title: Appropriate use of personal protective equipment among healthcare workers in public sector hospitals and primary healthcare polyclinics during the SARS outbreak in Singapore.

text: BACKGROUND Singapore was affected by an outbreak of severe acute respiratory syndrome (SARS) from 25 February to 31 May 2003, with 238 probable cases and 33 deaths. AIMS To study usage of personal protective equipment (PPE) among three groups of healthcare workers (HCWs: doctors, nurses, and administrative staff), to determine if the appropriate PPE were used by the different groups and to examine the factors that may determine inappropriate use. METHODS A self-administered questionnaire survey of 14,554 HCWs in nine healthcare settings, which included tertiary care hospitals, community hospitals, and polyclinics, was carried out in May-July 2003. Only doctors, nurses, and clerical staff were selected for subsequent analysis. RESULTS A total of 10 236 valid questionnaires were returned (70.3% response); 873 doctors, 4404 nurses, and 921 clerical staff were studied. A total of 32.5% of doctors, 48.7% of nurses, and 77.1% of the administrative staff agreed that paper and/or surgical masks were "useful in protecting from contracting SARS". Among this group, 23.6% of doctors and 42.3% of nurses reported working with SARS patients. The view that a paper and/or surgical mask was adequate protection against SARS was held by 33.3% of doctors and 55.9% of nurses working at the A&E unit, 30.5% of doctors and 49.4% of nurses from medical wards, and 27.5% of doctors and 37.1% of nurses from intensive care units. Factors which predicted for agreement that paper and/or surgical masks were protective against SARS, included HCW's job title, reported contact with SARS patients, area of work, and Impact Events Scale scores. CONCLUSION A variety of factors determine appropriate use of personal protective equipment by HCWs in the face of a major SARS outbreak.


title: Experimental reproduction of Haemophilus parasuis infection in swine: clinical, bacteriological, and morphologic findings.

text: Haemophilus parasuis is a common cause of polyserositis and polyarthritis in swine. Little is known about the mucosal and systemic sites of replication and lesions which follow an aerosol exposure to H. parasuis. In this experiment 5-week-old cesarean-derived, colostrum-deprived (CDCD) pigs were inoculated intranasally with an inoculum containing 2 x 10(9) colony-forming units of H. parasuis. Two principals and one control pig were necropsied at 12, 36, 84, and 108 hours postinoculation (PI) and samples obtained for bacteriologic culture and microscopic examination. Inoculated pigs developed clinical signs of inappetence, reluctance to move, lameness, and a serous nasal discharge. Macroscopic findings included a fibrinous polyserositis and polyarthritis 36 hours PI which became progressively more severe at 84 and 108 hours PI. No lung lesions were grossly visible. Microscopic lesions included a mild purulent rhinitis at each post inoculation interval and fibrinous to fibrinopurulent synovitis and serositis at 36, 84, and 108 hours PI. A focal suppurative bronchopneumonia was observed in one pig examined at 36 hours PI. The nasal cavity and trachea were the only mucosal sites from which H. parasuis was reisolated. Haemophilus parasuis was isolated from the blood and systemic sites at 36, 84, and 108 hours PI. Findings presented indicated that intranasal inoculation of 5-week-old CDCD pigs with H. parasuis results in clinical signs and lesions of polyserositis and polyarthritis typical of field cases and is a useful model for the study of H. parasuis pathogenesis. The results also suggest that H. parasuis initially colonizes the nasal mucosa.


SARS virus identified, but the disease is still spreading.


title: Preparation of recombinant proteins in milk to improve human and animal health.

text: Milk is a very abundant source of proteins for animal and human consumption. Milk composition can be modified using transgenesis, including exogenous gene addition and endogenous gene inactivation. The study of milk protein genes has provided researchers with regulatory regions capable of efficiently and specifically driving the expression of foreign genes in milk. The projects underway are aimed at modifying milk composition, improving its nutritional value, reducing mammary infections, providing consumers with antipathogen proteins and preparing purified recombinant proteins for pharmaceutical use. The present paper summarises the current progress in this field.


SARS: market, toilet, hospital, and laboratory.


title: Fecal shedding of feline coronavirus in adult cats and kittens in an Abyssinian cattery.

text: OBJECTIVE To determine patterns of fecal shedding of feline coronavirus (FCV) by cats, age at which kittens first began to shed FCV in their feces, and whether there was any relationship between fecal shedding of FCV and serum antibody titers in adult cats or kittens. DESIGN Prospective observational study. ANIMALS 15 adult cats and 18 kittens from a single cattery. PROCEDURE Blood and fecal samples were collected from adult cats every other month for 13 months. Serum FCV antibody titers were measured by use of an indirect immunofluorescence assay. A reverse-transcriptase, nested polymerase chain reaction assay was used to detect FCV in feces. Blood and fecal samples were collected from kittens at approximately 2-week intervals from 3 weeks to 15 weeks of age. RESULTS Adult cats shed FCV intermittently. All adult cats shed virus in their feces at least once during the year, and 4 of 15 shed virus > 75% of the time. Serum antibody titer was not significantly associated with shedding of FCV. For the kittens, median age at the time FCV was first detected in feces was 67 days (range, 33 to 78 days). All except 1 of the kittens was found to be shedding virus in their feces before or at the time of seroconversion. CONCLUSIONS AND CLINICAL RELEVANCE Results suggest that serum FCV antibody titers are not a good indicator of shedding of FCV in the feces. Kittens may shed FCV in their feces before they seroconvert, and all kittens in a cattery in which FCV infection is endemic may be infected before 12 weeks of age.


Pandemic risks from bird flu.


title: Acute disseminated encephalomyelitis--a case series.

text: Acute disseminated encephalomyelitis(ADEM) is an uncommon inflammatory demyelinating disease involving central nervous system white matter. A series of seven cases seen over a period of one year have been described. The patients presented with acute onset of focal neurological deficit (3 patients), alteration of sensorium(3) and ataxia(1). CT scan showed non specific hypodensity in 4 cases and was normal in 3 patients . MRI showed characteristic radiological changes. Complete recovery was seen in 3 patients , one died and 3 were left with sequelae.


title: Antigen-presenting properties of gingival fibroblasts in chronic adult periodontitis.

text: Chronic periodontitis is characterized by dense infiltrations of T lymphocytes in the connective tissue, which consists mainly of gingival fibroblasts. It is becoming increasingly clear that T lymphocytes and gingival fibroblasts are capable of influencing each other. For example, the T cell cytokine interferon-gamma (IFN-gamma) is able to induce MHC class II molecules on the surface of several cell types, including gingival fibroblasts. Histological sections of chronically inflamed gingival tissue showed a great number of CD4+ and CD8+ T cells that produced IFN-gamma, and in addition showed abundant expression of MHC class II molecules on gingival fibroblasts. Therefore, we investigated whether these gingival fibroblasts acquire the capacity to carry out MHC class II-restricted functions such as antigen presentation to local T cells. In this study, we show that IFN-gamma-treated gingival fibroblasts were able to function as antigen-presenting cells (APC) for superantigen-mediated T cell proliferation. However, these fibroblasts failed to present whole-cell antigens of periodontitis-associated bacteria. Moreover, gingival fibroblasts inhibited the presentation of the whole-cell antigens of these bacteria by professional APC. This inhibition could be overcome by the addition of IL-2. These results suggest that gingival fibroblasts play an important role in the local specific immune response in chronic inflammatory periodontal lesions by regulating the response of infiltrating T cells.


title: Early death after feline infectious peritonitis virus challenge due to recombinant vaccinia virus immunization.

text: The gene encoding the fusogenic spike protein of the coronavirus causing feline infectious peritonitis was recombined into the genome of vaccinia virus. The recombinant induced spike-protein-specific, in vitro neutralizing antibodies in mice. When kittens were immunized with the recombinant, low titers of neutralizing antibodies were obtained. After challenge with feline infectious peritonitis virus, these animals succumbed earlier than did the control group immunized with wild-type vaccinia virus (early death syndrome).


SARS: understanding the coronavirus: accuracy of WHO criteria was similar in a "non-SARS" hospital in Singapore.


AMERICAN Association of Immunologists.


title: The cytoplasmic tail of the severe acute respiratory syndrome coronavirus spike protein contains a novel endoplasmic reticulum retrieval signal that binds COPI and promotes interaction with membrane protein.

text: Like other coronaviruses, severe acute respiratory syndrome coronavirus (SARS CoV) assembles at and buds into the lumen of the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC). Accumulation of the viral envelope proteins at this compartment is a prerequisite for virus assembly. Previously, we reported the identification of a dibasic motif (KxHxx) in the cytoplasmic tail of the SARS CoV spike (S) protein that was similar to a canonical dilysine ER retrieval signal. Here we demonstrate that this motif is a novel and functional ER retrieval signal which reduced the rate of traffic of the full-length S protein through the Golgi complex. The KxHxx motif also partially retained two different reporter proteins in the ERGIC region and reduced their rates of trafficking, although the motif was less potent than the canonical dilysine signal. The dibasic motif bound the coatomer complex I (COPI) in an in vitro binding assay, suggesting that ER retrieval may contribute to the accumulation of SARS CoV S protein near the virus assembly site for interaction with other viral structural proteins. In support of this, we found that the dibasic motif on the SARS S protein was required for its localization to the ERGIC/Golgi region when coexpressed with SARS membrane (M) protein. Thus, the cycling of SARS S through the ER-Golgi system may be required for its incorporation into assembling virions in the ERGIC.


title: Serologic survey of giant pandas (Ailuropoda melanoleuca), and domestic dogs and cats in the Wolong Reserve, China.

text: Sera from captive and recently rescued giant pandas (Ailuropoda melanoleuca) in the Wolong Reserve, China, were examined by serum neutralization or hemagglutination inhibition for antibodies to canine distemper virus (CDV), canine coronavirus (CCV), canine herpesvirus (CHV), pseudorabies virus (PRV), canine adenovirus type 2 (CAV), and canine parvovirus (CPV). Serum samples from village domestic dogs and cats, which run free throughout the reserve also were examined. Antibodies against CPV were detected in six of eight giant pandas and all dogs and cats tested. The origin of the virus was not determined. Two of eight giant pandas and two of seven dogs had CDV antibody titers. Three of eight pandas and three of seven dogs had CCV antibody titers. Four of eight pandas and two of seven dogs had CAV titers; the titers in dogs were very high. No pandas or dogs had evidence of exposure to CHV or PRV.


title: JAM-A-independent, antibody-mediated uptake of reovirus into cells leads to apoptosis.

text: Apoptosis plays a major role in the cytopathic effect induced by reovirus following infection of cultured cells and newborn mice. Strain-specific differences in the capacity of reovirus to induce apoptosis segregate with the S1 and M2 gene segments, which encode attachment protein sigma1 and membrane penetration protein mu1, respectively. Virus strains that bind to both junctional adhesion molecule-A (JAM-A) and sialic acid are the most potent inducers of apoptosis. In addition to receptor binding, events in reovirus replication that occur during or after viral disassembly but prior to initiation of viral RNA synthesis also are required for reovirus-induced apoptosis. To determine whether reovirus infection initiated in the absence of JAM-A and sialic acid results in apoptosis, Chinese hamster ovary (CHO) cells engineered to express Fc receptors were infected with reovirus using antibodies directed against viral outer-capsid proteins. Fc-mediated infection of CHO cells induced apoptosis in a sigma1-independent manner. Apoptosis following this uptake mechanism requires acid-dependent proteolytic disassembly, since treatment of cells with the weak base ammonium chloride diminished the apoptotic response. Analysis of T1L x T3D reassortant viruses revealed that the mu1-encoding M2 gene segment is the only viral determinant of the apoptosis-inducing capacity of reovirus when infection is initiated via Fc receptors. Additionally, a temperature-sensitive, membrane penetration-defective M2 mutant, tsA279.64, is an inefficient inducer of apoptosis. These data suggest that signaling pathways activated by binding of sigma1 to JAM-A and sialic acid are dispensable for reovirus-mediated apoptosis and that the mu1 protein plays an essential role in stimulating proapoptotic signaling.


[Carcinoid syndrome].


title: PHMB: an effective antimicrobial in wound bioburden management.

text: The effective management of bacterial bioburden is an essential element of wound care. Recent years have seen the increased use of topical antimicrobial dressings to control colonisation and infection, yet there is concern that some may inhibit wound healing and may have systemic sequelae (World Union of Wound Healing Societies (WUWHS), 2008). This article focuses on the safety and effectiveness of PHMB, an antimicrobial compound that is relatively underused in the UK, and argues that it is an effective option for the management of bacterial colonisation and infection.


title: Moderate hypothermia and its effects in reducing the applied dose of anesthetics for patients with opium dependence in cardiac surgery: A randomized controlled trial.

text: BACKGROUND An increasing number of patients addicted to opium are experiencing awareness during coronary artery bypass surgery (CABG) as a result of tolerance to anesthetics. OBJECTIVES This research was primarily intended to determine the potential diminishing effects of moderate hypothermia on anesthetic dosage and recall of anesthesia during the procedure. METHODS In this double-blind randomized controlled trial, a total of 80 CABG candidates with known addiction to opium were divided into two groups: one normothermic (N) and the other moderately hypothermic (H), both undergoing induction as well as close monitoring from September 2014 to January 2016. The candidates were initially set for a target bispectral index (BIS) score of between 40 and 60. As the score rose to 60, an additional dose of propofol was administered, alongside rise in blood pressure and tear-shedding. To enhance the accuracy of our evaluation of anesthetic depth, we also used two questionnaires to test candidates' recall filled with the assistance of a colleague 24 hours following surgery. Independent-samples t-test and chi-square test were used by SPSS v 18 for data analysis. RESULTS Eighty patients were studied in two groups of normothermic (N) (n = 40) and hypothermic (H) (n = 40). Given similar demographic data as well as the duration of surgery, we arrived at a propofol dose of 122.52±13.11 cc for normothermic patients and 101.28±14.06 cc for hypothermic subjects (p=0.001). As for fentanyl, the total required sum came up to 39.60±21.04 cc and 31.72±5.81 cc for the above-mentioned groups in order (p=0.025). Moreover, the post-operative interview showed that there was no report of a patient with memory recall following surgery. CONCLUSIONS Moderate hypothermia can substantially reduce the need for anesthetics in patients with addiction to opium when undergoing CABG surgery. TRIAL REGISTRATION This study is registered in Iranian Registry of Clinical Trials with registration number of IRCT2014050513159N5. FUNDING This research was supported financially by the Research Council of Mashhad University of Medical Sciences (grant number 920405).


title: Viral proteomics.

text: Viruses have long been studied not only for their pathology and associated disease but also as model systems for molecular processes and as tools for identifying important cellular regulatory proteins and pathways. Recent advances in mass spectrometry methods coupled with the development of proteomic approaches have greatly facilitated the detection of virion components, protein interactions in infected cells, and virally induced changes in the cellular proteome, resulting in a more comprehensive understanding of viral infection. In addition, a rapidly increasing number of high-resolution structures for viral proteins have provided valuable information on the mechanism of action of these proteins as well as aided in the design and understanding of specific inhibitors that could be used in antiviral therapies. In this paper, we discuss proteomic studies conducted on all eukaryotic viruses and bacteriophages, covering virion composition, viral protein structures, virus-virus and virus-host protein interactions, and changes in the cellular proteome upon viral infection.


title: Epizootiologic investigations of selected infectious disease agents in free-ranging Eurasian lynx from Sweden.

text: Serum samples from 106 Eurasian lynx (Lynx lynx) from across Sweden, found dead or shot by hunters in 1993-99, were investigated for presence of antibodies to feline parvovirus (FPV), feline coronavirus, feline calicivirus, feline herpesvirus, feline immunodeficiency virus, Francisella tularensis, and Anaplasma phagocytophila, and for feline leukemia virus antigen. In addition, tissue samples from 22 lynx submitted in 1999 were analyzed by real-time polymerase chain reaction (PCR) to detect nucleic acids specific for viral agents and A. phagocytophila. Except for FPV antibodies in one lynx and A. phagocytophila in four lynx, all serology was negative. All PCR results also were negative. It was concluded that free-ranging Swedish lynx do not have frequent contact with the infectious agents considered in this study.


title: Recovery of a patient from clinical rabies--Wisconsin, 2004.

text: Rabies is a viral infection of the central nervous system, usually contracted from the bite of an infected animal, and is nearly always fatal without proper postexposure prophylaxis (PEP). In October 2004, a previously healthy female aged 15 years in Fond du Lac County, Wisconsin, received a diagnosis of rabies after being bitten by a bat approximately 1 month before symptom onset. This report summarizes the investigation conducted by the Wisconsin Division of Public Health (WDPH), the public health response in Fond du Lac County, and the patient's clinical course through December 17. This is the first documented recovery from clinical rabies by a patient who had not received either pre- or postexposure prophylaxis for rabies.


[A critical view about public health in Mexico].


title: Transmission of the severe acute respiratory syndrome on aircraft.

text: BACKGROUND The severe acute respiratory syndrome (SARS) spread rapidly around the world, largely because persons infected with the SARS-associated coronavirus (SARS-CoV) traveled on aircraft to distant cities. Although many infected persons traveled on commercial aircraft, the risk, if any, of in-flight transmission is unknown. METHODS We attempted to interview passengers and crew members at least 10 days after they had taken one of three flights that transported a patient or patients with SARS. All index patients met the criteria of the World Health Organization for a probable case of SARS, and index or secondary cases were confirmed to be positive for SARS-CoV on reverse-transcriptase polymerase chain reaction or serologic testing. RESULTS After one flight carrying a symptomatic person and 119 other persons, laboratory-confirmed SARS developed in 16 persons, 2 others were given diagnoses of probable SARS, and 4 were reported to have SARS but could not be interviewed. Among the 22 persons with illness, the mean time from the flight to the onset of symptoms was four days (range, two to eight), and there were no recognized exposures to patients with SARS before or after the flight. Illness in passengers was related to the physical proximity to the index patient, with illness reported in 8 of the 23 persons who were seated in the three rows in front of the index patient, as compared with 10 of the 88 persons who were seated elsewhere (relative risk, 3.1; 95 percent confidence interval, 1.4 to 6.9). In contrast, another flight carrying four symptomatic persons resulted in transmission to at most one other person, and no illness was documented in passengers on the flight that carried a person who had presymptomatic SARS. CONCLUSIONS Transmission of SARS may occur on an aircraft when infected persons fly during the symptomatic phase of illness. Measures to reduce the risk of transmission are warranted.


Applicability of an assay for routine monitoring of highly variable concentrations of olanzapine based on HPLC with mass spectrometric detection.


title: Amiodarone affects Ebola virus binding and entry into target cells.

text: Ebola Virus Disease is one of the most lethal transmissible infections characterized by a high fatality rate. Several research studies have aimed to identify effective antiviral agents. Amiodarone, a drug used for the treatment of arrhythmias, has been shown to inhibit filovirus infection in vitro by acting at the early step of the viral replication cycle. Here we demonstrate that amiodarone reduces virus binding to target cells and slows down the progression of the viral particles along the endocytic pathway. Overall our data support the notion that amiodarone interferes with Ebola virus infection by affecting cellular pathways/ targets involved in the viral entry process.


title: Influenza pandemic preparedness in France: modelling the impact of interventions.

text: BACKGROUND Influenza pandemics result in excess mortality and social disruption. To assist health authorities update the French pandemic plan, the authors estimated the number of health events (cases, hospitalisations, and deaths) in a pandemic and compared interventions in terms of impact and efficiency. METHOD A Monte Carlo simulation model, incorporating probability distributions of key variables, provided estimates of health events (HE) by age and risk group. Input variables were set after literature and expert consultation. The impact of targeted influenza vaccination and antiviral prophylaxis/treatment (oseltamivir) in high risk groups (elderly, chronic diseases), priority (essential professionals), and total populations was compared. Outcome measures were HE avoided, number of doses needed, and direct cost per HE avoided. RESULTS Without intervention, an influenza pandemic could result in 14.9 million cases, 0.12 million deaths, and 0.6 million hospitalisations in France. Twenty four per cent of deaths and 40% of hospitalisations would be among high risk groups. With a 25% attack rate, 2000-86,000 deaths could be avoided, depending on population targeted and intervention. If available initially, vaccination of the total population is preferred. If not, for priority populations, seasonal prophylaxis seems the best strategy. For high risk groups, antiviral treatment, although less effective, seems more feasible and cost effective than prophylaxis (respectively 29% deaths avoided; 1800 doses/death avoided and 56% deaths avoided; 18,500 doses/death avoided) and should be chosen, especially if limited drug availability. CONCLUSION The results suggest a strong role for antivirals in an influenza pandemic. While this model can compare the impact of different intervention strategies, there remains uncertainty surrounding key variables.


title: Selective adaptation and human rights to health in China.

text: This article advances an alternative paradigm for making judgments about China's compliance with its international obligations in the realm of health and human rights, grounded on the reality that non-local rule regimes are interpreted and applied according to the extent of commonality between the norms underlying these international rule regimes and local cultural norms. This paradigm, "selective adaptation", allows us to determine that China complied with its international obligations in the case of SARS, but not HIV/AIDS. It makes visible how during SARS China eventually complied with the spirit of the international sanitation regulations but the lack of commitment to improving access to health care for persons living with HIV/AIDS reflects a failure by China to guarantee the right to adequate health care.


title: The aromatic domain of the coronavirus class I viral fusion protein induces membrane permeabilization: putative role during viral entry.

text: Coronavirus (CoV) entry is mediated by the viral spike (S) glycoprotein, a class I viral fusion protein. During viral and target cell membrane fusion, the heptad repeat (HR) regions of the S2 subunit assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes; however, the exact mechanism is unclear. Here, we characterize an aromatic amino acid rich region within the ectodomain of the S2 subunit that both partitions into lipid membranes and has the capacity to perturb lipid vesicle integrity. Circular dichroism analysis indicated that peptides analogous to the aromatic domains of the severe acute respiratory syndrome (SARS)-CoV, mouse hepatitis virus (MHV) and the human CoV OC43 S2 subunits, did not have a propensity for a defined secondary structure. These peptides strongly partitioned into lipid membranes and induced lipid vesicle permeabilization at peptide/lipid ratios of 1:100 in two independent leakage assays. Thus, partitioning of the peptides into the lipid interface is sufficient to disorganize membrane integrity. Our study of the S2 aromatic domain of three CoVs provides supportive evidence for a functional role of this region. We propose that, when aligned with the fusion peptide and transmembrane domains during membrane apposition, the aromatic domain of the CoV S protein functions to perturb the target cell membrane and provides a continuous track of hydrophobic surface, resulting in lipid-membrane fusion and subsequent viral nucleocapsid entry.


title: Public health interventions to control the spread of a directly transmitted human pathogen within and between Hong Kong and Guangzhou.

text: The ability to detect and differentiate between fast and slow spatial spread of infectious disease depends on the density of the surveillance network. 2. The results of this study suggest that more concentrated surveillance networks are required in Guangzhou compared with other regions, such as Thailand and Europe, as long-distance travel is less frequent.


title: [Characterization of peripheral dendritic cell subsets and its implication in patients infected with severe acute respiratory syndrome].

text: OBJECTIVE To investigate the dynamic changes of dendritic cell subsets in peripheral blood of patients infected with severe acute respiratory syndrome (SARS) and evaluate their roles in the immunopathogenesis of SARS. METHODS Flow cytometry was applied to study the dynamic alteration of the number and frequencies in circulating DC cell subsets in 30 SARS patients including critical SARS (n = 11) and general SARS (n = 19). The reasons and clinic significances of the peripheral blood DC subsets changes in SARS patients were also analyzed in our study. RESULTS The patients in critical status had a 9-week course of disease, longer than the 6-week course observed in subjects in general status. The frequency of peripheral DC cell subsets significantly dropped beginning from the onset of symptom in SARS patients and was maintained at significant low levels during the following 4 - 5 weeks, 1.7 +/- 1.8, 5.3 +/- 5.0/ micro l for DC1, 0.57 +/- 1.02, 0.98 +/- 1.11/ micro l for DC2 for cases in critical and general statuses, respectively, compared with healthy subjects; more importantly, the pDC2 even disappeared in the patients who died from SARS diseases. The possible reasons responsible for the alteration of DC subsets in peripheral blood is likely to be the direct attack of SARS-CoVin circulation and be partially involved the application of large dose of steroid. The frequency in DC cell subsets returned to normal level in convalescent stage. CONCLUSION Our results showed SARS patients had a significant decrease of circulating DC cell subset frequency, which maybe lead to the host immunodeficiency response to SARS-associated coronavirus (SARS-CoV).


title: V1 neurons signal acquisition of an internal representation of stimulus location.

text: A fundamental aspect of visuomotor behavior is deciding where to look or move next. Under certain conditions, the brain constructs an internal representation of stimulus location on the basis of previous knowledge and uses it to move the eyes or to make other movements. Neuronal responses in primary visual cortex were modulated when such an internal representation was acquired: Responses to a stimulus were affected progressively by sequential presentation of the stimulus at one location but not when the location was varied randomly. Responses of individual neurons were spatially tuned for gaze direction and tracked the Bayesian probability of stimulus appearance. We propose that the representation arises in a distributed cortical network and is associated with systematic changes in response selectivity and dynamics at the earliest stages of cortical visual processing.


title: Duration and distance of exposure are important predictors of transmission among community contacts of Ontario SARS cases.

text: We report attack rates and contact-related predictors among community contacts of severe acute respiratory syndrome (SARS) cases from the 2003 Toronto-area outbreak. Community contact data was extracted from public health records for single, well-defined exposures to a SARS case. In total, 8662 community-acquired exposures resulted in 61 probable cases; a crude attack rate of 0.70% [95% confidence interval (CI) 0.54-0.90]. Persons aged 55-69 years were at higher risk of acquiring SARS (1.14%) than those either younger (0.60%) or older (0.70%). In multivariable analysis exposures for at least 30 min at a distance of <or=1 m increased the likelihood of becoming a SARS case 20.4-fold (95% CI 11.8-35.1). Risk related to duration of illness in the source case at time of exposure was greatest for illness duration of 7-10 days (rate ratio 3.4, 95% CI 1.9-6.1). Longer and closer proximity exposures incurred the highest rate of disease. Separate measures of time and distance from source cases should be added to minimum datasets for the assessment of interventions for SARS and other emerging diseases.


Threat from Emerging Vectorborne Viruses.


Antiviral Therapy during the Coronavirus Disease (COVID-19) Pandemic: Is It Appropriate to Treat Patients in the Absence of Significant Evidence?


title: Protection from lethal coronavirus infection by immunoglobulin fragments.

text: Molecular mechanisms of in vitro and in vivo virus neutralization by specific Ab remain largely undefined. Murine coronaviruses provide an excellent animal model for such studies. To determine the role of Ab bivalency and the contribution of its Fc portion in the neutralization of viral infectivity and passive protection of mice by an in vitro neutralizing and in vivo protective mAb (7-10A), F(ab')2 and Fab fragments were generated and their biologic properties were examined. The two fragments reacted in ELISA like the whole Ab against viral Ag or specific anti-idiotypic Abs. The affinity constants of the different Ab preparations were determined by surface plasmon resonance using immobilized anti-idiotypic Abs. The apparent affinity constant of the whole Ab molecule was 7.0 x 10(9) M-1 and was reduced 2-fold for F(ab')2 fragments and 14-fold for Fab molecules. Like whole Ab, both F(ab')2 and Fab fragments could neutralize virus in vitro and passively protect mice in vivo. However, the efficiency of in vivo neutralization by Fab fragments was reduced compared with the bivalent molecules, despite almost identical half-lives of both types of Ab fragments. These results demonstrate that in vitro and in vivo virus neutralization mechanisms by this Ab are independent of Fc-mediated functions and bivalency, but are probably influenced by Ab avidity. Also, this is the first report of in vivo protection against a viral infection by Fab fragments of antiviral Ab.


title: CT response assessment combining reduction in both size and arterial phase density correlates with time to progression in metastatic renal cancer patients treated with targeted therapies.

text: BACKGROUND Response assessment is critical in evaluating effectiveness of anticancer treatment. Tyrosine kinase inhibitors (TKIs) in renal cell carcinoma (RCC) are associated with significant clinical benefit but may not result in significant tumor size reduction. Thus standard size-based response assessment with RECIST is insensitive, resulting in low response rates which do not reflect disease control measured by time to progression. We compared the use of combined size and density response criteria with standard size based criteria in metastatic RCC patients treated with TKI's. RESULTS Partial response (PR) and stable disease (SD) defined by modified criteria successfully identified patients with a long TTP (448 days) or short TTP (89 days) respectively (p = 0.002). Neither RECIST nor standard Choi criteria successfully discriminated between patients having a short or long clinical benefit. PATIENTS AND METHODS CT scans from 32 patients with metastatic RCC treated with either sunitinib (18) or cediranib (14) were assessed. Twelve patients were excluded from the analysis as ten had non-contrast enhanced scans due to renal impairment and two stopped treatment due to toxicity. Scans from 20 evaluable patients at baseline and 12 w on treatment were assessed using RECIST, Choi and modified criteria in which both a 10% decrease in size and 15% decrease in density were required to define a partial response (PR). Response assessment performed using each of the three methods was compared with time to disease progression (TTP) defined by RECIST using Kaplan-Meier statistics and Log-rank test with significance at 5%. CONCLUSION A combined reduction in both size and arterial phase density of RCC metastases treated with TKIs correlates with TTP. RECIST and standard Choi criteria appear inferior.


title: Development and evaluation of a novel loop-mediated isothermal amplification method for rapid detection of severe acute respiratory syndrome coronavirus.

text: The development and evaluation of a one-step single-tube accelerated real-time quantitative reverse transcription (RT) loop-mediated isothermal amplification (LAMP) assay is reported for rapid detection of the severe acute respiratory syndrome coronavirus (SARS-CoV) replicase gene. A total of 49 samples (15 throat washes, 13 throat swabs, and 21 combined throat and nasal swabs) collected from patients admitted to the Hanoi-French and Ninhbinh hospitals in Vietnam during the SARS epidemic were evaluated and compared to conventional RT-PCR. The RT-LAMP assay demonstrated 100-fold-greater sensitivity, with a detection limit of 0.01 PFU. The sensitivity and specificity of RT-LAMP assay for detecting viral RNA in clinical specimens with regard to RT-PCR were 100 and 87%, respectively. The specificity of the RT-LAMP assay was further validated by restriction analysis as well as nucleotide sequencing of the amplified product. The concentration of virus in most of the clinical samples was 0.1 PFU (0.1 to 10(2) PFU), as determined from the standard curve of SARS RT-LAMP and based on the time of positivity. The assay procedure is quite simple, wherein the amplification is carried out in a single tube under isothermal conditions at 63 degrees C, and the result can be obtained in less than 1 h (as early as 11 min). Thus, the RT-LAMP assay reported here has the advantages of rapid amplification, simple operation, and easy detection and will be useful for rapid and reliable clinical diagnosis of SARS-CoV in developing countries.


[Avian influenza virus].


The growing threat of avian influenza.


title: An evaluation of information dissemination during the severe acute respiratory syndrome (SARS) outbreak among selected rural communities in Kuala Kangsar.

text: To assess the level of knowledge, attitude and practice (KAP) on SARS and its preventive measures among the rural population of Kuala Kangsar district. This KAP study was also done to identify the expectation and preference of rural population upon obtaining health information. This is a cross-sectional study of 201 households from four villages in Kuala Kangsar. Face-to-face interview was done regarding knowledge, attitude and practice on SARS and its preventive measures. Statistical analyses were performed with SPSS (Version 10.0). A scoring system was used to assess the level of knowledge, attitude and practice towards SARS. Ninety one percent of the study population was aware of SARS. Majority of them have good attitude towards SARS based on the formulated scoring system. Television was found to be the first hand information about SARS and most preferred source of information by the rural population. Knowledge and attitude of respondents concerning SARS were good. Television was found to be the preference among the rural population in obtaining health information.


title: "iBIM"--internet-based interactive modules: an easy and interesting learning tool for general surgery residents.

text: BACKGROUND The increased use of information technology supports a resident- centred educational approach that promotes autonomy, flexibility and time management and helps residents to assess their competence, promoting self-awareness. We established a web-based e-learning tool to introduce general surgery residents to bariatric surgery and evaluate them to determine the most appropriate implementation strategy for Internet-based interactive modules (iBIM) in surgical teaching. METHODS Usernames and passwords were assigned to general surgery residents at the University of Alberta. They were directed to the Obesity101 website and prompted to complete a multiple-choice precourse test. Afterwards, they were able to access the interactive modules. Residents could review the course material as often as they wanted before completing a multiple-choice postcourse test and exit survey. We used paired t tests to assess the difference between pre- and postcourse scores. RESULTS Out of 34 residents who agreed to participate in the project, 12 completed the project (35.3%). For these 12 residents, the precourse mean score was 50 ± 17.3 and the postcourse mean score was 67 ± 14 (p = 0.020). CONCLUSION Most residents who participated in this study recommended using the iBIMs as a study tool for bariatric surgery. Course evaluation scores suggest this novel approach was successful in transferring knowledge to surgical trainees. Further development of this tool and assessment of implementation strategies will determine how iBIM in bariatric surgery may be integrated into the curriculum.


title: Evidence Supporting a Phased Immuno-physiological Approach to COVID-19 From Prevention Through Recovery.

text: This paper presents an evidence-based strategy for improving clinical outcomes in COVID-19. Recommendations are based on the phases of the disease, because optimal interventions for one phase may not be appropriate for a different phase. The four phases addressed are: Prevention, Infection, Inflammation and Recovery. Underlying this phased approach is recognition of emerging evidence for two different components of pathophysiology, early infection and late stage severe complications. These two aspects of the disease suggest two different patterns of clinical emphasis that seem on the surface to be not entirely concordant. We describe the application of therapeutic strategies and appropriate tactics that address four main stages of disease progression for COVID-19. Emerging evidence in COVID-19 suggests that the SARS-CoV-2 virus may both evade the innate immune response and kill macrophages. Delayed innate immune response and a depleted population of macrophages can theoretically result in a blunted antigen presentation, delaying and diminishing activation of the adaptive immune response. Thus, one clinical strategy involves supporting patient innate and adaptive immune responses early in the time course of illness, with the goal of improving the timeliness, readiness, and robustness of both the innate and adaptive immune responses. At the other end of the disease pathology spectrum, risk of fatality in COVID-19 is driven by excessive and persistent upregulation of inflammatory mechanisms associated with cytokine storm. Thus, the second clinical strategy is to prevent or mitigate excessive inflammatory response to prevent the cytokine storm associated with high mortality risk. Clinical support for immune system pathogen clearance mechanisms involves obligate activation of immune response components that are inherently inflammatory. This puts the goals of the first clinical strategy (immune activation) potentially at odds with the goals of the second strategy(mitigation of proinflammatory effects). This creates a need for discernment about the time course of the illness and with that, understanding of which components of an overall strategy to apply at each phase of the time course of the illness. We review evidence from early observational studies and the existing literature on both outcomes and mechanisms of disease, to inform a phased approach to support the patient at risk for infection, with infection, with escalating inflammation during infection, and at risk of negative sequelae as they move into recovery.


Back-to-work Coronavirus infection control.


title: Italy in a Time of Emergency and Scarce Resources: The Need for Embedding Ethical Reflection in Social and Clinical Settings.

text: The COVID-19 virus is severely testing the Italian healthcare system, as the requests for intensive treatment are greater than the real capacity of the system to receive patients. Given this emergency situation, it follows that citizens are limited in their freedom of movement in order to limit infection, and that in hospitals a significant number of critical situations must be faced. This brief contribution aims to offer a reflection on the public and clinical role of the bioethicist: a figure able to promote dialogue between the world of medicine and the community, and to face ethical dilemmas even in emergent clinical settings.


Zika Virus: a re-emerging pathogen with rapidly evolving public health implications.


title: Human security in the Asia Pacific: perspective of food and health security.

text: As combined new factors could further complicate the food supply and health security for regional countries, new perspective on human security should be prioritized on securing health security in the region. In recent years, food production and supply has been affected by unpredictable climate change and unaccountable manmade factors in the region. With increased pressure from food security issues, personal health and human security is badly affected. It poses a threat to human security and becomes a concern of all states. In the new era, the pressing reality for all countries is that there is no exception for anyone before a pandemic. Threats to human security become not only a national security issue but also a transnational challenge.


title: Symptomatic predictors of influenza virus positivity in children during the influenza season.

text: BACKGROUND Symptomatic predictors of the etiology of infectious diseases are necessary when quick action is required in treatment, as with cases of influenza or anthrax, or for when patient isolation is required, as with cases of severe acute respiratory syndrome (SARS). Predictors of influenza virus infection during the influenza season have previously been evaluated in adult studies of the antiviral agent zanamivir; cough and temperature > or =37.8 degrees C predicted influenza virus positivity in 79% of those evaluated. METHODS Fever and other respiratory symptoms were examined to determine their value in predicting influenza virus-positive status in children. Data analyzed were from a clinical trial of zanamivir in children 5-12 years of age and from a trial of oseltamivir in children 1-12 years of age. RESULTS In the pediatric study of zanamivir, as in the adult zanamivir study, cough and fever were the best predictors of influenza virus infection; a temperature > or =38.2 degrees C plus cough predicted 83% (95% CI, 79%-88%) of illnesses that were determined to be influenza virus positive. Cough (positive predictive value, 70%; 95% CI, 64%-75%), but not fever, was the best predictor of influenza virus-positive status in children aged 5-12 years in the oseltamivir trials, but neither cough nor fever were successful predictors in young children 1-4 years of age. The latter findings appeared to be the result of less symptomatic diversity among patients recruited for this trial, such that subjects who were determined to be influenza virus positive and subjects who were influenza virus negative had similar symptoms. CONCLUSIONS The results of these studies suggest that, during the influenza season, symptomatic predictors of influenza virus infection are applicable to identification of cases in children, although confirmation of predictive values in subjects 1-4 years of age may require further study of additional signs/symptoms.


Asymptomatic animal traders prove positive for SARS virus.


title: Prevalence of coronary heart disease--United States, 2006-2010.

text: Age-adjusted mortality rates for coronary heart disease (CHD) have declined steadily in the United States since the 1960s. Multiple factors likely have contributed to this decline in CHD deaths, including greater control of risk factors, resulting in declining incidence of CHD, and improved treatment. Greater control of risk factors and declining incidence can reduce CHD prevalence, whereas improved treatment that results in lower mortality rates and more persons living with CHD can increase prevalence. To estimate state-specific CHD prevalence and recent trends by age, sex, race/ethnicity, and education, CDC analyzed data from Behavioral Risk Factor Surveillance System (BRFSS) surveys for the period 2006-2010. This report summarizes the results of that analysis, which determined that, although self-reported CHD prevalence declined overall, substantial differences in prevalence existed by age, sex, race/ethnicity, education, and state of residence. These data can enable state and national health agencies to monitor CHD prevalence as a measure of progress toward meeting the Healthy People 2020 objective to reduce the U.S. rate of CHD deaths 20% from the 2007 baseline.


title: The epidemiological transition: the current status of infectious diseases in the developed world versus the developing world.

text: Wealthy, industrialized countries of the developed world successfully underwent the "epidemiologic transition" from infectious diseases to degenerative diseases, but developing countries have not yet achieved that transition. This article reviews the current status of Omran's Theory of Epidemiologic Transition, comparing the burden of infectious diseases in the developed world versus the developing world. The advent of modern sanitation and hygiene practices, effective vaccines, and antibiotics have significantly diminished the burden in the developed world, but infectious diseases remain the most common cause of death worldwide. The persistence of this disease burden has been due to a failure to employee effective strategies and to unforeseen developments, such as the emergence of HIV and the re-emergence of malaria and tuberculosis driven by newly developed drug resistance. The challenge in accurately assessing infectious disease burden and developing effective interventions is reviewed along with the most common diseases and current intervention strategies.


The emerging threat of MERS.


title: Artificial oxygen carriers: a current review.

text: Artificial oxygen carriers are not blood substitutes. They serve to carry oxygen to tissues and are either hemoglobin based or perfluorocarbon based. Driving the development of artificial oxygen carriers are concerns involving both the safety and quantity of the blood supply. No artificial oxygen carriers are currently approved for clinical use in the United States. Hemopure has been approved for use in South Africa. The companies producing Hemopure and PolyHeme, both of which are hemoglobin-based oxygen carriers, have filed a Biologic License Application in the United States. Phase III trials have been completed for Hemopure, while PolyHeme is currently undergoing phase III trials in the PolyHeme Urban Ambulance Trial. No North American trials are under way for perfluorocarbons.


title: Societal responses to familiar versus unfamiliar risk: comparisons of influenza and SARS in Korea.

text: This study examines the connections between familiar (influenza) and unfamiliar (SARS) risks among the general public in a SARS affected society. Using a survey of 350 respondents in Chonju, we find that risk perceptions and a belief that influenza vaccination reduces the incidence of SARS explain behavioral intentions for influenza vaccination and purchase responses to a hypothetical SARS vaccine. Those respondents who believe that an influenza vaccination will very likely reduce SARS incidence have a high probability (79%) of intending to vaccinate, but a much lower WTP for a SARS vaccine than those without such a belief. This belief undoubtedly was influenced by a reframing of influenza vaccination as preventing SARS. Such reframing may lead to short-term improvements in vaccination rates to the detriment of long-term SARS vaccination development. When compared with a similar study in Taiwan, societal risk perceptions of SARS and WTP for a vaccine vary greatly according to the extent of a society's experience with SARS.


Medical marijuana center opens doors.


title: Maintenance of airway pressure during filter exchange due to auto-triggering.

text: BACKGROUND Daily routine ventilator-filter exchange interrupts the integrity of the ventilator circuit. We hypothesized that this might reduce positive airway pressure in mechanically ventilated ICU patients, inducing alveolar collapse and causing impaired oxygenation and compliance of the respiratory system. METHODS We studied 40 consecutive ICU subjects (P(aO2)/F(IO2) ratio ≤ 300 mm Hg), mechanically ventilated with pressure-regulated volume control or pressure support and PEEP ≥ 5 cm H2O. Before the filter exchange, (baseline) tidal volume, breathing frequency, end-inspiratory plateau pressure, and PEEP were recorded. Compliance of the respiratory system was calculated; F(IO2), blood pressure, and pulse rate were registered; and P(aO2), P(aCO2), pH, and base excess were measured. Measurements were repeated 15 and 60 min after the filter exchange. In addition, a bench test was performed with a precision test lung with similar compliance and resistance as in the clinical study. RESULTS The exchange of the filter took 3.5 ± 1.2 s (mean ± SD). There was no significant change in P(aO2) (89 ± 16 mm Hg at baseline vs 86 ± 16 mm Hg at 15 min and 88 ± 18 mm Hg at 60 min, P = .24) or in compliance of the respiratory system (41 ± 11 mL/cm H2O at baseline vs 40 ± 12 mL/cm H2O at 15 min and 40 ± 12 mL/cm H2O at 60 min, P = .32). The bench study showed that auto-triggering by the ventilator when disconnecting from the expiratory circuit kept the tracheal pressure above PEEP for at least 3 s with pressure controlled ventilation. CONCLUSIONS This study showed that a short disconnection of the expiratory ventilator circuit from the ventilator during filter exchange was not associated with any significant deterioration in lung function 15 and 60 min later. This result may be explained by auto-triggering of the ventilator with high inspiratory flows during the filter exchange, maintaining airway pressure.


title: Health impacts of climate change and biosecurity in the Asian Pacific region.

text: Our climate is changing as a result of human activity, and such changes have the potential to have a significant impact on human health. The basic requirements for health--clean air, safe drinking water, sufficient food and secure shelter--are all vulnerable to climate change. Low-income developing countries are especially vulnerable; no country, however, is totally immune. In Australia, we are already seeing evidence of the health effects of climate change with an increase in temperature-related food poisoning events and an increase in mosquito-borne infections, including Ross River virus and Dengue fever. In the Asian Pacific region the issues identified as most pressing vary from country to country, but a common theme is a lack of public understanding and education and lack of capacity for implementing mitigation strategies. Strategies addressing the health impacts of climate change must incorporate the principles of social justice and equity within the region.


title: Profile of Kawasaki disease in children referred to two pediatric rheumatology services in Rio de Janeiro, Brazil.

text: OBJECTIVES To describe a population of children diagnosed with Kawasaki's disease (KD) in pediatric rheumatology centers of Rio de Janeiro, Brazil, defining the magnitude of the delay period in diagnosing KD and initiating treatment due to confusion with common childhood febrile illnesses and the impact of this delay on the frequency of coronary sequels. METHODS Data analysis from hospital records summarized in a dedicated form, including name, gender, age, date of first recorded clinical signs, date of admission to the specialty service, information about symptoms, clinical evolution, intravenous immunoglobulin (IVIG) use and coronary sequels. RESULTS Of 125 patients, 63% were males. 40% were under 2 years at diagnosis. Average lapse between earliest signs and KD diagnosis was 12 days (mean fever duration, 14 d). Only 22.4% had a diagnosis of KD before entering the specialty service. For the remainder, initial hipotheses included: bacterial (60%) and viral infections (12%), rheumatological diseases (4%) and adverse vaccination reactions (1.6%). Hence, prevalent febrile illnesses of childhood were major confounding factors. For records (85.6%) mentioning treatment, 46.7% reported IVIG treatment, beginning after day 10 in 23 cases (21.5%). 20 patients (16%) presented coronary sequels, 9 of which were diagnosed late, including 3 given IVIG after day 10, and 6 given no IVIG. We found no significant association between the frequency of coronary sequels and: a) sex; b) age; c) clinical criteria; d) initiation of IVIG treatment (before or after day 10). CONCLUSIONS Common febrile illnesses of childhood often confound the diagnosis of KD.


title: Detection of coronavirus in the central nervous system of a child with acute disseminated encephalomyelitis.

text: We present a case in which human coronavirus was detected in the cerebrospinal fluid of a child presumed to have acute disseminated encephalomyelitis. In murine models, coronavirus has been found to cause a chronic demyelinating condition that resembles multiple sclerosis. Additionally, there is in vitro evidence of human coronavirus's ability to infect neural cells. This case report provides additional support for the hypothesis that coronavirus may be an important etiologic factor in the pathogenesis of demyelinating disease in humans.


title: Myopathic changes associated with severe acute respiratory syndrome: a postmortem case series.

text: BACKGROUND The March 2003 outbreak of the severe acute respiratory syndrome (SARS) resulted in significant morbidity and mortality. Muscle weakness and elevated serum creatine kinase levels are commonly encountered in patients with SARS. However, the nature and cause of myopathy associated with a SARS infection are unknown because, to our knowledge, there has been no report of histological or postmortem examination of the skeletal muscle from SARS-infected patients. OBJECTIVE To determine the exact nature of the myopathy associated with SARS. METHOD Postmortem skeletal muscles from 8 consecutive patients who died of SARS in March 2003 were studied under light and electron microscopy as well as immunohistochemistry. RESULTS Focal myofiber necrosis was identified in 4 of 8 cases. Macrophage infiltration and regenerative fiber were scanty. All 4 patients treated with a steroid had significant myofiber atrophy. In situ hybridization for coronavirus was negative in all subjects. Viral cultures for coronavirus and examination for viral particles under electron microscopy were performed in 2 patients. The viral culture yielded no organisms and there were no viral particles seen on electron microscopic examination. CONCLUSIONS There is a spectrum of myopathic changes associated with a SARS infection. Focal myofiber necrosis is common and possibly is immune mediated. Critical illness myopathy and superimposed steroid myopathy may also play an important role in SARS.


title: Pseudotyped viruses permit rapid detection of neutralizing antibodies in human and equine serum against Venezuelan equine encephalitis virus.

text: Virus envelope proteins are the primary targets of neutralizing antibody responses. The epitopes recognized differ sufficiently between virus subtypes and species to distinguish viruses and provide an important basis for disease diagnosis. Venezuelan equine encephalitis virus (VEEV) causes acute febrile illness in humans and has high mortality in equines. The most specific detection methods for serum antibodies use live virus in neutralization assays or in blocking enzyme linked immunosorbent assays. However, work with Venezuelan equine encephalitis virus requires biosafety level 3 containment and select agent security in the United States. We report two new assays for detection of Venezuelan equine encephalitis virus neutralizing antibody responses, based on virus pseudotypes. The first provides detection by marker gene expression after 20 hours and is particularly suited for high-throughput screening; the second uses a new, rapid virus entry assay to give readouts within 1 hour. Both assays are safe, sensitive, and in general recapitulate neutralizing antibody titers obtained by conventional plaque reduction assays. Each is suitable as a rapid primary screen for detection of neutralizing antibodies against Venezuelan equine encephalitis virus.


Improving patient flow through the emergency department.


Benign familial tremor treated with primidone.


title: An epidural arteriovenous fistula studied with time-resolved imaging of contrast kinetics (TRICKS) sequence.

text: We describe the use of time-resolved MR angiography in the diagnosis of cervical epidural arteriovenous fistula before final diagnosis and embolization was achieved by digital subtraction angiography. A 42-year-old woman was referred to us because of headache and dizziness, in addition to radiculopathy of the right superior limb. Angiographic examinations documented a direct high-flow arteriovenous fistula between the right vertebral artery and the cervical epidural venous plexus. The point of fistula was located in the upper third of the cervical segment below the C2 arch. Time-resolved MR angiography might add important information in case of suspected arteriovenous fistula, helpful both for therapeutic decisions and follow-up.


title: Association of enterotoxigenic Bacteroides fragilis with diarrheal disease in young pigs.

text: Enterotoxigenic Bacteroides fragilis (ETBF) was isolated from intestinal contents of 10 of 45 pigs with diarrhea. Of 10 ETBF-positive pigs, seven were 1 to 4 weeks of age, whereas three pigs had diarrhea after weaning (6 to 8 weeks of age). Of ten pigs infected with ETBF, nine were also infected with K88-positive Escherichia coli, rotavirus, coronavirus, coccidia, or Cryptosporidium. Of 11 conventional pigs exposed to ETBF at 1 to 2 days of age, two subsequently developed fatal postweaning diarrhea. An ETBF isolate, serologically similar to the challenge-exposure strain, was isolated from the feces of the two diarrheal pigs, but not from three healthy littermates. Fatal enteric disease occurred in 11 of 12 adult rabbits with ligated ceca after approximately 5 X 10(9) colony-forming units of ETBF were injected into the ileum. Disease in rabbits was characterized by anorexia and severe, mucoid, hemorrhagic diarrhea. Of 11 rabbits given non-ETBF or sterile brain-heart infusion broth, ten remained clinically normal during the 7-day observation period.


title: [A rapid solid-phase immunoenzyme method in the diagnosis of viral infections].

text: An accelerated solid-phase enzyme-immunoassay has been developed which permits identification of antigens and antibodies to them within 30-40 min, even directly at the site of specimen collection. The method was tested on the models of foot-and-mouth disease virus, vesicular disease of swine, vesicular exanthema of swine, Aujeszky's disease, leukemia, and coronavirus infection of cattle.


title: Longitudinal assessment of community psychobehavioral responses during and after the 2003 outbreak of severe acute respiratory syndrome in Hong Kong.

text: BACKGROUND In previous literature, the stability and temporal evolution of psychobehavioral responses to an outbreak remained undefined, because of the exclusively cross-sectional nature of such study designs. METHODS Using random-digit dialing, we sampled 4481 Hong Kong residents in 6 population-based surveys that were conducted at different times during and after the 2003 outbreak of severe acute respiratory syndrome (SARS). RESULTS Respondents' State-Trait Anxiety Inventory score (range, 10-40) showed a decreasing temporal trend, from a high mean value of 24.8 during the peak of the Amoy Gardens outbreak to a postepidemic mean baseline value of 14.5. Those who perceived a higher likelihood of contracting or dying of SARS had significantly higher anxiety scores. Female respondents, individuals aged 30-49 years, and individuals with only a primary education or less were predisposed to greater anxiety. There was a positive dose-response gradient between anxiety level and uptake of personal protective measures. Males respondents, individuals at the extremes of age, and individuals with lower educational levels were less likely to engage in self-protective behavior. The presence of symptoms was the only consistent predictor for greater use of health services. There was remarkable stability in the magnitude and the direction of associations between predictors and outcomes over time. CONCLUSIONS Our findings can assist in modifying public service announcements in the future, which should be tailored to psychobehavioral surveillance intelligence to achieve the desired behavioral outcomes. Future research should explore the use of more-sophisticated techniques, including structural equation modeling and game-theoretical frameworks, to analyze population psychology and behavior, and it should integrate such findings with transmission dynamics modeling.


Extension of US trade embargoes to science editing.


Ischemic cerebrovascular disease: differences between ethnic South Asian and ethnic Chinese patients.


title: Role of metapneumovirus in viral respiratory infections in young children.

text: The contribution of human metapneumovirus (hMPV) relative to that of other respiratory viruses as a cause of respiratory infections in children less than 1 year old has been evaluated. From October 2003 to April 2004, nasopharyngeal samples from 211 children less than 1 year old were analyzed to detect respiratory viruses. Respiratory syncytial virus (RSV) was the predominant virus isolated (96 children [45.5%]), followed by influenza A virus, parainfluenza virus, adenovirus, cytomegalovirus, and herpes simplex virus type 1, which were only occasionally detected. From January 2004 to April 2004, a nested retrotranscription-PCR, using in-house primers directed to the matrix protein gene of hMPV, was carried out on samples in which no other viruses were detected. hMPV was detected in 18 (16.2%) children, indicating that this virus was the second-most-frequent cause of viral respiratory infections in children less than 1 year old. The rate of hospitalization for RSV- and hMPV-infected children was higher than 75%. While RSV had a peak from December to February, hMPV was increasingly detected from January to April. The mean age of hMPV-infected children (6.44 +/- 3.64 [mean +/- standard deviation] months) was significantly higher than that of RSV-infected children (3.99 +/- 2.96 [mean +/- standard deviation] months). On the other hand, 64.3% of the RSV-infected children and 12.5% of the hMPV-infected children showed high levels of C-reactive protein. Although several authors have reported that clinical symptoms of hMPV-positive patients mirrored those of RSV-positive patients, differences between the two viruses can be found.


title: Characterization of Berne virus genomic and messenger RNAs.

text: From 380S particles of Berne virus (proposed family Toroviridae) one species of polyadenylated RNA was isolated. Using agarose gel electrophoresis its length was estimated as 20 kb or greater. When assayed under hypertonic transfection conditions genomic RNA was found to be infectious; RNase treatment destroyed the infectivity. The positive polarity of the molecule was confirmed by filter spot hybridization using cDNA prepared against poly(A)-selected RNA from infected cells. In embryonic mule skin cells infected with Berne virus the presence of five virus-specific, polyadenylated RNA species of 7.5, 2.1, 1.4, 0.8 and at least 20 kb was demonstrated. In vitro translation of the 7.5, 2.1 and 0.8 kb RNAs followed by immunoprecipitation showed that they encode a 151K product (possibly the precursor to the peplomer proteins), the envelope protein and the nucleocapsid protein, respectively.


Hong Kong SARS sequence.


title: The evolution of liver-directed treatments for hepatic colorectal metastases.

text: The liver is the most common site of metastases from colorectal cancer. Over the past 3 decades, surgical resection has proved to be the most effective and potentially curative therapy for such metastases. This article will review the current practice of hepatic resection for colorectal liver metastases, including the possibility of combined resection of hepatic metastases at the time of resection of the primary cancer. Effective use of neoadjuvant and adjuvant chemotherapy has further expanded the pool of treatable patients. Most recently, ablative therapies based on needle-delivered thermoablation or radiation therapy have become additional weapons for effective treatment. The relative roles and combined use of these local therapies will be highlighted in this article. Overall, the recent combined advances in surgery, radiation therapy, ablative therapy, and chemotherapy have provided more patients with a chance for long-term survival.


Feline infectious peritonitis in servals (Felis serval).


title: Opportunistic mycobacterial granuloma in a cat associated with a member of the Mycobacterium terrae complex.

text: An 18-month-old domestic short-haired neutered male cat presented with a nodular dermal thickening on a digit. Biopsy demonstrated pyogranulomatous inflammation with moderately frequent acid-fast bacilli. A member of theMycobacterium terrae complex was isolated. There was no evidence of systemic involvement. Treatment was initiated with enrofloxacin, rifampicin and clarithromycin. After 2 months there was no longer any clinically apparent dermal thickening. Treatment was continued for a further 3 months using enrofloxacin and rifampicin.


title: Chemokine up-regulation in SARS-coronavirus-infected, monocyte-derived human dendritic cells.

text: Lymphopenia and increasing viral load in the first 10 days of severe acute respiratory syndrome (SARS) suggested immune evasion by SARS-coronavirus (CoV). In this study, we focused on dendritic cells (DCs) which play important roles in linking the innate and adaptive immunity. SARS-CoV was shown to infect both immature and mature human monocyte-derived DCs by electron microscopy and immunofluorescence. The detection of negative strands of SARS-CoV RNA in DCs suggested viral replication. However, no increase in viral RNA was observed. Using cytopathic assays, no increase in virus titer was detected in infected DCs and cell-culture supernatant, confirming that virus replication was incomplete. No induction of apoptosis or maturation was detected in SARS-CoV-infected DCs. The SARS-CoV-infected DCs showed low expression of antiviral cytokines (interferon alpha [IFN-alpha], IFN-beta, IFN-gamma, and interleukin 12p40 [IL-12p40]), moderate up-regulation of proinflammatory cytokines (tumor necrosis factor alpha [TNF-alpha] and IL-6) but significant up-regulation of inflammatory chemokines (macrophage inflammatory protein 1alpha [MIP-1alpha], regulated on activation normal T cell expressed and secreted [RANTES]), interferon-inducible protein of 10 kDa [IP-10], and monocyte chemoattractant protein 1 [MCP-1]). The lack of antiviral cytokine response against a background of intense chemokine up-regulation could represent a mechanism of immune evasion by SARS-CoV.


title: Antigenic and polypeptide structure of turkey enteric coronaviruses as defined by monoclonal antibodies.

text: Twenty-nine hybridoma cells lines, producing monoclonal antibodies (MAbs) to the Minnesota strain of turkey enteric coronavirus (TCV), have been established by fusion of Sp2/0 myeloma cells with spleen cells from BALB/c mice immunized with purified preparations of the egg-adapted or tissue culture-adapted virus. The hybridomas produced mainly IgG2a or IgG1 antibodies. Western immunoblotting experiments with purified virus, and immunoprecipitation tests with [35S]methionine-labelled infected cell extracts, allowed assessment of the polypeptide specificity of the MAbs. Sixteen hybridomas secreted antibodies directed to the peplomeric protein (E2, gp200/gp100) and putative intracellular precursors of apparent Mr 170K to 180K and 90K. Four hybridomas produced antibodies that selectively reacted with a glycoprotein with an Mr of 140K (E3). This polypeptide species corresponded to the major structural component of small granular projections, located near the base of the larger bulbous peplomers, and was found to be responsible for haemagglutination. The major neutralization-mediating determinants were found to be carried by both E2 and E3 glycoproteins. Eight hybridomas produced MAbs directed to the major nucleocapsid protein (N, 52K), and only one MAb reacted with a low Mr structural glycoprotein (24K), corresponding to the matrix (E1) protein. By indirect immunofluorescence, MAbs of different specificity also revealed distinct patterns of distribution of the viral antigens within the cells. The location on the virion of the antigenic determinants recognized by MAbs of different specificity was determined by the use of an immunogold electron microscopy technique. Comparison of nine TCV Quebec strains, using MAbs directed to peplomer and haemagglutinin proteins of the prototype Minnesota strain, confirmed their close antigenic relationship, but also revealed the occurrence of at least two distinct antigenic groups.


title: Multimodality intraoperative neurophysiological monitoring during Onyx embolization of cerebrovascular malformations.

text: General anesthesia prohibits neurological examination during embolization of cerebrovascular malformations when provocative testing prior to pedicle occlusion is needed. Intraoperative neurophysiological monitoring (IONM) has the potential to fill this gap but remains relatively unexplored. We conduct a retrospective review of consecutive patients with cerebrovascular malformations treated with Onyx (ethylene vinyl alcohol copolymer, dissolved in dimethyl sulfoxide) embolization under general anesthesia with IONM from 2009 to 2012. Somatosensory evoked potentials (SSEPs), transcranial motor evoked potentials (TcMEPs), visual evoked potential (VEPs), auditory brainstem response (ABR), and electroencephalography (EEG) were used selectively in all patients depending on the location of the malformation. Provocative testing combined with IONM was performed in 28 patients over 75 sessions. Three patients demonstrated changes in TcMEPs or ABR during provocative testing, which halted the planned embolization. Two patients demonstrated changes in baseline SSEPs after embolization, despite normal IONM during provocative testing, correlating with postprocedural contralateral weakness. Six patients developed visual deficits after arterial occlusion despite unchanged VEPs and occipital EEG during provocative testing and embolization. We therefore conclude that the sensitivity of TcMEPs and SSEPs is preferable to EEG, and we strongly caution against relying on occipital recorded VEPs to predict visual deficits.


title: Anesthesia for arthroscopic shoulder surgery in the beach chair position: monitoring of cerebral oxygenation using combined bispectral index and near-infrared spectroscopy.

text: Recent research has shown that cerebrovascular complications following shoulder surgery performed in the beach chair position under general anesthesia arise secondary to cerebral ischemia. Appropriate management of cerebral oxygenation is thus one of the primary goals of anesthetic management during such procedures. The present report describes the case of a 65-year-old male patient, in which both bispectral index (BIS) and near-infrared spectroscopy (NIRS) were used to monitor cerebral oxygenation. During the positioning, we observed an increased suppression ratio (SR) while BIS and regional cerebral oxygen saturation (rSO2) were at adequate level. In view of the difference in blood pressure between the heart and the base of the brain, blood pressure was maintained to ensure adequate cerebral perfusion. Although intraoperative rSO2 was at or around the cut-off point (a 12% relative decrease from baseline), no marked decrease in BIS or further increase in the SR was observed. Monitoring of cerebral perfusion using combined BIS and NIRS optimized anesthetic management during the performance of arthroscopic shoulder surgery in the beach chair position.


title: Pulmonary thromboembolism in leukaemic children undergoing bone marrow transplantation.

text: Of 67 leukaemic children transplanted in our BMT unit 3 presented with severe acute respiratory syndrome associated with pulmonary thromboembolism (PTE) as diagnosed by scintiscan and/or angiography in the first month after BMT. Intervention with continuous positive pressure ventilation, urokinase (loading dose, then continuous infusion for 12-18 h) and heparin (continuous infusion for an average of 10 days) has been carried out successfully in two cases. In conclusion, when evaluating patients undergoing BMT and developing early pulmonary complications, PTE must be considered. The pathogenesis of PTE is still difficult to ascertain but urokinase therapy may reduce early morbidity.


title: Incidence and risk of adverse perioperative events among surgical patients taking traditional Chinese herbal medicines.

text: BACKGROUND The use of traditional Chinese herbal medicines (TCHMs) among the presurgical population is widespread, but their impact on perioperative patient care is unclear. The authors estimated the incidence and risk of TCHM-related perioperative events. METHODS In a Hong Kong cohort study, 601 patients undergoing major elective surgery were asked about their Western medicine and TCHM use in the 2 weeks before surgery. Unanticipated perioperative events were noted by attending anesthesiologists, blinded to patients' use of specific TCHMs. Modified Poisson regression models were used to obtain the relative risk of combined endpoints of perioperative events associated with TCHM use. RESULTS Of the 601 patients, 483 patients (80%) took self-prescribed TCHM, and 47 (8%) took TCHM by prescription (with or without self-prescribed TCHM) in the 2 weeks before surgery. The crude incidences of any combined endpoints of preoperative, intraoperative, and postoperative events were 23% (95% confidence interval, 19-26%), 74% (95% confidence interval, 71-78%), and 63% (95% confidence interval, 59-66%), respectively. Compared with nonusers, patients who took TCHM by prescription were more likely to have a preoperative event (adjusted relative risk, 2.21; 95% confidence interval, 1.14-4.29). The authors present four case reports to highlight the effect of TCHM by prescription on prolonged activated partial thromboplastin time and hypokalemia in the preoperative period. In contrast, there was no significant association between the use of any type of TCHM and the occurrence of either intraoperative or postoperative events. CONCLUSIONS The use of TCHM by prescription near the time of surgery should be discouraged because of the increased risk of adverse events in the preoperative period.


title: Analysis of second-site revertants of a murine coronavirus nucleocapsid protein deletion mutant and construction of nucleocapsid protein mutants by targeted RNA recombination.

text: The Alb4 mutant of the coronavirus mouse hepatitis virus (MHV) is both temperature sensitive and thermolabile owing to a deletion in the gene encoding its nucleocapsid (N) protein. The deletion removes 29 amino acids that constitute a putative spacer region preceding the carboxyl-terminal domain of the protein. As a step toward understanding the structure and function of the MHV N protein, we isolated multiple independent revertants of Alb4 that totally or partially regained the ability to form large (wild-type-sized) plaques at the nonpermissive temperature. The N proteins of these revertant viruses concomitantly regained the ability to bind to RNA in vitro at a temperature that was restrictive for RNA binding by Alb4 N protein. Sequence analysis of the N genes of the revertants revealed that each contained a single second-site point mutation that compensated for the effects of the deletion. All reverting mutations were clustered within a stretch of 40 amino acids centered some 80 residues on the amino side of the Alb4 deletion, within a domain to which the RNA-binding activity of N had been previously mapped. By means of a targeted RNA recombination method that we have recently developed, two of the reverting mutations were introduced into a wild-type MHV genomic background. The resulting recombinants were stable and showed no gross phenotypic differences from the wild type. A detailed analysis of one, however, revealed that it was at a selective disadvantage with respect to the wild type.


title: Conformational change of the coronavirus peplomer glycoprotein at pH 8.0 and 37 degrees C correlates with virus aggregation and virus-induced cell fusion.

text: We have obtained biochemical and electron microscopic evidence of conformational changes at pH 8.0 and 37 degrees C in the coronavirus spike glycoprotein E2 (S). The importance of these changes is reflected in the loss of virus infectivity, the aggregation of virions, and increased virus-induced cell fusion at the same pH. Coronavirus (MHV-A59) infectivity is exquisitely sensitive to pH. The virus was quite stable at pH 6.0 and 37 degrees C (half-life, approximately 24 h) but was rapidly and irreversibly inactivated by brief treatment at pH 8.0 and 37 degrees C (half-life, approximately 30 min). Virions treated at pH 8.0 and 37 degrees C formed clumps and large aggregates. With virions treated at pH 8.0 and 37 degrees C, the amino-terminal peptide E2N (or S1) was released from virions and the remaining peptide, E2C (S2), was aggregated. Viral spikes isolated from detergent-treated virions also aggregated at pH 8.0 and 37 degrees C. Loss of virus infectivity and E2 (S) aggregation at pH 8.0 and 37 degrees C were markedly enhanced in the presence of dithiothreitol. On the basis of the effects of dithiothreitol on the reactions of the peplomer, we propose that release of E2N (S1) and aggregation of E2C (S2) may be triggered by rearrangement of intramolecular disulfide bonds. The aggregation of virions and the isolated E2 (S) glycoprotein at pH 8.0 and 37 degrees C or following treatment with guanidine and urea at pH 6.0 and 37 degrees C indicate that an irreversible conformational change has been induced in the peplomer glycoprotein by these conditions. It is interesting that coronavirus-induced cell fusion also occurred under mildly alkaline conditions and at 37 degrees C. Some enveloped viruses, including influenza viruses and alphaviruses, show conformational changes of spike glycoproteins at a low pH, which correlates with fusion and penetration of those viruses in acidified endocytic vesicles. For coronavirus MHV-A59, comparable conformational change of the spike glycoprotein E2 (S) and cell fusion occurred at a mildly alkaline condition, suggesting that coronavirus infection-penetration, like that of paramyxoviruses and lentiviruses, may occur at the plasma membrane, rather than within endocytic vesicles.


title: Laparoscopic Repair of Morgagni Hernia Using Polyvinylidene Fluoride (PVDF) Mesh.

text: We report the cases of two patients diagnosed with Morgagni hernia who presented with nonspecific abdominal symptoms. Both underwent laparoscopic surgery that used a dual-sided mesh, polyvinylidene fluoride (PVDF; Dynamesh IPOM®). The procedures were successful and both patients were discharged with no complications. There was no recurrence in 18 months of follow up.Herein is the report of these cases and a literature review.


title: Skin and wound issues in patients with Parkinson's disease: an overview of common disorders.

text: Parkinson's Disease is a chronic neurodegenerative disorder that is expected to increase in coming decades as the American population continues to age. Although the motor dysfunction (bradykinesia, tremor, rigidity) of Parkinson's Disease is well described in the literature, the nonmotor dysfunction related to autonomic system changes is not as commonly addressed. Ironically, nonmotor changes, such as seborrhea, sialorrhea, hyperhidrosis, and sensory denervation occur earlier in the disease process and exert a profound effect on patients' quality of life. The depletion of dopamine, a critically important neurotransmitter, is the critical pathology of Parkinson's disease. Therapies targeting this abnormality and the effect of insufficient dopamine itself can affect the integumentary system and potentially wound healing. The purpose of this review is to describe changes in the autonomic nervous system due to Parkinson's Disease with a focused overview of common skin and wound care issues that may affect wound care clinician practice. Implications for nurses and other clinicians caring for Parkinson's Disease patients include surveillance for melanoma and other skin cancers, skin protection against excessive moisture or the effects of insufficient moisture, monitoring of wound healing progress, and interventions to prevent or ameliorate complications of immobility.


Lifestyle as medicine - Past precepts for present problems.


title: Tumorigenic potential of a myc-containing strain of feline leukemia virus in vivo in domestic cats.

text: The oncogenic capacity of a myc-containing strain of feline leukemia virus (FeLV), termed LC-FeLV, has been examined after inoculation of the virus into neonatal kittens. Like other myc-containing strains of FeLV, LC-FeLV may induce with relatively short latency, but does not necessarily induce, thymic lymphosarcoma in viremic animals. Naturally occurring and experimentally induced tumors are T-cell lymphomas which contain clonally integrated LC-FeLV proviral DNA and which cannot readily be cultivated in vitro in the presence or absence of exogenously supplied interleukin-2. Acquisition of myc by FeLV decreases the period of latency before the appearance of tumors but does not expand the spectrum of tumors induced by FeLV alone.


title: Pulmonary disease empirically treated as tuberculosis-a retrospective study of 107 cases.

text: Pulmonary disease is sometimes treated empirically as tuberculosis (TB) in the absence of microbial confirmation if the clinical suspicion of active TB is high. In a country of relatively high TB and low HIV burden, we retrospectively studied 107 patients (69.2% male; mean age (SD): 45 (17) years) who received empirical anti-TB treatment for intrapulmonary opacities or pleural effusions suspected of active TB in our hospitals between 1998 and 2002. The diagnosis of definite or probable 'smear-negative' pulmonary TB was made based on treatment outcome at two months with rifampicin, isoniazid, pyrazinamide and ethambutol (or streptomycin). At this end-point, 81 patients (84.4%) had both clinical and radiological improvement (definite cases), 12 (12.5%) had clinical improvement alone and 3 (3.1%) had radiological improvement alone (probable cases). Confirmation of acid-fast bacilli was subsequently obtained in 12 patients (all definite cases) from culture of initial pulmonary specimens. Eleven patients (10.5%) were diagnosed as 'non-TB' based on absence of both clinical and radiological improvement or discovery of another cause for the pulmonary condition at or before this two-month study end-point. In the 'non-TB' group, 2 had carcinoma, 2 had HIV-related pulmonary diseases, 1 had bronchiectasis, while in 6 causes were indeterminate. Six (6.3%) and 3 (27.3%) patients reported adverse effects from anti-TB drugs from the 'TB' and 'non-TB' groups respectively. Our findings suggest that empirical anti-TB treatment is an acceptable practice if clinical suspicion is high in patients coming in our region.


title: International infectious disease law: revision of the World Health Organization's International Health Regulations.

text: The International Health Regulations (IHR), the only global regulations for infectious disease control, have not been significantly changed since they were first issued in 1951. The World Health Organization (WHO) is currently engaged in a process to modernize the IHR. This article reviews WHO's draft revised IHR and recommends new reforms to improve global health, which include (1) a robust mission, emphasizing the WHO's core public health purposes, functions, and essential services; (2) broad scope, flexibly covering diverse health threats; (3) global surveillance, developing informational networks of official and unofficial data sources; (4) national public health systems, setting performance criteria, measuring outcomes, and holding states accountable; (5) human rights protection, setting science-based standards and fair procedures; and (6) good governance, adopting the principles of fairness, objectivity, and transparency. The WHO should ensure state compliance with health norms and generous economic and technical assistance to poorer countries. An important issue for the international community is how sovereign countries can join together to make global health work for everyone, the poor and the wealthy alike.


Severe acute respiratory syndrome: preparedness, management, and impact.


Editorial comments--anticipated behaviors of emergency prehospital medical care providers during an influenza pandemic.


title: Coronaviruses from pheasants (Phasianus colchicus) are genetically closely related to coronaviruses of domestic fowl (infectious bronchitis virus) and turkeys.

text: Reverse-transcriptase polymerase chain reactions (RT-PCRs) were used to examine RNA extracted from mouth/nasal swabs from pheasants exhibiting signs of respiratory disease. The oligonucleotides used were based on sequences of infectious bronchitis virus (IBV), the coronavirus of domestic fowl. A RT-PCR for the highly conserved region II of the 3' untranslated region of the IBV genome detected a coronavirus in swabs from 18/21 estates. Sequence identity with the corresponding region of IBVs and coronaviruses from turkeys was > 95%. A RT-PCR for part of the S1 region of the spike protein gene was positive with 13/21 of the samples. Sequence analysis of the RT-PCR products derived from nine of the pheasant viruses revealed that some of the viruses differed from each other by approximately 24%, similar to the degree of difference exhibited by different serotypes of IBV. Further analysis of the genome of one of the viruses revealed that it contained genes 3 and 5 that are typical of IBV but absent in both the transmissible gastroenteritis virus and murine hepatitis virus groups of mammalian coronaviruses. The nucleotide sequences of genes 3 and 5 of the pheasant virus had a similar degree of identity (approximately 90%) with those of coronaviruses from turkeys and chickens, as is observed when different serotypes of IBV are compared. This work: (a) confirms that coronaviruses are present in pheasants (indeed, commonly present in pheasants with respiratory disease); (b) demonstrates that their genomes are IBV-like in their organization; and (c) shows that there is sequence heterogeneity within the group of pheasant coronaviruses, especially within the spike protein gene. Furthermore, the gene sequences of the pheasant viruses differed from those of IBV to similar extents as the sequence of one serotype of IBV differs from another. On the genetic evidence to date, there is a remarkably high degree of genetic similarity between the coronaviruses of chickens, turkeys and pheasants.


title: Keeping SARS out: an education program for SARS screeners in one Ontario hospital.

text: On March 14, 2003, the Ontario (Canada) Ministry of Health and Long-Term Care alerted healthcare providers about four cases of atypical pneumonia resulting in two deaths within a single family in Toronto, Ontario. These cases were just the first of many that occurred in Toronto, Ontario, Canada, in the months to come. This article describes one community hospital's response to the severe acute respiratory syndrome (SARS) crisis and the important, although initially overlooked, role of staff development in keeping SARS out of this Ontario hospital.


Background paper. Coronavirus M and HE: two peculiar glycoproteins.


title: Tissue localization, shedding, virus carriage, antibody response, and aerosol transmission of Porcine epidemic diarrhea virus following inoculation of 4-week-old feeder pigs.

text: We determined tissue localization, shedding patterns, virus carriage, antibody response, and aerosol transmission of Porcine epidemic diarrhea virus (PEDV) following inoculation of 4-week-old feeder pigs. Thirty-three pigs were randomly assigned to 1 of 3 groups for the 42-day study: inoculated (group A; n = 23), contact transmission (group B; n = 5), and aerosol transmission (group C; n = 5). Contact transmission occurred rapidly to group B pigs whereas productive aerosol transmission failed to occur to group C pigs. Emesis was the first clinical sign noted at 3 days postinoculation (dpi) followed by mild to moderate diarrhea lasting 5 more days. Real-time PCR detected PEDV in fecal and nasal swabs, oral fluids, serum, and gastrointestinal and lymphoid tissues. Shedding occurred primarily during the first 2 weeks postinoculation, peaking at 5-6 dpi; however, some pigs had PEDV nucleic acid detected in swabs collected at 21 and 28 dpi. Antibody titers were measurable between 14 and 42 dpi. Although feces and intestines collected at 42 dpi were PEDV negative by PCR and immunohistochemistry, respectively, small intestines from 70% of group A pigs were PCR positive. Although disease was relatively mild and transient in this age group, the results demonstrate that 4-week-old pigs are productively infected and can sustain virus replication for several weeks. Long-term shedding of PEDV in subclinically affected pigs should be considered an important source for PEDV transmission.


title: A pregnancy-specific glycoprotein is expressed in the brain and serves as a receptor for mouse hepatitis virus.

text: Mouse hepatitis virus (MHV), a murine coronavirus known to cause encephalitis and demyelination, uses murine homologues of carcinoembryonic antigens as receptors. However, the expression of these receptors is extremely low in the brain. By low-stringency screening of a mouse brain cDNA library, we have identified a member of the pregnancy-specific glycoprotein (PSG) subgroup of the carcinoembryonic antigen gene family. Unlike other PSG that are expressed in the placenta, it is expressed predominantly in the brain. Transfection of the cDNA into COS-7 cells, which lack a functional MHV receptor, conferred susceptibility to infection by some MHV strains, including A59, MHV-2, and MHV-3, but not JHM. Thus, this is a virus strain-specific receptor. The detection of multiple receptors for MHV suggests the flexibility of this virus in receptor utilization. The identification of this virus in receptor utilization. The identification of a PSG predominantly expressed in the brain also expands the potential functions of these molecules.


title: Spring-loaded heptad repeat residues regulate the expression and activation of paramyxovirus fusion protein.

text: During viral entry, the paramyxovirus fusion (F) protein fuses the viral envelope to a cellular membrane. Similar to other class I viral fusion glycoproteins, the F protein has two heptad repeat regions (HRA and HRB) that are important in membrane fusion and can be targeted by antiviral inhibitors. Upon activation of the F protein, HRA refolds from a spring-loaded, crumpled structure into a coiled coil that inserts a hydrophobic fusion peptide into the target membrane and binds to the HRB helices to form a fusogenic hairpin. To investigate how F protein conformational changes are regulated, we mutated in the Sendai virus F protein a highly conserved 10-residue sequence in HRA that undergoes major structural changes during protein refolding. Nine of the 15 mutations studied caused significant defects in F protein expression, processing, and fusogenicity. Conversely, the remaining six mutations enhanced the fusogenicity of the F protein, most likely by helping spring the HRA coil. Two of the residues that were neither located at "a" or "d" positions in the heptad repeat nor conserved among the paramyxoviruses were key regulators of the folding and fusion activity of the F protein, showing that residues not expected to be important in coiled-coil formation may play important roles in regulating membrane fusion. Overall, the data support the hypothesis that regions in the F protein that undergo dramatic changes in secondary and tertiary structure between the prefusion and hairpin conformations regulate F protein expression and activation.


title: Distinct functions between toll-like receptors 3 and 9 in retinal pigment epithelial cells.

text: Retinal pigment epithelial cells (RPE cells) are key players in the first-line defense against invading organisms such as viruses and bacteria. The interaction between RPE cells and viral or bacterial components is very important for clearance of these organisms. Toll-like receptors are a family of recognition receptors involved in innate immunity. Each TLR acts as a primary sensor of conserved microbial components and drives the induction of specific biological responses. TLR 3 is involved in the recognition of viral components, such as double-stranded RNA (dsRNA) and poly(I:C), while TLR 9 recognizes viral or bacterial DNA without methylation at CpG motifs. In the present study, we investigated the expression and function of TLR 3 and 9 in RPE cells. PCR analysis revealed expression of genes for TLR 3 and 9 in RPE cells. Expression of TLR 3 and 9 protein was detected in RPE cells by flow cytometry. TLR 3 and 9 showed strong intracellular expression. To detect angiogenetic factors produced by RPE cells, culture supernatant was examined with the Human Angiogenesis Antibody Array, which can simultaneously detect 20 different angiogenetic factors including cytokines, chemokines, soluble cytokine receptors, and growth factors. RPE cells showed high production of interleukin-8 (IL-8) and monocyte chemotactic protein-I (MCP-I). Furthermore, stimulation of RPE cells with the dsRNA analogue poly(I:C) enhanced the secretion of IL-8 and MCP-I, as well as enhancing the expression of junctional adhesion molecule-I (Jam-I) and intracellular adhesion molecule-I (ICAM-I), and promoted the adhesion of monocyte to these cells. In contrast, stimulation with the CpG-DNA motif only enhanced the secretion of IL-8. However, CpG-DNA motif enhanced phagocytosis in RPE cells. These results may indicate that TLR 3 and 9 play a distinct role in the inflammatory response that clears viruses from the retina.


Messenger RNAs of mouse hepatitis virus A59: isolation and characterization, translation in Xenopus laevis oocytes of RNAs 3, 6 and 7, UV target sizes of the transcription templates.


title: Infection of cultured human type II pneumonocytes with certain respiratory viruses.

text: Human type II alveolar pneumonocytes were grown either as monolayers derived from a clone or as organotypic cultures of fetal lung. The type II cells in these cultures retained in their cytoplasm multilamellar bodies which were morphologically identical to similar organelles present in type II cells of intact human fetal and adult lung. A number of respiratory viruses infected the cells and produced a cytopathic effect in the cultures. Viral components were also detected in some of the infected cells. Adenovirus type 3, human coronavirus 229E, and rhinovirus types 2 and 9 produced new infectious virus, but influenza A and parainfluenza 3 virus apparently did not.


Lowering Australia's defence against infectious diseases.