title: Type IV hypersensitivity in the pathogenesis of FIPV-induced lesions.

text: In focal lesions of feline infectious peritonitis (FIP), the cells involved in the delayed-type hypersensitivity were identified in formalin-fixed paraffin-embedded and frozen samples taken from 35 affected cats. The clinical diagnosis of FIP was confirmed by necropsy, histology and direct immunofluorescence against the coronaviruses on cryostatic sections. The immune cells were detected immunohistochemically by the Avidin-Biotin-Complex (ABC) method using either polyclonal antibodies against lymphoid antigens (CD3) or monoclonal antibodies against lymphoid (PAN-T, CD4, CD8) and myeloid antigens (MAC387). Better identification of T cells and macrophages was found on formalin-fixed paraffin-embedded sections than on cryostatic ones, while T lymphocyte subpopulations could be differentiated only in cryostatic sections. Type IV hypersensitivity was detected in focal feline infectious peritonitis virus (FIPV)-induced lesions from progressive activation of T lymphocytes, mainly CD4+, and the presence of granulocytes and macrophages. The FIPV-induced lesions could be studied as examples of granulomas caused by unconventional antigens, such as viruses or immune complexes.


title: Evaluation of syndromic surveillance in the Netherlands: its added value and recommendations for implementation.

text: In the last decade, syndromic surveillance has increasingly been used worldwide for detecting increases or outbreaks of infectious diseases that might be missed by surveillance based on laboratory diagnoses and notifications by clinicians alone. There is, however, an ongoing debate about the feasibility of syndromic surveillance and its potential added value. Here we present our perspective on syndromic surveillance, based on the results of a retrospective analysis of syndromic data from six Dutch healthcare registries, covering 1999–2009 or part of this period. These registries had been designed for other purposes, but were evaluated for their potential use in signalling infectious disease dynamics and outbreaks. Our results show that syndromic surveillance clearly has added value in revealing the blind spots of traditional surveillance, in particular by detecting unusual, local outbreaks independently of diagnoses of specific pathogens, and by monitoring disease burden and virulence shifts of common pathogens. Therefore we recommend the use of syndromic surveillance for these applications.


Urgent need for empirical research into whaling and whale watching.


title: [Lung Cancer and Respiratory Infections].

text: The frequency of respiratory infections as an infection in cancer patients is high. Several factors increase the risk of respiratory infections in cancer patients. These include airway obstruction, disruption of mucosal surfaces and treatment-related factors, such as radiation and chemotherapy. It has also been reported that the frequency and mortality of drug-induced lung injury associated with antineoplastic drugs are high in Japan. In the diagnosis and treatment of drug-induced lung disease, it is important to distinguish pneumonia as an infectious disorder. Immune checkpoint inhibitors(ICIs)have been widely introduced to treat several types of malignancies. It is currently believed that ICIs do not increase the risk of infections. However, immune-related adverse events(irAEs)induced by ICIs may necessitate the administration of immunosuppressive agents, which could cause opportunistic infections. Furthermore, several reports describe reactivation tuberculosis without irAEs or immunosuppressants. Further studies are needed to prevent the development of tuberculosis in patients receiving ICIs.


title: One Bioregion/One Health: An Integrative Narrative for Transboundary Planning along the US-Mexico Border.

text: Global megatrends-including climate change, food and water insecurity, economic crisis, large-scale disasters and widespread increases in preventable diseases-are motivating a bioregionalisation of planning in city-regions around the world. Bioregionalisation is an emergent process. It is visible where societies have begun grappling with complex socio-ecological problems by establishing place-based (territorial) approaches to securing health and well-being. This article examines a bioregional effort to merge place-based health planning and ecological restoration along the US-Mexico border. The theoretical construct underpinning this effort is called One Bioregion/One Health (OBROH). OBROH frames health as a transborder phenomenon that involves human-animal-environment interactions. The OBROH approach aims to improve transborder knowledge networking, ecosystem resilience, community participation in science-society relations, leadership development and cross-disciplinary training. It is a theoretically informed narrative to guide action. OBROH is part of a paradigm shift evident worldwide; it is redefining human-ecological relationships in the quest for healthy place making. The article concludes on a forward-looking note about the promise of environmental epidemiology, telecoupling, ecological restoration, the engaged university and bioregional justice as concepts pertinent to reinventing place-based planning.


Pandemic Influenza: public health preparedness for the next global health emergency.


title: Drug-induced tardive motor syndromes.

text: Drug-induced tardive motor syndromes (TMS) is a group of disorders, characterized by involuntary movements of the tongue, face, lips, trunk and extremities, occurring after long-term exposure to a variety of pharmacological agents, mostly neuroleptics. The diagnosis of TMS requires exposure to dopamine receptor blocking agents for a period at least of 3 months, although for people over 60 years old the necessary exposure period is limited to 1 month. The exact pathophysiology still remains obscure. The aim of this article is to review the phenomenology, epidemiology and treatment options of the TMS, as clinically distinct movement disorders. TMS include tardive dyskinesia, which is the most common movement disorder, tardive dystonia, tardive akathisia, tardive Tourettism, tardive tremor and tardive myoclonus as well as some specific syndromes less often presented such as Pisa, Meige and Rabbit syndromes. Prevention remains the cornerstone in good clinical practice. Preventive approach requires thorough diagnostic process with frequent reviews in order to determine the necessity of use and dosing of neuroleptic treatment. Clinical vigilance for early detection of signs of TMS as well as recording of early extrapyramidal side-effects in the patient's history is needed, as these may predict the occurrence of TMS. In case of occurrence of TMS, gradual discontinuation of the offending agent is required. Therapeutic interventions include the administration of the following agents: atypical antipsychotics (mainly clozapine), benzodiazepines, vitamin E, reserpine, tetrabenazine, anticholinergics, botulinum toxin A. The early management of TMS is crucial for the patients' better clinical outcome and improved quality of life.


Revised nomenclature for coronavirus structural proteins, mRNAs and genes.


title: [Viruses in the feces of patients with viral hepatitis and other enterovirus infections].

text: Direct and immune electron microscopy was used to determine the frequency of finding of hepatitis A virus (HAV) and other viral agents in feces of patients in relation to the diagnosis and epidemiological situation. HAV-containing excretions from patients were analysed ultrastructurally. The highest frequency of HAV detection was established in patients in a water-borne and food-borne outbreak of hepatitis A (HA) and was 40.9% and 36.9%, respectively. In patients with HA diagnosis in the period of a seasonal rise of HA incidence HAV particles were found in 11.8%, and in the interseasonal period in 5%. Apart from HAV particles, in a small per cent of patients with HA diagnosis adenovirus and enterovirus particles were found. In patients with the disease diagnosed as hepatitis B (HB) only adenovirus and enterovirus particles were found. In contrast to the patients with HAV and HB diagnosis, the patients who were combined into a conditional "non-hepatitis" group were found to have, in addition to HAV (in the period of seasonal rise of HA incidence), adenovirus and enterovirus particles, also particles of astrovirus, coronavirus, and rotavirus. In fecal specimens of patients containing typical HAV particles structures were found resembling individual fragments of empty HAV particles, antibody-covered 17-22 nm and 27 nm spherical structures poorly reacting with antibody.


title: [Covid-19 - deaths and analysis].

text: Mortality from Covid-19 is monitored in detail and compared between countries with different strategies against the virus. There is, however, often a lack of understanding of what is required in terms of measures and interpretation to enable correct comparisons. The number of deaths from Covid-19 is affected by the testing strategy and many other things that differ between countries. Therefore, today, the most reliable source for monitoring and comparing mortality from Covid-19 is total mortality. In Sweden, there is good correspondence of Covid-19 deaths and total mortality, with a tendency to a higher total mortality indicating some under-reporting of Covid-19 mortality.


Beijing/W Mycobacterium tuberculosis in Italy.


title: Borna Disease Virus Assembles Porous Cage-like Viral Factories in the Nucleus.

text: Animal-derived RNA viruses frequently generate viral factories in infected cells. However, the details of how RNA viruses build such intracellular structures are poorly understood. In this study, we examined the structure and formation of the viral factories, called viral speckle of transcripts (vSPOTs), that are produced in the nuclei of host cells by Borna disease virus (BDV). Super-resolution microscopic analysis showed that BDV assembled vSPOTs as intranuclear cage-like structures with 59-180-nm pores. The viral nucleoprotein formed the exoskeletons of vSPOTs, whereas the other viral proteins appeared to be mainly localized within these structures. In addition, stochastic optical reconstruction microscopy revealed that filamentous structures resembling viral ribonucleoprotein complexes (RNPs) appeared to protrude from the outer surfaces of the vSPOTs. We also found that vSPOTs disintegrated into RNPs concurrently with the breakdown of the nuclear envelope during mitosis. These observations demonstrated that BDV generates viral replication factories whose shape and formation are regulated, suggesting the mechanism of the integrity of RNA virus persistent infection in the nucleus.


title: Real-time PCR for diagnosis of human bocavirus infections and phylogenetic analysis.

text: The human bocavirus (hBoV) was first described in 2005 in respiratory tract samples. The clinical relevance of hBoV is still unclear. The aim of our study was to establish a real-time PCR assay for the detection and quantification of hBoV DNA, to apply the real-time assay for the analysis of stool and serum samples for the presence of hBoV DNA, and to perform a phylogenetic analysis of the hBoV positive samples. A total of 834 nasopharyngeal aspirates (NPA), 10 serum samples, and 31 stool samples of children with acute respiratory diseases were retrospectively tested. For phylogenetic analysis, 968 bp of the VP2 gene were sequenced from 69 hBoV-positive NPA samples. The qualitative results of the real-time hBoV PCR were in good agreement with a conventional hBoV PCR. We found that 12% of the NPA were positive for hBoV DNA. The median viral load in the NPA was 4.9 x 10(3) copies/ml (range, 2.7 x 10 degrees to 1.5 x 10(11) copies/ml). There was no difference of the hBoV load in NPA between children with or without known coinfection, but the load was significantly higher in children with bronchitis than in children with the diagnosis of febrile seizures. hBoV DNA was found in 1 of 10 serum samples and in 14 of 31 stool samples. hBoV sequence identity was >99% in the VP2 region. In conclusion, hBoV DNA can be found in NPA samples at very high titers. In addition to being found in the respiratory tract, hBoV was found in stool samples. The clinical relevance of these findings remains to be determined.


title: Experimental sialodacryoadenitis virus infection in severe combined immunodeficient mice.

text: Mice with a severe combined immunodeficiency in B and T lymphocytes and natural killer cells (SCID-beige) were inoculated intranasally with sialodacryoadenitis (SDA) virus, a coronavirus of rats. Animals were killed at designated intervals and tissues were examined for evidence of viral infection by light microscopy and immunofluorescence microscopy. Based on these criteria, there was no evidence that these immunodeficient mice were susceptible to infection with SDA virus.


Delayed immunisation and risk of pertussis in infants: unmatched case-control study.


title: Association of diarrhea in cattle with torovirus infections on farms.

text: An epidemiologic survey was performed to determine the incidence of torovirus infections in 2 disease entities of cattle: diarrhea of replacement calves up to 2 months old, and winter dysentery of adult cattle. Samples were obtained from 187 diarrheal and 115 healthy calves from 15 farms, as well as 149 diarrheal and 67 healthy cows from 27 farms with or without winter dysentery. Enzyme-linked immunosorbent assays for detection of torovirus, rotavirus, and coronavirus antigen in feces, and of torovirus and coronavirus antibodies in serum were used to monitor infections in these groups. Torovirus was detected in 9 of the 15 farms in the study, and in 6% of calves with diarrhea, which was significantly higher than in healthy calves (2%). Seroconversion to torovirus was found significantly more often after winter dysentery episodes than on farms without a disease history; coronavirus seroconversion was less common.


title: Prostheses Used in Laparoscopic Inguinal Hernia Repair: Biocompatibility, Postoperative Complications and Quality of Life - Review of the Literature.

text: INTRODUCTION There is a continuous concern about meshes used in laparoscopic inguinal hernia repair, which mainly relates to their biocompatibility and ability to decrease postoperative complications and recurrence rate; in other words, efforts are made to find the "ideal" prosthesis. OBJECTIVES To evaluate different prostheses used in laparoscopic inguinal hernia repair in terms of biocompatibility, postoperative complications, recurrence rate and quality of life, so that all the features could lead us to the "ideal" mesh. MATERIAL AND METHOD Randomized controlled trials, reviews, prospective and retrospective studies, retrospective cross-sectional and experimental studies on animals published between 2000 and 2016 were analysed with respect to several features of a mesh: biocompatibility, postoperative complications, recurrence rate and quality of life. OUTCOMES The most common comparison is between heavy-weight and light-weight mesh used in laparoscopic inguinal hernia repair. Experimental studies try to discover the "ideal" prosthesis, which could provide improved biocompatibility, low postoperative complications, decreased recurrence rate and good quality of life. The most commonly used mesh that meats the characteristics of an "ideal" prosthesis is a light-weight monofilament macroporous polypropylene mesh, with a minimum tensile strength >16 N/cm², measuring 10x15 cm. CONCLUSIONS Published data show that the "ideal" prosthesis used in laparoscopic inguinal hernia repair has not been discovered yet. Regarding heavy- or light-weight meshes, there is no significant effect on recurrence, acute or chronic pain, incidence of seroma or return to daily activity and quality of life (1).


title: [Genome-wide scan reveals the molecular mechanisms of functional differentiation of Myotis lucifugus and Pteropus vampyrus].

text: The physiological and behavioral differences between Myotis lucifugus and Pteropus vampyrus should be attributed to molecular mechanisms and deserve intensive investigation. We conducted genome-wide scan for coding sequences from the orthologue genes of seven mammalian species. Selection analyses were carried out by setting the branches leading to Myotis lucifugus and Pteropus vampyrus as foreground branches, respectively. Enrichment analyses were conducted for positively selected genes. Our results indicated that more genes exhibited positive selection in Myotis lucifugus than that in Pteropus vampyrus. The positively selected genes of the two species were enriched in different functions. The differences between Myotis lucifugus and Pteropus vampyrus represented their differentiation in biological functions, especially the functions of immunity, motor ability, energetic metabolism and sensory organ development.


title: Nephrotic syndrome under treatment with dasatinib: be aware of a possible adverse drug reaction.

text: The protein kinase inhibitor dasatinib, targeting BCR-ABL and Src family kinases, is used in chronic myeloid leukaemia and Philadelphia-chromosome positive acute lymphoblastic leukaemia. The Netherlands Pharmacovigilance Centre Lareb has received one report of nephrotic syndrome associated with the use of dasatinib. With some other protein kinase inhibitors, targeting vascular endothelial growth factor, nephrotic syndrome is a well-known adverse drug reaction. The Dutch and European pharmacovigilance databases and scientific literature contain several cases indicating a causal relationship between dasatinib and nephrotic syndrome. Nephrotic syndrome was recently added to the list of adverse drug reactions in the Dutch summary of product characteristics for dasatinib. It is important to recognise the possibility of this adverse drug reaction when a patient develops nephrotic syndrome under treatment with dasatinib.


title: CD147 and its interacting proteins in cellular functions.

text: CD147 (basigin, EMMPRIN, neurothelin, M6, HAb18G, etc.), a transmembrane glycoprotein, has a broad expression pattern on various epithelial cells with some differences between species, e.g. rat, mouse, chicken and human, but is highly enriched on the surface of cancer cells of epithelial origin such as lung cancer, breast cancer and hepatoma cells. The CD147 antigen consists of two IgSF domains, a transmembrane sequence containing a charged residue (Glu) and a cytoplasmic domain of 40 residues. The particular structural features suggest that it is involved in protein-protein interactions. Although the interacting molecules are still not well known due to unavailability of the 3D structure of CD147, adhesion, coimmunoprecipitation and other studies recently suggest that several proteins, including integrins, cyclophilins, MCT, etc., interact with CD147 as its ligand or receptor candidates to mediate a wide range of cellular functions.


title: Cryptic properties of a cluster of dominant flavivirus cross-reactive antigenic sites.

text: A number of flaviviruses are important human pathogens, including yellow fever, dengue, West Nile, Japanese encephalitis, and tick-borne encephalitis (TBE) viruses. Infection with or immunization against any of these viruses induces a subset of antibodies that are broadly flavivirus cross-reactive but do not exhibit significant cross-neutralization. Nevertheless, these antibodies can efficiently bind to the major envelope protein (E), which is the main target of neutralizing and protective antibodies because of its receptor-binding and membrane fusion functions. The structural basis for this phenomenon is still unclear. In our studies with TBE virus, we have provided evidence that such cross-reactive antibodies are specific for a cluster of epitopes that are partially occluded in the cage-like assembly of E proteins at the surfaces of infectious virions and involve-but are not restricted to-amino acids of the highly conserved internal fusion peptide loop. Virus disintegration leads to increased accessibility of these epitopes, allowing the cross-reactive antibodies to bind with strongly increased avidity. The cryptic properties of these sites in the context of infectious virions can thus provide an explanation for the observed lack of efficient neutralizing activity of broadly cross-reactive antibodies, despite their specificity for a functionally important structural element in the E protein.


title: Survey of infectious agents involved in acute respiratory disease in finishing pigs.

text: Outbreaks of respiratory disease constitute a major health problem in herds of finishing pigs and their aetiology often remains unclear. In this study, 16 outbreaks of respiratory disease with acute clinical signs in finishing pigs were investigated to determine which infectious agents were involved. From each herd four diseased and two clinically healthy pigs were examined pathologically and for the presence of viruses, bacteria and mycoplasmas. In addition, paired blood samples from 10 groupmates of the diseased pigs were tested for antibodies against commonly known causal agents of respiratory disease. A clear diagnosis was possible in 12 of the 16 outbreaks. Seven were due to an infection with influenza virus and five were due to an infection with Actinobacillus pleuropneumoniae. A combination of influenza virus and A pleuropneumoniae may have caused one other outbreak, but no clear cause could be established for the other three outbreaks.


title: Epidemiology and Clinical Features of Coronavirus Disease 2019 in Moroccan Children.

text: OBJECTIVES This study aims to analyze the epidemiological and clinical features of coronavirus disease 19 (COVID-19) in a Moroccan pediatric population. METHODS A retrospective study of a cohort of 74 children with RT-PCR confirmed COVID-19. We collected information on clinical and laboratory features of all children (age <18 years) admitted between 2 March, 2020 and 1 April, 2020. RESULTS The mean (SD) age of the 74 children (40 girls) was 7 (1.5) years. The mean (SD) time from illness onset to diagnosis was 2 (1) days. 54 children were asymptomatic, while eight had fever, and five cases had cough. Recovery was after a mean (SD) of 12 (1) days. CONCLUSION COVID-19 was mostly mild in the pediatric population in Morocco.


Public health and epidemiological research: a blind spot among the European Union priorities?


title: Respiratory syncytial virus polypeptides. IV. The oligosaccharides of the glycoproteins.

text: The cell-associated glycoproteins of respiratory syncytial (RS) virus included GP1 (90K), VP70 (70K), VGP48 (48K) and GP26 (26K). Although present in infected cells, there was no VP70 in purified virus. Trypsin treatment of infected cells removed 80 to 90% of VP70 as well as its products VGP48 and GP26. This suggested that most of the VP70 in the cell is located on the plasma membrane. The glycoproteins of purified RS virus (GP1, VGP48 and GP26) contain mannose, galactose and fucose as well as glucosamine, but the quantity of mannose in GP1 is low when compared to that of the other three sugars. The effects that follow the treatment of infected cells with the glycosylation inhibitors tunicamycin and monensin, and the treatment of the immunoprecipitated product of pulse-chase experiments with endonuclease H demonstrated that VP70 and its products contained N-linked oligosaccharides, and that the oligosaccharides of the mature VGP48 subunit were of the complex type, while GP1 contained both N- and O-linked oligosaccharides. The non-glycosylated forms of VP70 and GP1 have estimated mol. wt. of 50K and 33K respectively. Therefore, the carbohydrate contribution to the mol. wt. of VP70 and GP1, as determined by PAGE, was equivalent to 20K for the former and 57K for the latter. The majority of the GP1 oligosaccharides were O-linked, a form of sugar linkage not previously found among paramyxoviruses.


title: Endoluminal abdominal aortic aneurysm repair: the latest advances in prevention of distal endograft migration and type 1 endoleak.

text: Endovascular abdominal aortic aneurysm repair (EVAR) is an attractive alternative to open surgical repair. Distal endograft migration and type 1 endoleak are recognized to be the 2 main complications of EVAR. First-generation endografts had a stronger propensity for distal migration, modular component separation, thrombosis, and loss of structural integrity. Substantial progress has been made in recent years with 2nd- and 3rd-generation devices to prevent these complications. Some of the most common predictors of endograft failure are angulated and short infrarenal necks, large-diameter necks, and thrombus in the aneurysmal sac. The purpose of this study is to describe and review our experience in using innovative techniques and a newer generation of endografts to prevent distal migration and type 1 endoleak in patients with challenging infrarenal neck anatomy. The use of these innovative EVAR techniques and the new generation of endografts in patients with challenging infrarenal neck anatomy has yielded encouraging procedural and intermediate-term results.


title: Neuromodulation device therapy for treatment of hypertensive heart disease.

text: Hypertensive heart disease (HHD) is the leading cause of mortality and morbidity in the United States. Despite the availability of medical therapy it remains a challenge to treat. Autonomic nervous system imbalance resulting in overactivity of the sympathetic nervous system and under activity of the parasympathetic nervous system is integral in the development of hypertension and ultimately the development of HHD. Emerging data suggest that neuromodulation device therapy for treatment of HHD is promising.


title: Prevalence of IgG antibody to SARS-associated coronavirus in animal traders--Guangdong Province, China, 2003.

text: Severe acute respiratory syndrome (SARS) was identified in 2003 as an infectious disease caused by the SARS-associated coronavirus (SARS-CoV), a member of the coronavirus family not observed previously in humans. Because its sequence data differ from that of known human coronaviruses, SARS-CoV is suspected to have crossed the species barrier between an animal host and humans. The SARS outbreak began in China's Guangdong Province, where approximately 1,500 probable cases were identified during November 2002-June 2003. Detection of SARS-like coronavirus has been reported previously in masked palm civets (sometimes called civet cats) and a raccoon dog for sale in a live animal market in Shenzhen municipality. This report summarizes results of an investigation conducted by public health authorities in Guangdong Province, which compared the seroprevalence of SARS-CoV IgG antibody in animal traders (i.e., workers in live animal markets) with that of persons in control groups. The results indicated that 13% of the animal traders, none of whom had SARS diagnosed, had IgG antibody to SARS-CoV, compared with 1%-3% of persons in three control groups. Although the results provide indirect support for the hypothesis of an animal origin for SARS, they also underscore the need for detailed patient histories and more focused animal studies to confirm an animal origin for SARS.


Evaluating Routine Upper Gastrointestinal Series after Laparoscopic Sleeve Gastrectomy.


title: Design and Coordination Kinematics of an Insertable Robotic Effectors Platform for Single-Port Access Surgery.

text: Single port access surgery (SPAS) presents surgeons with added challenges that require new surgical tools and surgical assistance systems with unique capabilities. To address these challenges, we designed and constructed a new insertable robotic end-effectors platform (IREP) for SPAS. The IREP can be inserted through a Ø15 mm trocar into the abdomen and it uses 21 actuated joints for controlling two dexterous arms and a stereo-vision module. Each dexterous arm has a hybrid mechanical architecture comprised of a two-segment continuum robot, a parallelogram mechanism for improved dual-arm triangulation, and a distal wrist for improved dexterity during suturing. The IREP is unique because of the combination of continuum arms with active and passive segments with rigid parallel kinematics mechanisms. This paper presents the clinical motivation, design considerations, kinematics, statics, and mechanical design of the IREP. The kinematics of coordination between the parallelogram mechanisms and the continuum arms is presented using the pseudo-rigid-body model of the beam representing the passive segment of each snake arm. Kinematic and static simulations and preliminary experiment results are presented in support of our design choices.


title: Expression of ICAM-1 in nasal epithelium and levels of soluble ICAM-1 in nasal lavage fluid during human experimental rhinovirus infection.

text: Most rhinovirus serotypes use intercellular adhesion molecule-1 (ICAM-1) as the receptor to enter cells, but ICAM-1 expression has not been detected on normal nasal epithelial cells. During experimental rhinovirus infection, expression of ICAM-1 on nasal epithelial cells was examined with immunohistochemical staining of nasal scrape biopsy specimens, and levels of soluble ICAM-1 in nasal lavage fluid were measured by sandwich enzyme-linked immunosorbent assay technique. Expression of ICAM-1 on nasal epithelial cells increased following inoculation in 20 of 23 infected subjects. The median number of ICAM-1-positive cells per 6.25-mm(2) area of stained biopsy specimen was 0 in control samples (day 20 or 33 after inoculation), and in those without infection, 6 on day 1 (P< or =.05), 14.5 on day 3 (P< or =.01), 1.5 on day 5, and 0 on day 9. In a different group of volunteers, soluble ICAM-1 in nasal lavage fluid was higher on days 1 and 3 compared with preinoculation levels (P< or =.001), but only 11 of 23 infected subjects had a 2-fold or greater increase. Up-regulation of ICAM-1 receptor expression on nasal epithelial cells occurred within 24 hours after inoculation in experimental rhinovirus infections (prior to onset of symptoms) and declined promptly by day 5.


COVID-19: early reflections.


title: Toxicological safety evaluation of DNA plasmid vaccines against HIV-1, Ebola, Severe Acute Respiratory Syndrome, or West Nile virus is similar despite differing plasmid backbones or gene-inserts.

text: The Vaccine Research Center has developed a number of vaccine candidates for different diseases/infectious agents (HIV-1, Severe Acute Respiratory Syndrome virus, West Nile virus, and Ebola virus, plus a plasmid cytokine adjuvant-IL-2/Ig) based on a DNA plasmid vaccine platform. To support the clinical development of each of these vaccine candidates, preclinical studies were performed to screen for potential toxicities (intrinsic and immunotoxicities). All treatment-related toxicities identified in these repeated-dose toxicology studies have been confined primarily to the sites of injection and seem to be the result of both the delivery method (as they are seen in both control and treated animals) and the intended immune response to the vaccine (as they occur with greater frequency and severity in treated animals). Reactogenicity at the site of injection is generally seen to be reversible as the frequency and severity diminished between doses and between the immediate and recovery termination time points. This observation also correlated with the biodistribution data reported in the companion article (Sheets et al., 2006), in which DNA plasmid vaccine was shown to remain at the site of injection, rather than biodistributing widely, and to clear over time. The results of these safety studies have been submitted to the Food and Drug Administration to support the safety of initiating clinical studies with these and related DNA plasmid vaccines. Thus far, standard repeated-dose toxicology studies have not identified any target organs for toxicity (other than the injection site) for our DNA plasmid vaccines at doses up to 8 mg per immunization, regardless of disease indication (i.e., expressed gene-insert) and despite differences (strengths) in the promoters used to drive this expression. As clinical data accumulate with these products, it will be possible to retrospectively compare the safety profiles of the products in the clinic to the results of the repeated-dose toxicology studies, in order to determine the utility of such toxicology studies for signaling potential immunotoxicities or intrinsic toxicities from DNA vaccines. These data build on the biodistribution studies performed (see companion article, Sheets et al., 2006) to demonstrate the safety and suitability for investigational human use of DNA plasmid vaccine candidates for a variety of infectious disease prevention indications.


title: Respiratory viruses and influenza-like illness: a survey in the area of Rome, winter 2004-2005.

text: Limited information is available on the viral aetiology of influenza-like illness (ILI) in Southern European countries. Hereby we report the main findings of a survey conducted in the area of Rome during the 2004-2005 winter season.ILI cases were defined as individuals with fever >37.5 degrees C and at least one constitutional symptom and one respiratory symptom, recruited during the survey period. Influenza and other respiratory viruses were identified using polymerase chain reaction (PCR) on throat swabs. Basic individual information was collected through a standard form. Of 173 ILI cases enrolled, 74 tested positive for one virus, and two tested positive for two viruses. Overall, 33.5% of the cases were positive for influenza viruses, 5.2% for adenoviruses, 3.5% for parainfluenza viruses, 1.7% for coronaviruses, and 1.2% for the respiratory syncitial virus. The proportion of influenza virus detection was higher in the 'high influenza activity' period. The distribution of viral agents varied across age groups, influenza viruses being more likely to be detected in younger patients. Viral pathogens were identified in less than 50% of ILI cases occurred during a high activity influenza season. The detection of other than influenza viruses was sporadic, without evidence of large outbreaks due to specific agents.


Why I won't see you on the barricades: Disability and COVID-19.


title: Detection of feline coronavirus infection in captive cheetahs (Acinonyx jubatus) by polymerase chain reaction.

text: Feline coronavirus genetic elements were detected by polymerase chain reaction from blood, fecal samples, and effusive fluid collected from 33 cheetahs in the U.S.A. Feline coronavirus-specific serum antibodies were also measured by indirect immunofluorescence. Ten cheetahs were positive for viral shedding by polymerase chain reaction, whereas 13 were seropositive by immunofluorescence. Results of serology did not consistently correlate with shedding of virus, and the capture antigen used for detection of feline coronavirus-specific antibodies had a significant impact on results. Testing of samples from one population over a 1-yr period indicated chronic infection in some animals. These relatively healthy carrier animals were a source of virus for contact animals. Screening programs in cheetah populations for feline coronavirus infection may be most reliable if a combination of serologic analysis and viral detection by polymerase chain reaction is used.


title: Amino acids from both N-terminal hydrophobic regions of the Lassa virus envelope glycoprotein GP-2 are critical for pH-dependent membrane fusion and infectivity.

text: Lassa virus glycoprotein 2 (LASV GP-2) belongs to the class I fusion protein family. Its N terminus contains two stretches of highly conserved hydrophobic amino acids (residues 260-266 and 276-298) that have been proposed as N-terminal or internal fusion peptide segments (N-FPS, I-FPS) by analogy with similar sequences of other viral glycoproteins or based on experimental data obtained with synthetic peptides, respectively. By using a pH-dependent, recombinant LASV glycoprotein mediated cell-cell fusion assay and a retroviral pseudotype infectivity assay, an alanine scan of all hydrophobic amino acids within both proposed FPSs was performed. Fusogenicity and infectivity were correlated, both requiring correct processing of the glycoprotein precursor. Most point mutations in either FPS accounted for reduced or abolished fusion or infection, respectively. Some mutations also had an effect on pre-fusion steps of virus entry, possibly by inducing structural changes in the glycoprotein. The data demonstrate that several amino acids from both hydrophobic regions of the N terminus, some of which (W264, G277, Y278 and L280) are 100 % conserved in all arenaviruses, are involved in fusogenicity and infectivity of LASV GP-2.


title: Offering lung cancer screening to high-risk medicare beneficiaries saves lives and is cost-effective: an actuarial analysis.

text: BACKGROUND By a wide margin, lung cancer is the most significant cause of cancer death in the United States and worldwide. The incidence of lung cancer increases with age, and Medicare beneficiaries are often at increased risk. Because of its demonstrated effectiveness in reducing mortality, lung cancer screening with low-dose computed tomography (LDCT) imaging will be covered without cost-sharing starting January 1, 2015, by nongrandfathered commercial plans. Medicare is considering coverage for lung cancer screening. OBJECTIVE To estimate the cost and cost-effectiveness (ie, cost per life-year saved) of LDCT lung cancer screening of the Medicare population at high risk for lung cancer. METHODS Medicare costs, enrollment, and demographics were used for this study; they were derived from the 2012 Centers for Medicare & Medicaid Services (CMS) beneficiary files and were forecast to 2014 based on CMS and US Census Bureau projections. Standard life and health actuarial techniques were used to calculate the cost and cost-effectiveness of lung cancer screening. The cost, incidence rates, mortality rates, and other parameters chosen by the authors were taken from actual Medicare data, and the modeled screenings are consistent with Medicare processes and procedures. RESULTS Approximately 4.9 million high-risk Medicare beneficiaries would meet criteria for lung cancer screening in 2014. Without screening, Medicare patients newly diagnosed with lung cancer have an average life expectancy of approximately 3 years. Based on our analysis, the average annual cost of LDCT lung cancer screening in Medicare is estimated to be $241 per person screened. LDCT screening for lung cancer in Medicare beneficiaries aged 55 to 80 years with a history of ≥30 pack-years of smoking and who had smoked within 15 years is low cost, at approximately $1 per member per month. This assumes that 50% of these patients were screened. Such screening is also highly cost-effective, at <$19,000 per life-year saved. CONCLUSION If all eligible Medicare beneficiaries had been screened and treated consistently from age 55 years, approximately 358,134 additional individuals with current or past lung cancer would be alive in 2014. LDCT screening is a low-cost and cost-effective strategy that fits well within the standard Medicare benefit, including its claims payment and quality monitoring.


title: Debate on MERS-CoV respiratory precautions: surgical mask or N95 respirators?

text: Since the emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in mid-2012, there has been controversy over the respiratory precaution recommendations in different guidelines from various international bodies. Our understanding of MERS-CoV is still evolving. Current recommendations on infection control practices are heavily influenced by the lessons learnt from severe acute respiratory syndrome. A debate on respiratory precautions for MERS-CoV was organised by Infection Control Association (Singapore) and the Society of Infectious Disease (Singapore). We herein discuss and present the evidence for surgical masks for the protection of healthcare workers from MERS-CoV.


title: Perinatal changes of cardiac troponin-I in normal and intrauterine growth-restricted pregnancies.

text: Intrauterine growth restriction (IUGR) implies fetal hypoxia, resulting in blood flow redistribution and sparing of vital organs (brain, heart). Serum cardiac Troponin-I (cTnI), a well-established marker of myocardial ischaemia, was measured in 40 mothers prior to delivery, the doubly clamped umbilical cords (representing fetal state), and their 20 IUGR and 20 appropriate-for-gestational-age (AGA) neonates on day 1 and 4 postpartum. At all time points, no differences in cTnI levels were observed between the AGA and IUGR groups. Strong positive correlations were documented between maternal and fetal/neonatal values (r > or = .498, P < or = .025 in all cases in the AGA and r > or = .615, P < or = .009 in all cases in the IUGR group). These results may indicate (a) normal heart function, due to heart sparing, in the IUGR group (b) potential crossing of the placental barrier by cTnI in both groups.


title: Pathological and immunological effects of ingesting L-tryptophan and 1,1'-ethylidenebis (L-tryptophan) in Lewis rats.

text: The eosinophilia-myalgia syndrome (EMS) has been associated with ingestion of L-tryptophan (L-TRP) produced by a single manufacturer. Epidemiological data implicated 1,1'-ethylidenebis (L-tryptophan) (EBT) (peak 97 or peak E) as a possible etiologic agent. We showed previously that Lewis rats treated with the L-TRP implicated in EMS develop fasciitis and perimyositis similar to those seen in human EMS. We now report the pathology associated with the treatment of Lewis rats with synthetic EBT and/or L-TRP. All animals treated for 6 wk with case-associated L-TRP or EBT developed significant myofascial thickening, compared with animals in the vehicle control and control L-TRP groups. However, even those animals receiving the control L-TRP showed a mild but significant increase in the thickness of the myofascia, compared with vehicle-treated control animals. All animals except vehicle controls also exhibited significant pancreatic pathology, including fibrosis and acinar changes. Only animals treated with case-associated L-TRP for 6 wk showed evidence of immune activation with increased frequency of CD8, Ia, and IL-2 receptor-positive cells in the peripheral blood. Animals receiving L-TRP or EBT for < 6 wk did not show significant differences in myofascial thickness, although these animals did show pancreatic acinar changes. Although these results demonstrate for the first time the pathological effects of EBT, they do not rule out the possibility that other impurities in the EMS-case-associated L-TRP may also contribute to some of the features of EMS.


title: An outbreak of severe acute respiratory syndrome among hospital workers in a community hospital in Hong Kong.

text: BACKGROUND During outbreaks, hospital workers are at high risk for nosocomial infection with severe acute respiratory syndrome (SARS)-associated coronavirus. OBJECTIVE To examine how hospital workers became infected and whether they transmit the virus to their families. DESIGN Retrospective descriptive study. SETTING 529-bed community hospital in Hong Kong. PATIENTS 40 hospital workers infected with SARS-associated coronavirus over a 6-week period (25 March through 5 May 2003). MEASUREMENTS Percentage of infected hospital workers according to job category. RESULTS The cumulative incidence was highest among health care assistants, followed by physicians and nurses (8%, 5%, and 4%, respectively). Most hospital workers were infected from direct contact with patients with SARS, who primarily were in general wards and had unsuspected infection. At the time of contact, all hospital workers had used masks but not necessarily other protective devices. Affected hospital workers did not infect their families. CONCLUSION Before isolation of all patients with clinically confirmed or suspected SARS, routine use of several protective devices, and training of staff in infection control, many health care workers were infected with SARS from patients with unsuspected cases.


title: Induction of glial cell MHC antigen expression in neurotropic coronavirus infections. Characterization of the H-2-inducing soluble factor elaborated by infected brain cells.

text: Neurotropic coronavirus (mouse hepatitis virus strain A59) infection induces major histocompatibility complex class I (H-2) surface antigens on oligodendrocytes and astrocytes, cells that do not normally express detectable MHC antigens on their surface. The induction on MHC antigen expression potentially allows immunocytes to interact with infected glial cells and may play a critical role in the development of virus-induced, immune-mediated demyelination in the central nervous system, a possible model of human multiple sclerosis. In this study, we characterized the soluble factor involved in MHC antigen induction, quantitated induction of MHC antigens, and analyzed the central nervous system cell type involved in the production of the factor. The H-2-inducing factor, most likely produced by astrocytes, was found to be nondialyzable, heat- and trypsin-sensitive, but resistant to treatment at pH 2.0. The m.w. of the factor was estimated as 50 to 100 kDa. Studies on fractionation by ultrafiltration and sucrose density gradient along with antibody-blocking experiments indicate that the factor is not interferon or virus particles.


Possible prevention of tick-borne relapsing fever in patients infected with Borrelia recurrentis.


title: Using Electromagnetic Navigation Bronchoscopy and Dye Injection to Aid in Video-Assisted Lung Resection.

text: Small (2 cm) peripheral lung lesions and ground glass opacities remain a difficult subset of lung lesions for the diagnosis and management of lung cancer. Surgical biopsy is more difficult for these lesions because intraoperative localization has to be made without the aid of direct visualization or manual palpation. Electromagnetic navigation bronchoscopy can be used in the operating room to identify a small peripheral lesion and marked using an injection of methylene blue, which can be seen on the visceral pleura of the lung. We present our initial experience using this technique. The sample was eight patients who had peripheral lesions with an average size of 19 mm. Surgical wedge biopsy was diagnostic in all cases, with an average procedure time of 28 minutes. There were no complications from this procedure. In conclusion, these data suggest that electromagnetic navigation bronchoscopy can be performed safely with high diagnostic accuracy by the operating thoracic surgeon, but further data are needed to establish its utility and safety.


[Digestive symptoms in coronavirus disease 2019 (COVID-19)].


title: Design and synthesis of dipeptidyl glutaminyl fluoromethyl ketones as potent severe acute respiratory syndrome coronovirus (SARS-CoV) inhibitors.

text: This paper describes the design and synthesis of dipeptidyl N,N-dimethyl glutaminyl fluoromethyl ketones (fmk) as severe acute respiratory syndrome coronovirus (SARS-CoV) inhibitors. The compounds were tested against SARS-CoV-induced cell death in Vero or CaCo2 cells as a measurement of the inhibiting effects of the compounds on the replication of the virus. Z-Leu-Gln(NMe(2))-fmk (6a) was found to be a potent inhibitor with low toxicity in cells, protecting cells with an EC(50) value of 2.5 microM and exhibiting a selectivity index of >40.


title: Microtiter plate based chemistry and in situ screening: a useful approach for rapid inhibitor discovery.

text: The use of libraries extracted from nature or constructed by combinatorial chemistry, have been widely appreciated in the drug discovery area. In this perspective, we present our contribution to the field of enzyme inhibitor discovery using a useful approach that allows diversification of a common core in a microtiter plate followed by in situ screening. Our method relies on an organic reaction that is highly selective, high yielding, amenable to the microscale and preferably can be performed in water. The core can be a designed molecule based on the structural and mechanistic information of the target, a compound with a weak binding affinity, or a natural product. Several reactions were found useful for this approach and were applied to the rapid discovery of potent inhibitors of representative enzymes.


title: Using models to identify routes of nosocomial infection: a large hospital outbreak of SARS in Hong Kong.

text: Two factors dominated the epidemiology of severe acute respiratory syndrome (SARS) during the 2002-2003 global outbreak, namely super-spreading events (SSE) and hospital infections. Although both factors were important during the first and the largest hospital outbreak in Hong Kong, the relative importance of different routes of infection has not yet been quantified. We estimated the parameters of a novel mathematical model of hospital infection using SARS episode data. These estimates described levels of transmission between the index super-spreader, staff and patients, and were used to compare three plausible hypotheses. The broadest of the supported hypotheses ascribes the initial surge in cases to a single super-spreading individual and suggests that the per capita risk of infection to patients increased approximately one month after the start of the outbreak. Our estimate for the number of cases caused by the SSE is substantially lower than the previously reported values, which were mostly based on self-reported exposure information. This discrepancy suggests that the early identification of the index case as a super-spreader might have led to biased contact tracing, resulting in too few cases being attributed to staff-to-staff transmission. We propose that in future outbreaks of SARS or other directly transmissible respiratory pathogens, simple mathematical models could be used to validate preliminary conclusions concerning the relative importance of different routes of transmission with important implications for infection control.


title: Transvaginal cholecystectomy versus single-incision laparoscopic cholecystectomy versus four-port laparoscopic cholecystectomy: a prospective cohort study.

text: OBJECTIVE This report describes the first prospective cohort study comparing transvaginal cholecystectomies (TVC) with single incision laparoscopic cholecystectomies (SILC) and four-port laparoscopic cholecystectomies (4PLC). METHODS Between May 2009 and August 2010, 14 patients underwent a TVC. These patients were compared with patients who underwent SILC (22 patients) or 4PLC (11 patients) in a concurrent, randomized, controlled trial. Demographic data, operative time, numerical pain scales, complications, and return to work were recorded. RESULTS Mean age (TVC: 33.5 ± 3.0 year; SILC: 38.4 ± 3.3 year; 4PLC: 35.5 ± 4.1 year; p = 0.58) and mean BMI (TVC: 28.8 ± 1.5 kg/m(2); SILC: 31.8 ± 1 kg/m(2); 4PLC: 31.4 ± 2.2 kg/m(2); p = 0.35) were not statistically significant. However, mean operative time (TVC: 67 ± 3.9 min; SILC: 48.9 ± 2.6 min; 4PLC: 42.3 ± 3.9 min; p < 0.001) was significantly longer for TVC. Numerical pain scales showed significantly lower pain scores on POD 1 and 3 for TVC compared with SILC and 4PLC (TVC: 4.1 ± 0.5 and 2.9 ± 0.7; SILC: 6.1 ± 0.5 and 5.3 ± 0.5; 4PLC: 5.7 ± 0.4 and 4.7 ± 0.3; p = 0.02) with equilibration of pain scores by days 14 and 30. Return to work (TVC: 6.4 ± 1.5 days; SILC: 13.1 ± 1.3 days; 4PLC: 14.1 ± 1.4 days; p < 0.001) also was significantly faster for patients in the TVC group. One conversion in the TVC group to a 4PLC was necessary due to adhesions within the pelvis. One dislodged IUD was seen and immediately replaced in the TVC group. One hernia was observed in the SILC group. CONCLUSIONS Transvaginal cholecystectomy is a safe and well-tolerated procedure with statistically significantly less pain at 1 and 3 days after surgery, with a faster return to work but longer operative times compared with single incision and four-port laparoscopic cholecystectomy.


title: Genetic diversity of avian infectious bronchitis viruses in Japan based on analysis of s2 glycoprotein gene.

text: To understand the genetic diversity of the S2 gene of infectious bronchitis viruses (IBV) isolated in Japan, we determined the nucleotide sequences of these IBVs using the reverse transcriptase polymerase chain reaction method coupled with direct sequencing. IBV isolated in Japan were classified into six different groups by phylogenetic analysis based on the S2 gene. However, the classification based on the S2 gene of IBV isolated in Japan was different for some of the strains from those obtained with our previous analysis of the S1 gene. This suggested that genetic recombination between the virus strains classified into different genetic groups had occurred in poultry, and that recombinant viruses might be epidemic in Japan.


title: Detection of airborne rhinovirus and its relation to outdoor air supply in office environments.

text: Rhinoviruses are major causes of morbidity in patients with respiratory diseases; however, their modes of transmission are controversial. We investigated detection of airborne rhinovirus in office environments by polymerase chain reaction technology and related detection to outdoor air supply rates. We sampled air from 9 A.M. to 5 P.M. each workday, with each sample run for 1 work week. We directly extracted RNA from the filters for nested reverse transcriptase-polymerase chain reaction analysis of rhinovirus. Nasal lavage samples from building occupants with upper respiratory infections were also collected. Indoor carbon dioxide (CO2 concentrations were recorded every 10 minutes as a surrogate for outdoor air supply. To increase the range of CO2 concentrations, we adjusted the outdoor air supply rates every 3 months. Generalized additive models demonstrated an association between the probability of detecting airborne rhinovirus and a weekly average CO2 concentration greater than approximately 100 ppm, after controlling for covariates. In addition, one rhinovirus from a nasal lavage contained an identical nucleic acid sequence similar to that in the building air collected during the same week. These results suggest that occupants in buildings with low outdoor air supply may have an increased risk of exposure to infectious droplet nuclei emanating from a fellow building occupant.


title: Technical Improvement Using a Three-Dimensional Video System for Laparoscopic Partial Nephrectomy.

text: BACKGROUND Laparoscopic partial nephrectomy is one of the major surgical techniques for small renal masses. However, it is difficult to manage cutting and suturing procedures within acceptable time periods. To overcome this difficulty, we applied a three-dimensional (3D) video system with laparoscopic partial nephrectomy, and evaluated its utility. MATERIALS AND METHODS We retrospectively enrolled 31 patients who underwent laparoscopic partial nephrectomy between November 2009 and June 2014. A conventional two-dimensional (2D) video system was used in 20 patients, and a 3D video system in 11. Patient characteristics and video system type (2D or 3D) were recorded, and correlations with perioperative outcomes were analyzed. RESULTS Mean age of the patients was 55.8±12.4, mean body mass index was 25.7±3.9 kg/m2, mean tumor size was 2.0±0.8 cm, mean R.E.N.A.L nephrometry score was 6.9±1.9, and clinical stage was T1a in all patients. There were no significant differences in operative time (p=0.348), pneumoperitoneum time (p=0.322), cutting time (p=0.493), estimated blood loss (p=0.335), and Clavien grade of >II complication rate (p=0.719) between the two groups. However, warm ischemic time was significantly shorter in the 3D group than the 2D group (16.1 min vs. 21.2min, p=0.021), which resulted from short suturing time (9.1 min vs. 15.2 min, p=0.008). No open conversion occurred in either group. CONCLUSIONS A 3D video system allows the shortening of warm ischemic time in laparoscopic partial nephrectomy and thus may be useful in improving the procedure.


title: Fringed membranous particles and viruses in faeces from healthy turkey poults and from poults with putative poult enteritis complex/spiking mortality.

text: The purpose of the present study was to use clinical epidemiologic tools to define the relationship between production performance data, virus particles, and intestinal fringed membranous particles (FMPs) in healthy turkey poults and in poults that were experiencing an outbreak of poult enteritis complex (PEC) and spiking mortality syndrome (SMS). Small and large intestines from flocks of healthy poults and poults with PEC/SMS were collected, processed, and examined for viruses. Production performance parameters were collected and analyzed. Hocks of turkeys with PEC/SMS in the present study had low survival expectancy (livability) and poor growth compared to their healthy turkey counterparts. The only significant association between sickness and intestinal virus was the presence of coronavirus.


title: Serological and molecular characterization of three enteric isolates of infectious bronchitis virus of chickens.

text: Three coronaviruses isolated from the intestines of laying chickens were partially characterized. Serological and molecular assays indicated that the enteric coronaviruses are infectious bronchitis virus (IBV) isolates. Although the three isolates were recovered from three unrelated chicken flocks, their RNase T1-resistant oligonucleotide fingerprints were almost identical. The three isolates were not neutralized by antisera specific to IBV serotype Connecticut, but their RNase T1-resistant oligonucleotide fingerprints closely matched the fingerprints of strain Conn-46, a Connecticut serotype. This and the co-fingerprinting data suggested that the three field isolates may have emerged from the Connecticut virus through mutation(s). The mutation(s) apparently involved the S1 protein gene that determines the virus serotype.


title: Transcription regulatory sequences and mRNA expression levels in the coronavirus transmissible gastroenteritis virus.

text: The transcription regulatory sequences (TRSs) of the coronavirus transmissible gastroenteritis virus (TGEV) have been characterized by using a helper virus-dependent expression system based on coronavirus-derived minigenomes to study the synthesis of subgenomic mRNAs. The TRSs are located at the 5' end of TGEV genes and include a highly conserved core sequence (CS), 5'-CUAAAC-3', that is essential for mediating a 100- to 1,000-fold increase in mRNA synthesis when it is located in the appropriate context. The relevant sequences contributing to TRS activity have been studied by extending the CS 5' upstream and 3' downstream. Sequences from virus genes flanking the CS influenced transcription levels from moderate (10- to 20-fold variation) to complete mRNA synthesis silencing, as shown for a canonical CS at nucleotide (nt) 120 from the initiation codon of the S gene that did not lead to the production of the corresponding mRNA. An optimized TRS has been designed comprising 88 nt from the N gene TRS, the CS, and 3 nt 3' to the M gene CS. Further extension of the 5'-flanking nucleotides (i.e., by 176 nt) decreased subgenomic RNA levels. The expression of a reporter gene (beta-glucuronidase) by using the selected TRS led to the production of 2 to 8 microg of protein per 10(6) cells. The presence of an appropriate Kozak context led to a higher level of protein expression. Virus protein levels were shown to be dependent on transcription and translation regulation.


Role of endoscopy in the management of GERD.


title: Incidence and characteristics of viral community-acquired pneumonia in adults.

text: BACKGROUND In adults, viral causes of community-acquired pneumonia (CAP) are poorly characterised. The aims of this study were to characterise the viral aetiology of CAP in adults by using an extensive array of viral diagnostic tests and to compare the characteristics of viral pneumonia with those of pneumococcal pneumonia. METHODS Adults admitted to Christchurch Hospital over a 1-year period with CAP were included in the study. Microbiological testing methods included blood and sputum cultures, urinary antigen testing for Streptococcus pneumoniae and Legionella pneumophila, antibody detection in paired sera and detection of respiratory viruses in nasopharyngeal swabs by immunofluorescence, culture and PCR. RESULTS Of 304 patients with CAP, a viral diagnosis was made in 88 (29%), with rhinoviruses and influenza A being the most common. Two or more pathogens were detected in 49 (16%) patients, 45 of whom had mixed viral and bacterial infections. There were no reliable clinical predictors of viral pneumonia, although several variables were independently associated with some aetiologies. The presence of myalgia was associated with pneumonia caused by any respiratory virus (OR 3.62, 95% CI 1.29 to 10.12) and influenza pneumonia (OR 190.72, 95% CI 3.68 to 9891.91). Mixed rhinovirus/pneumococcal infection was associated with severe disease. CONCLUSIONS Virus-associated CAP is common in adults. Polymicrobial infections involving bacterial and viral pathogens are frequent and may be associated with severe pneumonia.


title: Topology of double-membraned vesicles and the opportunity for non-lytic release of cytoplasm.

text: Infection of mammalian cells with several positive-strand RNA viruses induces double-membraned vesicles whose cytosolic surfaces serve as platforms for viral RNA replication. Our recent publication (Jackson et al. PLoS Biol 2005; 3:861-71) chronicled several similarities between poliovirus-induced membranes and autophagosomes, including induced co-localization of GFP-LC3 and LAMP1. Occasionally, the cytosolic lumen of these structures also contains viral particles; this likely results from wrapping of cytosol, which can contain high viral concentrations late in infection, by newly formed double membranes. Interestingly, RNAi treatment to reduce LC3 or Atg12p concentrations reduced yields of extracellular virus even more than intracellular virus. It is often assumed that exit of non-enveloped viruses such as poliovirus requires cell lysis. However, we hypothesize that autophagosome-like double-membranes, which can become single-membraned upon maturation, provide a long-sought mechanism for the observed non-lytic release of cytoplasmic viruses and possibly other cytoplasmic material resistant to the environment of maturing autophagosomes.


title: Human coronavirus OC43 interacts with major histocompatibility complex class I molecules at the cell surface to establish infection.

text: Human coronaviruses have been associated with common colds, diarrhea and enterocolitis, and have been implicated in multiple sclerosis. HLA class I molecules may play a critical role as receptor for OC43 because monoclonal antibody (mAb)W6/32 to HLA-A, -B and -C specificities completely blocks infectivity in human rhabdomyosarcoma (RD) cells. The role of HLA class 1 antigen as the virus receptor was examined using HLA-A3.1 stably transfected human plasma cells and untransfected HMY.C1R cells which do not express HLA-A and -B molecules. When the cells (5 x 10(6)) were infected at a multiplicity of one, the HLA.A3 transfected cells produced 10(8) PFU of virus whereas no replication occurred in the HMY.C1R cells mAb W6/32 reduced the virus yield by 99.9%. Cell membranes from HMY.C1R, HMY.A3 cells and chicken erythrocytes were biotinylated as live cells. Immunoprecipitation with polyclonal antiviral antibody to detect binding of biotinylated cell membranes to virus revealed that biotinylated HMY.A3 membranes coprecipitated with virus-antibody complexes when the immunoprecipitates were electrophoresed on SDS-PAGE gel, electroblotted and stained with Avidin-horseradish peroxidase. The results provide direct evidence that OC43 virus can recognize HLA class I as receptor on the cell surface.


title: Allergen challenge-induced acute exudation of IL-8, ECP and alpha2-macroglobulin in human rhinovirus-induced common colds.

text: Rhinovirus infections cause exacerbations of eosinophilic airway disease. The acute effects of allergen-challenge on nasal interleukin-8 (IL-8), eosinophil cationic protein (ECP), and alpha2-macroglobulin were examined in atopic subjects with common cold symptoms. Twenty-three patients with seasonal allergic rhinitis were inoculated with human rhinovirus 16 outside the pollen season. Diluent and allergen challenges, followed by nasal lavages, were carried out about 3 months before and 4 days after virus inoculation. Seventeen patients developed significant common cold symptoms with increased nasal lavage fluid levels of alpha2-macroglobulin, IL-8, and ECP at baseline (p<0.001-0.05 versus before inoculation), and were further increased by allergen challenge (p< 0.001-0.05); IL-8 and ECP levels were correlated (r = 0.63, p<0.001). Before inoculation, the six patients who later did not develop common cold symptoms had high levels of IL-8 and myeloperoxidase (MPO), and exhibited strong allergen-induced plasma exudation responses (alpha2-macroglobulin). After inoculation, IL-8 and ECP did not increase in these symptomless subjects. In conclusion, high nasal interleukin-8 and myeloperoxidase levels and exudative hyperresponsiveness may protect against infection. The association between nasal interleukin-8 and eosinophil cationic protein in common cold, particularly that observed in nasal lavage fluids after allergen-induced acute exudation of plasma, suggests the involvement of interleukin-8 in exacerbation of airway mucosal eosinophil activity.


title: Clathrin-dependent entry of severe acute respiratory syndrome coronavirus into target cells expressing ACE2 with the cytoplasmic tail deleted.

text: The penetration of various viruses into host cells is accomplished by hijacking the host endocytosis machinery. In the case of severe acute respiratory syndrome coronavirus (SARS-CoV) infection, viral entry is reported to require a low pH in intracytoplasmic vesicles; however, little is known about how SARS-CoV invades such compartments. Here we demonstrate that SARS-CoV mainly utilizes the clathrin-mediated endocytosis pathway for its entry to target cells by using infectious SARS-CoV, as well as a SARS-CoV pseudovirus packaged in the SARS-CoV envelope. The SARS-CoV entered caveolin-1-negative HepG2 cells, and the entry was significantly inhibited by treatment with chlorpromazine, an inhibitor for clathrin-dependent endocytosis, and by small interfering RNA-mediated gene silencing for the clathrin heavy chain. Furthermore, the SARS-CoV entered COS7 cells transfected with the mutant of ACE2 with the cytoplasmic tail deleted, SARS-CoV receptor, as well as the wild-type ACE2, and their entries were significantly inhibited by treatment with chlorpromazine. In addition, ACE2 translocated into EEA1-positive early endosomes immediately after the virus attachment to ACE2. These results suggest that when SARS-CoV binds ACE2 it is internalized and penetrates early endosomes in a clathrin-dependent manner and that the cytoplasmic tail of ACE2 is not required for the penetration of SARS-CoV.


title: Community-acquired pneumonia in the post 13-valent pneumococcal conjugate vaccine era.

text: PURPOSE OF REVIEW This review covers the outpatient management of pediatric community-acquired pneumonia (CAP), discussing the changing microbiology of CAP since the introduction of the 13-valent pneumococcal conjugate vaccine in 2010, and providing an overview of national guideline recommendations for diagnostic evaluation and treatment. RECENT FINDINGS Rates of invasive pneumococcal disease and pneumococcal antibiotic resistance have plummeted since widespread 13-valent pneumococcal conjugate vaccine immunization. Viruses remain the most common cause of CAP in young children; children over age 5 years have increased rates of Mycoplasma pneumoniae. A recent national guideline offers recommendations for office-based diagnostic evaluation and treatment of pediatric CAP. SUMMARY This review offers a discussion of the above findings with practical recommendations for the office-based practitioner in the evaluation and treatment of an infant (>3 months) or child with suspected CAP.


title: Nurses' fears and professional obligations concerning possible human-to-human avian flu.

text: This survey aimed to illustrate factors that contribute to nurses' fear when faced with a possible human-to-human avian flu pandemic and their willingness to care for patients with avian flu in Taiwan. The participants were nursing students with a lesser nursing credential who were currently enrolled in a bachelor degree program in a private university in southern Taiwan. Nearly 42% of the nurses did not think that, if there were an outbreak of avian flu, their working hospitals would have sufficient infection control measures and equipment to prevent nosocomial infection in their working environment. About 57% of the nurse participants indicated that they were willing to care for patients infected with avian influenza. Nurses' fear about an unknown infectious disease, such as the H5N1 influenza virus, could easily be heightened to levels above those occurring during the 2003 severe acute respiratory syndrome outbreak in Taiwan.


title: Abdominal ultrasonographic findings associated with feline infectious peritonitis: a retrospective review of 16 cases.

text: The feline infectious peritonitis virus (FIPV) is a mutated form of the feline enteric coronavirus (FeCV) that can present with a variety of clinical signs. The purpose of this retrospective study was to analyze abdominal ultrasonographic findings associated with cats with confirmed FIPV infection. Sixteen cases were included in the study from a review of medical records at two academic institutions; inclusion was based either on necropsy lesions (n=13) or a combination of histopathological, cytological, and clinicopathological findings highly suggestive of FIPV infection (n=3). The liver was judged to be normal in echogenicity in 11 (69%) cats, diffusely hypoechoic in three cats, focally hyperechoic in one cat, and focally hypoechoic in one cat. Five cats had a hypoechoic subcapsular rim in one (n=3) or both (n=2) kidneys. Free fluid was present in the peritoneal cavity in seven cats and in the retroperitoneal space in one cat. Abdominal lymphadenopathy was noted in nine cats. The spleen was normal in echogenicity in 14 cats and was hypoechoic in two. One cat had bilateral orchitis with loss of normal testicular architecture. Although none of these ultrasonographic findings are specific for FIPV infection, a combination of these findings should increase the index of suspicion for FIPV infection when considered along with appropriate clinical signs.


Meeting the survival needs of the world's least healthy people: a proposed model for global health governance.


Caught napping in the time of tropical diseases.


title: Molecular epidemiology of the foot-and-mouth disease virus outbreak in the United Kingdom in 2001.

text: The objective of this study was to quantify the extent to which the genetic diversity of foot-and-mouth disease virus (FMDV) arising over the course of infection of an individual animal becomes fixed, is transmitted to other animals, and thereby accumulates over the course of an outbreak. Complete consensus sequences of 23 genomes (each of 8,200 nucleotides) of FMDV were recovered directly from epithelium tissue acquired from 21 farms infected over a nearly 7-month period during the 2001 FMDV outbreak in the United Kingdom. An analysis of these consensus sequences revealed very few apparently ambiguous sites but clear evidence of 197 nucleotide substitutions at 191 different sites. We estimated the rate of nucleotide substitution to be 2.26 x 10(-5) per site per day (95% confidence interval [CI], 1.75 x 10(-5) to 2.80 x 10(-5)) and nucleotide substitutions to accrue in the consensus sequence at an average rate of 1.5 substitutions per farm infection. This is a sufficiently high rate showing that detailed histories of the transmission pathways can be reliably reconstructed. Coalescent methods indicated that the date at which FMDV first infected livestock in the United Kingdom was 7 February 2001 (95% CI, 20 January to 19 February 2001), which was identical to estimates obtained on the basis of purely clinical evidence. Nucleotide changes appeared to have occurred evenly across the genome, and within the open reading frame, the ratio of nonsynonymous-to-synonymous change was 0.09. The ability to recover particular transmission pathways of acutely acting RNA pathogens from genetic data will help resolve uncertainties about how virus is spread and could help in the control of future epidemics.


title: Colorectal endoscopic submucosal dissection: a systematic review and meta-analysis.

text: Background and study aims: Endoscopic submucosal dissection (ESD) is an advanced endoscopic technique that allows en-bloc resection of gastrointestinal tumor. We systematically review the medical literature in order to evaluate the safety and efficacy of colorectal ESD. Patients and methods: We performed a comprehensive literature search of MEDLINE, EMBASE, Ovid, CINAHL, and Cochrane for studies reporting on the clinical efficacy and safety profile of colorectal ESD. Results: Included in this study were 13833 tumors in 13603 patients (42 % female) who underwent colorectal ESD between 1998 and 2014. The R0 resection rate was 83 % (95 % CI, 80 - 86 %) with significant between-study heterogeneity (P < 0.001) which was partly explained by difference in continent (P = 0.004), study design (P = 0.04), duration of the procedure (P = 0.009), and, marginally, by average tumor size (P = 0.09). Endoscopic en bloc and curative resection rates were 92 % (95 % CI, 90 - 94 %) and 86 % (95 % CI, 80 - 90 %), respectively. The rates of immediate and delayed perforation were 4.2 % (95 % CI, 3.5 - 5.0 %) and 0.22 % (95 % CI, 0.11 - 0.46 %), respectively, while rates of immediate and delayed major bleeding were 0.75 % (95 % CI, 0.31 - 1.8 %) and 2.1 % (95 % CI, 1.6 - 2.6 %). After an average postoperative follow up of 19 months, the rate of tumor recurrence was 0.04 % (95 % CI, 0.01 - 0.31) among those with R0 resection and 3.6 % (95 % CI, 1.4 - 8.8 %) among those without R0 resection. Overall, irrespective of the resection status, recurrence rate was 1.0 % (95 % CI, 0.42 - 2.1 %). Conclusions: Our meta-analysis, the largest and most comprehensive assessment of colorectal ESD to date, showed that colorectal ESD is safe and effective for colorectal tumors and warrants consideration as first-line therapy when an expert operator is available.


title: Fifteen years post-SARS: Key milestones in Canada's public health emergency response.

text: This year marks the 15th anniversary of Severe Acute Respiratory Syndrome (SARS) in Canada and the 100th anniversary of the 1918 Spanish influenza pandemic. These, and other recent public health events, provide an opportunity for us to review and reflect on the evolution of Canada's public health emergency response over the past 15 years-from SARS, to the 2009 H1N1 pandemic influenza, to Ebola virus and Zika virus disease. Key lessons have been learned and milestones achieved that have shaped and sharpened our response approach and structures. While SARS was a wake-up-call to strengthen infection prevention and control capacity in health care settings and led to the formation of the Public Health Agency of Canada, it also strengthened our Federal/Provincial/Territorial (FPT) senior-level governance and led to agreements for pan-Canadian mutual aid and infectious disease information sharing. As well, our collective public health laboratory capacity has been strengthened through ongoing response and sharing of advanced diagnostics and research. As we move forward, it will be important to explore the design of scalable or modular emergency response strategies and structures that are socio-culturally appropriate and employ evidence-based strategic risk communications that continue to be critical, especially given the volume and spread of misinformation. With the current global reality, we must recognize that public health threats that go unchecked anywhere in the world have the potential to very rapidly become a public health threat in Canada. We need to build, maintain and share our best public health practices globally, for we neglect these at our peril.


A report from the Communicable Diseases Network Australia, January to March 2004.


title: [Current status for urpper tract transitional cell carcinoma during COVID-19 pandemia.]

text: INTRODUCTION First cases of COVID-19 were reported in China on December 2019 and rapidly spread globally. The explosive increase in number of cases requiring hospitalization has led to a delay in a big number of surgical interventions, including oncologic surgeries. Collateral effects of this increase means a challenge for urologists, who have been forced to redistribute their resources. Due to its poor pronostic, patients suffering from by upper tract urinary tumours will be negatively affected by this pandemic. METHODS: A non sistematic review was performed using literature published until May 23, 2020, using "Uppertract urothelial tumours", "COVID-19" and "nephroureterectomy".as keywords. The resulting manuscript was critically revised by national authors in order to establish common criteria about treatment and follow up. EVIDENCE SYNTHESIS: Four studies were identified that assessed the impact of delaying radical nephrouretrectomy as curative treatment. These studies showed that surgery delays decrease overall survival and cancer specific survival rates in high-risk groups. On the other hand, delaying radical nephrouretrectomy due to ureteroscopy did not affect survival in cohorts of patients with predominately low-grade disease. CONCLUSIONS: A delay in curative treatment of upper tract urothelial tumours for more than three months results in adverse outcomes as overal survival and cancer specific survival. Hence, it is important to prioritize the timely care of this group of patients as far as COVID-19 pandemic allows it.


title: [Severe acute respiratory syndrome--SARS].

text: Severe Acute Respiratory Syndrome (SARS) is an acute respiratory illness caused by SARS coronavirus. This virus was possibly transmitted from an animal reservoir to humans, and from February 2003, the epidemic was spread internationally by further person-to-person transmission. The SARS epidemic was managed by well-known principles of infection control, including prompt diagnosis, isolation of patients, and quarantine of contacts. The successful control of the outbreak is a remarkable international achievement, though much about SARS remains poorly understood.


title: Lactate dehydrogenase-elevating virus variants: cosegregation of neuropathogenicity and impaired capability for high viremic persistent infection.

text: Neuropathogenic isolates of lactate dehydrogenase virus (LDV) differ from non-neuropathogenic isolates in their unique ability to cause a paralytic disease (age-dependent poliomyelitis, ADPM) in immunosuppressed C58 and AKR mice by cytocidally infecting their anterior horn neurons. We have recently reported that an original neuropathogenic LDV isolate, LDV-C-BR, contained a low level of a coexisting non-neuropathogenic LDV which, in a mixed infection of mice, rapidly outcompeted the former resulting in apparent loss of neuropathogenicity of the reisolated LDV. This correlated with an impaired ability of the neuropathogenic LDV to establish a viremic persistent infection. In the present study we identified the presence of three different quasispecies in another original neuropathogenic LDV by sequence analysis of cDNA clones of ORF 5 (encoding the primary envelope glycoprotein VP-3P) obtained from the isolate. Successful development of differential reverse transcription-polymerase chain reaction assays allowed us to biologically clone all three quasispecies through repeated end point dilutions. Only one of the quasispecies (LDV-v) was neuropathogenic. The other two, LDV-vP (probably the same as LDV-P) and LDV-vx (a novel LDV quasispecies that had not been previously identified), were non-neuropathogenic and found to be the common LDV quasispecies associated with almost all LDVs originally isolated from mice carrying various other transplantable tumors. The neuropathogenic LDV-v became selectively amplified in the spinal cords of paralyzed mice, but possessed an impaired ability to establish a persistent viremic infection and was rapidly out-competed by LDV-vP and LDV-vx in mixed infections, just as reported previously for LDV-C-BR. The results further support our hypothesis that neuropathogenicity and impaired capability for viremic persistence of LDV are determined by the same molecular feature. The only consistent and biologically relevant molecular difference we have observed between neuropathogenic and non-neuropathogenic LDVs is the number of polylactosaminoglycan chains associated with the ectodomain of VP-3P.


title: Comparison of different ligation techniques in laparoscopic varicocelectomy.

text: AIM To evaluate the effects of different intracorporeal ligation techniques with titanium clips, Plasma Trisector (Gyrus, USA) (PTG), and surgical silk on bilateral laparoscopic varicocelectomy (LPVx). MATERIALS AND METHODS Between May 2009 and August 2012, 100 patients who underwent bilateral LPVx were evaluated. The demographic parameters of patients, preoperative radiological findings, semen analysis, operative data, and follow-up were recorded. All of the patients were divided into 3 groups, randomized prospectively. The patients whose veins were ligated by 5-mm titanium clips were included in group I, those whose veins were ligated by PTG were included in group II, and those whose veins were ligated by surgical silk were included in group III. The recorded data of the groups were analyzed. RESULTS Mean follow-up time was 18.8 + 1.1 months. According to the demographics of age, body mass index, spermiogram, and diameter of veins before surgery, there were no statistical differences between any of the groups (P > 0.05). However, operation time was longer in group III (P < 0.0001), while total numbers ofligated veins did not differ among the groups (P > 0.05). Additionally, hospital stay, oral intake, and complications were not different among the groups (P > 0.05). In follow-up the sperm count analysis was higher than the preoperative count analysis for all of the groups (P < 0.05). CONCLUSION PTG may provide a shorter operation time than using titanium clips and/or surgical silk in LPVx. Additionally, PTG may increase sperm count with fewer complications than the other ligation techniques in LPVx. Therefore, PTG may be the new candidate electrosurgical standard device for LPVx in the nearby future.


title: Isolation of respiratory bovine coronavirus, other cytocidal viruses, and Pasteurella spp from cattle involved in two natural outbreaks of shipping fever.

text: OBJECTIVE To identify cytocidal viruses and Pasteurella spp that could be isolated from cattle involved in 2 natural outbreaks of shipping fever. ANIMALS 105 and 120 castrated male 4- to 8-month-old feedlot cattle involved in 1997 and 1998 outbreaks, respectively. PROCEDURES Nasal swab specimens and blood samples were collected, and cattle were vaccinated on arrival at an order-buyer barn from 4 local auction houses. Four days later, they were transported to a feedlot, and additional nasal swab specimens and blood samples were collected. Nasal swab specimens were submitted for virus isolation and bacterial culture; blood samples were submitted for measurement of respiratory bovine coronavirus (RBCV) hemagglutinin inhibition titers. RESULTS 93 of 105 cattle and 106 of 120 cattle developed signs of respiratory tract disease during 1997 and 1998, respectively, and RBCV was isolated from 81 and 89 sick cattle, respectively, while at the order-buyer's barn or the day after arrival at the feedlot. During the 1997 outbreak, bovine herpesvirus 1 was isolated from 2 cattle at the order-buyer's barn and from 5 cattle 7 and 14 days after arrival at the feedlot, and parainfluenza virus 3 was isolated from 4 cattle 14 days after arrival at the feedlot. During the 1998 outbreak, bovine herpesvirus 1 was isolated from 2 cattle at the order-buyer's barn and on arrival at the feedlot and from 5 cattle 7 and 14 days after arrival at the feedlot, and parainfluenza virus 3 was isolated from 1 animal the day of, and from 18 cattle 7 and 14 days after, arrival at the feedlot. Pasteurella spp was cultured from 4 and 6 cattle at the order-buyer's barn and from 92 and 72 cattle on arrival at the feedlot during the 1997 and 1998 outbreaks, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Results suggest that RBCV may play a causative role in outbreaks of shipping fever in cattle. More than 80% of the sick cattle shed RBCV at the beginning of 2 outbreaks when the Pasteurella spp infection rate was low.


title: Studies on the mechanism of RNA synthesis of a murine coronavirus.

text: The mechanism of viral RNA replication in mouse hepatitis virus (MHV)-infected cells was studied by oligonucleotide mapping of every mRNA. We discovered that an oligonucleotide, No. 10, was localized at the 5'-end of every mRNA, and was not colinear with the sequences of the virion genomic RNA. This result indicates that all of the mRNAs contain a leader sequence which is joined to the body sequences of the mRNAs. We have also studied the structure of the replicative intermediate (RI) RNA in the MHV-infected cells. This RI RNA consists of a single species corresponding to the MHV genomic RNA. No subgenomic RI structures were detected. Furthermore, the nascent RNA chains in the RI structure contained the leader sequences, suggesting that the leader RNA was not added to the mRNA post- transcriptionally , but rather, it was probably synthesized independently and then used as a primer for the synthesis of mRNAs. We have also shown that the poly (A) sequences in the MHV genome were transcribed from the poly (U) sequences present in the negative-strand template. The RNA polymerases involved in the MHV RNA synthesis were also characterized. The early polymerase synthesizes a single negative-stranded, full-length RNA. The late polymerases could be separated into two activities, one synthesizing positive-stranded genomic RNA, and the other synthesizing genomic as well as subgenomic RNAs. Thus, the replication and transcription functions of MHV could probably be separated. A plausible model of MHV replication is presented.


title: Open inguinal hernia repair with self-gripping Parietex ProGrip mesh: a retrospective study of 204 cases.

text: Chronic pain and recurrence rates are the main challenge in modern inguinal hernia surgery. Several trials have investigated the role of self-adhesive mesh repair for inguinal hernia, with special attention to the incidence of chronic postoperative inguinal pain and recurrence. The purpose of our study was to retrospectively evaluate the early and long-term results using a self-gripping mesh (Parietex Progrip® , Covidien) in our institution. A total of 204 patients, mean age 50.3 standard deviation (SD) 15.3, was included in the study. The repair was performed under local anaesthesia in 159 (78%) cases and locoregional anaesthesia in remaining 45 (22%). Mean operative time was 39 ± 20 minutes. The time for self-gripping mesh placement ranged from 5 to 9 minutes (mean 7 ± 2 minutes). There were no intraoperative complications. Clinical follow-up was performed at 1 month, 1 year and 2 years and consisted in the evaluation of complications, discomfort/pain and recurrence. One case of cutaneous infection and three cases of seroma were observed at one-month follow-up and were all treated conservatively. 8 patients were lost at one year follow-up, and another 4 were lost at 2 years. 3 patients died for other causes during follow-up. At 1 year and 2 years follow-up no cases of seroma, testicular complications or mesh infection were observed. Two cases of recurrence were recorded at 2 years follow up. No patient reported VAS score > 2 at one month, 1 year and 2 years follow-up. There were no readmissions, systemic complications or death during 2 years follow-up. Lichtenstein open repair using Parietex Progrip® mesh is a simple, rapid, effective and safe method for inguinal hernia repair. The main advantage of self-fixing mesh is the reduced operative time. A suturless fixation seems to prevent the development of postoperative chronic pain, without increasing recurrence rate in the majority of the trials.


title: Andes and Prospect Hill hantaviruses differ in early induction of interferon although both can downregulate interferon signaling.

text: Hantavirus pulmonary syndrome (HPS) is a severe respiratory disease which is thought to result from a dysregulated immune response to infection with pathogenic hantaviruses, such as Sin Nombre virus or Andes virus (ANDV). Other New World hantaviruses, such as Prospect Hill virus (PHV), have not been associated with human disease. Activation of an antiviral state and cell signaling in response to hantavirus infection were examined using human primary lung endothelial cells, the main target cell infected in HPS patients. PHV, but not ANDV, was found to induce a robust beta interferon (IFN-beta) response early after infection of primary lung endothelial cells. The level of IFN induction correlated with IFN regulatory factor 3 (IRF-3) activation, in that IRF-3 dimerization and nuclear translocation were detected in PHV but not ANDV infection. In addition, phosphorylated Stat-1/2 levels were significantly lower in the ANDV-infected cells relative to PHV. Presumably, this reflects the lower level of IRF-3 activation and initial IFN induced by ANDV relative to PHV. To determine whether, in addition, ANDV interference with IFN signaling also contributed to the low Stat-1/2 activation seen in ANDV infection, the levels of exogenous IFN-beta-induced Stat-1/2 activation detectable in uninfected versus ANDV- or PHV-infected Vero-E6 cells were examined. Surprisingly, both viruses were found to downregulate IFN-induced Stat-1/2 activation. Analysis of cells transiently expressing only ANDV or PHV glycoproteins implicated these proteins in this downregulation. In conclusion, while both viruses can interfere with IFN signaling, there is a major difference in the initial interferon induction via IRF-3 activation between ANDV and PHV in infected primary endothelial cells, and this correlates with the reported differences in pathogenicity of these viruses.


title: Importance of the positive-strand RNA secondary structure of a murine coronavirus defective interfering RNA internal replication signal in positive-strand RNA synthesis.

text: The RNA elements that are required for replication of defective interfering (DI) RNA of the JHM strain of mouse hepatitis virus (MHV) consist of three discontinuous genomic regions: about 0.46 to 0.47 kb from both terminal sequences and an internal 58-nucleotide (nt)-long sequence (58-nt region) present at about 0.9 kb from the 5' end of the DI genome. The internal region is important for positive-strand DI RNA synthesis (Y. N. Kim and S. Makino, J. Virol. 69:4963-4971, 1995). We further characterized the 58-nt region in the present study and obtained the following results. (i) The positive-strand RNA structure in solution was comparable with that predicted by computer modeling. (ii) Positive-strand RNA secondary structure, but not negative-strand RNA structure, was important for the biological function of the region. (iii) The biological function had a sequence-specific requirement. We discuss possible mechanisms by which the internal cis-acting signal drives MHV positive-strand DI RNA synthesis.


title: Modelling respiratory infection control measure effects.

text: One of the most pressing issues in facing emerging and re-emerging respiratory infections is how to bring them under control with current public health measures. Approaches such as the Wells-Riley equation, competing-risks model, and Von Foerster equation are used to prioritize control-measure efforts. Here we formulate how to integrate those three different types of functional relationship to construct easy-to-use and easy-to-interpret critical-control lines that help determine optimally the intervention strategies for containing airborne infections. We show that a combination of assigned effective public health interventions and enhanced engineering control measures would have a high probability for containing airborne infection. We suggest that integrated analysis to enhance modelling the impact of potential control measures against airborne infections presents an opportunity to assess risks and benefits. We demonstrate the approach with examples of optimal control measures to prioritize respiratory infections of severe acute respiratory syndrome (SARS), influenza, measles, and chickenpox.


title: Management of a case with misdiagnosed spinal dural arterio-venous fistula.

text: PURPOSE Spinal dural arterio-venous fistula (SDAVF) is an uncommon and easily misdiagnosed vascular malformation. We aimed to report the diagnosis and management of a case with SDAVF. CASE REPORT A 62-year-old man suffered from acute paraparesis about 15 months before this study. He underwent a neurosurgical procedure for herniated discs of the cervical spine at that time but there was no relief and the symptoms worsened despite the surgery. Neurologically, he had spastic paraparesis and decreased vibration sensation of the lower limbs. Spinal magnetic resonance imaging (MRI) revealed intra-medullary hyper-intensity lesion at T8 to T10 levels and tubular-like signal void structures in the corresponding posterior sub-arachnoid space. Further trans-arterial angiography through right T6 intercostal artery catheterization revealed engorged veins, thereby confirming the diagnosis of SDAVF. The patient was treated via endovascular embolization (18% Onyx, EV3TM MIT, Bonn, Germany) through spinal angiography and the results showed a marked decrease in engorged veins. After a 4-month follow-up, the patient was symptomatic but stable. Follow-up MRI showed a complete disappearance of the hyper-intensity change of the spinal cord. Spinal MR angiography did not reveal any recurrence of SDAVF. CONCLUSION This case study demonstrated the easily misdiagnosed state of SDAVF. Serial neuroimage studies including spinal MRI, endovascular embolization through spinal angiography and MR angiography can be useful tools for its diagnostic confirmation, management and follow-up study.


ACCF/AHA/CDC conference report on emerging infectious diseases and biological terrorism threats. Task Force I: direct cardiovascular implications of emerging infectious diseases and biological terrorism threats.


title: Bioactive coumarins from Boenninghausenia sessilicarpa.

text: Bioassay guided fractionation of Boenninghausenia sessilicarpa (Rutaceae) resulted in the isolation of a new dimeric coumarin glucoside 9'-methoxyl rutarensin (1) and a cytotoxic compound rutamarin (4), as well as an antivirus component leptodactylone (8), together with six known coumarins. Their structures were elucidated by 1D- and 2D NMR spectroscopy and ESI-MS analyses, respectively. Rutamarin (4) showed significant inhibitory activities against A-549, Bel-7402, HepG-2 and HCT-8 tumour cell lines with IC50s of 1.318, 2.082, 2.306 and 2.497 microg/ml. In addition, leptodactylone (8) showed potent protective activity on cells infected by SARS-CoV with ratio of 60% at 100 microg/ml.


Severe acute respiratory syndrome: lab accidents prompt calls for new containment program.


title: Awareness With Recall: A Systematic Review.

text: This article provides a systematic review of awareness with recall, also called intraoperative awareness. Major topics of this review include the incidence and causes of this phenomenon, in addition to an examination of current strategies for prevention of intraoperative awareness. Awareness with recall creates substantial physical and/or psychological distress for the patient, representing a continued threat to patient safety. Factors related to cases of awareness include those of the patient, surgical procedure, anesthesia provider, and system in which providers deliver care. Anesthesia providers today consider use of electroencephalographic depth-of-anesthesia monitors such as the bispectral index monitor (BIS, Covidien, now Medtronic), as a potential tool for preventing awareness. This Journal course explores evidence related to the utility and limitations of this monitor in clinical practice. It also reviews evidence-based practices that may decrease the incidence of awareness with recall, including avoidance of muscle relaxants and protocol-driven approaches to awareness prevention.


title: Degenerative changes in neutrophils: an indicator of bacterial infection.

text: A review was made of 195 peripheral blood smears of 157 neonates who required sepsis work-up in the first month of life. Degenerative changes of neutrophils including vacuolization and toxic granulation were observed frequently in infants with culture-proven bacterial sepsis. Of 21 peripheral blood smears from 20 neonates subsequently proven to have bacterial infection, 17 had vacuolization present in the neutrophils for a sensitivity of 81%, a specificity of 93%, and a positive predictive accuracy of 59%. Toxic granulation changes in neutrophils showed similar results. This simple test can be performed easily in all hospitals; it does not require special laboratory facilities. The test appears to provide a valuable adjunct in the early detection of neonatal bacterial infection.