significantly increased in 12.5 and 25 mg/kg females. GENETIC TOXICOLOGY Methylene blue trihydrate was mutagenic in Salmonella typhimurium strains TA98 and TA100 with and without rat or hamster liver S9 activation enzymes; mutagenicity was also observed in Escherichia coli strain WP2 uvrA/pKM101 with and without rat liver S9. In cytogenetic tests with cultured Chinese hamster ovary cells, methylene blue trihydrate induced sister chromatid exchanges and chromosomal aberrations with and without S9. (ABSTRACT TRUNCATED).


title: Cross-reactive antibody responses to nsp1 and nsp2 of Porcine reproductive and respiratory syndrome virus.

text: Porcine reproductive and respiratory syndrome virus (PRRSV) non-structural proteins (nsps) play a key role in processing and maturation of the repertoire of structural and nsps of the virion, but little is known about the anti-nsp immune response. Here, it was hypothesized that pronounced antibody responses are generated to PRRSV nsp1 and nsp2, as they are present in infected cells and cytolytic infection releases viral proteins into interstitial spaces. Accordingly, nsp1 and nsp2 were cloned and expressed, and antibody responses in the sera of infected and vaccinated pigs were determined. Pigs mounted significant cross-reactive antibody responses that appeared equivalent to or greater than the response to nucleocapsid (N). Antibody reactivity to nsp1 and N was highly dependent on refolding of denatured proteins, suggesting that the porcine antibody response is directed primarily to conformational epitopes. The proteins reacted with sera from pigs infected with other PRRSV strains, indicating that multiple epitopes are conserved. Antibody responses to nsp1 and nsp2 were much higher than those to nsp4, which is encoded on the same RNA molecule and is equivalent in predicted antigenicity. These findings suggest either that nsp1 and nsp2 are highly immunogenic or that they are expressed at higher levels than nsp4 in PRRSV-infected cells, or both. Strong antibody responses to nsp1 and nsp2 may benefit the host by limiting potentially pathological consequences of viral protease activities encoded in these proteins that are released from dying cells. The identification of strain-specific antibody responses to a highly variable region of nsp2 may also provide the basis for immunoassays that differentiate serological responses of vaccines from field isolates.


Subgroup demographic may have skewed ALLHAT results.


title: Vaccines in the public eye.

text: Preventive vaccines are widely acknowledged as the best hope for protection against infectious pathogens such as avian flu, HIV and SARS. As a result, they have received much recent attention in the media that has exposed some of the challenges involved in optimally using vaccine technology.


title: Development of antigen-capture enzyme-linked immunosorbent assay and RT-PCR for detection of turkey astroviruses.

text: Turkey astrovirus (TAstV) is an important agent of poult enteritis. The diagnosis of astroviruses has been dependent mainly on electron microscopy (EM) or immune EM (IEM). To develop other simple, rapid, and reliable diagnostic assays, two antigen-capture enzyme-linked immunosorbent assays (AC-ELISAs), polyclonal AC-ELISA and monoclonal AC-ELISA, were developed in this study. Monoplex and multiplex reverse transcription-polymerase chain reactions (RT-PCRs) were also developed using nondegenerate primer sets specific to the capsid region and degenerate primer pairs specific to the polymerase area of two TAstV. EM was included for comparison. Fecal or intestinal contents samples from naturally and experimentally infected poults with enteritis were examined using the developed assays. The polyclonal AC-ELISA had higher sensitivity and wider detection spectrum than the monoclonal AC-ELISA with group-specific monoclonal antibody (MAb), whereas the monoclonal AC-ELISA had very high specificity but lower sensitivity, which was estimated at 0.06 microg of viral proteins. Small round viruses (SRV) that could be astroviruses or other small viruses were detected in 34.4% of the samples examined by EM. The monoplex RT-PCR results amplified with primers SRV-1-3 and SRV-1-5 revealed that the positive rate of astroviruses was 45.3%, which was 10.9% higher than that of EM even if other SRVs were not excluded. Multiplex RT-PCR with SRV-1-3 and SRV-1-5 and AFCP-F1 and AFCP-R1 and the monoplex RT-PCR with degenerate primers verified that the positive rate of astroviruses was 59.4%, which was 25% higher than that of EM. Both RT-PCRs showed good specificity and wider detection spectrum compared with earlier published data.


title: Salmonella arizonae sepsis in a lynx.

text: A 4.5-wk-old lynx (Felis lynx) was presented for necropsy with a history of poor growth, mild diarrhea, anemia, and lethargy. The liver was enlarged and had a 7 mm long fracture that resulted in severe intraabdominal hemorrhage and death. Microscopic lesions were indicative of severe ulcerative cystitis and septicemia. Pure cultures of Salmonella arizonae were isolated from the liver, kidney, and spleen. Based on differences in the chronicity of inflammation in the urinary bladder versus other organs, we speculate that chronic cystitis caused by S arizonae lead to septicemic infection.


title: Implementation of an innovative postoperative monitoring approach for patients with obstructive sleep apnea.

text: This article shares how William Osler Health System (Osler) achieved improved quality of care for clinically challenging patients using state-of-the-art technology combined with interprofessional and intermanagerial teamwork in an acute care setting. Obstructive sleep apnea, a respiratory disorder caused by upper airway obstruction, increases the risk of complications after anesthesia. Although an initial postoperative monitoring strategy designed for patients with obstructive sleep apnea at Osler ensured patient safety, it required reorganization to resolve operational challenges. Concerned stakeholders at all levels contributed to the development and implementation of a new program approach focused on remote pulse oximetry monitoring as a component of the standard of care. Osler has developed a case study to share its experience with other hospitals and health systems that are already engaged in or that are considering implementing such a program.


title: The V-ATPase a2-subunit as a putative endosomal pH-sensor.

text: V-ATPase (vesicular H(+)-ATPase)-driven intravesicular acidification is crucial for vesicular trafficking. Defects in vesicular acidification and trafficking have recently been recognized as essential determinants of various human diseases. An important role of endosomal acidification in receptor-ligand dissociation and in activation of lysosomal hydrolytic enzymes is well established. However, the molecular mechanisms by which luminal pH information is transmitted to the cytosolic small GTPases that control trafficking events such as budding, coat formation and fusion are unknown. Here, we discuss our recent discovery that endosomal V-ATPase is a pH-sensor regulating the degradative pathway. According to our model, V-ATPase is responsible for: (i) the generation of a pH gradient between vesicular membranes; (ii) sensing of intravesicular pH; and (iii) transmitting this information to the cytosolic side of the membrane. We also propose the hypothetical molecular mechanism involved in function of the V-ATPase a2-subunit as a putative pH-sensor. Based on extensive experimental evidence on the crucial role of histidine residues in the function of PSPs (pH-sensing proteins) in eukaryotic cells, we hypothesize that pH-sensitive histidine residues within the intra-endosomal loops and/or C-terminal luminal tail of the a2-subunit could also be involved in the pH-sensing function of V-ATPase. However, in order to identify putative pH-sensitive histidine residues and to test this hypothesis, it is absolutely essential that we increase our understanding of the folding and transmembrane topology of the a-subunit isoforms of V-ATPase. Thus the crucial role of intra-endosomal histidine residues in pH-dependent conformational changes of the V-ATPase a2-isoform, its interaction with cytosolic small GTPases and ultimately in its acidification-dependent regulation of the endosomal/lysosomal protein degradative pathway remain to be determined.


[Common cold syndrome].


title: Can Abdominal Wall Reconstruction Be Safely Performed Without Drains?

text: The use of closed suction drains in the abdominal wall is a common practice in abdominal wall reconstruction (AWR) operations. Drains can be a conduit for bacteria and can cause pain and discomfort for patients after surgery. A single hernia program has implemented the principles of clinical quality improvement in an attempt to improve outcomes for hernia patients. An attempt at a process improvement was implemented to eliminate the use of drains in AWR by adapting the technique. A total of 102 patients undergoing AWR were included between 8/11 and 9/15 (49 months). Compared with the group before the attempt at eliminating the use of abdominal wall drains (8/11-9/13), the group of patients after the implementation of the attempted process improvement (9/13-9/15) had less wound and pulmonary complications, a shorter hospital stay, less time in the postanesthesia care unit, and less opioid use in the postanesthesia care unit as well as for the entire hospital stay. In this group of AWR patients, an attempt at process improvement that eliminated the use of drains led to improved outcomes. Abdominal wall drains may be able to be safely eliminated with appropriate technique adaptation for AWR.


Human coronavirus HCoV-229E enters susceptible cells via the endocytic pathway.


MHV-A59 gene 1 proteins are associated with two distinct membrane populations.


title: Isolation of animal viruses from farm livestock waste, soil and water.

text: Ten porcine enteroviruses, 2 porcine adenoviruses and 1 coronavirus were isolated directly from 32 samples of slurry collected from a pig fattening house. Concentration of the same samples by adsorption with the polyelectrolyte PE-60 yielded 24 porcine enteroviruses and 3 porcine adenoviruses. A porcine enterovirus was isolated, following PE-60 concentration, from 1 to 6 slurry samples from a sow farrowing house. No virus was isolated from 12 samples of slurry from dairy cows nor from 6 slurry samples from a calf-rearing unit. A porcine enterovirus was isolated from soil samples, after concentration with PE-60, collected 1, 2 and 8 days after pig slurry was spread on hay stubble. Two porcine enteroviruses were isolated by membrane filtration from 26 samples of surface run-off from land on which pig slurry was routinely spread, and 2 bovine enteroviruses were isolated from cattle feedlot run-off after adsorption to layers of talc and celite followed by hydroextraction. A porcine enterovirus was also isolated from 1 of 33 samples of surface water collected on farms on which pig slurry was routinely spread on the land, but no virus was isolated from 36 samples of ground water from the same farms. The surface water and ground water samples were concentrated by talc-celite adsorption and hydroextraction.


title: Travel medicine considerations for North American immigrants visiting friends and relatives.

text: CONTEXT In the United States, 10% of the population was born outside of its borders. Immigrants and their children frequently return to visit their homeland, referred to as visiting friends and relatives (VFRs). They account for a disproportionately high volume of international travel. EVIDENCE ACQUISITION Searches of MEDLINE, World Health Organization, Centers for Disease Control and Prevention, International Society of Travel Medicine, and American Society of Tropical Medicine computerized databases, conference proceedings and abstracts, US Census Bureau, bibliographies of pertinent articles, and travel medicine texts. Priority was given to recent (1996-2003) evidence, addressing VFR travelers. General sources including travel medicine and immigrant health were also used. EVIDENCE SYNTHESIS Immigrants visiting friends and relatives experience excessive rates of travel-related morbidity and mortality. Lack of pretravel care is common due to patient and clinician barriers to care, preexisting health beliefs, and incomplete childhood vaccinations. Travel patterns increase risk with VFRs traveling to high-risk destinations. Susceptibility to infectious and noninfectious illnesses is often increased because of multiple preexisting medical problems and extremes of age. Infectious diseases differ in etiology and magnitude from those of traditional travelers. For example with malaria, VFRs are frequently prescribed inappropriate prophylaxis or take none at all, have longer stays, spend time in high-risk areas, and do not appropriately adhere to chemoprophylaxis regimens. Effective pretravel health advice, guidelines, and services for this high-risk population are essential. There are already a number of useful and readily available databases that may aid clinicians in providing optimal travel-related preventive and therapeutic care. CONCLUSIONS Immigrants who are visitors of friends and relatives in other countries account for a high volume of international travelers and are at markedly increased risk of travel-related illness. New strategies are needed to properly address the needs of VFR travelers. Pretravel services should be convenient, accessible, affordable, culturally competent, and if possible, located within clinics serving immigrant populations. Clinicians caring for VFRs should be knowledgeable about their travel-related risks and have access to regularly updated, detailed pretravel health information.


title: Kawasaki disease: four case reports of cardiopathy with an institutional and literature review.

text: Kawasaki disease (KD) is a systemic vasculitis condition with a relatively unknown etiology. First described in 1967 by Tomisaku Kawasaki in Japan, KD has come to be widely diagnosed in every region of the world. The disease has a high prevalence in children ages 6 months to 5 years, particularly in those of Japanese descent. Patients often present with a high fever, rash, lymphadenopathy, and conjunctival injections, but there is no diagnostic test for KD. This paper presents data from our Kawasaki registry including 99 patients with emphasis on Kawasaki cardiopathy. Three patients died from complications of KD, and 1 patient underwent heart transplant for massive aneurysmal dilatation. The 4 explanted hearts showed a spectrum of pathological findings (acute thrombosis, vasculitis, and myocarditis), and 1 patient showed the long-term sequelae of vasculitis in the form of massive aneurysmal dilatation. Among the survivors, 30% showed aneurysmal dilatation. This paper reviews the most recent information regarding Kawasaki cardiopathy and underlying molecular mechanisms.


title: The versatility of oligonucleotides as potential therapeutics.

text: Oligonucleotides can in a variety of ways inhibit gene expression by interfering with translation. Oligonucleotides that are complementary to a target mRNA, antisense oligonucleotides, can prevent translation either by cleaving the target or by physically blocking the process. Additionally, oligonucleotides can correct the undesired splicing of pre-mRNA. RNA interference using double-stranded oligoribonucleotides also results in cleavage of the target mRNA. Catalytically competent ribozymes and DNAzymes can have the same effect. Even with no RNA as target, oligonucleotides can be selected as aptamers to bind to any protein to inhibit its activity. Moreover, oligonucleotides can act as decoys particularly for transcription factors to prevent binding to the promoter. A different mode of action is the activation of Toll-like receptors to induce an immune response. Several pathways for drug development are still in their infancy, for example microRNAs and antagomirs.


title: [Renal transplantation during COVID-19 period in Spain.]

text: INTRODUCTION The COVID-19 pandemic poses significant challenges in the area of kidney donation and transplantation. The objective of this article is to establish general recommendations for surgical teams to manage the kidney transplant program duringthe COVID-19 era. MATERIAL AND METHODS: This document is based on the scientific evidence available on the infection caused by SARS-CoV-2 and the experience of authors during the COVID-19 pandemic. A web and Pubmed search was performed using the keywords "SARS-CoV-2"," COVID-19", "COVID Urology", "COVID-19 surgery", and "kidney transplantation." A modified nominal group technique was used. RESULTS: When health system saturation occurs, kidney transplants should be deferred, except in patients with low transplant possibilities and an optimal kidney available, combined transplants or life-threatening situations. Screening for the SARS-CoV-2 virus should be done in all those donors and recipients with clinical symptoms consistent with COVID-19, who have visited or live inhigh-risk areas, or who have been in close contact with confirmed cases of COVID-19. Donation and transplantation will not proceed in confirmed cases of COVID-19. Surgeries should be based on general recommendations in the COVID-19 era and will be efficient, short, and focused on those with the shortest hospital stay. In emergencies, protective measures will be taken with persona lprotection equipment. Surgical staff will be only the strictly necessary, and permanence in the OR should be minimized. Transplant urology consultations will be conducted by teleconsultation when possible. CONCLUSION: The safety of potential donors and recipients must be guaranteed, adopting individual protection measures and screening for SARS-CoV-2. Kidney transplant surgery must be efficient in terms of health, human resources, and clinical benefit. All non-urgent transplant activities should be delayed until the improvement of the local condition of each center.


title: Viral agents associated with poult enteritis and mortality syndrome: the role of a small round virus and a turkey coronavirus.

text: Intestinal samples from turkey poults affected with poult enteritis and mortality syndrome (PEMS) were examined for viruses by immune electron microscopy and double-stranded RNA virus genome electropherotyping. Turkey coronavirus (TCV), avian rotaviruses, reovirus, and a yet undefined small round virus (SRV) were detected. The SRV and TCV were isolated and propagated in turkey embryos. Challenge of specific-pathogen-free turkey poults with SRV, TCV, or both resulted in mortality and clinical responses similar to those of natural PEMS. Our experiments indicate that SRV and TCV are possibly important agents in the etiology of PEMS and the combination of these infections might result in outbreaks with high mortality. The severity of clinical signs and mortality of PEMS are postulated to be partly related to the virus agents involved in individual outbreaks.


title: Application of microbial genomic science to advanced therapeutics.

text: Since the publication of the first complete microbial genome sequence of Haemophilus influenzae in 1995, more than 200 additional microbial genome sequences have become available in the public domain. Approximately 40% of these represent important human pathogens. Comparative in silico methods, along with large-scale approaches such as transcriptomics and proteomics, are beginning to reveal insights into new virulence genes, pathogen-host interactions, and the molecular basis of host specificity. Sequence data are also starting to accumulate from multiple isolates or strains of a single pathogen, and this type of data has proven to be quite valuable in providing new insights into the genetic variability that is present in a particular species as well as in facilitating correlations between genotype and phenotype. Ultimately, a major goal of genome-enabled infectious disease research is the development of novel diagnostics, therapeutics, and vaccines.


title: An H9N2 influenza virus vaccine prepared from a non-pathogenic isolate from a migratory duck confers protective immunity in mice against challenge with an H9N2 virus isolated from a girl in Hong Kong.

text: H9N2 influenza viruses circulate in wild birds and poultry in Eurasian countries, and have been isolated from pigs and humans in China. H9N2 viruses isolated from birds, pigs and humans have been classified into three sublineages based on antigenic and genetic features. Chicken antisera to H9N2 viruses of the Korean sublineage reacted with viruses of different sublineages by the hemagglutination-inhibition test. A test vaccine prepared from a non-pathogenic A/duck/Hokkaido/49/1998 (H9N2) strain of the Korean sublineage, obtained from our influenza virus library, induced immunity in mice to reduce the impact of disease caused by the challenge with A/Hong Kong/1073/1999 (H9N2), which is of a different sublineage. The present results indicate that an inactivated whole virus vaccine prepared from a non-pathogenic influenza virus from the library could be used as an emergency vaccine during the early stage of a pandemic caused by H9N2 infection.


[SARS (Severe Acute Respiratory Syndrome)].


title: Critically ill patients with severe acute respiratory syndrome.

text: CONTEXT Severe acute respiratory syndrome (SARS) is a newly recognized infectious disease capable of causing severe respiratory failure. OBJECTIVE To determine the epidemiological features, course, and outcomes of patients with SARS-related critical illness. DESIGN, SETTING, AND PATIENTS Retrospective case series of 38 adult patients with SARS-related critical illness admitted to 13 intensive care units (ICUs) in the Toronto area between the onset of the outbreak and April 15, 2003. Data were collected daily during the first 7 days in the ICUs, and patients were followed up for 28 days. MAIN OUTCOME MEASURES The primary outcome was mortality at 28 days after ICU admission. Secondary outcomes included rate of SARS-related critical illness, number of tertiary care ICUs and staff placed under quarantine, and number of health care workers (HCWs) contracting SARS secondary to ICU-acquired transmission. RESULTS Of 196 patients with SARS, 38 (19%) became critically ill, 7 (18%) of whom were HCWs. The median (interquartile range [IQR]) age of the 38 patients was 57.4 (39.0-69.6) years. The median (IQR) duration between initial symptoms and admission to the ICU was 8 (5-10) days. Twenty-nine (76%) required mechanical ventilation and 10 of these (34%) experienced barotrauma. Mortality at 28 days was 13 (34%) of 38 patients and for those requiring mechanical ventilation, mortality was 13 (45%) of 29. Six patients (16%) remained mechanically ventilated at 28 days. Two of these patients had died by 8 weeks' follow-up. Patients who died were more often older, had preexisting diabetes mellitus, and on admission to hospital were more likely to have bilateral radiographic infiltrates. Transmission of SARS in 6 study ICUs led to closure of 73 medical-surgical ICU beds. In 2 university ICUs, 164 HCWs were quarantined and 16 (10%) developed SARS. CONCLUSIONS Critical illness was common among patients with SARS. Affected patients had primarily single-organ respiratory failure, and half of mechanically ventilated patients died. The SARS outbreak greatly strained regional critical care resources.


title: Biochemical and genetic analyses of murine hepatitis virus Nsp15 endoribonuclease.

text: The goal of this project was to better define the relationship between the endoribonuclease activity of murine hepatitis virus (MHV) Nsp15 (mNsp15) and its role in virus infection. Molecular modeling demonstrated that the catalytic residues of mNsp15 are superimposable with its severe acute respiratory syndrome coronavirus ortholog. Alanine substitutions at three key residues in the mNsp15 catalytic pocket (H262, H277, and G275) and a double-mutant version (H262P and H277A) generated proteins with greatly reduced but detectable endoribonuclease activities. Furthermore, these mutant proteins demonstrated lower cleavage specificities for uridylate than wild-type (WT) mNsp15. These mutations were successfully incorporated into viruses named vH262A, vH277A, vG275A, and vH262P+H277A. All four mutant viruses formed plaques with diameters similar to that of MHV-A59 1000 (WT virus) on several different cell lines. Interestingly, viruses with a mutation at a noncatalytic residue, D324A, could not be recovered despite repeated attempts, and expression of mNsp15 containing the D324A mutation in Escherichia coli resulted in an insoluble protein. Plaques derived from vH262A produced approximately 6- to 13-fold fewer PFU than those from WT virus. Cells infected with mNsp15 mutant viruses accumulated lesser amounts of plus- and minus-sense subgenomic RNAs and spike protein than WT virus. The expression of mNsp15 in trans by transient transfection partially restored RNA synthesis by vH262A. These results demonstrate that mNsp15 is required for optimal infection by MHV.


Esophageal leakage after surgical repair of spontaneous rupture: successful closure with endoscopic suture device.