title: Endovascular treatment of carotico-cavernous fistulas with acrylic glue: a series of nine cases.

text: INTRODUCTION Injuries to the internal carotid artery close to the cavernous sinus may result in a fistulous connection between the artery and the venous sinus. Symptoms include pulsatile tinnitus, intracranial bruit, ophthalmological symptoms, and risk of intracerebral hematoma in cases of cortical venous reflux. Previous treatment strategies have included detachable latex balloons, coils, covered stents, or combinations thereof. Today, detachable latex balloons are phased out or withdrawn from several markets. Acrylic glue is a proven stable material used for embolization of arteriovenous shunts. It is a precise, fast, and cost-effective method of endovascular embolization, and it does not cause artifacts on MRI or MRA. METHODS We treated nine patients suffering from direct fistulas with acrylic glue without any permanent neurological adverse events. RESULTS Four patients were treated with glue embolization of the fistula without occlusion of the parent artery. Five patients with long-lasting symptomatology, large tears in the ICA, and with full collateral cerebral circulation were treated with glue embolization of the fistula and sacrifice of the ICA antero- and retrograde via the ICA and the posterior communicating artery. CONCLUSION We suggest acrylic glue to be added to the panel of embolic materials used to treat CCFs.


Prognosis for South Asian and white patients with heart failure in the United Kingdom: counterintuitive findings on heart failure in South Asians may be artefactual.


title: [Logical Explanation of Medical Condition for Patients with Terminal Cancer at Home-Retrospective Analysis of 145 Cases].

text: Frequently, patients with advanced cancer are suffered by various symptoms at the end of life. Furthermore, sometime experience unexpected loss of consciousness(LOC)and/or respiratory arrest. I examined carefully following neck stiffness, LOC, masked face, urinary retention, tonic and/or clonic convulsions, apnea, dysphagia, head rotation, neurogenic pain, hyperthermia, mydriasis 145 patients with advanced cancer. By assuming meningeal carcinomatosis, multifocal neurological findings are logically expected. As a result, before the LOC or respiratory arrest, I was able to logically explain to almost all families of patients, who with suspected neurological signs, expected multifocal neurological signs including LOC or respiratory arrest.


title: Selective infection of lower respiratory tract by respiratory viruses in children with recurrent respiratory tract infections.

text: Thirty preschool children presenting with recurrent respiratory infections and their unaffected siblings were observed prospectively for a year. The index children experienced more episodes of acute respiratory infection than their siblings. Respiratory viruses were the major cause of respiratory infections. The index children had lower respiratory tract disease, predominantly wheeze, during 34% of proved respiratory virus infections compared with 11% of such infections experienced by the control children (p less than 0.02). Atopic children had an increased tendency to wheeze that did not reach significance, but atopy was not associated with increased susceptibility to respiratory infections.


docid: iptkkwai

title: Interference of coronavirus infection by expression of IgG or IgA virus neutralizing antibodies.

text: Mouse immunoglobulin gene fragments encoding the variable modules of the heavy (VH) and light (VL) chains of a transmissible gastroenteritis coronavirus (TGEV) neutralizing monoclonal antibody (MAb) have been cloned and sequenced. The selected MAb recognizes a highly conserved viral epitope and does not lead to the selection of neutralization escape mutants. Chimeric immunoglobulin genes with the variable modules from the murine MAb and constant modules of human gamma 1 and kappa chains were constructed using RT-PCR. These chimeric immunoglobulins were stably or transiently expressed in murine myelomas and COS cells, respectively. The secreted recombinant antibodies had radioimmunoassay (RIA) titers higher than 10(3) and reduced the infectious virus more than 10(4)-fold. Recombinant dimeric IgA showed a 50-fold enhanced neutralization of TGEV relative to a recombinant monomeric IgG1 which contained the identical antigen binding site. Epithelial cell lines stably-transformed with these constructs and expressing either recombinant IgG or IgA TGEV neutralizing antibodies reduced virus production by > 10(5)-fold after infection with homologous virus, although a residual level of virus production (< 10(2) PFU/ml) remained in less than 0.1% of the cells.


docid: jpednkoz

title: Characterization of determinants involved in the feline infectious peritonitis virus receptor function of feline aminopeptidase N.

text: Feline aminopeptidase N (fAPN) is a major cell surface receptor for feline infectious peritonitis virus (FIPV), transmissible gastroenteritis virus (TGEV), human coronavirus 229E (HCV 229E) and canine coronavirus (CCV). By using chimeric molecules assembled from porcine, human and feline APN we have analysed the determinants involved in the coronavirus receptor function of fAPN. Our results show that amino acids 670-840 of fAPN are critically involved in its FIPV and TGEV receptor function whereas amino acids 135-297 are essential for the HCV 229E receptor function. We also demonstrate that a chimeric molecule assembled from human and porcine APN is able to act as a receptor for FIPV. This is surprising as neither human nor porcine APN by themselves mediate FIPV infection. These results suggest that different determinants in the APN protein are involved in mediating the coronavirus receptor function.


title: A coding RNA sequence acts as a replication signal in cardioviruses.

text: Theiler's virus and Mengo virus are representatives of the Cardiovirus genus within the picornavirus family. Their genome is an 8-kilobase long positive strand RNA molecule. This RNA molecule plays three roles in infected cells: It serves as a messenger RNA, acts as a template for genome replication, and is encapsidated to form progeny virions. We observed that a cis-acting signal required for replication of Theiler's virus was contained within a 130-nt stretch of the region encoding the capsid protein VP2. This RNA sequence does not influence internal ribosome entry site-mediated translation initiation and thus likely acts directly as a signal for the replication complex. We found a similar signal in the VP2-coding sequence of Mengo virus, and both signals could be functionally exchanged. Within the replication element, a 9-nt sequence that is highly conserved among cardioviruses was shown to be essential for replication. This conserved sequence was contained in mostly unpaired regions of the RNA secondary structure predicted for the replication elements of the various cardioviruses. Interestingly, a similar replication element has been reported to occur in the distantly related human rhinovirus type 14, suggesting that such elements could be conserved throughout the picornavirus family. However, the different location of the replication elements in rhinovirus and cardioviruses, and the fact that they were not functionally exchangeable, is raising intriguing questions about the evolution of such signals in picornaviruses.


title: How will Australian general practitioners respond to an influenza pandemic? A qualitative study of ethical values.

text: OBJECTIVES To explore general practitioners' perceptions of their preparedness for an influenza pandemic, the changes they would make to their practice, and the ethical justifications for their planned actions. DESIGN AND SETTING A qualitative study was performed among South Australian GPs between March and October 2007. A semi-structured interview was carried out with each participant in his or her practice, and the interviews were audio-recorded, transcribed and analysed thematically. PARTICIPANTS 10 GPs were recruited: five from a metropolitan Division and five from a rural Division of General Practice. RESULTS Some participants felt they would not be able to cope with an influenza pandemic, while others felt it would simply mean an increase in their workloads. Most respondents considered creating separate waiting rooms, moving the reception desk outside of the practice and delaying all non-urgent consultations in order to deal with a pandemic more effectively. Respondents mentioned the conflict between their various roles and responsibilities as a primary source of tension when thinking about the way they would organise their work in the event of a pandemic. A number of GPs said they would not practise in the event of a pandemic, as they felt their responsibility to their families outweighed that to their patients. CONCLUSIONS Professional codes of ethics should include guidance about the scope of the duty to treat during infectious disease outbreaks. The community has to uphold the value of reciprocity, and ensure that GPs and their families are provided with support during a pandemic and are given the opportunity to be actively involved in pandemic preparedness planning.


title: Comparison of complement fixation with two enzyme-linked immunosorbent assays for the detection of antibodies to respiratory viral antigens.

text: We compared complement fixation (CF) for the measurement of antibodies against influenza A, influenza B, respiratory syncytial virus (RSV), human adenovirus, and parainfluenza viruses 1, 2, and 3 (para-1, para-2, and para-3) with 2 enzyme-linked immunosorbent assays (ELISA kits, A and B). The IgG ELISA kits compared very well with each other except for the influenza A and B IgG ELISAs. The IgG ELISAs, in general, did not agree with CF In contrast, the IgM ELISAs compared well with CF and each other except for the consensus parainfluenza panel from ELISA B. The poor agreement of the IgG ELISAs with the CF test can be explained by the increased sensitivity of the ELISAs and differences between CF antigens and the ELISA antigens. The influenza A and influenza B ELISA antigens differed between both kits, which may explain their poor agreement. The ELISA is a suitable replacement for CF, providing greater sensitivity, isotype specificity, and ease of use.


COVID-19 in hem/onc news.


title: The effect of doxorubicin loading on response and toxicity with drug-eluting embolization in resectable hepatoma: a dose escalation study.

text: AIM The dose-response relationship between doxorubicin and superabsorbent drug-eluting microspheres has not been established. In this study, we investigated the relationships between dose and delivery parameters as they pertain to toxicity and response in surgically resectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS Twenty-five patients with resectable HCC were randomly assigned and divided into four groups, each receiving either bland, 25 mg, 50 mg or 75 mg of doxorubicin loaded Super Absorbent Polymer microspheres, with 24 patients undergoing surgical resection. Response Evaluation and Criteria in Solid Tumors (RECIST) 1.0 and European Association for the Study of the Liver (EASL)-based volumetric response was performed at one month and surgical resection of the reference tumor was performed at two months. Adverse events were collected at regular intervals. RESULTS Fifty-six percent of patients demonstrated complete response according to EASL criteria as opposed to 0% according to RECIST (v1.0) criteria. Residual tumor was identified in all groups (0 mg: 35%±28.5%; 25 mg: 42%±30.4%; 50 mg: 3.6%±3.3%; and 75 mg: 49.29%±32.6%. A total of 112 adverse events of grades 1-3 occurred (average 5.1 per patient), with no grade 4 or 5. No difference was noted between bland embolic and drug-loaded groups. Subset analysis did demonstrate a significantly increased degree of necrosis in the 50 mg-loaded group (p=0.018). Strong correlation existed between arterial phase Computer Tomography EASL-based response and histopathology (r=0.81; p<0.0001). All groups had residual tumor. CONCLUSION Histology correlates strongly with one-month post-procedural imaging and response optimized at 50 mg of loading per vial. Adverse events were a reflection of embolization, with no relationship between loading dose or administered dose of doxorubicin.


title: Pharmacotherapy Considerations in CKD Patients With COVID-19, A Narrative Review.

text: Treatment of coronavirus disease 2019 (COVID-19) among patients with CKD requires special pharmacotherapy considerations that are reviewed here. Literature review was done for several pharmacotherapy aspects in CKD patients including selection and modification of COVID-19 treatment, drug interactions, nephrotoxicity of drugs that are used for treatment of COVID-19 and potential risks/benefits of routine medications of CKD patients during COVID-19 pandemic. CKD patients should be treated according to local or national COVID-19 protocols as other patients. But, there is no data on using remdesivir in patients with severe CKD. Oseltamivir and ribavirin require dose modification in patients with moderate to severe CKD. Nephrolithiasis, CKD, and acute interstitial nephritis have been reported with protease inhibitors. Acute kidney injury has been reported with remdesivir in patients with severe COVID-19. Pharmacokinetic-enhanced protease inhibitors increase the concentration of some drugs such as statins, cinacalcet, steroids, calcineurin inhibitors (CNIs). Some hypothetical benefits and harms have been suggested for statins and renin-angiotensinaldosterone system inhibitors in COVID-19 patients. Continuing guideline-directed administration of these drugs is recommended. Among different immunomodulating/immunosuppressive drugs, hydroxychloroquine and CNIs are the safest ones during COVID-19. Antimetabolites are suggested to be withheld during moderate to severe COVID-19. Fluid therapy and anticoagulant prophylaxis/ treatment need special attention in CKD patients with COVID-19. CKD patients with COVID-19 are treated as other patients, with some dose modifications if needed. Be mindful for management of drug interactions as well as modification of immunosuppressive drugs in patients with moderate to severe COVID-19.


title: Norwalk virus RNA is infectious in mammalian cells.

text: Human noroviruses are positive-sense RNA viruses and are the leading cause of epidemic acute viral gastroenteritis in developed countries. The absence of an in vitro cell culture model for human norovirus infection has limited the development of effective antivirals and vaccines. Human histo-blood group antigens have been regarded as receptors for norovirus infection, and expression of the alpha(1,2) fucosyltransferase gene (FUT2) responsible for the secretor phenotype is required for susceptibility to Norwalk virus (NV) infection. We report for the first time that transfection of NV RNA, isolated from stool samples from human volunteers, into human hepatoma Huh-7 cells leads to viral replication, with expression of viral antigens, RNA replication, and release of viral particles into the medium. Prior treatment of the RNA with proteinase K completely abolishes RNA infectivity, suggesting a key role of an RNA-protein complex. Although overexpression of the human FUT2 gene enhances virus binding to cells, it is not sufficient to allow a complete viral infection, and viral spread from NV-transfected cells to naïve cells does not occur. Finally, no differences in NV RNA replication are observed between Huh-7 and Huh-7.5.1 cells, which contain an inactivating mutation in retinoic acid-inducible gene I (RIG-I), suggesting that the RIG-I pathway does not play a role in limiting NV replication. Our results strongly suggest that the block(s) to NV replication in vitro is at the stage of receptor and/or coreceptor binding and/or uncoating, either because cells lack some specific factor or activation of cellular antiviral responses independent of RIG-I inhibits virus replication.


title: The UCUAAAC promoter motif is not required for high-frequency leader recombination in bovine coronavirus defective interfering RNA.

text: The 65-nucleotide leader on the cloned bovine coronavirus defective interfering (DI) RNA, when marked by mutations, has been shown to rapidly convert to the wild-type leader of the helper virus following DI RNA transfection into helper virus-infected cells. A model of leader-primed transcription in which free leader supplied in trans by the helper virus interacts by way of its flanking 5'UCUAAAC3' sequence element with the 3'-proximal 3'AGAUUUG5' promoter on the DI RNA minus strand to prime RNA replication has been used to explain this phenomenon. To test this model, the UCUAAAC element which occurs only once in the BCV 5' untranslated region was either deleted or completely substituted in input DI RNA template, and evidence of leader conversion was sought. In both cases, leader conversion occurred rapidly, indicating that this element is not required on input RNA for the conversion event. Substitution mutations mapped the crossover region to a 24-nucleotide segment that begins within the UCUAAAC sequence and extends downstream. Although structure probing of the bovine coronavirus 5' untranslated region indicated that the UCUAAAC element is in the loop of a prominent stem and thus theoretically available for base pair-directed priming, no evidence of an unattached leader early in infection that might have served as a primer for transcription was found by RNase protection studies. These results together suggest that leader conversion on the DI RNA 5' terminus is not guided by the UCUAAAC element and might arise instead from a high-frequency, region-specific, homologous recombination event perhaps during minus-strand synthesis rather than by leader priming during plus-strand synthesis.


title: Normothermia is Best Achieved by Warming Above and Below with Pre-warming Adjunct: A Comparison of Conductive Fabric Versus Forced-air and Water.

text: BACKGROUND Although forced-air warming is the most commonly used method for perioperative patient warming, it is fundamentally problematic because it disturbs the carefully designed airflow in the operating room. Because unintended hypothermia has significant consequences, there is a need for more effective warming strategies. The effectiveness of warming technologies that apply heat through the skin is based on surface-area contact with the heat source and the duration of pre-warming. Therefore, we sought to test the therapeutic effectiveness of combined above- and below-warming therapies. Our hospital prohibits forced-air warming before the patient is draped, so a secondary goal was to determine the effect of preoperative warming using a system that does not interfere with airflow in the operating room. METHODS We prospectively randomized 35 patients undergoing total knee arthroplasty into two groups: 1) forced-air warming/water mattress, using both WarmTouch® upper-body forced-air warming (Medtronic/Covidien Inc., Dublin, Ireland) and a Norm-O-Temp® underbody water mattress (CSZ/Gentherm Inc., Cincinnati, OH, USA), and 2) conductive fabric warming, using a HotDog® electric upper-body blanket (Augustine Temperature Management LLC, Eden Prairie, MN, USA) and a HotDog® underbody mattress. RESULTS Throughout the surgical procedure, group 2 patients had significantly higher temperatures; this group experienced superior pre-warming during preoperative preparations and thus the redistribution temperature drop following the induction of anesthesia was reduced. Both groups achieved 100% normothermia by the end of surgery. CONCLUSION Based solely on the temperatures at the end of surgery, these data indicate that forced-air warming in conjunction with a water mattress warming system is as effective as a conductive fabric electric warming system alone.


Reduction of rotavirus-, coronavirus- and E. coli-associated calf-diarrheas in a large-size dairy herd by means of dam vaccination with a triple-vaccine.


title: Natural cytotoxicity against mouse hepatitis virus-infected target cells. I. Correlation of cytotoxicity with virus binding to leukocytes.

text: Spleen cells from uninfected control mice selectively lysed BALB/c 3T3 fibroblasts infected with mouse hepatitis virus (MHV), a murine coronavirus. Lysis of infected cells occurred within 3 hr, and histocompatibility between effector and target cells was not required. This natural, cell-mediated, virus-associated cytotoxicity differed from NK cell- and T cell-mediated lysis. Spleen cells from animals infected with MHV were enriched in NK activity and were more cytotoxic to YAC-1 target cells, but did not show enhanced cytotoxicity for MHV-infected target cells. Spleen cells from beige mice, which are deficient in NK cell activity, were able to lyse MHV-infected target cells, as were spleen cells from nude mice, which are deficient in T cell activity. Lysis of MHV-infected target cells could be mediated by cells from the spleen and, to a lesser extent, by cells from the bone marrow, but not by resident peritoneal cells or thymocytes. We suggest the term "virus killer (VK) activity" for this phenomenon. VK activity of splenocytes from different mouse strains correlated with the ability of the splenocytes to bind purified radiolabeled MHV virions. MHV virions caused agglutination of spleen leukocytes from susceptible mouse strains, indicating that leukocyte agglutination or adsorption may provide a useful assay for coronaviruses such as MHV which lack hemagglutinating activity. SJL mouse splenocytes did not bind MHV and did not lyse infected targets. MHV bound relatively well to splenocytes of other mouse strains, but poorly to thymocytes and erythrocytes. Binding of MHV to leukocytes was not influenced by 6 mM EDTA or EGTA, indicating a lack of requirement for Mg++ or Ca++. VK activity was also resistant to EDTA and EGTA, in contrast to NK activity, which was sensitive to those chelating agents. VK activity was also unaffected by actinomycin D, cycloheximide, or puromycin, indicating that new protein synthesis was not required for lysis. Antibody to interferon-alpha/beta did not block lysis, nor was there substantially enhanced lysis mediated by leukocytes from mice infected with virus and thus exposed to high levels of interferon. VK activity was blocked by antibody directed against the peplomeric glycoprotein E2 of MHV. VK activity required infected target cells, because cells with adsorbed MHV virions were not lysed by splenocytes.(ABSTRACT TRUNCATED AT 400 WORDS)


title: IP-10 Is Elevated in Virus-Induced Acute Exacerbations in Childhood Asthma.

text: OBJECTIVE Viral infections and sensitization to aeroallergens are major factors in the exacerbation of asthma and its development during early childhood. However, the cytokine profiles and eosinophil activation status linked to the association between viral infections and sensitization to aeroallergens are incompletely understood. Here we investigated respiratory viruses, serum eosinophil cationic protein (ECP), and various cytokines/chemokines in acute exacerbation of childhood asthma. METHODS We analyzed peripheral eosinophil counts, serum ECP, and 27 cytokines/chemokines in 76 virus-induced acute asthma cases with or without aeroallergen sensitization. Asthma due to sensitization was defined by a positive reaction to at least one aeroallergen in serum specific IgE antibody tests. Virus detection was performed using antigen detection kits and/or RT-PCR, followed by direct DNA sequencing analysis. Serum cytokines/chemokines were measured using a multi-cytokine detection system. RESULTS Peripheral eosinophil counts and serum ECP and IL-5 levels were significantly elevated in sensitized cases compared with nonsensitized cases. Conversely, IP-10 values were significantly higher in nonsensitized cases. An inverse correlation between IP-10 and IL-5 production was identified in virus-induced acute exacerbations of asthma but not in controls. CONCLUSIONS Cytokine profiles and eosinophil activation status might be different between sensitized and nonsensitized cases of virus-induced acute exacerbations of asthma.


title: Amiloride derivatives inhibit coxsackievirus B3 RNA replication.

text: Amiloride derivatives are known blockers of the cellular Na(+)/H(+) exchanger and the epithelial Na(+) channel. More recent studies demonstrate that they also inhibit ion channels formed by a number of viral proteins. We previously reported that 5-(N-ethyl-N-isopropyl)amiloride (EIPA) modestly inhibits intracellular replication and, to a larger extent, release of human rhinovirus 2 (HRV2) (E. V. Gazina, D. N. Harrison, M. Jefferies, H. Tan, D. Williams, D. A. Anderson and S. Petrou, Antiviral Res. 67:98-106, 2005). Here, we demonstrate that amiloride and EIPA strongly inhibit coxsackievirus B3 (CVB3) RNA replication and do not inhibit CVB3 release, in contrast to our previous findings on HRV2. Passaging of plasmid-derived CVB3 in the presence of amiloride generated mutant viruses with amino acid substitutions in position 299 or 372 of the CVB3 polymerase. Introduction of either of these mutations into the CVB3 plasmid produced resistance to amiloride and EIPA, suggesting that they act as inhibitors of CVB3 polymerase, a novel mechanism of antiviral activity for these compounds.


docid: lervcwqv

title: Therapeutic potential of adenovirus as a vaccine vector for chronic virus infections.

text: Therapeutic vaccines for chronic infections and cancer are needed. Challenges faced by therapeutic vaccines differ from those of preventative vaccines. Whereas the latter target a naive immune system, the former have to readjust an antigen-experienced immune system that is subverted due to sustained exposure to antigen. E1-deleted adenoviral vectors have succeeded preclinically as preventative vaccines and are now in clinical trials. Their potential as therapeutic vaccines for diseases caused by chronic virus infections or virus-associated malignancies remains to be explored in more depth and may require modifications to circumvent negative immunoregulatory pathways that develop following chronic infections or during tumour progression.


title: Multiple functions of angiotensin-converting enzyme 2 and its relevance in cardiovascular diseases.

text: Angiotensin-converting enzyme 2 (ACE2) is a negative regulator of the renin-angiotensin system, and functions as the key SARS coronavirus receptor and stabilizer of neutral amino acid transporters. ACE2 catalyzes the conversion of angiotensin II to angiotensin 1-7, thereby counterbalancing ACE activity. Accumulating evidence indicates that the enzymatic activity of ACE2 has a protective role in cardiovascular diseases. Loss of ACE2 can be detrimental, as it leads to functional deterioration of the heart and progression of cardiac, renal, and vascular pathologies. Recombinant soluble human ACE2 protein has been demonstrated to exhibit beneficial effects in various animal models, including cardiovascular diseases. ACE2 is a multifunctional enzyme and thus potentially acts on other vasoactive peptides, such as Apelin, a vital regulator of blood pressure and myocardium contractility. In addition, ACE2 is structurally a chimeric protein that has emerged from the duplication of 2 genes: homology with ACE at the carboxypeptidase domain and homology with Collectrin in the transmembrane C-terminal domain. ACE2 has been implicated in the pathology of Hartnup's disease, a disorder of amino acid homeostasis, and, via its function in amino acid transport, it has been recently revealed that ACE2 controls intestinal inflammation and diarrhea, thus regulating the gut microbiome. This review summarizes and discusses the structure and multiple functions of ACE2 and the relevance of this key enzyme in disease pathogenesis.


title: Approaches to antiviral chemotherapy for acute respiratory infections.

text: The causative agents of acute respiratory infections (ARI) in infants and children are mostly thought to be viruses. Some ARI in adult patients may be caused by bacteria but most often the causes are virus infections. When ARI affect immunocompromised patients or the elderly the mortality rates are significantly higher than in immunocompetent individuals. Many types of viruses cause ARI. Among them, influenza viruses A and B and respiratory syncytial virus (RSV) are thought to be the most important because of the severity of illness after infection and their high communicability in the human population. Recently, several novel antiviral drugs against ARI have been developed and some are proceeding in clinical trials. This review covers current investigations into antiviral compounds targeted at several points in the virus life-cycle. This includes PM-523, which broadly inhibits ortho- and paramyxo-viruses, two neuraminidase inhibitors for influenza virus, neutralizing antibody to RSV and chimeric soluble ICAM-1-IgA molecules targeted against rhinoviruses.


title: Value of Genetic Testing for Hereditary Colorectal Cancer in a Probability-Based US Online Sample.

text: BACKGROUND . While choices about genetic testing are increasingly common for patients and families, and public opinion surveys suggest public interest in genomics, it is not known how adults from the general population value genetic testing for heritable conditions. We sought to understand in a US sample the relative value of the characteristics of genetic tests to identify risk of hereditary colorectal cancer, among the first genomic applications with evidence to support its translation to clinical settings. METHODS . A Web-enabled choice-format conjoint survey was conducted with adults age 50 years and older from a probability-based US panel. Participants were asked to make a series of choices between 2 hypothetical blood tests that differed in risk of false-negative test, privacy, and cost. Random parameters logit models were used to estimate preferences, the dollar value of genetic information, and intent to have genetic testing. RESULTS . A total of 355 individuals completed choice-format questions. Cost and privacy were more highly valued than reducing the chance of a false-negative result. Most (97% [95% confidence interval (CI)], 95%-99%) would have genetic testing to reduce the risk of dying of colorectal cancer in the best scenario (no false negatives, results disclosed to primary care physician). Only 41% (95% CI, 25%-57%) would have genetic testing in the worst case (20% false negatives, results disclosed to insurance company). CONCLUSIONS . Given the characteristics and levels included in the choice, if false-negative test results are unlikely and results are shared with a primary care physician, the majority would have genetic testing. As genomic services become widely available, primary care professionals will need to be increasingly knowledgeable about genetic testing decisions.


title: [Dynamic changes of T-lymphocytes and immunoglobulins in patients with severe acute respiratory syndrome].

text: OBJECTIVE To study the immunological changes in patients suffered from severe acute respiratory syndrome (SARS). METHODS T-lymphocyte subsets of peripheral blood from 124 patients with different phases of SARS were measured by flow cytometry. Immunoglobulins were examined simultaneously. Blood specimens from 51 patients with AIDS and 57 normal persons were collected as controls and subjected to the same measurements. RESULTS The levels of CD3(+), CD4(+) and CD8(+) T-lymphocytes in SARS group [(589 +/- 435) x 10(6)/L, (316 +/- 267) x 10(6)/L and (215 +/- 165) x 10(6)/L, respectively] were significantly lower than those of the normal group (P < 0.01). When compared the SARS group with AIDS group, we found the level of CD4(+) T-lymphocyte in the former was higher (P < 0.01), while the CD3(+) and CD8(+) T-lymphocytes were lower (P < 0.01). There were 54 (44%) patients in SARS group and 39 (76%) patients in AIDS group showed low levels of CD4(+) T-lymphocyte (< 200 x 10(6)/L). The count of T-lymphocyte subsets of SARS group decreased to the lowest level during the 10(th) and 12(th) day after the onset of symptoms. Both serum IgG and IgE in SARS group [(15.1 +/- 8.5) g/L and (0.6 +/- 0.9) g/L, respectively] were higher than those of the normal group. CONCLUSION The levels of CD3(+), CD4(+) and CD8(+) T-lymphocyte subsets in peripheral blood of SARS patients decrease significantly and go down to the lowest point at days 10 approximately 12 after onset of the disease.


docid: uvchrgov

title: Pathogenicity studies of feline coronavirus isolates 79-1146 and 79-1683.

text: Two feline coronavirus isolates were characterized by their disease-causing potential in cats. The 79-1683 feline coronavirus isolate caused an inapparent-to-mild enteritis when given oronasally to specific-pathogen-free kittens and was not a cause of feline infectious peritonitis (FIP). Target tissues for the virus were the mature apical epithelium of the small intestine, mesenteric lymph nodes, tonsils, thymus, and (to a lesser extent) the lungs. Inoculated kittens shed high numbers of virus in their feces for 14 to 17 days, but remained infectious to susceptible kittens for longer periods of time, as evidenced by contact-exposure studies. Because the 79-1683 isolate induced only enteritis, it was designated feline enteric coronavirus (FECV) 79-1683. The 79-1146 feline coronavirus isolate induced effusive abdominal FIP in specific-pathogen-free kittens after oronasal and intraperitoneal inoculation. Clinical signs of disease appeared within 12 to 14 days in almost all inoculated kittens. Because this isolate caused FIP, it was designated FIP virus (FIPV) 79-1146. Cross-protective immunity was not induced by the various coronavirus infections. Kittens preimmunized with the UCD strain of FECV (FECV-UCD) or with FECV-79-1683 were not immune to infection with FIPV-79-1146. Likewise, kittens previously inoculated with FECV-79-1683 were not immune to infection with FIPV-UCD1. In fact, preexisting heterologous FECV-79-1683 immunity often accelerated and enhanced the severity of disease caused by inoculation with FIPV-UCD1.(ABSTRACT TRUNCATED AT 250 WORDS)


Real-time polymerase chain reaction to diagnose lymphogranuloma venereum.


Atypical pneumonia.


title: Retroviral vectors pseudotyped with severe acute respiratory syndrome coronavirus S protein.

text: The worldwide outbreak of severe acute respiratory syndrome (SARS) was shown to be associated with a novel coronavirus (CoV) now called SARS CoV. We report here the generation of SARS CoV S protein-pseudotyped murine leukemia virus (MLV) vector particles. The wild-type S protein pseudotyped MLV vectors, although at a low efficiency. Partial deletion of the cytoplasmic tail of S dramatically increased infectivity of pseudotypes, with titers only two- to threefold lower than those of pseudotypes generated in parallel with the vesicular stomatitis virus G protein. S-pseudotyped MLV particles were used to analyze viral tropism. MLV(SARS) pseudotypes and wild-type SARS CoV displayed similar cell types and tissue and host restrictions, indicating that the expression of a functional receptor is the major restraint in permissiveness to SARS CoV infection. Efficient gene transfer could be detected in Vero and CaCo2 cells, whereas the level of gene marking of 293T, HeLa, and HepG2 cells was only slightly above background levels. A cat cell line and a dog cell line were not susceptible. Interestingly, PK-15, a porcine kidney cell line, and primary porcine kidney cells were also highly permissive for SARS S pseudotypes and wild-type SARS CoV. This finding suggests that swine may be susceptible to SARS infection and may be a source for infection of humans. Taken together, these results indicate that MLV(SARS) pseudotypes are highly valuable for functional studies of viral tropism and entry and, in addition, can be a powerful tool for the development of therapeutic entry inhibitors without posing a biohazard to human beings.


title: Cluster of severe acute respiratory syndrome cases among protected health-care workers--Toronto, Canada, April 2003.

text: Infections among health-care workers (HCWs) have been a common feature of severe acute respiratory syndrome (SARS) since its emergence. The majority of these infections have occurred in locations where infection-control precautions either had not been instituted or had been instituted but were not followed. Recommended infection-control precautions include the use of negative-pressure isolation rooms where available; N95 or higher level of respiratory protection; gloves, gowns, and eye protection; and careful hand hygiene. This report summarizes a cluster of SARS cases among HCWs in a hospital that occurred despite apparent compliance with recommended infection-control precautions.


title: [COVID-19 and pregnancy].

text: The current COVID-19 pandemic has resulted in an unprecedented worldwide health crisis. The increased vulnerability of pregnant women as well as past experience from previous coronavirus epidemics are cause for concern of maternal and fetal complications. The rapid outbreak of the disease combined with the uncertainty, as a direct result of the lack of strong scientific data, has forced obstetricians to adapt their current practices pragmatically. This article reviews obstetrical management of pregnant patients infected by SARS-CoV-2 based on the current knowledge.


title: Sensitivity comparison for detection of respiratory bovine coronaviruses in nasal samples from feedlot cattle by ELISA and isolation with the G clone of HRT-18 cells.

text: A monoclonal antibody-based capture enzyme-linked immunosorbent assay (ELISA) was developed to detect respiratory bovine coronavirus (RBCV) antigens in nasal swabs collected from cattle showing signs of respiratory tract disease following shipping. These samples had been previously tested for RBCV by inoculation of G clone cultures of human rectal tumor cells (HRT-18G) and for bovine herpes virus 1, parainfluenza virus 3, bovine adenovirus, bovine respiratory syncytial virus, and bovine viral diarrhea virus on other specifically permissive cell cultures. RBCV has not previously been recognized as an important etiological factor in the bovine respiratory disease complex of feedlot cattle. Thirty of 100 samples tested positive for RBCV antigen by capture ELISA in contrast to 38 of 100 samples that yielded RBCV isolates in G clone cells. Samples yielding other bovine respiratory viruses in the absence of RBCV were negative in the capture ELISA, which was based on the use of a single monoclonal antibody that recognizes one RBCV epitope on the S glycoprotein with the broadest reactivity with different strains of RBCV tested. Some RBCV strains may not be detected by this ELISA, which may account for the higher percentage of RBCV-infected cattle detected by RBCV isolation. However, the ELISA was simple to perform, sensitive, and specific and was more rapid than virus isolation. This assay will be useful for processing large numbers of field samples in future epidemiologic and diagnostic studies of RBCV infections of cattle.


title: Diagnosis of porcine and bovine enteric coronavirus infections using cloned cDNA probes.

text: Molecular clones representing the first 2,000 bases from the 3' end of the porcine transmissible gastroenteritis coronavirus genome and the first 2,160 bases from the 3' end of the bovine enteric coronavirus genome were used in dot blot hybridization assays to detect viral RNA from cell culture and from fecal specimens. In each case, the cloned DNA represents approximately 10% of the genome. The cloned sequence for each virus encompasses the 3' noncoding region, the nucleocapsid protein gene, and a large portion of the matrix protein gene. 32P-labeled cDNA probes prepared from these clones detected as little as 25 pg of RNA from the parental virus but did not detect RNA from the nonparental virus even when amounts of up to 10 ng per dot were used. This specificity reflects the antigenic diversity between these two coronaviruses. The hybridization assay could also detect coronaviruses antigenically closely related to the parental virus but not coronaviruses belonging to an antigenically unrelated subgroup. Dot blot hybridization for transmissible gastroenteritis coronavirus diagnosis was compared with the routine procedures of virus isolation and electron microscopy as a diagnostic test.


title: Binding of the coronavirus mouse hepatitis virus A59 to its receptor expressed from a recombinant vaccinia virus depends on posttranslational processing of the receptor glycoprotein.

text: Recently, we showed that a murine member of the carcinoembryonic antigen family of glycoproteins serves as a cellular receptor (MHVR) for the coronavirus mouse hepatitis virus A59 (MHV-A59) (G. S. Dveksler, M. N. Pensiero, C. B. Cardellichio, R. K. Williams, G.-S. Jiang, K. V. Holmes, and C. W. Dieffenbach, J. Virol. 65:6881-6891, 1991; R. K. Williams, G.-S. Jiang, and K. V. Holmes, Proc. Natl. Acad. Sci. USA 88:5533-5536, 1991). To examine the role of posttranscriptional modification of MHVR on virus-receptor interactions, a vaccinia virus-based expression system was employed. Expression from the vaccinia virus recombinant (Vac-MHVR) in BHK-21 cells resulted in high levels of MHVR glycoprotein on the cell surface and made these cells susceptible to MHV-A59 infection. Nonglycosylated core MHVR proteins were made in Vac-MHVR-infected BHK-21 cells in the presence of tunicamycin by in vitro translation of MHVR mRNA in a rabbit reticulocyte cell-free system in the absence of microsomal membranes and by expression of an N-terminal deletion clone of MHVR lacking its signal peptide. These three nonglycosylated MHVR proteins were recognized by polyclonal antibody against affinity-purified receptor but did not bind antireceptor monoclonal antibody (MAb) CC1 or MHV-A59 virions. Partial glycosylation of MHVR, either expressed in Vac-MHVR-infected cells treated with monensin or synthesized by in vitro translation with microsomal membranes, restored both the MAb CC1- and the virus-binding activities of the MHVR glycoprotein. Deletion of 26 amino acids at the carboxyl terminus of MHVR resulted in a secreted protein which was able to bind MAb CC1 and MHV-A59. These results suggest that either a carbohydrate moiety is an element of the MHVR-binding site(s) for virus and MAb CC1 or a posttranslational membrane-associated process is required for functional conformation of the receptor glycoprotein.


title: Cloning of the mouse hepatitis virus (MHV) receptor: expression in human and hamster cell lines confers susceptibility to MHV.

text: The cellular receptor for murine coronavirus mouse hepatitis virus (MHV)-A59 is a member of the carcinoembryonic antigen (CEA) family of glycoproteins in the immunoglobulin superfamily. We isolated a cDNA clone (MHVR1) encoding the MHV receptor. The sequence of this clone predicts a 424-amino-acid glycoprotein with four immunoglobulinlike domains, a transmembrane domain, and a short intracytoplasmic tail, MHVR1 is closely related to the murine CEA-related clone mmCGM1 (Mus musculus carcinoembryonic antigen gene family member). Western blot (immunoblot) analysis performed with antireceptor antibodies detected a glycoprotein of 120 kDa in BHK cells stably transfected with MHVR1. This corresponds to the size of the MHV receptor expressed in mouse intestine and liver. Human and hamster fibroblasts transfected with MHVR1 became susceptible to infection with MHV-A59. Like MHV-susceptible mouse fibroblasts, the MHVR1-transfected human and hamster cells were protected from MHV infection by pretreatment with monoclonal antireceptor antibody CC1. Thus, the 110- to 120-kDa CEA-related glycoprotein encoded by MHVR1 is a functional receptor for murine coronavirus MHV-A59.


title: An outbreak of Middle East Respiratory Syndrome (MERS) due to coronavirus in Al-Ahssa Region, Saudi Arabia, 2015.

text: Between 19 April and 23 June 2015, 52 laboratory-confirmed cases of Middle East Respiratory Syndrome due to coronavirus (MERS) were reported from Al-Ahssa region, eastern Saudi Arabia. The first seven cases occurred in one family; these were followed by 45 cases in three public hospitals. The objectives of this investigation were to describe the epidemiological characteristic of the cluster and identify potential risk factors and control measures to be instituted to prevent further occurrence of MERS. We obtained the medical records of all confirmed cases, interviewed the members of the affected household and reviewed the actions taken by the health authorities. All the cases were connected. The index case was a 62-year-old man with a history of close contact with dromedary camels; three of the seven infected family members and 18 people in hospitals died (case-fatality rate, 40.4%). The median incubation period was about 6 days. The cluster of cases appeared to be due to high exposure to MERS, delayed diagnosis, inadequate risk communication and inadequate compliance of hospital health workers and visitors with infection prevention and control measures.


title: Resident training in single-incision laparoscopic colectomy.

text: Single-incision laparoscopic colectomy (SLC) is touted as an improved approach to minimally invasive surgery, although no data currently exist regarding the acquisition of this technique. The aim of this study was to evaluate resident performance and outcomes in patients undergoing SLC performed by residents vs. staff colorectal surgeons. A retrospective case-control study was conducted, including 220 patients who underwent elective surgical intervention with multiport laparoscopic colectomy (MLC, n=141) or SLC (n=79) for colon cancer over a 24-month period at Yao Municipal Hospital (Yao, Japan). Data on patient demographics, operative data, oncological outcomes and short-term outcomes were evaluated for statistical significance. To investigate issues regarding the surgical procedures, the entire operation was recorded on video for all patients and was divided into 6 procedures, with each procedure measured in seconds. Senior-level residents were able to safely perform MLC under appropriate experienced supervision. For SLC, 1 case required conversion to an open procedure. No case required additional trocar placement. The mean operative times were similar for the staff and resident groups for total colon cancer (192.5 and 217.5 min, respectively; P=0.88), whereas the operative times of the staff group for right-sided colon cancer were significantly longer, and the operative times of the resident group for left-sided colon cancer were significantly longer. In addition, the overall perioperative outcomes, including blood loss, number of harvested lymph nodes, length of the surgical margin and complications, were similar between the two groups. When video recordings were evaluated by dividing the surgical process for the right colon into 4 procedures and that for the left colon into 6 procedures, the results demonstrated that the residents required more time to close the mesenteric margin for the left colon compared with the staff performing the same procedure (3,470.1±1,258.5 vs. 5,218.6±2,341.2 sec; P=0.01). Therefore, senior-level residents were able to safely perform SLC under appropriate experienced supervision. For the left colon, the main challenge for the residents appeared to be the closure of the mesenteric margin. Our data support that it is possible to train senior residents to complete a SLC safely and with the same efficacy as staff surgeons.


Catheter-based renal denervation: treating hypertension or beyond?


title: Impact of non-pharmaceutical interventions on URIs and influenza in crowded, urban households.

text: OBJECTIVES We compared the impact of three household interventions-education, education with alcohol-based hand sanitizer, and education with hand sanitizer and face masks-on incidence and secondary transmission of upper respiratory infections (URIs) and influenza, knowledge of transmission of URIs, and vaccination rates. METHODS A total of 509 primarily Hispanic households participated. Participants reported symptoms twice weekly, and nasal swabs were collected from those with an influenza-like illness (ILI). Households were followed for up to 19 months and home visits were made at least every two months. RESULTS We recorded 5034 URIs, of which 669 cases reported ILIs and 78 were laboratory-confirmed cases of influenza. Demographic factors significantly associated with infection rates included age, gender, birth location, education, and employment. The Hand Sanitizer group was significantly more likely to report that no household member had symptoms (p < 0.01), but there were no significant differences in rates of infection by intervention group in multivariate analyses. Knowledge improved significantly more in the Hand Sanitizer group (p < 0.0001). The proportion of households that reported > or = 50% of members receiving influenza vaccine increased during the study (p < 0.001). Despite the fact that compliance with mask wearing was poor, mask wearing as well as increased crowding, lower education levels of caretakers, and index cases 0-5 years of age (compared with adults) were associated with significantly lower secondary transmission rates (all p < 0.02). CONCLUSIONS In this population, there was no detectable additional benefit of hand sanitizer or face masks over targeted education on overall rates of URIs, but mask wearing was associated with reduced secondary transmission and should be encouraged during outbreak situations. During the study period, community concern about methicillin-resistant Staphylococcus aureus was occurring, perhaps contributing to the use of hand sanitizer in the Education control group, and diluting the intervention's measurable impact.


docid: mhwjshow

title: Bats as the reservoir for outbreaks of emerging infectious diseases.


title: Ex-vivo release of Pipeline Embolization Device polytetrafluoroethylene (PTFE) sleeves for improved distal landing zone accuracy in-vivo: A technical note.

text: BACKGROUND Distal landing zone accuracy is critical in some intracranial aneurysms treated with the Pipeline Embolization Device (PED), and delayed opening of the distal end of the device can complicate the procedure. Here, we report a technical nuance that facilitates accurate placement of the distal end of the PED by ex-vivo, pre-implantation release of the PED Flex polytetrafluoroethylene (PTFE) sleeves. TECHNICAL NOTE The PED Flex is partially pushed out of the introducer sheath ex-vivo, pre-implantation until the distal PED opens entirely and the PTFE sleeves are located distal to the device. Without inverting the PTFE sleeves, the PED is carefully pulled back into the introducer sheath placing the PTFE sleeves inside the device. The PED is loaded into the microcatheter and advanced toward the site of implantation. When the PED is initially deployed and pushed out of the microcatheter, it opens immediately and provides an anchor for the remainder of the deployment process. We present a video (supplementary material) that illustrates the technique along with an illustrative case. CONCLUSION Ex-vivo, pre-implantation release of the PTFE sleeves is an option in aneurysm treatment where distal landing accuracy is critical. Even without the protection of the PTFE sleeves, our clinical observation shows that the PED can be advanced safely through the microcatheter in selected cases.


title: Computer Aided Detection of SARS Based on Radiographs Data Mining.

text: This paper introduces our work on how to use image mining techniques to detect SARS, the severe acute respiratory syndrome, automatically as the prototype of computer aided detection/diagnosis (CAD) system. Data used in this paper are digitalized PA(posterior anterior) X-ray images stored in the real-life picture archiving and communication system (PACS) of the 2nd Affiliation Hospital of Guangzhou Medical College. Association rule mining was applied first but results showed there was no significant difference between the locations of the lesions or infiltrate. Classification based on image textures was performed. A sample set contains both the pneumonia and SARS X-ray images was built in the first place. After modeling each sample by a feature vector, the sample set was partitioned to match the detection purpose: classification. Three methods were used: C4.5, neural network (NN) and CART. Final result shows that 70.94% SARS cases can be detected by CART. Data preparation, segmentation, feature extraction and data mining steps, with corresponding techniques are included in this paper. ROC charts and confusion matrix by all three methods are given and analyzed.


title: The influence of different dialysis modalities on the quality of life of patients with end-stage renal disease: A systematic literature review.

text: OBJECTIVES This study aims to generate evidence regarding the relationships of different dialysis modalities with HR-QOL. DESIGN A systematic review was conducted to investigate the HR-QOL of patients treated with different dialysis modalities. METHODS A literature search was conducted for English language articles in the CINAHL, Medline and PubMed databases published from January 1990 through May 2016. Specifically, we sought articles that would compare the HR-QOL of hemodialysis (HD) and peritoneal dialysis (PD) patients in terms of physiological, psychological and social functioning, as well as disease symptoms. Thirty-four articles met the study inclusion criteria and were included into the analysis. RESULTS The research results indicated no significant differences in HR-QOL between HD and PD treatment. However, a higher percentage of patients who received PD had a better HR-QOL in terms of physiological, psychological, social and disease symptoms. CONCLUSIONS Despite the fact that the results of this study showed no difference in HR-QOL between HD and PD treatment, its review of relevant references can serve as a reference for health professionals. However, patients' conditions must still be taken into account when making suggestions about which dialysis modality a patient should use.


title: Investigation of the control of coronavirus subgenomic mRNA transcription by using T7-generated negative-sense RNA transcripts.

text: The subgenomic mRNAs of the coronavirus transmissible gastroenteritis virus (TGEV) are not produced in equimolar amounts. We have developed a reporter gene system to investigate the control of this differential subgenomic mRNA synthesis. Transcription of mRNAs by the TGEV polymerase was obtained from negative-sense RNA templates generated in situ from DNA containing a T7 promoter. A series of gene cassettes was produced; these cassettes comprised the reporter chloramphenicol acetyltransferase (CAT) gene downstream of transcription-associated sequences (TASs) (also referred to as intergenic sequences and promoters) believed to be involved in the synthesis of TGEV subgenomic mRNAs 6 and 7. The gene cassettes were designed so that negative-sense RNA copies of the CAT gene with sequences complementary to the TGEV TASs, or modified versions, at the 3' end would be synthesized in situ by T7 RNA polymerase. Using this system, we have demonstrated that CAT was expressed from mRNAs derived from the T7-generated negative-sense RNA transcripts only in TGEV-infected cells and only from transcripts possessing a TGEV negative-sense TAS. Analysis of the CAT mRNAs showed the presence of the TGEV leader RNA sequence at the 5' end, in keeping with observations that all coronavirus mRNAs have a 5' leader sequence corresponding to the 5' end of the genomic RNA. Our results indicated that the CAT mRNAs were transcribed from the in situ-synthesized negative-sense RNA templates without the requirement of TGEV genomic 5' or 3' sequences on the T7-generated negative-sense transcripts (3'-TAS-CAT-5'). Modification of the TGEV TASs indicated (i) that the degree of potential base pairing between the 3' end of the leader RNA and the TGEV negative-sense TAS was not the sole determinant of the amount of subgenomic mRNA transcribed and (ii) that other factors, including nucleotides flanking the TAS, are involved in the regulation of transcription of TGEV subgenomic mRNAs.


docid: aehrcrht

title: Pharmacotherapy for obesity.

text: BACKGROUND Obesity is a serious, chronic, relapsing disease of energy regulation, with strong genetic and early-life environmental determinants. Pharmacotherapy can be a useful adjunct to lifestyle intervention in effecting and maintaining clinically meaningful weight loss. OBJECTIVE The aim of this article is to discuss the role of pharmacotherapy in obesity management. The efficacy, side effects and contraindications of available weight-loss medications are reviewed. DISCUSSION Long-term pharmacotherapy options, which can be effective in providing moderate weight loss, are available to treat obesity. Pharma-cotherapy should be considered an adjunct to lifestyle intervention in those with a body mass index (BMI) >30 kg/m30 kg/m2, or in those with a BMI of 27-30 kg/m2 and obesity-related complications. Safety and efficacy should be monitored closely on commencement, and the medication should be discontinued if there are safety or tolerability issues, or if.


title: Civets are equally susceptible to experimental infection by two different severe acute respiratory syndrome coronavirus isolates.

text: Severe acute respiratory syndrome (SARS) was caused by a novel virus now known as SARS coronavirus (SARS-CoV). The discovery of SARS-CoV-like viruses in masked palm civets (Paguma larvata) raises the possibility that civets play a role in SARS-CoV transmission. To test the susceptibility of civets to experimental infection by different SARS-CoV isolates, 10 civets were inoculated with two human isolates of SARS-CoV, BJ01 (with a 29-nucleotide deletion) and GZ01 (without the 29-nucleotide deletion). All inoculated animals displayed clinical symptoms, such as fever, lethargy, and loss of aggressiveness, and the infection was confirmed by virus isolation, detection of viral genomic RNA, and serum-neutralizing antibodies. Our data show that civets were equally susceptible to SARS-CoV isolates GZ01 and BJ01.


Targeting diversity.


Leading through COVID-19 crisis.


title: Challenges for the development of ribonucleoside analogues as inducers of error catastrophe.

text: RNA viruses are responsible for numerous human diseases; some of these viruses are also potential agents of bioterrorism. In general, the replication of RNA viruses results in the incorporation of at least one mutation per round of replication, leading to a heterogeneous population, termed a quasispecies. The antiviral nucleoside ribavirin has been shown to cause an increase in the mutation frequency of RNA viruses. This increase in mutation frequency leads to a loss of viability due to error catastrophe. In this article, we review lethal mutagenesis as an antiviral strategy, emphasizing the challenges remaining for the development of lethal mutagenesis into a practical clinical approach.


docid: vaffeywy

title: Predictors of postoperative atrial fibrillation after on-pump coronary artery bypass grafting: is duration of mechanical ventilation time a risk factor?

text: PURPOSE This study aimed to establish the role of risk factors in the etiology of postoperative atrial fibrillation (AF) after coronary artery bypass grafting (CABG). METHODS Between September 2001 and March 2008, 1040 patients underwent isolated CABG at our clinic. Nine hundred and eleven of these patients did not have any AF(Non-AF Group) and the other one hundred and twenty-nine had AF (AF Group). A retrospective study was performed for patient, disease and treatment related factors and multivariate analysis was used to identify independent clinical predictors of postoperative AF. RESULTS Postoperative AF was identified in 129 (12.4%) of the patients, and those were significantly older and had significantly higher additive EuroSCORE score as compared with patients without AF. During the postoperative course, patients with postoperative AF also had significantly higher and prolonged (≥6 hours) mechanical ventilation time, longer and prolonged intensive care unit stay and longer hospital stay. Logistic regression analysis revealed that postoperative AF development ratio was 1.690 times higher when the ventilation time was over 6 hours (OR 1.690, 95% CI 1.092-2.615, p = 0.018); 1.240 times higher in the presence of elevated additive EuroSCORE score (OR 1.240, 95% CI1.109-1.385, p = 0.0001); 1.052 times higher in the presence of advanced age (OR 1.052,95% CI 1.031-1.0741, p = 0.0001). CONCLUSION Analysis of our data reveals that, patient's age, additive EuroSCORE score, and prolonged ventilation are predictors of postoperative AF. Identification of risk factors might lead to better prevention of this problem and its potential consequences. However, to support our investigation and obtain more reliable evidence, prospective randomized controlled trials are needed.


docid: ahzcjdxs

title: Viruses and asthma exacerbations.


title: [Glucocorticoid-induced diabetes in severe acute respiratory syndrome: the impact of high dosage and duration of methylprednisolone therapy].

text: OBJECTIVE Over-dose glucocorticoid was frequently used in patients with severe acute respiratory syndrome (SARS), the aim of the present study is to investigate the frequency and risk factors of corticosteroid-induced diabetes in this situation. METHODS One hundred thirty-three cases of SARS admitted from May to June 2003 in our hospital were included in the study. Maximal dose, average daily dose, treatment course and fasting plasma glucose level (FPG) were recorded. Corticosteroid-induced diabetes was diagnosed if FPG was equal to or higher than 7 mmol/L twice or more after the administration of glucocorticoids. RESULTS Ninety five patients (71.9%) were prescribed with glucocorticoid among the 132 patients. Thirty-three patients (36.3%) were diagnosed as corticosteroid-induced diabetes according to the FPG. Significant differences were found in daily maximal dosage, duration of treatment and average dosage of methylprednisolone between the patients with and without corticosteroid-induced diabetes (275 mg/d vs 136 mg/d, 24 d vs 16 d, 139 mg/d vs 91 mg/d, P < 0.01). As compared with the lowest tertile, the frequency of diabetes in SARS patients treated with highest tertile of maximal daily dosage, treatment duration, average dosage or total dosage were significantly higher (64.7% vs 13.0, 61.9% vs 17.4%, 62.5% vs 21.7%, and 59.2% vs 13.6%, P < 0.05 for all comparisons). If the patients were treated with an average dose less than 90 mg/d and treatment duration shorter than 15 days, the diabetes incidence was 10.5%. After adjusting age and sex, the daily maximal dosage of methylprednisolone was the only factor that might predict the occurrence of diabetes. CONCLUSIONS Over-dose administration of methylprednisolone in SARS patients leads to a high frequency of diabetes. Decreasing the daily maximal dosage may be beneficial to the reduction of corticosteroid-induced of diabetes.


Critical care medicine in China: history and perspective.


title: COVID-19 and Cardiovascular diseases. Scoping review study.

text: BACKGROUND Many patients with COVID-19 have pre-existing cardiovascular (CV) co-morbidities or develop acute heart damage during the course of the disease. OBJECTIVES To study the risk of COVID-19 infection in the presence of preexisting CV diseases and to describe new CV manifestations during COVID-19. METHODS A "scoping review" was carried out via PubMed, to synthesize the results of research currently published on this subject. RESULTS Patients with cardiovascular disease were at greater risk of developing COVID-19, especially in its severe form. These patients were five to ten times more at risk of death. Cardiac manifestations, de novo, were dominated by acute myocardial damage, defined by a significant elevation of cardiac troponins. These occurred in 7 to 17% of hospitalized patients. The presence of a new heart lesion in patients with COVID-19 was consistently associated with a poor prognosis. CONCLUSION Given the enormous cardiovascular challenge posed by the COVID-19 pandemic and the prognostic impact of heart damage, additional research at a high level of evidence will be necessary.


title: [Prostate cancer and COVID-19 pandemia: Current recommendations.]

text: OBJECTIVE The objective of this publicationis to provide recommendations in the management of prostate cancer (PC) in a new reality framework based on the presence of COVID-19 disease. MATERIAL AND METHODS The document is based on the scarce evidence on SARS/Cov-2 and the experience of the authors in handling COVID-19 in their institutions, including specialists from Andalusia, Cantabria, Catalonia, Madrid and the Valencian Community. RESULTS The authors defined different priorities for the different clinical situations in PC. Emergency/urgency (life-threatening or urgent even in normal situation), highpriority/elective urgency (potentially dangerous if postponed for more than 1 month), intermediate/electivepriority (it is recommended not to delay more than 6 months), low priority/delayed (can be postponed more than 6 months). According to this classification, the working panel agreed on the distribution of the different diagnostic, therapeutic and follow-up scenarios for PC. The risk of severe morbidity as a result of SARS-CoV-2 infection may out weigh the risk of PC morbidity/mortalityin many men; therefore, in the short term it is unlikely that delays in diagnosis or treatment can led to worse cancer outcomes. CONCLUSIONS The COVID-19 pandemic has resulted in a challenge for our health system, which raises several considerations in the treatment of patients with PC. The redistribution of surgical procedures according to the degrees of priority is essential during the period of the pandemic and the transition to the new normality. The change of the out-clinics with the adequate security measures for healthcare practitioners and patients, andt he development of a telemedicine program is highly recommended.


The professor of "telepreventive medicine".


title: Computational approaches for the discovery of cysteine protease inhibitors against malaria and SARS.

text: Cysteine proteases are implicated in a variety of human physiological processes and also form an essential component of the life cycle of a number of pathogenic protozoa and viruses. The present review highlights the drug design approaches utilized to understand the mechanism of inhibition and discovery of inhibitors against protozoal cysteine protease, falcipain (a cysteine protease of P. falciparum which causes malaria), and viral cysteine protease, SARS-CoV M(pro) (a cysteine protease of severe acute respiratory syndrome corona virus). The article describes rational approaches for the design of inhibitors and focuses on a variety of structure as well as ligand-based modeling strategies adopted for the discovery of the inhibitors. Also, the key features of ligand recognition against these targets are accentuated. Although no apparent similarities exist between viral and protozoal cysteine proteases discussed here, the goal is to provide examples of rational drug design approaches adopted to design inhibitors against these proteases. The current review would be of interest to scientists engaged in the development of drug design strategies to target the cysteine proteases present in mammals and other lower order organisms.


title: Antibody to virus components in volunteers experimentally infected with human coronavirus 229E group viruses.

text: Antibody rises to various virus subcomponents were measured by enzyme-linked immunosorbent assay in the paired sera of volunteers experimentally infected with human coronavirus 229E group viruses. Most of the antibody made during infection was directed against the virus surface projections, with only small amounts of antibody made against membrane or ribonucleoprotein components.


title: Retargeting of coronavirus by substitution of the spike glycoprotein ectodomain: crossing the host cell species barrier.

text: Coronaviruses generally have a narrow host range, infecting one or just a few species. Using targeted RNA recombination, we constructed a mutant of the coronavirus mouse hepatitis virus (MHV) in which the ectodomain of the spike glycoprotein (S) was replaced with the highly divergent ectodomain of the S protein of feline infectious peritonitis virus. The resulting chimeric virus, designated fMHV, acquired the ability to infect feline cells and simultaneously lost the ability to infect murine cells in tissue culture. This reciprocal switch of species specificity strongly supports the notion that coronavirus host cell range is determined primarily at the level of interactions between the S protein and the virus receptor. The isolation of fMHV allowed the localization of the region responsible for S protein incorporation into virions to the carboxy-terminal 64 of the 1,324 residues of this protein. This establishes a basis for further definition of elements involved in virion assembly. In addition, fMHV is potentially the ideal recipient virus for carrying out reverse genetics of MHV by targeted RNA recombination, since it presents the possibility of selecting recombinants, no matter how defective, that have regained the ability to replicate in murine cells.


title: Antigenic relationships among homologous structural polypeptides of porcine, feline, and canine coronaviruses.

text: Transmissible gastroenteritis virus of swine (TGEV), feline infectious peritonitis virus (FIPV), and canine coronavirus were studied with respect to their serological cross-reactivity in homologous and heterologous virus neutralization, immune precipitation of radiolabeled TGEV, electroblotting, and enzyme-linked immunosorbent assay using individual virion polypeptides prepared by polyacrylamide gel electrophoresis. TGEV was neutralized by feline anti-FIPV serum, and the reaction was potentiated by complement; heterologous neutralization involved antibody reacting with the peplomer protein (P), the envelope protein (E), and cellular (glycolipid) components incorporated into the TGEV membrane. Electrophoretic analysis of immune precipitates containing [35S]methionine-labeled disrupted TGEV and feline anti-FIPV antibody confirmed the reaction with the P and E polypeptides and showed the nucleocapsid protein (N) in addition. Electroblotting, followed by incubation with antibody, 125I-labeled protein A, and fluorography, disclosed cross-reactions between the three viruses at the N and E levels and revealed differences in the apparent molecular weights of the latter. Enzyme immunoassays performed with standard amounts of immobilized P, N, and E polypeptides of the three viruses showed recognition of the antigens by homologous and heterologous antibody to comparable degrees. These results indicate a close antigenic relationship between TGEV, FIPV, and canine coronavirus due to common determinants on the three major virion proteins. The taxonomic implications of these findings are discussed.


title: Immunogenicity of recombinant feline infectious peritonitis virus spike protein in mice and kittens.

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


title: Human metapneumovirus infection in the Canadian population.

text: Human metapneumovirus (hMPV), a newly discovered paramyxovirus, has been associated with acute respiratory tract infections (ARIs) ranging from upper ARIs to severe bronchiolitis and pneumonia. Important questions remain on the contribution of hMPV to ARIs and its impact on public health. During the 2001-2002 season, we conducted a collaborative study with four provincial public health laboratories to study the prevalence of this new virus in the Canadian population. A total of 445 specimens were collected from patients of all age groups with ARIs and were tested for the presence of hMPV by reverse transcription-PCR. Of these, 66 (14.8%) tested positive for hMPV. Positive specimens were found in all age groups and in all four provinces studied. Virus activity peaked in February and March. The age range of the patients with hMPV infection was 2 months to 93 years (median age, 25 years), with similar numbers of females (35%) and males (41%). Thirty-three percent (n = 22) of hMPV-infected patients were hospitalized; of these, 27% (n = 6) had rhinitis and pneumonia, 23% (n = 5) had bronchiolitis, and 9% (n = 2) had bronchitis. The hospitalization rates were significantly higher among patients <5 years of age (P = 0.0005) and those >50 years of age (P = 0.0044) than among those 6 to 50 years of age. Phylogenetic analysis of the F gene showed that two hMPV genetic clusters were cocirculating in the 2001-2002 season, and comparison with earlier studies suggests a temporal evolutionary pattern of hMPV isolates. These results provide further evidence of the importance of hMPV in ARIs, particularly in young children and elderly individuals.


title: A randomised trial comparing 0.02% mitomycin C and limbal conjunctival autograft after excision of primary pterygium.

text: BACKGROUND Mitomycin C (MMC) and limbal conjunctival autograft (LCAU) are two known useful adjuvants in the prevention of pterygial recurrence. This study was conducted to compare the outcome of these two treatments. METHODS Prospective study on consecutive cases of primary pterygium (February 2001 to March 2002) randomised into two adjuvant groups: (1) intraoperative 0.02% MMC for 5 minutes or (2) LCAU. Patients were followed for recurrence (defined as fibrovascular tissue invading the cornea >1.5mm) and complications for a period of one year. RESULTS 115 eyes in 114 patients who completed the study were randomised to receive MMC (n = 63) and LCAU (n = 52). There were 10 recurrences (15.9%) in the MMC group and only one recurrence (1.9%) in the LCAU group. There was a statistically significant difference in the recurrence rate between the two groups (p = 0.04). There were a total of three conjunctival cysts, three symblephara, one granuloma, and one dellen. No other visually significant complications were encountered in either group. CONCLUSION Although LCAU resulted in better one year success rates, it is technically more difficult and inapplicable in cases with previous limbal disturbance. Simple excision followed by MMC or LCAU are both safe and acceptable adjuvants for pterygium excision. Choice of adjuvant should be carefully made based on assessment of recurrence risk, local practices, and surgeon's expertise.


title: Development of reverse transcriptase PCR and nested PCR to detect porcine hemagglutinating encephalomyelitis virus.

text: Porcine hemagglutinating encephalomyelitis virus (HEV) causes encephalomyelitis, or vomiting and wasting disease, in suckling piglets. The mortality rate for piglets under 3 weeks old is 100%, but they are usually protected by maternal antibodies. Recently, the risk of an HEV outbreak has increased in the pig industry, because of widely using specific pathogen-free pigs that have no antibodies to HEV. We developed reverse transcription (RT) PCR and nested PCR to detect HEV. Primer sets of polymerase, non-structural protein, and spike protein were designed for RT-PCR and nested PCR based on the nucleotide sequences of the HEV 67N strain. The PCR designated primer sets of spike protein detected only HEV viral RNA among other related nidoviruses. Detection of HEV viral RNA by nested PCR was more sensitive than virus isolation in cell cultures. Nested PCR detected HEV viral RNA from experimentally infected samples of mice and field samples of piglets. The RT-PCR and nested PCR methods to detect HEV is considered a good way to show the HEV etiology on pig farms.


title: Associations between ambient ozone, hydrocarbons, and childhood wheezy episodes: a prospective observational study in south east London.

text: OBJECTIVES To explore the hypothesis that hydrocarbon species and other air pollutants which accumulate at low and high concentrations of ozone are more directly associated with childhood wheezy episodes than ozone. METHODS Prospective observational study over 1 year set in the Lewisham district of south east London. The daily attendance rate of children with acute wheeze at the accident and emergency department of Lewisham Hospital was related to local measurements of ozone, hydrocarbon species, nitrogen dioxide (NO2), sulphur dioxide (SO2) and small particulate matter with diameter < 10 microns (PM10). RESULTS An inverse relation was found between the air pollutants and ozone. After seasonal and meteorological adjustment a non-linear U shaped trend was found between incidence of wheeze and ozone. The trend was significant in children < 2 years of age but not in older children. In the younger age group, after adjustment for season, temperature, wind speed, and respiratory infection, the incidence relative to that at the mean daily ozone concentration of 32.7 micrograms/m3, was estimated to increase by 65% (95% confidence interval (95% CI) 22% to 122%) at an ozone concentration of 5 micrograms/m3 (1.5 SDs below the mean) and by 63% (95% CI -6% to 184%) at 80 micrograms/m3 (2.5 SDs above the mean). For several hydrocarbons there were significant positive linear relations found, again in children < 2 years of age but not older children. For benzene, the incidence increased by 8% (95% CI 2 to 13%) per SD (SD 2.8 micrograms/m3) increase in benzene concentration. A same day association between incidence and ozone was found to be the most significant but for other pollutants a lag of 2 days gave the most significant associations. No significant association was found for the non-hydrocarbon pollutants including SO2, NO2, and PM10. CONCLUSIONS A U shaped relation was found between ozone and the incidence of wheezy episodes in young children. Certain hydrocarbon pollutants accumulate in the atmosphere when ozone concentrations are low, and are associated with childhood wheezy episodes. However, the U shaped association of ozone on incidence cannot be explained by these other pollutants. The finding supports an earlier finding that incidences of wheeze are at a minimum when ozone concentrations are 30-40 micrograms/m3.


title: Defining moments in risk communication research: 1996-2005.

text: Ten years ago, scholars suggested that risk communication was embarking on a new phase that would give increased attention to the social contexts that surround and encroach on public responses to risk information. A decade later, many researchers have answered the call, with several defining studies examining the social and psychological influences on risk communication. This article reviews risk communication research appearing in the published literature since 1996. Among studies, social trust, the social amplification of risk framework, and the affect heuristic figured prominently. Also common were studies examining the influence of risk in the mass media. Among these were content analyses of media coverage of risk, as well as investigations of possible effects resulting from coverage. The use of mental models was a dominant method for developing risk message content. Other studies examined the use of risk comparisons, narratives, and visuals in the production of risk messages. Research also examined how providing information about a risk's severity, social norms, and efficacy influenced communication behaviors and intentions to follow risk reduction measures. Methods for conducting public outreach in health risk communication rounded out the literature.


title: [Antigenicity characterization of six different fragments of SARS-CoV N protein expressed in E. coli].

text: OBJECTIVE To determine the antigen characteristics of different fragments of SARS-CoV N protein expressed in E. Coli and their application in the serological diagnosis. METHODS Based on preliminary analysis of 39 different segments of the N protein, We choosed six purified N protein for further antigenicity characterization in this study, including that PN360 (1 -360aa), PN301 (1-301aa), PN199 (30-228aa), PN185 (30-214aa), PN155b (60-214aa), and PN125 (90-214aa). We developed Western-Bolt and ELISA to detect antibody reactivity between truncated N fragments with sera from SARS-CoV-negative normal adults or SARS-CoV patient convalescent sera. RESULTS Western-Bolt results show that all the six fragments have reacted with the SARS patient convalescent sera, but the PN360 and PN301 showed obvious cross-reaction with sera from SARS-CoV-negative normal adults; sensitivity analysis using an ELISA coating with PN199, PN185, PN155b, PN125 as antigen showed that the PN185 and PN155b are better than PN125. CONCLUSION Truncated N protein PN185 and PN155b expressed in E. Coli are better antigen candidates used for detection of SARS-CoV specific antibody.


Post-influenza pneumonia: everything old is new again.


title: How pH opens a H+ channel: the gating mechanism of influenza A M2.

text: The tetrameric M2 protein from influenza A is one of the simplest pH-gated H+ channels known, offering the potential of structurally characterizing its gating mechanism. Since the only ionizable groups in the pore are four histidines, we investigated the stability and dynamics of all six possible protonation states of the protein by using molecular dynamics. We show that while all channel protonation states are surprisingly stable, only systems with two or more charged histidines are appreciably conductive. The structural switch, from a uniprotonated to a biprotonated channel, causes an electrostatic repulsion between the charged histidines that pushes the helices apart. This results in the formation of a continuous water file that conducts protons via a H+ wire. pKa calculations place this transition at a pH of 5.6, in remarkable agreement with the experimental value. Since the conversion from uniprotonation to biprotonation occurs during endosome acidification, this explains how M2 is activated in vivo.


title: [Expression of immune cells and their roles in the involved tissues of SARS patients].

text: OBJECTIVE To study the expression of the immune cell markers and their active antigens in the involved tissues of patients with severe acute respiratory syndrome (SARS). METHODS Specimens of the lungs, spleens and lymph nodes were obtained from autopsy of 3 SARS cases to investigate the expression of the immune cells and their activities with double immunohistochemical staining (DAB and AP) by using 14 immune cell markers and their active antigens. RESULTS A large quantity of proliferated macrophages could be observed in the lungs, spleens and lymph nodes of the SARS patients, some of which were positive for CD25 marker (active macrophages). In the lungs of the 3 patients, localized necrosis occurred where infiltration of CD45RO (+) T lymphocytes was observed, with only scarce Ki67 (+) T lymphocytes (active T lymphocytes) and B lymphocytes. In the lymph nodes, scattered T lymphocytes positive for Ki67 and CD45RO markers (active T lymphocytes) were seen, but the T lymphocytes subpopulations were obviously decreased, which was especially so with CD4+ and CD8+ T lymphocytes and NK cells. CONCLUSION Significantly enhanced activity of the macrophages occurs in SARS as the major reactive cells, but T lymphocyte subsets are obviously decreased, indicating the important roles of the macrophages and T lymphocytes in the pathogenesis of SARS.


title: Electronic laboratory reporting for the infectious diseases physician and clinical microbiologist.

text: BACKGROUND One important benefit of electronic health information is the improved interface between infectious diseases practice and public health. Electronic communicable disease reporting (CDR), given its legal mandate and clear public health importance, is a significant early step in the sifting and pooling of health data for purposes beyond patient care and billing. Over the next 5-10 years, almost all CDR will move to the internet. METHODS This paper reviews the components of electronic laboratory reporting (ELR), including sifting through data in a laboratory information management system for reportable results, controlled "vocabularies" (e.g., LOINC, Logical Observation Identifiers Names and Codes [Regenstrief Institute], and SNOMED, Systematized Nomenclature of Medicine [College of American Pathologists]), the "syntax" of an electronic message (e.g., health level 7 [HL7]), the implications of the Health Insurance Portability and Accountability Act for ELR, and the obstacles to and potential benefits of ELR. RESULTS There are several ways that infectious diseases physicians, infection control professionals, and microbiology laboratorians will participate in electronic CDR, including web-based case reporting and ELR, the direct, automated messaging of communicable disease reports from clinical lab information management systems to the appropriate public health jurisdiction's information system. CONCLUSIONS ELR has the potential to make a large impact on the timeliness and the completeness of communicable disease reporting, but it does not replace the clinician's responsibility to submit a case report with important demographic and epidemiologic information.


title: [Sequencing and Phylogenetic Analyses of Structural and Accessory Proteins of Middle East Respiratory Syndrome Coronavirus from the First Imported Case in China, 2015].

text: To investigate the genetic character and origin of the first imported infection case of middle East respiratory syndrome coronavirus (named as MERS-CoV_China GD01), RNA was extracted from swabs of this patient followed by RT-PCR amplification. All coding gene of structural (S, E, M, E) and accessory (ORF3, ORF4a, ORF4b, ORF5, ORF8b) proteins were sequenced and analyzed. Phylogenetic analyses of structural protein coding genes of MERS-CoV_ China GD01 indicates that several substitutes exists in S coding gene and its origin belong group 5 of MERS-CoV, which were recent circulated in Saudi Arabia area, while other three structural genes (N, E, M) were very conserved. Phylogenetic analyses of accessory protein coding genes of MERS-CoV China GD01 indicates that several substitutes exists among ORF3, ORF4a, ORF4b and ORF5, while ORF8b was conserved. In conclusion, genome of MERS-CoV_ China GD01 was general conserved although several genetic variations were found among structural and accessory protein coding genes. This is the first report on sequencing and phylogenetic analyses of the first imported MERS case in China, which may pay the way for prevention and control of imported MERS-CoV infection.


Characterization of IBV variant strain PL 84084 isolated in France.


title: Reducing the burden of maternal and child morbidity and mortality in the Eastern Mediterranean Region? Yes, we can.

text: Maternal and child morbidity and mortality are a major public health, development and human rights challenge globally and in the WHO Eastern Mediterranean Region. The Region is diverse, with high-, middle- and low- income countries, many suffering from political instability, conflicts and other complex development challenges. Although progress has been made towards Millennium Development Goals 4 and 5, it has been uneven both between and within countries. This paper makes an analysis of the strengths, weaknesses, opportunities and threats to improving maternal and child mortality and morbidity with a focus on the Region. In answer to the question whether we can reduce the burden of maternal and child morbidity and mortality in the Region: yes, we can. However, commitment and collaboration are needed at the country, regional and international levels.


title: Sequence and in vitro expression of the M2 gene of turkey rhinotracheitis pneumovirus.

text: Negative-stranded virion RNA and oligonucleotide primers complementary to fusion (F) protein gene sequences were used to generate cDNA clones, revealing that the gene 5'-proximal to the F protein corresponded to the M2 (22K) gene, as in respiratory syncytial (RS) virus. The transcription start signal, GGGACAAGU, was identical to that of the F and matrix (M) proteins of turkey rhinotracheitis virus (TRTV). There were two sequences with the potential to function as transcription termination/poly(A) signals, located at nucleotides 751 to 762 and 777 to 787; 15 clones derived from mRNA indicated that the first of these sequences formed the major signal. Part of the next downstream (5') gene was sequenced; unlike mammalian pneumoviruses the TRTV M2 gene did not overlap the beginning of the 5'-proximal gene. Northern blotting indicated that infected Vero cells contained less M2 mRNA than F mRNA and that about half of the M2 mRNA was present as a F-M2 dicistronic mRNA. The M2 gene contained two overlapping open reading frames (ORFs 1 and 2), as with RS virus. ORF 1 comprised 558 nucleotides with the coding potential for a 186 amino acid polypeptide, M(r) 20959, eight or nine residues shorter than for human RS virus strains. The overall amino acid identity was 40%, the N-terminal one-third of the proteins sharing 62% of residues, the remainder 29%. A hydropathy plot of the TRTV M2 protein had close similarity to that of the M2 or RS virus. The protein was predicted to have a basic character with no N-terminal signal sequence or other major highly hydrophobic sequences. In vitro translation of a transcript comprising both ORFs 1 and 2 produced a single product of apparent M(r) 23000, corresponding to the M2 product of ORF 1. Site-directed mutagenesis confirmed that this product was derived from ORF 1 and that frameshifting was not involved. The second ORF was expressed only from a transcript which lacked the AUG codons of ORF 1 and, although occupying a similar position to that in the RS virus M2 gene, had virtually no amino acid identity in its 73 residue length and was approximately 25% shorter than the corresponding RS virus ORF 2. The hydropathy plot of the potential products of the second ORFs of TRTV and RS virus showed little resemblance. Taken together these results suggest that ORF 2 is unlikely to be expressed in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)


title: Development of high-throughput liquid chips for respiratory virus detection.

text: BACKGROUND Diagnosis of viral respiratory tract infections clinically is often nonspecific, and a rapid, high-throughput laboratory technique which can detect major respiratory viruses is desirable. METHODS Two liquid chip panels were developed which used a target-enriched multiplexed RT-PCR amplification followed by Luminex liquid chip hybridization based on xMAP technology. One was for the detection of 5 type/ subtypes of the influenza virus (called Influenza Panel), the other was for the identification of 14 major respiratory viruses, including emerging human metapneumovirus (HMPV), coronavirus (CoV NL63, HKU1), human bocavirus (HBoV), and WU polyomavirus (WUPyV) (called Respiratory Panel). The analytical sensitivity and specificity of these two panels were determined. 108 throat swabs from influenza-like-illness (ILI) cases and 88 nasopharyngeal aspirates (NPA) from hospitalized children with lower respiratory tract infections (LRTI) were used to evaluate the two panels. RESULTS The Influenza Panel returned the analytical sensitivity of 4 - 10 copies vRNA/microL of sample for seasonal H1N1, H3N2, pandemic H1N1, and B, and 200 copies vRNA/microL of sample for H5. The analytical sensitivity of the Respiratory Panel was as follows: 10 - 150 copies vRNA/microL of sample for most of the viral targets tested in this panel except RSV (400 copies vRNA/microL of sample). No cross reactivity was observed for both panels. As determined by commercial multi-PCR kit and conventional PCR (for HBoV and WUPyV), the diagnostic sensitivity of the Respiratory Panel for each viral targets ranged from 50.0% to 100.0%, the diagnostic specificity was 96.2%-100.0%, and accordance rate was 93.2% - 100.0%, the kappa correlation of eight viral targets was > 0.75. CONCLUSIONS Two liquid chip assay panels, developed based on xMAP technology, can detect 5 types/subtypes of influenza viruses and 14 respiratory viruses simultaneously in one reaction in 6 hours. They are potentially rapid, sensitive, specific, and high throughput diagnostic tools for major viral pathogens associated with respiratory tract infection.


title: Non-traumatic osteonecrosis of the femoral head - from clinical to bench.

text: Non-traumatic osteonecrosis of the femoral head commonly affects young adults between the third and fifth decade of life. It is the leading cause of hip joint replacements in many Asian countries including Taiwan. The ultimate goal is the preservation of the involved hip. However, this is often challenging since early diagnosis is difficult, the etiologies are miscellaneous, the pathogenesis is unclear, and successful treatment is undetermined. As a consequence, this disease remains well-known but not fully-understood. This review provides an update of the progress from clinical studies to basic bench work in terms of natural history, risk factors, genetic predilections, diagnosis, staging, and miscellaneous therapeutic modalities.


title: Thoracoscopic wedge resection through a single incision using a thin puncture device.

text: Video-assisted thoracic surgery (VATS) has been enthusiastically used as a less-invasive diagnostic or therapeutic surgical procedure in recent years. VATS results in considerably less postoperative pain than traditional thoracotomy incisions. The current trend is to reduce the number of ports and minimize the length of incisions to further reduce postoperative pain, chest wall paresthesia, and length of hospitalization. Although several accounts of reduced port surgery, such as single-incision laparoscopic surgery (SILS), have been reported, there are few descriptions of single-incision thoracoscopic surgery (SITS) using a thin puncture device for a variety of diseases. Herein, we describe a minimally invasive SITS technique using a thin puncture device.


title: Human coronavirus polyadenylated RNA sequences in cerebrospinal fluid from multiple sclerosis patients.

text: Human coronaviruses, represented by the two prototype strains HCV-OC43 and HCV-229E, are important human respiratory pathogens, also associated with necrotizing enterocolitis. Two previous studies, one describing the electron microscopic observation of doughnut-shaped particles, resembling coronaviruses, in a perivascular inflammatory lesion of brain tissue taken at autopsy from a multiple sclerosis patient, and the other one reporting the isolation of coronaviruses from the brains of two multiple sclerosis patients, suggested the possible association between coronaviruses and human demyelinating diseases. We analysed polyadenylated RNAs extracted from cerebrospinal fluid of twenty randomly selected multiple sclerosis patients and ten patients with other neurological diseases (medullary atrophy, Parkinson's disease, polyneuropathy, senile dementia, headache and toxic polyneuropathy) by reverse transcription and polymerase chain reaction searching for HCV-OC43 and HCV-229E sequences. By hybridization analysis of amplification products, we detected HCV-OC43 polyadenylated RNAs in ten specimens of patients with multiple sclerosis. Furthermore, we found positive hybridization signals for HCV-OC43 in the other neurological diseases, except for the toxic polyneuropathy specimen. Positivity for HCV-229E was observed in seven specimens of multiple sclerosis cerebrospinal fluid; one headache cerebrospinal fluid and the medullary atrophy specimen also resulted positive for HCV-229E. Moreover, using a solid phase technique, we report for the first time the sequence of a cDNA fragment derived from RNA extracted from cerebrospinal fluid of multiple sclerosis patient, belonging to the open reading frame which codes for the HCV-OC43 nucleoprotein N. Furthermore, cDNA sequences revealed the presence of a mixed viral population.


title: Transradial Approach for Hepatic Radioembolization: Initial Results and Technique.

text: OBJECTIVE The transradial approach (TRA) has been shown to reduce the morbidity and mortality associated with arterial coronary interventions. Selective internal radiation therapy (SIRT) performed via the TRA can enhance patient comfort, compared with the traditional transfemoral approach (TFA), by allowing immediate ambulation and precluding potential complications associated with the TFA, such as closure device injury or retroperitoneal hematoma. We report our initial experience with and technique for using the TRA for SIRT. MATERIALS AND METHODS Between May 1, 2012, and April 30, 2015, a total of 574 procedures, including planning angiograms (n = 329) and infusions of 90Y (n = 245), were performed for 318 patients (mean age, 64.5 years). Of the 245 patients who received 90Y infusions, 52 had SIRT performed with the use of a permanent single-use implant of 90Y resin microspheres and 193 had SIRT performed with the use of millions of small glass microspheres containing radioactive 90Y. Procedural details, technical success, the radial artery (RA) occlusion rate noted at 30 days (as assessed via pulse examination), and the major and minor adverse events noted at 30 days were evaluated. RESULTS Technical success was achieved in 561 of 574 cases (97.7%). The reasons for crossover to use of the TFA included an RA loop (n = 2), RA occlusion (n = 9), and type D response as determined by use of a Barbeau test (n = 2). Patients had undergone between zero and six previous TRA procedures. The mortality rate at 30 days was 0%. Superficial bruising occurred in 13 of 574 cases (2.3%). A grade 2 hematoma that required a second nonocclusive hemostasis cuff occurred in one case. Transient forearm numbness or pain occurred in two of 574 cases. One patient had a transient convulsive event occur after receiving intraarterial infusion of verapamil. RA occlusion occurred in nine of 574 cases (1.6%). CONCLUSION Use of the TRA for SIRT is safe, feasible, and well tolerated and is associated with high rates of technical success and rare complications.