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?


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.


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.


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.


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?


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.


title: Robotic Whipple Procedure for Pancreatic Cancer: The Moffitt Cancer Center Pathway.

text: BACKGROUND Resection of malignancies in the head and uncinate process of the pancreas (Whipple procedure) using a robotic approach is emerging as a surgical option. Although several case series of the robotic Whipple procedure have been reported, detailed descriptions of operative techniques and a clear pathway for adopting this technology are lacking. METHODS We present a focused review of the procedure as it applies to pancreatic cancer and describe our clinical pathway for the robotic Whipple procedure used in pancreatic cancer and review the outcomes of our early experience. A systematic review of the literature is provided, focusing on the indications, variations in surgical techniques, complications, and oncological results of the robotic Whipple procedure. RESULTS A clinical pathway has been defined for preoperative training of surgeons, the requirements for hospital privileges, patient selection, and surgical techniques for the robotic Whipple procedure. The robotic technique for managing malignant lesions of the pancreas head is safe when following well-established guidelines for adopting the technology. Preliminary data demonstrate that perioperative convalescence may exceed end points when compared with the open technique. CONCLUSIONS The robotic Whipple procedure is a minimally invasive approach for select patients as part of multidisciplinary management of periampullary lesions in tertiary centers where clinicians have developed robotic surgical programs. Prospective trials are needed to define the short- and long-term benefits of the robotic Whipple procedure.


Morphology of a latent virus associated with hamster cells BHK-21.


title: Performance of ICU ventilators during noninvasive ventilation with large leaks in a total face mask: a bench study.

text: OBJECTIVE Discomfort and noncompliance with noninvasive ventilation (NIV) interfaces are obstacles to NIV success. Total face masks (TFMs) are considered to be a very comfortable NIV interface. However, due to their large internal volume and consequent increased CO2 rebreathing, their orifices allow proximal leaks to enhance CO2 elimination. The ventilators used in the ICU might not adequately compensate for such leakage. In this study, we attempted to determine whether ICU ventilators in NIV mode are suitable for use with a leaky TFM. METHODS This was a bench study carried out in a university research laboratory. Eight ICU ventilators equipped with NIV mode and one NIV ventilator were connected to a TFM with major leaks. All were tested at two positive end-expiratory pressure (PEEP) levels and three pressure support levels. The variables analyzed were ventilation trigger, cycling off, total leak, and pressurization. RESULTS Of the eight ICU ventilators tested, four did not work (autotriggering or inappropriate turning off due to misdetection of disconnection); three worked with some problems (low PEEP or high cycling delay); and one worked properly. CONCLUSIONS The majority of the ICU ventilators tested were not suitable for NIV with a leaky TFM.


Is the Quarantine Act relevant?


title: [Development of Novel Multiplex Real-time RT-PCR Assays for Detection of MERS-CoV Infection].

text: We aimed to develop a novel laboratory assay for the detection of Middle East respiratory syndrome coronavirus (MERS-CoV) infection .Several novel multiplex real-time RT-PCR assays were developed using the upE,ORF1 band N2genes of MERS-CoV as targets; the novel assays were compared with previous monoplex real-time RT-PCR assays. For validation, we tested a MERS-CoV strain (hCoVEMC), clinical specimens from patients with fever in Shanghai, and specimens from the first imported MERS case in China. The detection limit of the novel multiplex real-time RT-PCR assays was 10 PFU of MERS-CoV per ml, the same as that in monoplex real-time RT-PCR assays based on upE or N2. The detection was specific for MERS-CoV. In validation using clinical samples, pharyngeal swabs from Shanghai patients were detected as negative, while swabs from the first imported MERS case in China were detected as positive. Using whole blood samples from a MERS case, better detection results were obtained with N2 as the target than upE. We conclude that all the novel assays established in this study could be used for the detection of MERS-CoV; they show potential for improvement compared with monoplex real-time RT-PCR assay based on upE.


title: Pathology of guinea pigs experimentally infected with a novel reovirus and coronavirus isolated from SARS patients.

text: Guinea pigs were inoculated with a reovirus (ReoV) and coronavirus (SARS-CoV) isolated from SARS patients to determine their potential role in the etiology of SARS. Animals infected with ReoV died between day 22 and day 30 postinoculation (PI) while 70% of the animals inoculated with ReoV and SARS-CoV died between day 4 to day 7 PI. The titer of neutralizing antibodies against ReoV and SARS-CoV ranged from 80 to 160 when the animals were inoculated with the two viruses, respectively, while the titer of the antibodies was just below 10 in coinfections. The animal inoculated with ReoV developed diffuse alveolar damage similar to the exudative and leakage inflammation found in SARS patients, and was characterized by diffuse hemorrhage, fibroid exudation, hyaline membrane formation, and type II pneumocytes hyperplasia in alveolar interstitia. The pulmonary epithelial necrosis, excoriation, and early fibrosis of pulmonary tissue were only observed in ReoV-SARS-CoV groups and in SARS-CoV/ReoV groups. Other typical pathological changes included hemorrhagic necrosis in lymph nodes and spleen and hydropic degeneration in the liver. On the contrary, guinea pigs infected with SARS-CoV only developed interstitial pneumonitis. Our experiment demonstrate that ReoV might be one of the primary causes of SARS, since simultaneous coinfection can duplicate the typical pathological changes similar to that of SARS patients. This guinea pig model may provide a useful animal model for SARS.


title: Novel Coronavirus Disease (COVID-19) and Central Nervous System Complications: What Neurologist Need to Know.

text: The novel coronavirus (Covid-19) is a family of large enveloped non-segmented positive-sense RNA viruses which has been considered as a global health concern as it has a very high transmissibility potential. Regarding to the similarity of the virus to SARS-CoV, it is postulated that the Covid-19 accumulates mainly in the nasal epithelia and lower respiratory airways. However, there is evidence suggesting the Covid-19 neurotropism which might contribute to respiratory failure. Here in we aim to review the central nervous system complications of the Covid-19 CoV since the emergence of the virus. Keywords: Novel Coronavirus, Covid19-Cov, CNS Complication, Nervous System.


title: 5-millimeter trocar-site bowel herniation following laparoscopic surgery.

text: BACKGROUND AND OBJECTIVES This is a case report of a 5-mm trocar-site large bowel herniation following laparoscopic tubal sterilization. During laparoscopic sterilization, the 5-mm port site was closed initially. Large bowel herniation was recognized at the end of the case and managed immediately by laparoscopically reducing the hernia and closing the port site without any short- or long-term complications. Trocar-site bowel hernia is a rare complication after laparoscopic surgery. It is usually associated with trocar size > 10 mm. We describe a case of bowel herniation through a 5-mm trocar site, which was managed after laparoscopic surgery. CASE REPORT A 36-year-old multigravid patient underwent a laparoscopic tubal fulguration. Two 5-mm ports were used for the procedure. At the end of the procedure, the lateral trocar site was found to have fat protrusion that looked like appendices epiploicae. A laparoscopic camera was reintroduced into the abdominal cavity that showed a large bowel herniation through the 5-mm lateral port site. The hernia was reduced laparoscopically, and the fascial defect was repaired. CONCLUSION Bowel herniation can occur through a 5-mm port. All port sites should be closed to avoid such complications.


title: A human rights approach to the WHO Model List of Essential Medicines.

text: Since the first WHO Model List of Essential Medicines was adopted in 1977, it has become a popular tool among health professionals and Member States. WHO's joint effort with the United Nations Committee on Economic, Social and Cultural Rights has resulted in the inclusion of access to essential medicines in the core content of the right to health. The Committee states that the right to health contains a series of elements, such as availability, accessibility, acceptability and quality of health goods, services and programmes, which are in line with the WHO statement that essential medicines are intended to be available within the context of health systems in adequate amounts at all times, in the appropriate dosage forms, with assured quality and information, and at a price that the individual and the community can afford. The author considers another perspective by looking at the obligations to respect, protect and fulfil the right to health undertaken by the states adhering to the International Covenant of Economic, Social and Cultural Rights (ICESCR) and explores the relationship between access to medicines, the protection of intellectual property, and human rights.


title: Downregulation of autophagy by herpesvirus Bcl-2 homologs.

text: The critical role of the cellular autophagy pathway in viral infection and pathogenesis has become increasingly apparent. Mounting evidences suggest that viruses have developed different strategies to meticulously modulate intracellular autophagy for their own benefits, thereby either promoting efficient viral replication or facilitating viral persistence. While our understanding of these strategies is still in its incipient stage, recent advances demonstrate that gamma herpesvirus Bcl-2 homolog (vBcl-2), which protects virus-infected cells from apoptosis, also suppresses cellular autophagy pathway through its direct interaction with the autophagy protein Beclin1. Interestingly, vBcl-2 has evolved to harbor the enhanced anti-autophagic activity compared to its host counterpart, suggesting an important role of cellular autophagy in response to viral infection and virus-associated pathogenesis. Thus, a detailed study of vBcl-2-mediated regulation of autophagy signal transduction pathway may lead to a better understanding of not only how virus escapes from host innate immunity but also how autophagy regulates viral infection and environmental stresses.


title: Day-night differences in mucosal plasma proteins in common cold.

text: Aggravation of symptoms in inflammatory airway diseases is common in the early morning hours, but little is known about day-night differences in the occurrence of plasma exudate on the airway surface. We have therefore examined the plasma macromolecules on the nasal mucosa at different time points. The study comprised 20 subjects who had been inoculated (day 0) with coronavirus intranasally. Ten subjects remained healthy and 10 developed common cold with significant symptoms from day 2 to day 6. Starting on day 3 at 8.00 h and repeated at 4 h intervals until 4.00 h on day 4, nasal lavages were carried out by employment of a nasal pool-device which fills the entire unilateral nasal cavity and gently but effectively irrigates its surface. Lavage fluid levels of albumin (Mw 69,000 D) and fibrinogen (Mw 340,000 D) were determined. In the healthy subjects the levels of albumin and fibrinogen remained low throughout the experiment, however, with mean peak values of the two proteins occurring at 4.00 h (p < 0.05 compared to daytime nadir at 16.00 h). In subjects with common cold both albumin (p < 0.05) and fibrinogen (p < 0.01) exhibited marked variation with individual and mean peak levels recorded at 8.00 h day 3, and 4.00 h day 4. These mean peak values were 5-20 times higher (p < 0.01 - p < 0.05) than the mean levels recorded in these subjects at the other time periods. The present data indicate a marked day-night difference in the occurrence of plasma proteins on the airway surface in common cold, whereas in health the difference is much less. We conclude that different-sized plasma proteins may accumulate on the mucosa in healthy airways during late night hours and that in common cold this nocturnal accumulation may be considerably increased.


title: Effect of intranasal vaccination against bovine enteric coronavirus on the occurrence of respiratory tract disease in a commercial backgrounding feedlot.

text: OBJECTIVE To measure antibody titers against bovine coronavirus (BCV), determine frequency of BCV in nasal swab specimens, and compare calves treated for bovine respiratory tract disease (BRD) between those given an intranasally administered vaccine and control calves. DESIGN Randomized clinical trial. ANIMALS 414 heifer calves. PROCEDURE Intranasal BCV antigen concentration and antibody titer against BCV were measured on entry to a feedlot. Calves were randomly assigned to receive 3.0 mL of a modified-live virus vaccine against bovine enteric coronavirus and rotavirus or 3.0 mL of saline (0.9% NaCl) solution. Calves were confined to 1 of 2 pens, depending on vaccination status, for a minimum of 17 days of observation (range, 17 to 99). Selection of calves for treatment of BRD and scoring for severity of disease were done by veterinarians unaware of treatment status. RESULTS Intranasal BCV (125/407 [31%]) and serum antibody titers > or = 20 against BCV (246/396 [62%]) were identified in calves entering the feedlot. Vaccination was associated with significant decrease in risk of treatment for BRD; intranasal BCV on entry to the feedlot was associated with increased risk of treatment. Univariate analysis revealed that control calves with intranasal BRD on entry to the feedlot and those with antibody titer < 20 were significantly more likely to be treated for BRD. CONCLUSIONS AND CLINICAL RELEVANCE These data provide further evidence of an association between BCV and respiratory tract disease in feedlot calves. An intranasally administered vaccine appeared to reduce risk of treatment for BRD.


title: Chemoprevention by resveratrol: molecular mechanisms and therapeutic potential.

text: Resveratrol, a polyphenol found in numerous plant species, including mulberries, peanuts and grapes, has shown to possess chemopreventive properties against several cancers, and cardiovascular diseases. Recently, resveratrol has been shown to have positive effects on age longevity, lipid levels and a preventative quality against certain cancers and viral infections. Resveratrol induces apoptosis by up-regulating the expression of Bax, Bak, PUMA, Noxa, Bim, p53, TRAIL, TRAIL-R1/DR4 and TRAIL-R2/DR5 and simultaneously down-regulating the expression of Bcl-2, Bcl-XL, Mcl-1 and survivin. Resveratrol causes growth arrest at G1 and G1/S phases of cell cycle by inducing the expression of CDK inhibitors p21/WAF1/CIP1 and p27/KIP1. Resveratrol has also been shown to reduce inflammation via inhibition of prostaglandin production, cyclooxygenase-2 activity, and nuclear factor-kappaB activity. Modulation of cell signaling pathway by resveratrol explains its diverse bioactivities related with human health. Resveratrol also potentiates the apoptotic effects of cytokines, chemotherapeutic agents and gamma-radiation. Pharmacokinetic and pharmacodynamic studies demonstrated that the main target organs of resveratrol are liver and kidney, and it is metabolized by hydroxylation, glucuronidation, sulfation and hydrogenation. As a chemoprevention agent, resveratrol has been shown to inhibit tumor initiation, promotion, and progression. There is growing evidence that resveratrol can prevent or delay the onset of various cancers, heart diseases, ischemic and chemically induced injuries, pathological inflammation and viral infections. This review summarizes the molecular mechanisms of resveratrol and its clinical benefits for human diseases.


Fact sheet on Middle East respiratory syndrome coronavirus (June 2015).


title: Evaluation of concurrent shedding of bovine coronavirus via the respiratory tract and enteric route in feedlot cattle.

text: OBJECTIVE To assess the relationship between shedding of bovine coronavirus (BCV) via the respiratory tract and enteric routes and the association with weight gain in feedlot cattle. ANIMALS 56 crossbred steers. PROCEDURES Paired fecal samples and nasal swab specimens were obtained and were tested for BCV, using antigen-capture ELISA. Paired serum samples obtained were tested for antibodies to BCV, using antibody-detection ELISA. Information was collected on weight gain, clinical signs, and treatments for enteric and respiratory tract disease during the study period. RESULTS Number of samples positive for bovine respiratory coronavirus (BRCV) or bovine enteric coro navirus (BECV) was 37/224 (17%) and 48/223 (22%), respectively. Some cattle (25/46, 45%) shed BECV and BRCV. There were 25/29 (86%) cattle positive for BECV that shed BRCV, but only 1/27 (4%) cattle negative to BECV shed BRCV. Twenty-seven of 48 (56%) paired nasal swab specimens and fecal samples positive for BECV were positive for BRCV. In contrast, only 10/175 (6%) paired nasal swab specimens and fecal samples negative for BECV were positive for BRCV. Only shedding of BECV was associated with significantly reduced weight gain. Seroconversion to BCV during the 21 days after arrival was detected in 95% of the cattle tested. CONCLUSIONS AND CLINICAL IMPLICATIONS Feedlot cattle infected with BCV after transport shed BCV from the respiratory tract and in the feces. Fecal shedding of BCV was associated with significantly reduced weight gain. Developing appropriate control measures for BCV infections could help reduce the decreased weight gain observed among infected feedlot cattle.


title: Natural history of a recurrent feline coronavirus infection and the role of cellular immunity in survival and disease.

text: We describe the natural history, viral dynamics, and immunobiology of feline infectious peritonitis (FIP), a highly lethal coronavirus infection. A severe recurrent infection developed, typified by viral persistence and acute lymphopenia, with waves of enhanced viral replication coinciding with fever, weight loss, and depletion of CD4+ and CD8+ T cells. Our combined observations suggest a model for FIP pathogenesis in which virus-induced T-cell depletion and the antiviral T-cell response are opposing forces and in which the efficacy of early T-cell responses critically determines the outcome of the infection. Rising amounts of viral RNA in the blood, consistently seen in animals with end-stage FIP, indicate that progression to fatal disease is the direct consequence of a loss of immune control, resulting in unchecked viral replication. The pathogenic phenomena described here likely bear relevance to other severe coronavirus infections, in particular severe acute respiratory syndrome, for which multiphasic disease progression and acute T-cell lymphopenia have also been reported. Experimental FIP presents a relevant, safe, and well-defined model to study coronavirus-mediated immunosuppression and should provide an attractive and convenient system for in vivo testing of anticoronaviral drugs.


title: [Recommendations for resource management in intensive care units during the COVID-19 pandemic].

text: This document aims to provide evidence-based recommendations to estimate the personal protective equipments (PPE), medical devices, and drugs commonly used in the Intensive Care Unit during the COVID-19 pandemic. A systematic literature review and gray literature assessment was performed, and the evidence was categorized using the GRADE methodology. Then a predictive model was built to support the estimation of resources needed during 30 days of the pandemic. In the development of these recommendations, 33 publications were included, with variable quality of evidence (low to very low quality). They refer to the use of PPE according to the risk of exposure; management and reuse of PPE, and the stock of drugs and medical devices needed for the care of patients with COVID-19. It is important to remark the difficult in estimating and managing the number of essential supplies and equipment required during a pandemic. The model allowed us to predict the resources required to provide critical care during 30 days of pandemic activity. Given the constant evolution of COVID-19, these recommendations might change as evidence evolves.


title: Endovascular management of internal carotid artery injuries secondary to endonasal surgery: case series and review of the literature.

text: OBJECTIVE Internal carotid artery (ICA) injury is a rare but severe complication of endonasal surgery. The authors describe their endovascular experience managing ICA injuries after transsphenoidal surgery; they review and summarize the current literature regarding endovascular techniques; and they propose a treatment algorithm based on the available evidence. METHODS A retrospective review of 576 transsphenoidal pituitary adenoma resections was performed. Cases of ICA injury occurring at our institution and transfers from other hospitals were evaluated. Endovascular treatments for ICA injury reported in the literature were also reviewed and summarized. RESULTS Seven cases were identified from the institutional cohort (mean age 46.3 years, mean follow-up 43.4 months [1-107 months]) that received endovascular treatment for ICA injury. Five injuries occurred at our institution (5 [0.9%] of 576), and 2 injuries occurred at outside hospitals. Three patients underwent ICA sacrifice by coil placement, 2 underwent lesion embolization (coil or stent-assisted coil placement), and 2 underwent endoluminal reconstruction (both with flow diversion devices). Review of the literature identified 98 cases of ICA injury treated with endovascular methods. Of the 105 total cases, 46 patients underwent ICA sacrifice, 28 underwent lesion embolization, and 31 underwent endoluminal reconstruction. Sacrifice of the ICA proved a durable solution in all cases; however, the rate of persistent neurological complications was relatively high (10 [21.7%] of 46). Lesion embolization was primarily performed by coil embolization without stenting (16 cases) and stent-assisted coiling (9 cases). Both techniques had a relatively high rate of at least some technical complication (6 [37.5%] of 16 and 5 [55.6%] of 9, respectively) and major technical complications (i.e., injury, new neurological deficit, or ICA sacrifice) (5 [31.3%] of 16 and 2 [22.2%] of 9, respectively). Endoluminal reconstruction was performed by covered stent (24 cases) and flow diverter (5 cases) placement. Covered stents showed a reasonably high rate of technical complications (10 [41.7%] of 24); however, 8 of these problems were resolved, leaving a small percentage with major technical complications (2 [8.3%] of 24). Flow diverter placement was also well tolerated, with only 1 minor technical complication. CONCLUSIONS Endovascular treatments including vessel sacrifice, coil embolization (with or without stent assistance), and endoluminal reconstruction offer a tailored approach to ICA injury management after endonasal surgery. Vessel sacrifice remains the definitive treatment for acute, uncontrolled bleeding; however, vessel preservation techniques should be considered carefully in select patients. Multiple factors including vascular anatomy, injury characteristics, and risk of dual antiplatelet therapy should guide best treatment, but more study is needed (particularly with flow diverters) to refine this decision-making process. Ideally, all endovascular treatment options should be available at institutions performing endonasal surgery.


title: [Optimum hepatic parenchymal dissection to prevent bile leak: a comparative study using electrosurgical and stapling devices in swine].

text: BACKGROUND Bile leakage is a serious complication of liver resection, and its treatment is very time-consuming. In open liver resection, Glisson's sheaths are usually disconnected by ligation to the extent possible during the parenchyma dissection. However, in laparoscopic surgery, the ligation, suture, and hemostasis are more difficult than in open surgery. For this reason, in laparoscopic liver resection, liver parenchyma dissection is generally accomplished using electrosurgical or stapling devices. PURPOSE The purpose of this study was to verify the authenticity of electrosurgical devices attached an automatic irrigation function (AI) and stapling devices for laparoscopic liver parenchymal dissection. METHODS Four devices were used for liver parenchymal dissection in laparoscopic hepatic wedge resection, in pigs: monopolar high-frequency electric cautery attached AI (MCI) (n = 6), bipolar high-frequency electric cautery attached AI (BCI) (n = 6), bipolar tissue sealing system (LigaSure) attached AI (BSI) and an endoscopic stapling device (ECHELON FLEX ENDOPATH) (ES). In each group, burst pressures were tested using an electronic manometer, paying special attention to the location (s) of the first disruption (s). The dissected tissues were examined histologically. RESULTS Pressures used in electrosurgical devices attach AI were significantly higher compared to pressures used in a ES (P < 0.001). While thermal denaturation of the liver parenchyma occurred at approximately 2-3 mm of depth when bipolar high-frequency electric cautery was used for dissection, it reached up to more than 10 mm with monopolar high-frequency electric cautery. All of the first disruption points of stapling were at stapling line. CONCLUSIONS Electrosurgical devices with an automatic irrigation function are useful devices to dissect the liver parenchyma.


title: The vaccinia virus 39-kDa protein forms a stable complex with the p4a/4a major core protein early in morphogenesis.

text: The vaccinia virus (VV) 39-kDa protein, the product of the A4L gene, is a highly antigenic protein of the viral core. Pulse-chase and immunoprecipitation experiments have shown that the 39-kDa protein interacts with p4a (encoded by the A10L gene), the precursor of the most abundant virion protein. This interaction is maintained with the processed 4a form that arises during virion maturation. The controlled disruption of mature viral particles showed that the 39-kDa and 4a proteins are tightly bound within the virion. Immunoelectron microscopy showed that both proteins first localize within the cytoplasm and later accumulate inside the viral factories, reaching these locations via a mechanism apparently unrelated to cellular membranes. Double labeling experiments showed a colocalization of both proteins in all virus-induced structures.


The Australian study of health and relationships: results for central Sydney, inner-eastern Sydney, and New South Wales.


title: Low prevalence of subclinical severe acute respiratory syndrome-associated coronavirus infection among hospital healthcare workers in Hong Kong.

text: We recruited 688 hospital healthcare workers who cared for patients with severe acute respiratory syndrome (SARS) and did not develop the disease in the Hong Kong outbreak in 2003. A questionnaire survey was conducted and serum samples were collected for SARS-associated coronavirus (SARS-CoV) antibody. The high-risk procedures performed and the types of unprotected exposures were recorded for analysis. Only 1 asymptomatic nurse had positive serological test. The result demonstrates the low rate of subclinical SARS-CoV infection in hospital healthcare workers and that the infection control practice against SARS in Hong Kong's hospitals during the outbreak was highly effective.


title: Localization of mouse hepatitis virus nonstructural proteins and RNA synthesis indicates a role for late endosomes in viral replication.

text: The aim of the present study was to define the site of replication of the coronavirus mouse hepatitis virus (MHV). Antibodies directed against several proteins derived from the gene 1 polyprotein, including the 3C-like protease (3CLpro), the putative polymerase (POL), helicase, and a recently described protein (p22) derived from the C terminus of the open reading frame 1a protein (CT1a), were used to probe MHV-infected cells by indirect immunofluorescence (IF) and electron microscopy (EM). At early times of infection, all of these proteins showed a distinct punctate labeling by IF. Antibodies to the nucleocapsid protein also displayed a punctate labeling that largely colocalized with the replicase proteins. When infected cells were metabolically labeled with 5-bromouridine 5'-triphosphate (BrUTP), the site of viral RNA synthesis was shown by IF to colocalize with CT1a and the 3CLpro. As shown by EM, CT1a localized to LAMP-1 positive late endosomes/lysosomes while POL accumulated predominantly in multilayered structures with the appearance of endocytic carrier vesicles. These latter structures were also labeled to some extent with both anti-CT1a and LAMP-1 antibodies and could be filled with fluid phase endocytic tracers. When EM was used to determine sites of BrUTP incorporation into viral RNA at early times of infection, the viral RNA localized to late endosomal membranes as well. These results demonstrate that MHV replication occurs on late endosomal membranes and that several nonstructural proteins derived from the gene 1 polyprotein may participate in the formation and function of the viral replication complexes.


Special report: highlights of the First Annual Scientific Meeting of the Canadian Orthopaedic Foot and Ankle Society, Winnipeg, Manitoba, October 4, 2003.