title: Human respiratory coronavirus OC43: genetic stability and neuroinvasion.

text: The complete genome sequences of the human coronavirus OC43 (HCoV-OC43) laboratory strain from the American Type Culture Collection (ATCC), and a HCoV-OC43 clinical isolate, designated Paris, were obtained. Both genomes are 30,713 nucleotides long, excluding the poly(A) tail, and only differ by 6 nucleotides. These six mutations are scattered throughout the genome and give rise to only two amino acid substitutions: one in the spike protein gene (I958F) and the other in the nucleocapsid protein gene (V81A). Furthermore, the two variants were shown to reach the central nervous system (CNS) after intranasal inoculation in BALB/c mice, demonstrating neuroinvasive properties. Even though the ATCC strain could penetrate the CNS more effectively than the Paris 2001 isolate, these results suggest that intrinsic neuroinvasive properties already existed for the HCoV-OC43 ATCC human respiratory isolate from the 1960s before it was propagated in newborn mouse brains. It also demonstrates that the molecular structure of HCoV-OC43 is very stable in the environment (the two variants were isolated ca. 40 years apart) despite virus shedding and chances of persistence in the host. The genomes of the two HCoV-OC43 variants display 71, 53.1, and 51.2% identity with those of mouse hepatitis virus A59, severe acute respiratory syndrome human coronavirus Tor2 strain (SARS-HCoV Tor2), and human coronavirus 229E (HCoV-229E), respectively. HCoV-OC43 also possesses well-conserved motifs with regard to the genome sequence of the SARS-HCoV Tor2, especially in open reading frame 1b. These results suggest that HCoV-OC43 and SARS-HCoV may share several important functional properties and that HCoV-OC43 may be used as a model to study the biology of SARS-HCoV without the need for level three biological facilities.


title: Clinical data analysis of 19 cases of community-acquired adenovirus pneumonia in immunocompetent adults.

text: The aim of this study was to investigate the characteristics of clinical manifestations, laboratory tests and imaging changes of community-acquired adenovirus pneumonia in immunocompetent adults. A retrospective study was performed on 19 adult community-acquired adenovirus pneumonia cases in Yantai, whereby the clinical data were collected and analyzed. Of 19 cases, 14 (73.68%) had fever and 17 (89.47%) had cough symptoms. Moreover, 14 cases (73.68%) had normal white blood cell counts, while 11 cases (57.89%) exhibited a reduction in lymphocyte proportion. Among the 19 cases, 17 cases exhibited lesions in a single lung, while 2 cases involved bilateral lungs. The lesions predominantly exhibited ground glass-like changes. The clinical manifestations of adult community-acquired adenovirus pneumonia patients with normal immune functions were mild, with such presenting symptoms as fever, cough, and sputum; most patients did not exhibit high levels of white blood cells or low lymphocyte counts, and the imaging features (ground glass-like effusion) were indicative of single-lung involvement.


Should paramedics intubate patients with SARS-like symptoms?


docid: edacnsgs

title: Development of a critical care triage protocol for pandemic influenza: integrating ethics, evidence and effectiveness.


title: Diagnosis of murine infections in relation to test methods employed.

text: Comparative investigations of Sendai virus, pneumonia virus of mice (PVM), mouse encephalomyelitis virus (mouse polio), minute virus of mice (MVM), and reovirus type 3 (Reo 3) infected murine colonies revealed a 30% higher incidence of positive sera when enzyme-linked immunosorbent assay (ELISA) was employed instead of hemagglutination inhibition (HI) tests. Equivalent sensitivity as in the ELISA was obtained when the same sera were investigated by indirect immunofluorescence (IF) tests. The virus purification techniques described resulted in highly suitable antigens for all indirect ELISA established. Since IIF requires no purified antigens, this test is recommended as an alternative to ELISA as well as to HI and complement fixation (CF) tests for laboratories lacking the necessary equipment for high speed centrifugation. A high incidence of false positive HI reactions was found particularly in Reo 3 routine serology. An updated survey of seromonitoring showed that European murine colonies appeared to be infected far less with Reo 3 if ELISA or IIF tests were employed. During 1982-1984, only 13% of the mouse colonies screened possessed Reo 3 positive sera whereas no natural Reo 3 infection was found in rat colonies. Mouse hepatitis virus (MHV) and the coronaviruses of rats exhibited the highest incidence in murine colonies. A total of 60% of mouse and 41% of rat colonies were found to be infected by these viruses. In comparison with earlier serological surveys, the relative incidence of other murine infections was similar. Antibodies against Bacillus piliformis (Tyzzer's disease) were detected by the IIF test in 41% of the rat colonies screened.


title: Prophylactic fibrinogen administration during complex congenital cardiac surgery leading to thrombosis of a patient's brachial artery and the cardiopulmonary bypass circuit: a case report.

text: Cardiac surgery represents one of the largest consumers of blood products due to the level of blood loss in these patients. As such, there is considerable interest in hemostatic therapies for this patient population. A hemostatic agent that has recently garnered interest is fibrinogen. The conversion of fibrinogen to fibrin by activated thrombin results in clot formation, leading to hemostasis. Currently, a number of studies are underway to evaluate the efficacy of fibrinogen concentrate in cardiac surgery patients. While potentially beneficial in hemostasis for cardiac patients, the current case report provides evidence of the importance of timing in the administration of this product.


docid: gtejwjhp

title: Effect of restricted freedom on health in China.


title: Prevalence of Underlying Diseases in Hospitalized Patients with COVID-19: a Systematic Review and Meta-Analysis.

text: Introduction In the beginning of 2020, an unexpected outbreak due to a new corona virus made the headlines all over the world. Exponential growth in the number of those affected makes this virus such a threat. The current meta-analysis aimed to estimate the prevalence of underlying disorders in hospitalized COVID-19 patients. Methods A comprehensive systematic search was performed on PubMed, Scopus, Web of science, and Google scholar, to find articles published until 15 February 2020. All relevant articles that reported clinical characteristics and epidemiological information of hospitalized COVID-19 patients were included in the analysis. Results The data of 76993 patients presented in 10 articles were included in this study. According to the meta-analysis, the pooled prevalence of hypertension, cardiovascular disease, smoking history and diabetes in people infected with SARS-CoV-2 were estimated as 16.37% (95%CI: 10.15%-23.65%), 12.11% (95%CI 4.40%-22.75%), 7.63% (95%CI 3.83%-12.43%) and 7.87% (95%CI 6.57%-9.28%), respectively. Conclusion According to the findings of the present study, hypertension, cardiovascular diseases, diabetes mellitus, smoking, chronic obstructive pulmonary disease (COPD), malignancy, and chronic kidney disease were among the most prevalent underlying diseases among hospitalized COVID-19 patients, respectively.


title: Policy conflicts: gene patents and health care in Canada.

text: Several recent gene patent controversies have energized and refocused the human gene patent debate in Canada. These include the use of the Myriad test for breast cancer by the provinces, patenting of the Severe Acute Respiratory Syndrome virus and a recent Supreme Court decision rejecting the patenting of 'higher life forms'. These cases place the emerging policy conflicts between the innovation and commercialization agenda of the government and the desire to provide equitable access to health care in sharp focus. Another challenge faced by Canada is the powerful influence of the United States in policy decisions. Although these issues have raised awareness about the possibility of reforming the patent system, Parliament has yet to consider any of the suggested reforms of the Canadian patent system and there are no formal proposals pending.


title: Differential regulation of primary and secondary CD8+ T cells in the central nervous system.

text: T cell accumulation and effector function following CNS infection is limited by a paucity of Ag presentation and inhibitory factors characteristic of the CNS environment. Differential susceptibilities of primary and recall CD8+ T cell responses to the inhibitory CNS environment were monitored in naive and CD8+ T cell-immune mice challenged with a neurotropic coronavirus. Accelerated virus clearance and limited spread in immunized mice was associated with a rapid and increased CNS influx of virus-specific secondary CD8+ T cells. CNS-derived secondary CD8+ T cells exhibited increased cytolytic activity and IFN-gamma expression per cell compared with primary CD8+ T cells. However, both Ag-specific primary and secondary CD8+ T cells demonstrated similar contraction rates. Thus, CNS persistence of increased numbers of secondary CD8+ T cells reflected differences in the initial pool size during peak inflammation rather than enhanced survival. Unlike primary CD8+ T cells, persisting secondary CD8+ T cells retained ex vivo cytolytic activity and expressed high levels of IFN-gamma following Ag stimulation. However, both primary and secondary CD8+ T cells exhibited reduced capacity to produce TNF-alpha, differentiating them from effector memory T cells. Activation of primary and secondary CD8+ T cells in the same host using adoptive transfers confirmed similar survival, but enhanced and prolonged effector function of secondary CD8+ T cells in the CNS. These data suggest that an instructional program intrinsic to T cell differentiation, rather than Ag load or factors in the inflamed CNS, prominently regulate CD8+ T cell function.


title: Bariatric surgery in managing diabetes mellitus.

text: PURPOSE OF REVIEW Obesity is a worldwide epidemic, having profound effects on Western populations. Bariatric surgery has long been employed to treat obesity and its related comorbidities. Over time, researchers have amassed significant data to support bariatric surgery in the pursuit of treating diabetes mellitus. This review serves to introduce the most recent findings and their relation to the various bariatric surgical options as bariatric surgery will continue to cement itself in the treatment paradigm of diabetes mellitus. RECENT FINDINGS Numerous studies performed in the past 10 years have demonstrated the improvement or cessation of diabetes with bariatric surgical intervention. In comparing the vertical sleeve gastrectomy and Roux-en-Y gastric bypass, data demonstrate a more beneficial response of diabetes to the Roux-en-Y gastric bypass, and an even further exaggerated response with the biliopancreatic diversion/duodenal switch. The benefit has long been established, but what causes the improvement in diabetes mellitus after bariatric surgery? Recent data suggest a decrease in circulating bile salts as well as changes to inflammatory markers and circulating cytokines. Furthermore, tailoring of existing surgical procedures has led to the development of the SIPS procedure, and its benefit is demonstrated in bypassing a large portion of intestine while eliminating an enteroenterostomy, helping to reduce short gut syndrome and resultant diarrhea. SUMMARY The surgical climate within the bariatric field is changing and will continue to do so in the future. As the understanding of the causes or mechanisms in which bariatric surgery improves metabolic disorders becomes more evident, the process of individualizing care for specific patients will become more prevalent.


title: Pathogenesis of scrapie: agent multiplication in brain at the first and second passage of hamster scrapie in mice.

text: The intracerebral (i.c.) injection of mice with a particular source of hamster passaged scrapie produced disease after an incubation period of 325 +/- 6 days (mean +/- s.e.). The incubation period at the second i.e. passage in mice was reduced to 149 +/- 2 days. Studies were made of the dynamics of agent replication at 1st and 2nd passages in mice. At first passage, there was a 'zero phase' lasting about 175 days, when no infectious agent was detected in brain (or spleen), followed by a period of agent replication which lasted 150 days. At second passage, there was no significant 'zero phase' and agent replication occupied the whole of the incubation period. The occurrence of a 'zero phase' on interspecies passage of scrapie is discussed in relation to other reports of a 'zero phase' in mouse passaged scrapie.


title: Changes in cerebral oxygen saturation and haemoglobin concentration during paediatric cardiac surgery.

text: Although near-infrared spectroscopy (NIRS) enables bedside assessment of cerebral oxygenation, it provides little information on the cause of deoxygenation. The authors aimed to investigate the changes in cerebral oxygenation and haemoglobin concentration and their associations during paediatric cardiac surgery in order to elucidate the physiology underlying cerebral deoxygenation. An observational retrospective study on 399 patients who underwent paediatric cardiac surgery was conducted. With use of NIRS, cerebral oxygen saturation as expressed by tissue oxygen index (TOI) before and after surgery, concentration changes in oxygenated haemoglobin (Δ[HbO2]) and deoxygenated haemoglobin (Δ[HHb]) after surgery were studied as were the associations between these values and clinical variables. TOI decreased after surgery (preoperative versus postoperative value, 66.0% [56.9, 71.3] versus 63.2% [54.3, 69.4], median [25th, 75th percentile], P <0.001) and the decrease was greater in higher category groups in the Risk Adjusted Classification for Congenital Heart Surgery (RACHS-1). [HHb] increased from its baseline (+1.74 μmol/l [-1.57, +5.84], P <0.001) and the increase was greater in higher risk category groups. On the contrary, there was no evidence for a change in [HbO2] (+0.45 μmol/l [-4.76, +5.30], P=0.42). Cerebral oxygen saturation decreased after paediatric cardiac surgery and the decrease was greater in patients of higher risk groups. The increase in [HHb] was considered to play a predominant role in the cerebral deoxygenation noted, in particular in higher RACHS-1 category groups.


Calfhood coronavirus enterocolitis: a clue to the etiology of winter dysentery.


title: Complications of Roux-en-Y gastric bypass and sleeve gastrectomy.

text: Roux-en-Y gastric bypass and sleeve gastrectomy are two of the most common bariatric procedures performed in 2011. Although the complication rates associated with these procedures are low, the consequences of these complications are significant and can be associated with high morbidity and mortality. Timely diagnosis and proper management of these complications are extremely important. The most commonly used radiologic studies in bariatric surgery are the upper GI contrast study and the CT scan, which are used to rule out leak, obstruction, perforation, anastomotic stricture, or pouch dilatation. As with all imaging studies, a negative result should not override strong clinical suspicion of a complication.


title: Detection of porcine teschovirus and enterovirus type II by reverse transcription-polymerase chain reaction.

text: Porcine enteroviruses (PEVs) have been recognized as the causative agents of various clinical manifestations such as fertility disorders, neurological defects, and dermal lesions in pigs. Currently, the diagnosis of PEV infection is carried out by virus isolation, which although useful, is labor- and time-intensive. The present investigation describes the development of a reverse transcription-polymerase chain reaction (RT-PCR) assay for the rapid and sensitive detection of PEVs of cytopathic effect groups I (now known as porcine teschoviruses [PTVs]) and II. The assay described not only detects the PTVs and CPE group II of PEVs but also allows them to be differentiated on the basis of the size of the amplification product, using the same set of oligonucleotide primers. The availability of specific and sensitive molecular diagnostic tools such as the RT-PCR assay described herein should facilitate efficient diagnosis of PTV and CPE group II infections in pigs.


title: A large-volume nebulizer would not be an infectious source for severe acute respiratory syndrome.

text: We attempted to detect the presence of airborne SARS-coronavirus (CoV) in a healthcare setting when a patient with SARS used a humidifier or a large-volume nebulizer (LVN). All of the air samples from the humidifier and LVN were found to have negative SARS-CoV-specific DNA products.


title: Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels, Oman, 2013.

text: A countrywide survey in Oman revealed Middle Eastrespiratory syndrome coronavirus (MERS-CoV) nucleicacid in five of 76 dromedary camels. Camel-derivedMERS-CoV sequences (3,754 nucleotides assembled from partial sequences of the open reading frame (ORF)1a, spike, and ORF4b genes) from Oman and Qatar were slightly different from each other, but closely related to human MERS-CoV sequences from the same geographical areas, suggesting local zoonotic transmission. High viral loads in nasal and conjunctival swabs suggest possible transmission by the respiratory route.


docid: ljmexfzi

title: CD8+ T cells require perforin to clear West Nile virus from infected neurons.

text: Injury to neurons after West Nile virus (WNV) infection is believed to occur because of viral and host immune-mediated effects. Previously, we demonstrated that CD8+ T cells are required for the resolution of WNV infection in the central nervous system (CNS). CD8+ T cells can control infection by producing antiviral cytokines (e.g., gamma interferon or tumor necrosis factor alpha) or by triggering death of infected cells through perforin- or Fas ligand-dependent pathways. Here, we directly evaluated the role of perforin in controlling infection of a lineage I New York isolate of WNV in mice. A genetic deficiency of perforin molecules resulted in higher viral burden in the CNS and increased mortality after WNV infection. In the few perforin-deficient mice that survived initial challenge, viral persistence was observed in the CNS for several weeks. CD8+ T cells required perforin to control WNV infection as adoptive transfer of WNV-primed wild-type but not perforin-deficient CD8+ T cells greatly reduced infection in the brain and spinal cord and enhanced survival of CD8-deficient mice. Analogous results were obtained when wild-type or perforin-deficient CD8+ T cells were added to congenic primary cortical neuron cultures. Taken together, our data suggest that despite the risk of immunopathogenesis, CD8+ T cells use a perforin-dependent mechanism to clear WNV from infected neurons.


title: Diseases and pathogens associated with mortality in Ontario beef feedlots.

text: This study determined the prevalence of diseases and pathogens associated with mortality or severe morbidity in 72 Ontario beef feedlots in calves that died or were euthanized within 60 days after arrival. Routine pathologic and microbiologic investigations, as well as immunohistochemical staining for detection of bovine viral diarrhea virus (BVDV) antigen, were performed on 99 calves that died or were euthanized within 60 days after arrival. Major disease conditions identified included fibrinosuppurative bronchopneumonia (49%), caseonecrotic bronchopneumonia or arthritis (or both) caused by Mycoplasma bovis (36%), viral respiratory disease (19%), BVDV-related diseases (21%), Histophilus somni myocarditis (8%), ruminal bloat (2%), and miscellaneous diseases (8%). Viral infections identified were BVDV (35%), bovine respiratory syncytial virus (9%), bovine herpesvirus-1 (6%), parainfluenza-3 virus (3%), and bovine coronavirus (2%). Bacteria isolated from the lungs included M. bovis (82%), Mycoplasma arginini (72%), Ureaplasma diversum (25%), Mannheimia haemolytica (27%), Pasteurella multocida (19%), H. somni (14%), and Arcanobacterium pyogenes (19%). Pneumonia was the most frequent cause of mortality of beef calves during the first 2 months after arrival in feedlots, representing 69% of total deaths. The prevalence of caseonecrotic bronchopneumonia caused by M. bovis was similar to that of fibrinosuppurative bronchopneumonia, and together, these diseases were the most common causes of pneumonia and death. M. bovis pneumonia and polyarthritis has emerged as an important cause of mortality in Ontario beef feedlots.


title: High-resolution computed tomography is useful for early diagnosis of severe acute respiratory syndrome-associated coronavirus pneumonia in patients with normal chest radiographs.

text: OBJECTIVE We investigated the usefulness of high-resolution computed tomography (HRCT) in early detection of severe acute respiratory syndrome (SARS)-associated coronavirus pneumonia and analyzed HRCT findings associated with potentially more severe disease. METHODS All patients with suspected SARS and normal chest radiographs on admission within the study period were subjected to HRCT examination. The clinical, radiologic, and laboratory data of patients who were confirmed to have SARS-associated coronavirus infection by a positive nasopharyngeal aspirate, stool or urine reverse transcription-polymerase chain reaction (RT-PCR) and/or serological testing were prospectively followed up and analyzed. Characteristics of patients admitted to the intensive care unit (ICU) and those that were not were compared. RESULTS Among 47 suspected SARS patients with normal chest radiographs, 27 had SARS-associated coronavirus infection confirmed by RT-PCR and/or positive serological testing. Twenty-five of the 27 (93%) patients had HRCT changes compatible with atypical pneumonia, and all 25 patients developed SARS with progressive clinical deterioration. Ten (40%) had unifocal diseases, and 15 had multifocal diseases (60%). Ten (40%) patients had the diseases confined to 1 single lung in the first HRCT, and both lungs were involved at initial presentation in 15 (60%) patients. Concerning the overall extent of the disease at initial presentation, 3 (12%) patients had disease process in all lobes, and the disease was confined to 1 single lobe in 10 (40%) patients. The disease process was mainly peripheral in location (96%), and the lower lobes were more commonly involved (68% in the left lower lobe and 64% in the right lower lobe). Small parapneumonic effusions occurred in 1 (4%) patient. None of the patients with unifocal lesions or single-lung involvement were admitted to the ICU (P < 0.05) (in both comparisons). Subsequent follow-up of the 2 (7%) patients with normal HRCT on admission showed that they were having nonpneumonic SARS-associated coronavirus infection only and were eventually denotified from having SARS. CONCLUSIONS HRCT is useful for early diagnosis of SARS-associated coronavirus pneumonia in patients with normal chest radiographs. HRCT findings in these patients predict potentially severe disease.


title: An infectious recombinant equine arteritis virus expressing green fluorescent protein from its replicase gene.

text: Thus far, systems developed for heterologous gene expression from the genomes of nidoviruses (arteriviruses and coronaviruses) have relied mainly on the translation of foreign genes from subgenomic mRNAs, whose synthesis is a key feature of the nidovirus life cycle. In general, such expression vectors often suffered from relatively low and unpredictable expression levels, as well as genome instability. In an attempt to circumvent these disadvantages, the possibility to express a foreign gene [encoding enhanced green fluorescent protein (eGFP)] from within the nidovirus replicase gene, which encodes two large polyproteins that are processed proteolytically into the non-structural proteins (nsps) required for viral RNA synthesis, has now been explored. A viable recombinant of the arterivirus Equine arteritis virus, EAV-GFP2, was obtained, which contained the eGFP insert at the site specifying the junction between the two most N-proximal replicase-cleavage products, nsp1 and nsp2. EAV-GFP2 replication could be launched by transfection of cells with either in vitro-generated RNA transcripts or a DNA launch plasmid. EAV-GFP2 displayed growth characteristics similar to those of the wild-type virus and was found to maintain the insert stably for at least eight passages. It is proposed that EAV-GFP2 has potential for arterivirus vector development and as a tool in inhibitor screening. It can also be used for fundamental studies into EAV replication, which was illustrated by the fact that the eGFP signal of EAV-GFP2, which largely originated from an eGFP-nsp2 fusion protein, could be used to monitor the formation of the membrane-bound EAV replication complex in real time.


title: Clinical pathology and assessment of pathogen exposure in southern and Alaskan sea otters.

text: The southern sea otter (Enhydra lutris nereis) population in California (USA) and the Alaskan sea otter (E. lutris kenyoni) population in the Aleutian Islands (USA) chain have recently declined. In order to evaluate disease as a contributing factor to the declines, health assessments of these two sea otter populations were conducted by evaluating hematologic and/or serum biochemical values and exposure to six marine and terrestrial pathogens using blood collected during ongoing studies from 1995 through 2000. Samples from 72 free-ranging Alaskan, 78 free-ranging southern, and (for pathogen exposure only) 41 debilitated southern sea otters in rehabilitation facilities were evaluated and compared to investigate regional differences. Serum chemistry and hematology values did not indicate a specific disease process as a cause for the declines. Statistically significant differences were found between free-ranging adult southern and Alaskan population mean serum levels of creatinine kinase, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, calcium, cholesterol, creatinine, glucose, phosphorous, total bilirubin, blood urea nitrogen, and sodium. These were likely due to varying parasite loads, contaminant exposures, and physiologic or nutrition statuses. No free-ranging sea otters had signs of disease at capture, and prevalences of exposure to calicivirus, Brucella spp., and Leptospira spp. were low. The high prevalence (35%) of antibodies to Toxoplasma gondii in free-ranging southern sea otters, lack of antibodies to this parasite in Alaskan sea otters, and the pathogen's propensity to cause mortality in southern sea otters suggests that this parasite may be important to sea otter population dynamics in California but not in Alaska. The evidence for exposure to pathogens of public health importance (e.g., Leptospira spp., T. gondii) in the southern sea otter population, and the naïveté of both populations to other pathogens (e.g., morbillivirus and Coccidiodes immitis) may have important implications for their management and recovery.


title: Emerging zoonotic epidemics in the interconnected global community.

text: The rate at which epidemics of zoonotic disease in humans have surfaced over the past 25 years has shaken--some would say shattered--the assumption that zoonotic diseases are under control, says Paul Gibbs. In this review he analyses the global factors that have led to the increased emergence of zoonotic diseases, sketches several recent epidemics (and where relevant, their relationship to bioterrorism), discusses the lessons learned, and concludes by outlining an agenda for action.


title: Identification of mouse hepatitis virus papain-like proteinase 2 activity.

text: Mouse hepatitis virus (MHV) is a 31-kb positive-strand RNA virus that is replicated in the cytoplasm of infected cells by a viral RNA-dependent RNA polymerase, termed the replicase. The replicase is encoded in the 5'-most 22 kb of the genomic RNA, which is translated to produce a polyprotein of >800 kDa. The replicase polyprotein is extensively processed by viral and perhaps cellular proteinases to give rise to a functional replicase complex. To date, two of the MHV replicase-encoded proteinases, papain-like proteinase 1 (PLP1) and the poliovirus 3C-like proteinase (3CLpro), have been shown to process the replicase polyprotein. In this report, we describe the cloning, expression, and activity of the third MHV proteinase domain, PLP2. We show that PLP2 cleaves a substrate encoding the first predicted membrane-spanning domain (MP1) of the replicase polyprotein. Cleavage of MP1 and release of a 150-kDa intermediate, p150, are likely to be important for embedding the replicase complex in cellular membranes. Using an antiserum (anti-D11) directed against the C terminus of the MP1 domain, we verified that p150 encompasses the MP1 domain and identified a 44-kDa protein (p44) as a processed product of p150. Pulse-chase experiments showed that p150 is rapidly generated in MHV-infected cells and that p44 is processed from the p150 precursor. Protease inhibitor studies revealed that unlike 3CLpro activity, PLP2 activity is not sensitive to cysteine protease inhibitor E64d. Furthermore, coexpression studies using the PLP2 domain and a substrate encoding the MP1 cleavage site showed that PLP2 acts efficiently in trans. Site-directed mutagenesis studies confirmed the identification of cysteine 1715 as a catalytic residue of PLP2. This study is the first to report enzymatic activity of the PLP2 domain and to demonstrate that three distinct viral proteinase activities process the MHV replicase polyprotein.


title: Advancing availability of papillary muscle sandwich plasty from functional to organic mitral valve regurgitation.

text: An original papillary muscle heads approximation procedure, commonly known as a sandwich plasty, has been successfully used for the treatment of functional mitral regurgitation (MR) associated with ischemic cardiomyopathy (ICM) and aortic valve disease (AVD). In this study, we evaluated the availability of this method as the concomitant procedure for the plasty of organic MR in comparison with the operative results in patients with functional MR. Fifty-six patients who underwent sandwich plasty were reviewed, including 45 functional MR (29 ICM and 16 AVD) patients and 11 organic MR patients. The mean age of patients was 67 years. In the organic MR patients, predominant cardiac diseases were solitary MR in six patients and combined valve diseases including aortic valve stenosis in five. Mitral valve changes included prolapse in six patients and moderate cusp thickening with calcification in five. Two heads of the papillary muscle connecting to the choldae of both the anterior and posterior leaflets are fixed with two teflon-pledgeted 3-0 TiCron™ (Covidien, Dublin, Ireland) sutures in order to achieve coaptation of the two leaflets. Prominent MR was observed in a patient with functional MR after surgery, however residual MR was not detected in organic MR patients. The tenting height (coaptation distance) of mitral valve significantly decreased after surgery from 11±1 to 7±2mm in the organic MR patients, which was similar to the results in the functional MR patients (from 12±2 to 7±2 mm). The postoperative mean mitral orifice area in the organic MR patients was 4.3±0.1cm2 without stenosis. Sandwich plasty reduces the distance of choldae connecting to anterior and posterior leaflets and achieves the better coaptation of two leaflets. This procedure is effective in the treatment of both functional and organic MR.


title: Comparison of bovine coronavirus isolates associated with neonatal calf diarrhoea and winter dysentery in adult dairy cattle in Québec.

text: Cytopathic coronaviruses were isolated in HRT-18 cells from bloody faecal samples collected from cows in Québec dairy herds having experienced typical outbreaks of winter dysentery (WD). The formation of polykaryons in the infected cell cultures was found to be dependent on the presence of trypsin in the medium. The WD isolates differed from the prototype Mebus strain of bovine enteropathogenic coronavirus (BCV.Meb) in respect to haemagglutination inhibition (HI), haemagglutination patterns at 4 degrees C and 37 degrees C, and receptor destroying enzyme activity with rat erythrocytes. Other field strains of BCV associated with outbreaks of neonatal calf diarrhoea (NCD) also differed from the BCV.Meb strain by demonstrating differences in HI. In all cases, no differences were detected by virus neutralization and Western immunoblotting. Analysis and comparison of the nucleotide and deduced amino acid sequences of the PCR-amplified haemagglutinin esterase (HE) genes of one representative WD strain (BCQ.2590) and two highly cytopathic NCD strains (BCQ.3 and BCQ.571) revealed high degrees of similarities (nt and aa sequence homologies > 98%) with the BCV.Meb strain. The putative esterase active site FGDS was conserved among these four BCV strains, indicating that this domain is probably not a determinant for BCV virulence. Six amino acid substitutions occurred between the HE glycoproteins of BCV.Meb and BCQ.2590 strains; two proline substitutions occurred respectively in the signal peptide (at aa 5) and near the sequences of the putative esterase domain (at aa 53).


title: Severe acute respiratory syndrome (SARS) in Hong Kong in 2003: stress and psychological impact among frontline healthcare workers.

text: BACKGROUND The outbreak of severe acute respiratory syndrome (SARS) posed an unprecedented threat and a great challenge to health professionals in Hong Kong. The study reported here aimed at investigating the origin of stress and psychological morbidity among frontline healthcare workers in response to this catastrophe. METHOD Self-administered questionnaires were sent to frontline healthcare workers in three hospitals. The General Health Questionnaire was used to identify psychological distress. Socio-demographic and stress variables were entered into a logistic regression analysis to find out the variables associated with psychological morbidity. RESULTS The response rate was 40 %. Sixty-eight per cent of participants reported a high level of stress. About 57 % were found to have experienced psychological distress. The healthcare workers' psychological morbidity was best understood by the perceptions of personal vulnerability, stress and support in the workplace. CONCLUSION These findings shed light on the need for hospital administrators to be aware of the extent and sources of stress and psychological distress among frontline healthcare workers during disease outbreak.


title: Critical assessment of the diagnostic value of feline alpha1-acid glycoprotein for feline infectious peritonitis using the likelihood ratios approach.

text: Alpha-1-acid glycoprotein (AGP) increases in the blood of cats with feline infectious peritonitis (FIP), a lethal disease caused by feline coronavirus (FCoV). However, the diagnostic potential of AGP might be limited because AGP also increases in pathophysiological conditions other than FIP. In this retrospective study, the diagnostic potential of serum AGP concentration was evaluated on the basis of the pretest probability of disease, according to the Bayesian approach. Serum AGP levels from cats with FIP (group 1; n = 58) and without FIP (group 2; n = 104) were evaluated. Non-FIP cats were further subgrouped as follows: 2a) inflammation (n = 26), 2b) asymptomatic FCoV infection (n = 49), 2c) injection-site sarcoma (n = 19), 2d) postvaccination (n = 7), and 2e) specific pathogen free (n = 3). Standard descriptive analyses by group and empirical receiver-operating characteristic (ROC) curve estimation were performed. Ordinary logistic regression analysis was performed to derive an estimate of the continuous likelihood ratio to produce the posttest probability of disease for any combination of pretest probability and serum AGP value. The comparison of serum AGP levels in the different groups and the analysis of the ROC curve confirmed that serum AGP is a powerful discriminating marker for FIP. The Bayesian approach demonstrated that when the pretest probability of FIP is high, based on history and clinical signs (groups 1 or 2a), moderate serum AGP levels (1.5-2 mg/ml) can discriminate cats with FIP from others, while only high serum AGP levels (>3 mg/ml) can support a diagnosis of FIP in cats with a low pretest probability of disease (groups 2b to 2e).


Successful endoscopic vacuum therapy with new open-pore film drainage in a case of iatrogenic duodenal perforation during ERCP.


title: Joining the dots - understanding the complex interplay between the values we place on wildlife, biodiversity conservation, human and animal health: A review.

text: The value of wildlife has long been ignored or under-rated. However, growing concerns about biodiversity loss and emerging diseases of wildlife origin have enhanced debates about the importance of wildlife. Wildlife-related diseases are viewed through these debates as a potential threat to wildlife conservation and domestic animal and human health. This article provides an overview of the values we place on wildlife (positive: socio-cultural, nutritional, economic, ecological; and negative: damages, health issues) and of the significance of diseases for biodiversity conservation. It shows that the values of wildlife, the emergence of wildlife diseases and biodiversity conservation are closely linked. The article also illustrates why investigations into wildlife diseases are now recognized as an integral part of global health issues. The modern One Health concept requires multi-disciplinary research groups including veterinarians, human physicians, ecologists and other scientists collaborating towards a common goal: prevention of disease emergence and preservation of ecosystems, both of which are essential to protect human life and well-being.


title: A probabilistic transmission dynamic model to assess indoor airborne infection risks.

text: The purpose of this article is to quantify the public health risk associated with inhalation of indoor airborne infection based on a probabilistic transmission dynamic modeling approach. We used the Wells-Riley mathematical model to estimate (1) the CO2 exposure concentrations in indoor environments where cases of inhalation airborne infection occurred based on reported epidemiological data and epidemic curves for influenza and severe acute respiratory syndrome (SARS), (2) the basic reproductive number, R0 (i.e., expected number of secondary cases on the introduction of a single infected individual in a completely susceptible population) and its variability in a shared indoor airspace, and (3) the risk for infection in various scenarios of exposure in a susceptible population for a range of R0. We also employ a standard susceptible-infectious-recovered (SIR) structure to relate Wells-Riley model derived R0 to a transmission parameter to implicate the relationships between indoor carbon dioxide concentration and contact rate. We estimate that a single case of SARS will infect 2.6 secondary cases on average in a population from nosocomial transmission, whereas less than 1 secondary infection was generated per case among school children. We also obtained an estimate of the basic reproductive number for influenza in a commercial airliner: the median value is 10.4. We suggest that improving the building air cleaning rate to lower the critical rebreathed fraction of indoor air can decrease transmission rate. Here, we show that virulence of the organism factors, infectious quantum generation rates (quanta/s by an infected person), and host factors determine the risk for inhalation of indoor airborne infection.


title: Geldanamycin, a ligand of heat shock protein 90, inhibits the replication of herpes simplex virus type 1 in vitro.

text: Geldanamycin (GA) is an antibiotic targeting the ADP/ATP binding site of heat shock protein 90 (Hsp90). In screening for anti-herpes simplex virus type 1 (HSV-1) candidates, we found GA active against HSV-1. HSV-1 replication in vitro was significantly inhibited by GA with an 50% inhibitory concentration of 0.093 microM and a concentration that inhibited cellular growth 50% in comparison with the results seen with untreated controls of 350 microM. The therapeutic index of GA was over 3700 (comparable to the results seen with acyclovir). GA did not inhibit HSV-1 thymidine kinase. Cells infected with HSV-1 demonstrated cell cycle arrest at the G(1)/S transition; however, treatment with GA resulted in a cell cycle distribution pattern identical to that of untreated cells, indicating a restoration of cell growth in HSV-1-infected cells by GA treatment. Accordingly, HSV-1 DNA synthesis was suppressed in HSV-1(+) cells treated with GA. The antiviral mechanism of GA appears to be associated with Hsp90 inactivation and cell cycle restoration, which indicates that GA exhibits broad-spectrum antiviral activity. Indeed, GA exhibited activities in vitro against other viruses, including severe acute respiratory syndrome coronavirus. Since GA inhibits HSV-1 through a cellular mechanism unique among HSV-1 agents, we consider it a new candidate agent for HSV-1.


title: Efficient intratracheal delivery of airway epithelial cells in mice and pigs.

text: Cellular therapy via direct intratracheal delivery has gained interest as a novel therapeutic strategy for treating various pulmonary diseases including cystic fibrosis lung disease. However, concerns such as insufficient cell engraftment in lungs and lack of large animal model data remain to be resolved. This study aimed to establish a simple method for evaluating cell retention in lungs and to develop reproducible approaches for efficient cell delivery into mouse and pig lungs. Human lung epithelial cells including normal human bronchial/tracheal epithelial (NHBE) cells and human lung epithelial cell line A549 were infected with pSicoR-green fluorescent protein (GFP) lentivirus. GFP-labeled NHBE cells were delivered via a modified intratracheal cell instillation method into the lungs of C57BL/6J mice. Two days following cell delivery, GFP ELISA-based assay revealed a substantial cell-retention efficiency (10.48 ± 2.86%, n = 7) in mouse lungs preinjured with 2% polidocanol. When GFP-labeled A549 cells were transplanted into Yorkshire pig lungs with a tracheal intubation fiberscope, a robust initial cell attachment (22.32% efficiency) was observed at 24 h. In addition, a lentiviral vector was developed to induce the overexpression and apical localization of cystic fibrosis transmembrane conductance regulator (CFTR)-GFP fusion proteins in NHBE cells as a means of ex vivo CFTR gene transfer in nonprogenitor (relatively differentiated) lung epithelial cells. These results have demonstrated the convenience and efficiency of direct delivery of exogenous epithelial cells to lungs in mouse and pig models and provided important background for future preclinical evaluation of intratracheal cell transplantation to treat lung diseases.


title: Characterization of the expression and immunogenicity of the ns4b protein of human coronavirus 229E.

text: Sequencing of complementary DNAs prepared from various coronaviruses has revealed open reading frames encoding putative proteins that are yet to be characterized and are so far only described as nonstructural (ns). As a first step in the elucidation of its function, we characterized the expression and immunogenicity of the ns4b gene product from strain 229E of human coronavirus (HCV-229E), a respiratory virus with a neurotropic potential. The gene was cloned and expressed in bacteria. A fusion protein of ns4b with maltose-binding protein was injected into rabbits to generate specific antibodies that were used to demonstrate the expression of ns4b in HCV-229E-infected cells using flow cytometry. Given a previously reported contiguous five amino acid shared region between ns4b and myelin basic protein, a purified recombinant histidine-tagged ns4b protein and (or) human myelin basic protein were injected into mice to evaluate whether myelin-viral protein cross-reactive antibody responses could be generated. Each immunogen induced specific but not cross-reactive antibodies. We conclude that ns4b is expressed in infected cells and is immunogenic, although this does not involve amino acids shared with a self protein, at least in the experimental conditions used.


title: Identification of a novel coronavirus in bats.

text: Exotic wildlife can act as reservoirs of diseases that are endemic in the area or can be the source of new emerging diseases through interspecies transmission. The recent emergence of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) highlights the importance of virus surveillance in wild animals. Here, we report the identification of a novel bat coronavirus through surveillance of coronaviruses in wildlife. Analyses of the RNA sequence from the ORF1b and S-gene regions indicated that the virus is a group 1 coronavirus. The virus was detected in fecal and respiratory samples from three bat species (Miniopterus spp.). In particular, 63% (12 of 19) of fecal samples from Miniopterus pusillus were positive for the virus. These findings suggest that this virus might be commonly circulating in M. pusillus in Hong Kong.


title: No-scar transanal total mesorectal excision: the last step to pure NOTES for colorectal surgery.

text: HYPOTHESIS Because of the concerns over the operative platform, accidental organ injury, and viscerotomy closure, natural orifice transluminal endoscopic surgery (NOTES) currently remains an experimental technique. Transanal NOTES for colorectal surgery overcomes all of these issues; however, all of the reports to date have used hybrid laparoscopic techniques. We demonstrate herein the first case, to our knowledge, of pure transanal NOTES colorectal surgery. DESIGN Case report. SETTING University hospital. PATIENT The patient was a 56-year-old woman with a midrectal neoplasia. INTERVENTION Pure transanal NOTES total mesorectal excision with a coloanal anastomosis and without a diverting stoma. Using a transanal endoscopic operation device as a surgical platform, we created a viscerotomy distal to an endoluminal purse-string suture. We performed a total mesorectal excision using a “bottom-up” approach. The sigmoid colon was mobilized by a posterior, retroperitoneal approach and the colon was divided intraperitoneally. A hand-sewn, side-to-end, coloanal anastomosis was performed. Because the viscerotomy was incorporated into the anastomosis, the concerns of both accidental organ damage and viscerotomy closure were abrogated. RESULTS The procedure was completed entirely by a transanal fashion. We successfully mobilized the rectum, mesorectum, and sigmoid colon. The specimen length was more than 20 cm. The patient required minimal analgesia and her pain was nonabdominal. CONCLUSIONS To our knowledge, the first pure transanal NOTES total mesorectal excision with retroperitoneal sigmoid mobilization and coloanal, side-to-end anastomosis was successfully performed using what we called a peri-rectal oncologic gateway for retroperitoneal endoscopic single site surgery (PROGRESSS). This monumental case could pave the way for a new era in pure transanal NOTES for colorectal surgery.


title: [COVID-19 and kidney disease].

text: Acute kidney injury (AKI), albuminuria and hematuria are common in Covid-19 and have been shown to increase mortality. Assessment with a urinary dipstick and creatinine at admission should be completed with a urinary sediment and quantification of albuminuria if positive. SARS-Cov-2 seems to enter and infect the endothelium and kidney cells, and contributes to damage in addition to hypercoagulability, multi organ failure and hyperinflammation. Underhydration and rhabdomyolysis can contribute to acute tubular necrosis. Anti-inflammatory treatment may be considered and discussed with a nephrologist. Treatment with ACEi/ARBs should be continued if possible.


title: MRI of secondary cervical syringomyelia in four cats.

text: This report describes the use of magnetic resonance imaging (MRI) to diagnose cervical syringomyelia in 4 cats. MRI revealed enlargement of the lateral ventricle in all the cats. Of the 4 cases, MRI revealed herniation of the cerebellum in 3 cats, an isolated fourth ventricle in 1 cat, severe hydrocephalus in 2 cats and brain masses in 1 cat. In this report, the cervical syringomyelia in these cats may have been due to formation of a secondary syrinx (enlargement of the central canal) as a result of blockage of flow in the outlet of the fourth ventricle caused by FIP encephalomyelitis or secondary cerebellar tonsillar herniation caused by increased intracranial pressure due to intracranial masses or may have been due to caudal compression of the cerebellum caused by increased intracranial pressure due to hydrocephalus.


title: Understanding TLR9 action in Epstein-Barr virus infection.

text: The Epstein-Barr virus (EBV) establishes persistent latent infection in peripheral blood memory B cells, may cause infectious mononucleosis, and is associated with cancers including endemic Burkitt's lymphoma (BL). Although latent EBV transforms B cells in vitro, additional factors including immunocompromised status or, as in endemic BL, a co-infection with the malaria parasite Plasmodium falciparum seem to be required for the development of EBV-associated cancers. Toll-like receptors (TLRs) like TLR9 are capable to recognize EBV and launch innate immune responses, which may limit the spread of the virus and may contribute to control outgrowth of latently EBV-infected B cells. On the other hand, EBV may interfere with the expression and functionality of TLR9, thereby manipulating host immune responses towards favoring long-term survival of the virus. Triggering of TLR9 by bacterial, viral or P. falciparum DNA may impact on the proliferation of EBV-infected B cells and on the balance between latent and lytic EBV. Thus, TLR9 signaling in EBV-infected B cells may be beneficial for the host but also for the highly adapted human gammaherpesvirus EBV.


title: MERS-CoV- Low risk to Canadians.

text: Middle East respiratory syndrome - Coronavirus (MERS-CoV) -- is a novel coronavirus that has caused a number of community-acquired cases and health care associated outbreaks in Saudi Arabia and the United Arab Emirates (UAE) as well as sporadic cases in other countries, especially in the Middle East. The evidence to date links MERS-CoV cases with exposure to camels, including camel products or to probable or confirmed human cases of MERS-CoV. It typically presents as an acute respiratory illness and is associated with a 35% mortality rate. Based on available information at this time, the current risk to Canadians for acquiring MERS-CoV infections is considered low. However, the International Health Regulations Committee concerning MERS-CoV has cautioned that the upsurge of cases seen this past spring (2014) may be predictive of an increase in cases related to the Hajj - an annual pilgrimage to Mecca in Saudi Arabia that took place in early October 2014. Although the overall risk is low, the Public Health Agency of Canada and its National Microbiology Laboratory (NML) in close collaboration with provincial and territorial partners, the Canadian Public Health Laboratory Network (CPHLN) and infection prevention and control experts have developed a number of preparedness guidance documents and protocols to address the risk of an imported case of MERS-CoV in Canada.


title: [Investigation of proximal femoral marrow with magnetic resonance imaging in recovered patients with severe acute respiratory syndrome].

text: OBJECTIVE To determine the effect of corticosteroid treatment and severe acute respiratory syndrome (SARS) infection itself on the marrow conversion in the proximal femoral marrow in the recovered patients of health care workers with SARS. METHODS The distribution of proximal femoral marrow on MR imaging of 148 health care workers with recovered SARS including 106 cases treated with varied dosage of steroids and 42 cases without steroid, and 97 age and sex matched health adults as controls were observed. The index of marrow conversion (signal intensity of the femoral neck and intertrochanteric area divided by signal intensity of the greater trochanter multiplied by 100%) was quantitatively measured and compared between SARS patients treated with steroid and without steroid and the normal control group. RESULTS In 106 cases treated with steroid of the 148 health care workers, femoral head osteonecrosis was found in 4 cases, bilateral femoral marrow edema in 2 cases, femoral marrow infarction in 1 case. The index of marrow conversion in the normal controls, in SARS patients treated without and with steroids was (79.4 +/- 6.8)%, (86.9 +/- 7.4)%, (88.6 +/- 5.9)%, respectively. There was significantly statistical difference between groups (P < 0.05). CONCLUSION In addition to fat conversion in the proximal femoral marrow due to steroid treatment, the infection of SARS itself may promote an excessively conversion of the red marrow to yellow marrow of the femoral neck in SARS patients.


Were Eli Lilly unaware of this study?


Susceptibility of murine CNS to OC43 infection.


title: Illegal import of bushmeat and other meat products into Switzerland on commercial passenger flights.

text: Illegal imports of meat can present substantial risks to public and animal health. Several European countries have reported considerable quantities of meat imported on commercial passenger flights. The objective of this study was to estimate the quantity of meat illegally imported into Switzerland, with a separate estimation for bushmeat. Data were obtained by participation in intervention exercises at Swiss international airports and by analysing data on seizures during the four-year period 2008 to 2011. The study revealed that a wide array of animal species was imported into Switzerland. From the database, the average annual weight of meat seized during the period analysed was 5.5 tonnes, of which 1.4% was bushmeat. However, in a stochastic model the total annual inflow of illegal meat imports was estimated at 1,013 tonnes (95% CI 226 to 4,192) for meat and 8.6 tonnes (95% CI 0.8 to 68.8) for bushmeat. Thus, even for a small European country such as Switzerland the quantities of illegally imported meat and meat products are substantial and the consequences for public and animal health could be high. To reduce the risk, it is essential that surveillance at European airports is harmonised and that passenger information campaigns clarify the consequences of the illegal import of meat, particularly bushmeat.


Integrons in Salmonella Keurmassar, Senegal.


title: The S protein of bovine coronavirus is a hemagglutinin recognizing 9-O-acetylated sialic acid as a receptor determinant.

text: The S protein of bovine coronavirus (BCV) has been isolated from the viral membrane and purified by gradient centrifugation. Purified S protein was identified as a viral hemagglutinin. Inactivation of the cellular receptors by sialate 9-O-acetylesterase and generation of receptors by sialylation of erythrocytes with N-acetyl-9-O-acetylneuraminic acid (Neu5,9Ac2) indicate that S protein recognizes 9-O-acetylated sialic acid as a receptor determinant as has been shown previously for intact virions. The second glycoprotein of BCV, HE, which has been thought previously to be responsible for the hemagglutinating activity of BCV, is a less efficient hemagglutinin; it agglutinates mouse and rat erythrocytes, but in contrast to S protein, it is unable to agglutinate chicken erythrocytes, which contain a lower level of Neu5,9Ac2 on their surface. S protein is proposed to be responsible for the primary attachment of virus to cell surface. S protein is proposed to be responsible for the primary attachement of virus to cell surface receptors. The potential of S protein as a probe for the detection of Neu5,9Ac2-containing glycoconjugates is demonstrated.


title: Isolation prevalence of pulmonary nontuberculous mycobacteria in Ontario in 2007.

text: BACKGROUND The reported prevalence of pulmonary nontuberculous mycobacteria (NTM) infections is increasing. OBJECTIVE To determine the 'isolation prevalence' of NTM in 2007 and compare it with previously published research that examined the increasing rates of isolation of NTM from clinical pulmonary specimens between 1997 and 2003. METHODS Isolation prevalence was investigated retrospectively by reviewing a cohort of all positive pulmonary NTM culture results from the Tuberculosis and Mycobacteriology Laboratory, Public Health Laboratory (Toronto, Ontario) in 2007, which identifies at least 95% of NTM isolates in Ontario. Isolation prevalence was calculated as the number of persons with a pulmonary isolate in a calendar year divided by the contemporary population and expressed per 100,000 population. Changes in isolation prevalence from previous years were assessed for statistical significance using generalized linear models with a negative binomial distribution. RESULTS In 2007, 4160 pulmonary isolates of NTM were collected from 2463 patients. The isolation prevalence of all species (excluding Mycobacterium gordonae) was 19 per 100,000 population in 2007 - an increase from previous observations reported for Ontario - corresponding to an average annual increase of 8.5% from 1997 to 2007 (P<0.0001). Average annual increases in isolation prevalence of Mycobacterium avium complex (8.8%, P<0.0001) and Mycobacterium xenopi (7.3%, P=0.0005) were largely responsible for the overall increase, while prevalence rates of rapidly growing mycobacteria remained relatively stable. CONCLUSION The isolation prevalence of pulmonary NTM continues to increase significantly in Ontario, supporting the belief that pulmonary NTM disease is increasingly common.


title: Advancing the field of lung stem cell biology.

text: The adult mammalian lung is a beautifully complex, integrated system of numerous types of epithelial cells, supporting cells and matrix that synergize to make gas exchange possible. Recent identification of putative endogenous and extrinsic lung stem cell populations has added to the diversity of the respiratory system. Despite these new studies and data from years of analyses of lung injury models, careful cellular and molecular analyses are needed to further define the stem and differentiated cells in the pulmonary system. New tools enabling lineage tracing or transplantation in adult lung as well as understanding the key microenvironmental clues that control the response to lung injury will be important to advance the field of lung stem cell biology.


title: SARS Web information.

text: Where to find current information about Severe Acute Respiratory Syndrome (SARS), a new disease that can cause severe or fatal pneumonia.


title: Recurring and emerging questions related to management of HIV-related opportunistic infections.

text: The incidence of HIV-related opportunistic infections (OIs) has dramatically declined with the ability to achieve viral suppression and immune reconstitution with potent antiretroviral therapy. However, a large number of patients remain at risk for OIs because they are diagnosed at late stages of HIV disease, fail to stay in treatment, or fail to maintain viral suppression. Clinicians should remain vigilant for OIs and for changes in recommended management strategies. Issues that often arise in this regard include how to interpret polymerase chain reaction diagnostic results in individuals with HIV infection; whether primary prophylaxis for Mycobacterium avium complex is still needed; whether clinicians should screen asymptomatic patients for cryptococcal antigen; and need for amphotericin B in treatment regimens for cryptococcal meningitis. This article summarizes a presentation by Henry Masur, MD, at the IAS-USA continuing education program held in Washington, DC, in April 2018.


title: [Retrospective analysis of the corticosteroids treatment on severe acute respiratory syndrome (SARS)].

text: OBJECTIVE To analyze the usage of corticosteroids in the treatment of SARS. METHODS The usage of corticosteroids in 43 SARS patients were reviewed. The initial dosage and the highest dosage of prednisolone were investigated. RESULTS According to the dosage of the early 3 days, the initial dosage was calculated. The initial methyprednisonlone dosage was (170.82 +/- 15.89) mg.d-1, from 48 to 500 mg.d-1. The maximal dosage was (291.44 +/- 37.63) mg.d-1 (48-800 mg.d-1). Four patients recovered without corticosteroides therapy. Initial therapy was kept in 25 cases. Two had hyperglycemia, one of whom died of hyperosmotic coma and renal failure. 14 cases were not responsive and needed to increase the dosage of corticosteroids. 9 of them accepted pulse dosage therapy and acquired good outcome. None in the group had significant side effect. The severity of patients of the two groups had no significant difference. Those of nonresponsiveness had higher dosage and needed longer time to reach stable. CONCLUSION Sub-pulse dosage of methyprednisolone was effective for most SARS patients. Those who were less responsiveness might due to their poor sensitiveness to corticosteroids instead of SARS severity. Pulse treatment might be safe in carefully selected patients.


title: Effectiveness of an Electronic Alert for Hypotension and Low Bispectral Index on 90-day Postoperative Mortality: A Prospective, Randomized Trial.

text: BACKGROUND We tested the hypothesis that an electronic alert for a "double low" of mean arterial pressure less than 75 mmHg and a bispectral index less than 45 reduces the primary outcome of 90-day mortality. METHODS Adults having noncardiac surgery were randomized to receive either intraoperative alerts for double-low events or no alerts. Anesthesiologists were not blinded and not required to alter care based upon the alerts. The primary outcome was all-cause 90-day mortality. RESULTS Patients (20,239) were randomized over 33 months, and 19,092 were analyzed. After adjusting for age, comorbidities, and perioperative factors, patients with more than 60 min of cumulative double-low time were twice as likely to die (hazard ratio, 1.99; 95% CI, 1.2 to 3.2; P = 0.005). The median number of double-low minutes (quartiles) was only slightly lower in the alert arm: 10 (2 to 30) versus 12 (2 to 34) min. Ninety-day mortality was 135 (1.4%) in the alert arm and 123 (1.3%) in the control arm. The difference in percent mortality was 0.18% (99% CI, -0.25 to 0.61). CONCLUSIONS Ninety-day mortality was not significantly lower in patients cared for by anesthesiologists who received automated alerts to double-low states. Prolonged cumulative double-low conditions were strongly associated with mortality.


Is the 110K glycoprotein the only receptor for MHV and does its expression determine species specificity?


docid: wavtsgmw

title: Three new isolates of porcine respiratory coronavirus with various pathogenicities and spike (S) gene deletions.

text: Three new isolates of porcine respiratory coronavirus (PRCV) were isolated and partially characterized. These PRCV isolates showed a selective tropism for respiratory tissue and were antigenically related to transmissible gastroenteritis virus. PCR amplification of the 5' half of the spike (S) genes of the three PRCV isolates indicated that a large deletion, characteristic of PRCV, was present. By using cDNA probes specific for the transmissible gastroenteritis virus S gene, the PCR products were shown to be specific in a Southern blot. The three new PRCV isolates were shown to vary in S gene deletion size. In a separate study, these isolates have also been shown to vary in pathogenicity. These new PRCV isolates should serve as important tools in gaining a better understanding of the pathogenesis of coronavirus infections.


docid: cprxzlii

title: Effects of RNA interference of Atg4B on the limited proteolysis of LC3 in PC12 cells and expression of Atg4B in various rat tissues.

text: Atg4B, a mammalian homologue of yeast Atg4, has been shown to play an important role in the processing of LC3, a mammalian homologue of yeast Atg8, but the tissue distribution of Atg4B remains unknown. To better understand the role of Atg4B in rat tissue cells, we prepared antibodies against Atg4B, and PC12 cells in which the expression of Atg4B was knocked down by RNA interference. In the RNA interference-treated PC12 cells, for which the expression of Atg4B was 10% of wild-type PC12 cells, the expression of cytosolic LC3-I was similar to that in wild-type cells. Knockdown cell lysates, however, suppressed the cleavage of recombinant proLC3 to LC3-I. Moreover, the expression of Atg4B protein and mRNA was ubiquitous in rat tissues; however, the expression levels were not identical, but were dependent on the tissue, with the expression high in brain and testicular tissue, and low in muscular and heart tissue. In brain tissue, the expression of Atg4B protein and mRNA was higher in neurons, especially in the cerebellum and olfactory bulb, as evidenced by immunohistochemistry and in situ hybridization. These lines of evidence suggest that Atg4B plays a major role in the processing of LC3 and is widely distributed in rat tissues. In particular, in brain tissues, autophagy may be deeply associated with the metabolism of neurons, especially in the cerebellum.


title: Healthy workplaces: the case for shared clinical decision making and increased full-time employment.

text: Today, healthy work environments are recognized as essential to attain positive experiences and optimal clinical outcomes for patients, the well-being of healthcare providers and organizational effectiveness. Creating such environments is both a collective and an individual responsibility. It requires each of us to move away from the rhetoric, abandon our comfort zones and territorialities, adopt new evidence, and fully embrace the collective good. This commentary builds on the two excellent papers on this issue (Shamian and El-Jardali, and Clements, Dault and Priest), and adds two new necessary elements to build healthy workplaces and productive teamwork. The first is shared clinical decision making, the most substantive form of teamwork, and a necessary condition to build healthy work environments and deliver optimal patient care. The second is employment status: we cannot achieve healthy work environments and optimal teamwork with overreliance on part-time, casual or agency employment. The key premise for Ontario's 70% full-time employment policy is based on the fact that such a percentage is a necessary, minimal condition to ensure continuity of care and caregiver for patients, and continuity of relationships for our teams.


Phaeohyphomycotic ependymitis in a cat.


title: In the path of disasters: psychosocial issues for preparedness, response, and recovery.

text: The psychosocial impacts of disasters are profound. In recent years, there have been too many reminders of these impacts and the dire needs of the people involved. The purpose of this article is to present the following themes from the psychosocial literature on disasters and emergency management: (1) differential impacts of disasters according to gender and age; (2) prevention efforts to reduce racial discrimination, rape, and other forms of abuse; (3) readiness for cultural change toward prevention and preparedness; and (4) the need to involve aid beneficiaries as active partners in relief strategies, particularly during reconstruction of communities and critical systems. Psychosocial needs change throughout the disaster cycle, particularly as social support deteriorates over time. It is important to anticipate what psychosocial needs of the public, emergency responders, support staff, and volunteers might emerge, before advancing to the next stage of the disaster. Particular consideration needs to be directed toward differential impacts of disasters based on gender, age, and other vulnerabilities.


Antibody levels in milk of vaccinated and unvaccinated cows against organisms of neonatal diarrhoea.


title: Structural polypeptides of the murine coronavirus JHM.

text: Analysis by SDS-polyacrylamide gel electrophoresis shows that the purified coronavirus JHM contains six polypeptides. The apparent mol. wt. of the polypeptides (GP1, GP2, GP3, VP4, GP5 and VP6) are 170000; 125000; 97500; 60800; 24800 and 22700, respectively. Four polypeptides are glycosylated (GP1, GP2, GP3 and GP5). The analysis of particles obtained after limited proteolysis with pronase suggests that GP2 and GP3 are protruding from the lipid envelope and, together with GP1, form the spike layer. Protein VP6 and a part of GP5 are located within the lipid bilayer. Protein VP4 is susceptible to digestion at a concentration of pronase which changes the morphology of the virus particles making the interior of the virus accessible. Subviral particles produced after treatment with the detergent Nonidet P40 banded at a higher density than the virus and contained only VP4, GP5 and VP6.


title: Role of cell surface spikes in alphavirus budding.

text: Alphaviruses mature by budding at cell surfaces. According to a prevailing hypothesis, the viral membrane protein, which is a heterodimeric protein unit, is transported to the plasma membrane (PM), where it awaits binding to the viral nucleocapsid (NC). This hypothesis predicts that the viral membrane protein heterodimers accumulate at the cell surface when expressed in the absence of NCs. We have tested this prediction by analyzing the spike protein expression phenotype of a Semliki Forest virus (SFV) variant which contains a capsid gene deletion. We found that viral membrane protein heterodimers were formed and transported to the cell surface normally. However, instead of accumulating at the PM as expected, the membrane proteins were rapidly degraded. In the case of the E1 subunit, degradation resulted in the release of a soluble E1 fragment into the medium. The fact that this pathway of protein degradation is mostly inhibited during wild-type virus infection suggests that viral membrane proteins are very efficiently captured by NCs into budding complexes and that normally no sizeable pool of free membrane protein complexes exists at the PM.


title: RNA helicase activity of the plant virus movement proteins encoded by the first gene of the triple gene block.

text: Cell-to-cell and long-distance transport of some plant viruses requires coordinated action of three movement proteins encoded by triple gene block (TGB). The largest of TGB proteins, TGBp1, is a member of the superfamily I of DNA/RNA helicases and possesses a set of conserved helicase sequence motifs necessary for virus movement. A recombinant His-tagged form of TGBp1 of two hordeiviruses and potato virus X, a potexvirus, produced in Escherichia coli had unwinding activity on a partially duplexed RNA, but not DNA substrate. The helicase activity of these proteins was dependent on Mg2+ and ATP. The isolated C-terminal half of the PSLV TGBp1 retaining all helicase motifs was also able to unwind RNA duplex.


title: Virological and serological studies of porcine respiratory coronavirus infection on a Japanese farm.

text: We detected transmissible gastroenteritis virus (TGEV) antibodies in pig farms in Tochigi prefecture, although the farms had no past record of TGEV vaccination or TGE. Among the farms, Farm A showed a high antibody incidence. We could not confirm if either TGEV or porcine respiratory coronavirus (PRCV) induced the antibodies, since conventional tests failed to discriminate PRCV from TGEV. Therefore, we conducted virological and serological examinations of this farm for 4 years to establish the etiology - TGEV or PRCV. Although no TGEV was detected, PRCVs were isolated from the nasal samples of pigs. Using a commercial ELISA kit, it was found that the antibodies detected in pigs of all the raising stages and sows were raised against PRCV but not TGEV. The phylogenetic analysis of the nucleotide sequences of the isolates showed that they were closely related to each other, and formed a separate cluster apart from the U.S.A. and European strains. In Cesarean-derived, colostrums-deprived piglets inoculated with a PRCV isolate, no clinical signs were seen, and the viruses were mainly isolated from the nasal samples. Moreover, viral genes were detected from the nasal sample of the contact pig. The result suggested that PRCV infection was located in the nasal cavity of pigs, and horizontal transmission easily occurs. From these results, PRCVs with different origins from the exotic PRCVs might be prevalent in pig farms in Japan.


docid: ggqbslll

title: Diaphragmatic herniation following esophagogastric resectional surgery: an increasing problem with minimally invasive techniques? : Post-operative diaphragmatic hernias.

text: BACKGROUND Post-operative diaphragmatic hernias (PODHs) are serious complications following esophagectomy or total gastrectomy. The aim of this study was to describe and compare the incidence of PODHs at a high volume center over time and analyze the outcomes of patients who develop a PODH. METHODS A prospective database of all resectional esophagogastric operations performed for cancer between January 2001 and December 2015 was analyzed. Patients diagnosed with PODH were identified and data extracted regarding demographics, details of initial resection, pathology, PODH symptoms, diagnosis and treatment. RESULTS Out of 631 patients who had hiatal dissection for malignancy, 35 patients developed of PODH (5.5 % overall incidence). Median age was 66 (range 23-87) years. The incidence of PODH in each operation type was: 2 % (4/221) following an open 2 or 3 stage esophagectomy, 10 % (22/212) following laparoscopic hybrid esophagectomy, 7 % (5/73) following MIO, and 3 % (4/125) following total gastrectomy. The majority of patients had colon or small bowel in a left-sided hernia. Of the 35 patients who developed a PODH, 20 (57 %) patients required emergency surgery, whereas 15 (43 %) had non-urgent repair. The majority of the patients had had suture repair (n = 24) or mesh repair (n = 7) of the diaphragmatic defect. Four patients were treated non-operatively. In hospital post-operative mortality was 20 % (4/20) in the emergency group and 0 % (0/15) in the elective group. Further hernia recurrence affected seven patients (n = 7/27, 26 %) and 4 of these patients (15 %) presented with multiple recurrences. CONCLUSION PODH is a common complication following hybrid esophagectomy and MIO. Given the high mortality from emergency repair, careful thought is needed to identify surgical techniques to prevent PODH forming when minimal access esophagectomy are performed. Upper GI surgeons need to have a low index of suspicion to investigate and treat patients for this complication.


title: Bovine virus diarrhoea-mucosal disease: prevalence, epizootiology and control measures in the USSR.

text: Bovine virus diarrhoea-mucosal disease was described for the first time in the USSR in 1967. The disease occurs in 20 to 80% of farms, depending on geographic and climatic zones of the country. Control measures against the disease include quarantine restrictions and prevention by means of specific preparations of active and passive effect. Passive prophylaxis is conducted by aerosol methods for groups and individuals.


docid: pjnvgwgj

title: Screening for fever by remote-sensing infrared thermographic camera.

text: BACKGROUND Following the severe acute respiratory syndrome (SARS) outbreak, remote-sensing infrared thermography (IRT) has been advocated as a possible means of screening for fever in travelers at airports and border crossings, but its applicability has not been established. We therefore set out to evaluate (1) the feasibility of IRT imaging to identify subjects with fever, and (2) the optimal instrumental configuration and validity for such testing. METHODS Over a 20-day inclusive period, 176 subjects (49 hospital inpatients without SARS or suspected SARS, 99 health clinic attendees and 28 healthy volunteers) were recruited. Remotely sensed IRT readings were obtained from various parts of the front and side of the face (at distances of 1.5 and 0.5 m), and compared to concurrently determined body temperature measurements using conventional means (aural tympanic IRT and oral mercury thermometry). The resulting data were submitted to linear regression/correlation and sensitivity analyses. All recruits gave prior informed consent and our Faculty Institutional Review Board approved the protocol. RESULTS Optimal correlations were found between conventionally measured body temperatures and IRT readings from (1) the front of the face at 1.5m with the mouth open (r=0.80), (2) the ear at 0.5 m (r=0.79), and (3) the side of the face at 1.5m (r=0.76). Average IRT readings from the forehead and elsewhere were 1 degrees C to 2 degrees C lower and correlated less well. Ear IRT readings at 0.5 m yielded the narrowest confidence intervals and could be used to predict conventional body temperature readings of < or = 38 degrees C with a sensitivity and specificity of 83% and 88% respectively. CONCLUSIONS IRT readings from the side of the face, especially from the ear at 0.5 m, yielded the most reliable, precise and consistent estimates of conventionally determined body temperatures. Our results have important implications for walk-through IRT scanning/screening systems at airports and border crossings, particularly as the point prevalence of fever in such subjects would be very low.


title: Predictive factors for diabetes remission after bariatric surgery

text: Background Bariatric surgery has been shown to induce type 2 diabetes mellitus (T2DM) remission in severely obese patients. After laparoscopic Roux-en-Y gastric bypass (LRYGB), diabetes remission occurs early and independently of weight loss. Previous research has identified preoperative factors for remission, such as duration of diabetes and HbA1c. Understanding factors that predict diabetes remission can help to select patients who will benefit most from bariatric surgery. Methods We retrospectively reviewed all T2DM patients who underwent laparoscopic sleeve gastrectomy (LSG) or LRYGB between January 2008 and July 2014. The primary outcome was diabetes remission, defined as the absence of hypoglycemic medications, fasting blood glucose < 7.0 mmol/L and HbA1c < 6.5%. Data were analyzed using multivariable logistic regression analysis to identify predictive factors of diabetes remission. Results We included 207 patients in this analysis; 84 (40.6%) had LSG and 123 (59.4%) had LRYGB. Half of the patients (49.8%) achieved diabetes remission at 1 year. Multivariable logistic analysis showed that LRYGB had higher odds of diabetes remission than LSG (odds ratio [OR] 6.58, 95% confidence interval [CI] 2.79–15.50, p < 0.001). Shorter duration of diabetes (OR 0.91, 95% CI 0.83–0.99, p = 0.032) and the absence of long-acting insulin (OR 0.0011, 95% CI < 0.000–0.236, p = 0.013) predicted remission. Conclusion Type of bariatric procedure (LRYGB v. LSG), shorter duration of diabetes and the absence of long-acting insulin were independent predictors of diabetes remission after bariatric surgery.


title: [Ultrastructural changes in the cells of human embryo lung fibroblasts in the reproduction of the coronavirus HCoV/SPb/01/03].

text: The reproduction of the new coronavirus HCoV/SPb/01/03 in the cultured human embryo lung fibroblasts (HELFBs) was electron microscopically studied. The virus was shown to replicate in the cultured HELFBs, by using for this a cell membrane system and causing profound changes in its morphology. After 24 hours of cell infection, there were mature and defective HCoVISPb/01/03 virions were detected in the vacuoles near the peripheral cisterns of the Golgi apparatus. Some of the vacuoles contained folded membranous structures along with virions.


title: Diffuse alveolar damage in a young cat.

text: A 10-month-old cat was diagnosed with congenital subvalvular aortic stenosis. To resolve its hypoxia, oxygen therapy was administered a couple of times a week during two months. The oxygen partial pressure in the chamber was maintained between 30 and 35%, and the time for one procedure was 12-24 hr. The animal died due to severe respiratory failure. At necropsy, the lungs were voluminous and had a rubbery texture. Histologically, large type II pneumocytes with occasional atypia had diffusely proliferated within the lungs. Interstitial fibrosis was not observed, although some alveolar septa were thickened along with fibrinous exudates and neutrophilic infiltration. The histology of these lesions was consistent with diffuse alveolar damage (DAD), which might have been partially due to oxygen toxicity.


title: CURB-65, PSI, and APACHE II to assess mortality risk in patients with severe sepsis and community acquired pneumonia in PROWESS.

text: BACKGROUND Patients with community-acquired pneumonia (CAP) comprised 35.6% of the overall phase 3 Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study and 33.1% of the placebo arm. We investigated the use of CURB-65, the Pneumonia Severity Index (PSI), and Acute Physiology and Chronic Health Evaluation II (APACHE II) prediction scores to identify the CAP population from the PROWESS placebo arm at the greatest mortality risk. METHODS Patients were classified as having CAP if the lung was the primary infection site and the patient originated from home. The abilities of CURB-65, PSI, and APACHE II scores to determine the 28-day and in-hospital mortality were compared using receiver operator characteristic (ROC) curves and the associated areas under the curve. RESULTS PROWESS enrolled 278 patients with CAP in the placebo arm. The areas under the ROC curves for PSI = 5, CURB-65 ≥ 3, and APACHE II ≥ 25 for predicting 28-day (c = 0.65, 0.66, and 0.64, respectively) and in-hospital mortality (c = 0.65, 0.65, and 0.64, respectively) were not statistically different from each other. The 28-day mortality of patients with a PSI score of 5, CURB-65 ≥ 3, and APACHE II ≥ 25 was 41.6%, 37.9%, and 43.5%, respectively. CONCLUSIONS Despite early diagnosis and appropriate antibiotic therapy, conventionally treated CAP with PSI = 5, CURB-65 3, or APACHE II 25 has an unacceptably high mortality. In this study, PSI, CURB-65, and APACHE II scoring systems perform similarly in predicting the 28-day and in-hospital mortality; however, differences in the categorization of severe CAP were observed and there was a significant mortality in patients with a CURB-65 <3 and PSI <5.


Welcome to the genomic era.


title: Transparency during public health emergencies: from rhetoric to reality.

text: Effective management of public health emergencies demands open and transparent public communication. The rationale for transparency has public health, strategic and ethical dimensions. Despite this, government authorities often fail to demonstrate transparency. A key step in bridging the gap between the rhetoric and reality is to define and codify transparency to put in place practical mechanisms to encourage open public health communication for emergencies. The authors demonstrate this approach using the example of the development and implementation process of a public health emergency information policy.


title: Attachment and internalization of feline infectious peritonitis virus in feline blood monocytes and Crandell feline kidney cells.

text: In this study, kinetics of attachment and internalization of feline infectious peritonitis virus (FIPV) serotype I strain Black and serotype II strain 79-1146 were determined in feline monocytes from two cats and in Crandell feline kidney (CrFK) cells. Attached FIPV I (Black) particles were observed on almost all monocytes. Within 1 h, 17 particles were bound per cell and, within 1 min, 89 % of the bound particles were internalized. For FIPV II (79-1146), attachment was observed on 66 and 95 % of all monocytes from the two cats. After 1 h, respectively five and 20 particles were bound per cell (all cells considered). Within 1 min, 60 % of the bound particles were internalized. Internalization in monocytes was efficient and proceeded via endocytosis. In CrFK cells, attachment and internalization were less efficient, especially for FIPV I (Black), so this cell line is not suitable for studying FIPV entry.


COVID-19 and vitamin D deficiency, a fatal combination?


docid: kmgforkj

title: Recommendations for the health monitoring of rodent and rabbit colonies in breeding and experimental units.


title: Cessation of feline calicivirus shedding coincident with resolution of chronic gingivostomatitis in a cat.

text: Feline calicivirus (FCV) shedding and oral bacterial flora were monitored over a period of 22 months in a case of feline gingivostomatitis (FGS). The cat was treated daily with 50 mg thalidomide capsules by mouth, and 200 mg lactoferrin powder was applied directly to the lesions. Clinical signs began to resolve after 11 months when, in addition to treatment, the diet had been changed to an additive-free cat food supplemented with antioxidant vitamins A, D3 and E. Resolution of clinical signs of FGS coincided with the cessation of FCV shedding, and this is the first report documenting such an association. Which part of the treatment, if any, contributed to the cure requires further investigation.


title: Characterization of the structural proteins of the murine coronavirus strain A59 using monoclonal antibodies.

text: Monoclonal antibodies reacting with the A59 strain of mouse hepatitis virus (MHV-A59) were characterized and those specific to the E2 major envelope glycoprotein were studied in detail. Antibodies were tested for their ability to neutralize viral infectivity (N+ characteristic) and prevent viral-induced cell-to-cell fusion (F+ characteristic). All four possible combinations of activities reflecting E2 functions were found, i.e., N+F+, N-F-, N+F-, and N-F+. In addition, competitive binding studies with these monoclonal antibodies revealed two nonoverlapping antigenic regions. The first region, designated A, was recognized by antibodies which included each of the four functional types. Region B was identified by a single monoclonal antibody with N-F- activities. The existence of antibodies which only neutralize virus or only block viral-induced fusion implies that the structures on E2 which serve as targets for neutralization and which induce fusion are not identical. The critical determinants for neutralization and fusion must be closely related topographically on E2 since both N+F- and N-F+ antibodies recognize the same antigenic region.


title: Understanding PACS development in context: the case of China.

text: This paper describes the evolution of picture archiving and communication systems (PACS) in China and identifies several obstacles to its development, including vendors' opportunism, hospital administrators' IT ignorance, mindlessness in IT adoption, lack of system integration, and misfits between foreign PACS and local hospitals. Lessons learned from these obstacles are provided, which are of value to developing countries where PACS has just started diffusing.


title: Signal recognition particle-dependent insertion of coronavirus E1, an intracellular membrane glycoprotein.

text: The membrane insertion of the E1 protein of a coronavirus, mouse hepatitis virus A59, was studied in a wheat germ cell-free translation system. E1 is a transmembrane protein spanning the lipid bilayer several times. It is synthesized without a cleavable signal sequence, localized intracellularly, and not transported to the cell surface. It thus represents a model intracellular protein. We found that the synthesis of E1 is specifically and stably blocked by the addition of signal recognition particle to the wheat germ system. Subsequent addition of salt-extracted pancreatic microsomes resulted in the full release of this arrest as well as the completion and the correct membrane integration of E1. Such signal recognition particle-induced arrests failed to produce shorter peptides of a defined length. Addition of signal recognition particle to a synchronized translation at any time during the synthesis of about the first two thirds of E1 (150 amino acids) blocked further translation, suggesting that the most C-terminal of the three internal hydrophobic domains of E1 could function as its signal sequence.


Structuring information and incentives to improve health.


title: Proteolytic cleavage of the murine coronavirus surface glycoprotein is not required for fusion activity.

text: A cDNA copy of the murine coronavirus [otherwise known as murine hepatitis virus (MHV)] surface (S) glycoprotein gene was isolated and expressed in DBT cells by using a recombinant vaccinia virus system. The expressed S protein induced extensive syncytium formation at neutral pH. Oligonucleotide mutagenesis was used to engineer an S protein gene in which codons for the proteolytic cleavage site, Arg-Arg-Ala-Arg-Arg, were replaced with an equal number of codons for amino acids with aliphatic or aliphatic hydroxyl side-chains. The mutated S protein was stably expressed in DBT cells and, in contrast to the wild-type protein, was not proteolytically cleaved. Nevertheless, the non-cleaved protein induced extensive syncytium formation. These results clearly indicate that the non-cleaved form of the MHV S protein is able to mediate cell membrane fusion. Thus proteolytic cleavage is not an absolute requirement for fusion activity.


title: Survival characteristics of airborne human coronavirus 229E.

text: The survival of airborne human coronavirus 229E (HCV/229E) was studied under different conditions of temperature (20 +/- 1 degree C and 6 +/- 1 degree C) and low (30 +/- 5%), medium (50 +/- 5%) or high (80 +/- 5%) relative humidities (RH). At 20 +/- 1 degree C, aerosolized HCV/229E was found to survive best at 50% RH with a half-life of 67.33 +/- 8.24 h while at 30% RH the virus half-life was 26.76 +/- 6.21 h. At 50% RH nearly 20% infectious virus was still detectable at 6 days. High RH at 20 +/- 1 degree C, on the other hand, was found to be the least favourable to the survival of aerosolized virus and under these conditions the virus half-life was only about 3 h; no virus could be detected after 24 h in aerosol. At 6 +/- 1 degree C, in either 50% or 30% RH conditions, the survival of HCV/229E was significantly enhanced, with the decay pattern essentially similar to that seen at 20 +/- 1 degree C. At low temperature and high RH (80%), however, the survival pattern was completely reversed, with the HCV/229E half-life increasing to 86.01 +/- 5.28 h, nearly 30 times that found at 20 +/- 1 degree C and high RH. Although optimal survival at 6 degree C still occurred at 50% RH, the pronounced stabilizing effect of low temperature on the survival of HCV/229E at high RH indicates that the role of the environment on the survival of viruses in air may be more complex and significant than previously thought.


title: Characterization of a murine coronavirus defective interfering RNA internal cis-acting replication signal.

text: The mouse hepatitis virus (MHV) sequences required for replication of the JHM strain of MHV defective interfering (DI) RNA consist of three discontinuous genomic regions: about 0.47 kb from both terminal sequences and a 0.13-kb internal region present at about 0.9 kb from the 5' end of the DI genome. In this study, we investigated the role of the internal 0.13-kb region in MHV RNA replication. Overall sequences of the 0.13-kb regions from various MHV strains were similar to each other, with nucleotide substitutions in some strains; MHV-A59 was exceptional, with three nucleotide deletions. Computer-based secondary-structure analysis of the 0.13-kb region in the positive strand revealed that most of the MHV strains formed the same or a similar main stem-loop structure, whereas only MHV-A59 formed a smaller main stem-loop structure. The RNA secondary structures in the negative strands were much less uniform among the MHV strains. A series of DI RNAs that contained MHV-JHM-derived 5'- and 3'-terminal sequences plus internal 0.13-kb regions derived from various MHV strains were constructed. Most of these DI RNAs replicated in MHV-infected cells, except that MRP-A59, with a 0.13-kb region derived from MHV-A59, failed to replicate. Interestingly, replication of MRP-A59 was temperature dependent; it occurred at 39.5 degrees C but not at 37 or 35 degrees C, whereas a DI RNA with an MHV-JHM-derived 0.13-kb region replicated at all three temperatures. At 37 degrees C, synthesis of MRP-A59 negative-strand RNA was detected in MHV-infected and MRP-A59 RNA-transfected cells. Another DI RNA with the internal 0.13-kb region deleted also synthesized negative-strand RNA in MHV-infected cells. MRP-A59-transfected cells were shifted from 39.5 to 37 degrees C at 5.5 h postinfection, a time when most MHV negative-strand RNAs have already accumulated; after the shift, MRP-A59 positive-strand RNA synthesis ceased. The minimum sequence required for maintenance of the positive-strand major stem-loop structure and biological function of the MHV-JHM 0.13-kb region was about 57 nucleotides. Function was lost in the 50-nucleotide sequence that formed a positive-strand stem-loop structure identical to that of MHV-A59. These studies suggested that the RNA structure made by the internal sequence was important for positive-strand MHV RNA synthesis.


title: Outbreak of Shiga toxin-producing Escherichia coli O111 infections associated with a correctional facility dairy - Colorado, 2010.

text: On April 20, 2010, the Colorado Department of Public Health and Environment (CDPHE) was notified by correctional authorities regarding three inmates with bloody diarrhea at a minimum-security correctional facility. The facility, which houses approximately 500 inmates, is a designated work center where inmates are employed or receive vocational training. Approximately 70 inmates work at an onsite dairy, which provides milk to all state-run correctional facilities in Colorado. CDPHE immediately began an investigation and was later assisted by the High Plains Intermountain Center for Agricultural Health and Safety at Colorado State University and by CDC. This report describes the results of the investigation, which determined that the illnesses were caused by Shiga toxin-producing Escherichia coli O111 (STEC O111) infections. During April-July, 10 inmates at the facility received a diagnosis of laboratory-confirmed STEC O111 infection, and a retrospective prevalence study of 100 inmates found that, during March-April, 14 other inmates had experienced diarrheal illness suspected of being STEC O111 infection. Pulsed-field gel electrophoresis (PFGE) testing indicated that STEC O111 isolates from inmates matched STEC O111 isolates from cattle at the onsite dairy. An environmental investigation determined that inmates employed at the dairy might have acquired STEC O111 infection on the job or transported contaminated clothing or other items into the main correctional facility and kitchen, thereby exposing other inmates. To prevent similar outbreaks in correctional facilities, authorities should consult with public health officials to design and implement effective infection control measures.


title: Cardiovascular imaging in clinical and experimental acute infectious myocarditis.

text: Acute myocarditis can be caused by a variety of organisms. Congestive heart failure and death may occur as a consequence of these infections. In recent years cardiac imaging, by echocardiography and magnetic resonance and nuclear imaging has become a useful adjunct in the diagnosis and management of infectious myocarditis. Specific examples of their usefulness will be given in the discussions of chagasic myocarditis, bacterial myocarditis, acquired immunodeficiency syndrome and peripartum cardiomyopathy. Finally, we explore the exciting area of cardiac imaging of small animals, such as mice infected with Trypanosoma cruzi.


title: Improved scores for observed teamwork in the clinical environment following a multidisciplinary operating room simulation intervention.

text: AIMS We ran a Multidisciplinary Operating Room Simulation (MORSim) course for 20 complete general surgical teams from two large metropolitan hospitals. Our goal was to improve teamwork and communication in the operating room (OR). We hypothesised that scores for teamwork and communication in the OR would improve back in the workplace following MORSim. We used an extended Behavioural Marker Risk Index (BMRI) to measure teamwork and communication, because a relationship has previously been documented between BMRI scores and surgical patient outcomes. METHODS Trained observers scored general surgical teams in the OR at the two study hospitals before and after MORSim, using the BMRI. RESULTS Analysis of BMRI scores for the 224 general surgical cases before and 213 cases after MORSim showed BMRI scores improved by more than 20% (0.41 v 0.32, p<0.001). Previous research suggests that this improved teamwork score would translate into a clinically important reduction in complications and mortality in surgical patients. CONCLUSIONS We demonstrated an improvement in scores for teamwork and communication in general surgical ORs following our intervention. These results support the use of simulation-based multidisciplinary team training for OR staff to promote better teamwork and communication, and potentially improve outcomes for general surgical patients.


Methadone overdose.


Intraoperative transthoracic echocardiography: another arrow to the bow of perioperative medicine.