title: Comparative viral frequency in Mexican children under 5 years of age with and without upper respiratory symptoms.

text: In Mexico, there is a lack of up-to-date published data that show viruses to be the main cause of acute respiratory infection (ARI). The objective of this study was to estimate the comparative viral frequency between children under the age of 5 years with and without ARI (n = 179 in each group) in a suburban community (Nezahualcóyotl City). A nasopharyngeal sample was collected for viral culture and identification was carried out by indirect immunofluorescence (IIF) using mAbs. There were no sex differences between the two groups. Children under 1 year of age with ARI showed a higher frequency (56 %) of viral infections; this was statistically significant (P < 0.05) when compared with the same age group in ARI-free children (17 %). Respiratory syncytial virus (RSV) was the most prevalent type of virus isolated from both groups (38 vs 18 %). A statistically significantly higher number of subjects with ARI (33/179) than without (12/179) were infected with RSV (P < 0.003). Prevalences of four other viruses studied were similar in the two groups. The highest viral incidence of ARI in children was detected in the winter-spring seasonal period.


title: Characterization of the coronavirus mouse hepatitis virus strain A59 small membrane protein E.

text: The small envelope (E) protein has recently been shown to play an essential role in the assembly of coronaviruses. Expression studies revealed that for formation of the viral envelope, actually only the E protein and the membrane (M) protein are required. Since little is known about this generally low-abundance virion component, we have characterized the E protein of mouse hepatitis virus strain A59 (MHV-A59), an 83-residue polypeptide. Using an antiserum to the hydrophilic carboxy terminus of this otherwise hydrophobic protein, we found that the E protein was synthesized in infected cells with similar kinetics as the other viral structural proteins. The protein appeared to be quite stable both during infection and when expressed individually using a vaccinia virus expression system. Consistent with the lack of a predicted cleavage site, the protein was found to become integrated in membranes without involvement of a cleaved signal peptide, nor were any other modifications of the polypeptide observed. Immunofluorescence analysis of cells expressing the E protein demonstrated that the hydrophilic tail is exposed on the cytoplasmic side. Accordingly, this domain of the protein could not be detected on the outside of virions but appeared to be inside, where it was protected from proteolytic degradation. The results lead to a topological model in which the polypeptide is buried within the membrane, spanning the lipid bilayer once, possibly twice, and exposing only its carboxy-terminal domain. Finally, electron microscopic studies demonstrated that expression of the E protein in cells induced the formation of characteristic membrane structures also observed in MHV-A59-infected cells, apparently consisting of masses of tubular, smooth, convoluted membranes. As judged by their colabeling with antibodies to E and to Rab-1, a marker for the intermediate compartment and endoplasmic reticulum, the E protein accumulates in and induces curvature into these pre-Golgi membranes where coronaviruses have been shown earlier to assemble by budding.


title: Distinct signature type I interferon responses are determined by the infecting virus and the target cell.

text: BACKGROUND Type I interferons (IFN) include multiple IFN-alpha subtypes which exhibit considerable amino acid identity and activate the same cell-surface receptor. The promoter regions of the IFN-alpha genes, however, have different transcription factor binding sites, implying differential transcriptional activation. Evolutionary conservation of multiple subtypes may have resulted from external pressures associated with the crucial nature of an IFN response, namely that different viruses that are tropic for different target tissues determine the nature and extent of an IFN response, specifically the IFN-alpha subtype profile. METHODS Studies were undertaken to examine inducible IFN gene expression profiles in response to infection with single-stranded RNA viruses: Sendai virus (SeV), murine hepatitis virus (MHV-1) and coxsackie virus B3 (CVB3). RESULTS In vitro, distinct signature profiles of SeV and MHV-1-inducible gene expression for IFN-alpha2, IFN-alpha4 and IFN-alpha5 subtypes in L2 and L929 mouse fibroblast cells, in relation to the extent and kinetics of their induction, were identified. In vivo, whereas A/J mice are highly permissive for both MHV-1 and CVB3 infections and mount a poor IFN response, C57B1/6 mice are relatively resistant to both virus infections and mount a vigorous IFN response. CONCLUSIONS These data suggest that the infecting virus and the target cell type dictate the extent and signature of inducible type I IFN gene expression. The extent of IFN response to viral infection influences the subsequent biological outcome: a robust IFN response prescribes a level of resistance, whereas a poor IFN response contributes towards a permissive phenotype for infection.


title: Pandemic influenza and the hospitalist: apocalypse when?

text: Beginning with a cluster of human cases in Hong Kong in 1997, avian influenza (H5N1) has spread progressively through, and beyond, Asia in poultry and other birds; and has resulted in sporadic cases of human disease associated with high mortality. The potential for H5N1 influenza to cause a pandemic of human disease continues to be the subject of intense scrutiny by both the media and the scientific community. While the likelihood of such a prospect is uncertain, the inevitability of future pandemics of influenza is clear. Planning for the eventuality of a virulent influenza pandemic at the local, national and global level is critical to limiting the mortality and morbidity of such an occurrence. Hospitalists have a key role to play in institutional efforts to prepare for a influenza pandemic, and should be aware of lessons that my be applied from both the response to Hurricane Katrina, as well as the severe acute respiratory syndrome (SARS) epidemic.


title: Genetic recombination of poliovirus in vitro and in vivo: temperature-dependent alteration of crossover sites.

text: Genetic recombination that occurs with high frequency during poliovirus genome replication is a process whose molecular mechanism is poorly understood. Studies of genetic recombination in a cell-free system in vitro and in infected tissue culture cells in vivo have led to the unexpected observation that temperature strongly influences the loci at which cross-over between the two recombining RNA strands occurs. Specifically, cross-over between two genetically marked RNA strands in vitro and in vivo at 34 degrees C occurred over a wide range of the genome. In contrast, recombination in vivo at 37 and 40 degrees C yielded cross-over patterns that had shifted dramatically to a region encoding nonstructural proteins. Preferential selection of recombinants at 37 and 40 degrees C was ruled out by analyses of the growth kinetics of the recombinants. During the studies of recombination in the cell-free system we found that there is a direct correlation between the ability of a poliovirus RNA molecule to replicate in the cell-free system and its capacity to complement de novo virus synthesis programmed by another viral RNA.


title: Efficacy of a deletion mutant bovine herpesvirus-1 (BHV-1) vaccine that allows serologic differentiation of vaccinated from naturally infected animals.

text: Fifteen bovine herpesvirus-1 (BHV-1)-negative calves were vaccinated intramuscularly with 10(7.4) plaque-forming units of a double-deletion BHV-1 mutant (IBRV(NG)dltkdlgIII), and 6 remained as nonvaccinated controls. Thirty days after vaccination, the animals were challenged by nasal instillation of 10(8.2) CCID50 of a virulent BHV-1 strain (Cooper). The vaccinated calves were protected against wildtype virus challenge as demonstrated by clinical evaluation. Most of the vaccinates developed only a mild rhinitis (lasting an average of 6.5 days) with almost no systemic symptoms, whereas the controls developed a serious illness characterized by rhinitis (mean = 11.5 days), conjunctivitis, hyperthermia, apathy, loss of appetite, and dyspnea. The vaccinates also shed significantly less virus and for a shorter period of time (mean = 5.5 days) than the controls (mean = 9 days). Thirty days after vaccination, the vaccinates were negative in an anti-gIII specific blocking enzyme-linked immunosorbent assay (ELISA), despite the fact that most of them had developed neutralizing antibodies (serum neutralization titers ranging from 1:2 to 1:16). Seroconversion to gIII was detected as early as 7 days postinfection (dpi). Fourteen days after the challenge, all the animals exposed to wildtype BHV-1 had developed anti-gIII antibodies and were positive in this differential serologic test. Six controls plus 8 vaccinates kept in isolation were still positive to gIII when tested at 75 dpi. The use of the IBRV(NG)dltkdlgIII strain in conjunction with an anti-gIII specific blocking ELISA kit represents a powerful tool for BHV-1 control/eradication programs.


title: A case of giant mucinous cystic neoplasm of the pancreas resected with laparoscopic surgery.

text: We report a case of giant mucinous cystic neoplasm (MCN) of the pancreas that was successfully treated with laparoscopic surgery. A 29-year-old woman was admitted to our hospital for evaluation of an abdominal tumor that had been detected during a routine medical examination. The tumor was diagnosed as an MCN of the pancreas. We performed laparoscopic distal pancreatectomy and splenectomy. The patient could begin oral feeding 3 days after the operation. No complications occurred either during or after surgery. The outcome in this patient was excellent, with cosmetically acceptable small scars in the skin. Therefore, laparoscopic distal pancreatectomy may become a therapeutic option for patients with large MCNs of the pancreas.


title: Anogenital neoplasia in AIDS.

text: PURPOSE OF REVIEW We review the recent literature on anogenital neoplasms in AIDS, with emphasis on cancers associated with HPV infection. Immune reactivity to HPV as well as novel immunotherapeutic and preventative strategies are discussed. RECENT FINDINGS Many AIDS-associated neoplasms are associated with HPV infection. Whether cervical cancer is truly an AIDS-associated neoplasm has recently been questioned, while the association of anal cancer with AIDS in both males and females is more convincing. Recent reports cast doubt on the efficacy of HAART therapy for HPV-induced anogenital neoplasms, despite efficacy in improving disease caused by other infectious agents. We include here new data on humoral and cellular immune responses to HPV. VLP serology has been reported to be associated with outcome of cervical cancer. VLP seropositivity has been reported to be a favorable prognostic sign in women with HPV 16 positive cervical carcinoma. Several investigators have questioned the immunogenicity of the oncogenic HPV type 16 compared with other HPV types. It has recently been found that in HIV-infected patients, lymphoproliferative cellular immune responses (CMI) to HPV 16 peptides are not associated with CD4 counts, whereas responses to recall antigens and mitogens are associated with CD4 counts. CD4 + T cells may not be responsible for protective cellular immune responses to HPV. VLP serology and CMI responses may be the future intermediate surrogate biomarkers for HPV-associated anogenital neoplasia trials. Several new therapeutic vaccine strategies for management of HPV-induced neoplasia are reviewed. SUMMARY Most anogenital neoplasms occurring with increased frequency in patients with HIV/AIDS are associated with HPV infections. Current treatment strategies are not effective in clearing anogenital HPV infection and need improvement. Immunotherapy with novel vaccines will provide both prevention and therapy for these common malignancies.


title: [Comments on treatment of severe acute respiratory syndrome by integrated traditional Chinese and western medicine].

text: There are obvious advantages of the integrated traditional Chinese and western medicine on the treatment of severe acute respiratory syndrome (SARS). Combining the ancient and present literature with the special epidemic patterns, pathological changes and clinical symptoms of SARS, the paper discussed the methods of application of the integrated traditional Chinese and western medicine on the treatment of SARS, and some matters needing attention in clinic.


title: Photolabeling probes of ribavirin and EICAR.

text: Ribavirin, the only small molecule available so far for treating hepatitis C virus infection, was recently used in an emergency context to treat patients with severe acute respiratory syndrome in the early stages of the disease. EICAR, one of the most potent congeners of ribavirin, has 10 to 100 times greater antiviral potency than ribavirin. The mechanisms underlying the antiviral effects of ribavirin and EICAR have not yet been definitely elucidated, but they seem to be similar. In order to study the mechanisms responsible for their antiviral effects using a photolabeling approach, we have developed photolabeling probes of ribavirin and EICAR, in which an azido group was introduced into the pseudobases of triazole and imidazole, respectively. The ribavirin photoprobes were obtained by directly coupling the azidotriazole to the protected ribose sugar, while the EICAR probe was prepared by diazotizing AICAR and subsequently substituting with NaN3. All these probes showed a fast, clear-cut photochemical reaction, which suggests that they are promising tools for use in photolabeling studies.


title: Paramyxovirus infection in pigs with interstitial pneumonia and encephalitis in the United States.

text: In the last few years, newly recognized paramyxoviruses have been associated with severe disease in several animal species, including swine, as well as in human beings. Recently, a paramyxovirus was isolated from a swine herd in the northcentral United States that experienced an epizootic of respiratory and central nervous system disease. Affected pigs had interstitial pneumonia with necrotizing bronchiolitis and encephalitis characterized by lymphocytic perivasculitis and diffuse gliosis. Germ-free pigs inoculated with this isolate developed mild clinical illness and similar but less severe histopathologic lesions in lungs and brain.


title: Molecular mechanism of membrane protein integration into the endoplasmic reticulum.

text: As proteins are integrated into the membrane of the endoplasmic reticulum, some hydrophilic polypeptide segments are transported through the translocation channel, others remain in the cytosol, and hydrophobic transmembrane sequences are released into the lipid phase. We have addressed the molecular mechanism by which these events occur. We demonstrate that both the lumenal and the cytosolic domains of a membrane protein are synthesized while the ribosome is membrane bound, so that even cytosolic domains come in contact with the translocation channel. We also find that, before translation of the protein is terminated, transmembrane sequences can laterally exit the translocation channel and enter the lipid environment. These results have significant implications for the folding and assembly of membrane proteins.


title: Hepatitis B vaccination and first central nervous system demyelinating event: a case-control study.

text: OBJECTIVE To investigate the relationship between hepatitis B (HB) vaccination and a first central nervous system (CNS) demyelinating event in adults. METHODS In 1998, we conducted a multicentre, hospital-based case-control study which enrolled 402 cases of first CNS demyelinating event occurring between 1994 and 1995 and 722 controls matched for centre, age, sex and date of admission. An independent expert committee validated the diagnoses of cases and controls. Data on vaccinations were obtained from a standardized phone interview. Forty percent of eligible cases and 50% of eligible controls could not be localized or were excluded because they did not satisfy inclusion or matching criteria. RESULTS Conditional logistic regression performed on 236 and 355 matched controls showed that adjusted odds ratios for the first CNS demyelinating event within 2 months following an injection of HB vaccine were 1.8 [95% confidence interval (CI), 0.7-4.6] in the whole group and 1.4 (95% CI, 0.4-4.5) in the subgroup of cases (n = 152) and controls (n = 253) referring to vaccination certificates during the phone interview. Restricting the analyses to the cases with definite or probable multiple sclerosis, these odds ratios were 2.0 (95% CI, 0.8-5.4) and 1.6 (95% CI, 0.4-5.6), respectively. Odds ratios tend towards 1 for a longer interval between HB vaccine and demyelinating event. CONCLUSIONS This study was sufficiently powerful to rule out a strong association between HB vaccine exposure and a subsequent demyelinating event. However, it could not provide a clear indication of a moderately increased risk of a CNS demyelinating event shortly after HB vaccination in adults.


title: [Epidemiological features of severe acute respiratory syndrome in Beijing].

text: OBJECTIVE To describe the epidemiologic features of severe acute respiratory syndrome (SARS) in Beijing. METHOD Database of the 2 521 probable cases of SARS in Beijing Center for Disease Prevention and Control was used. RESULTS The course of SARS epidemic in Beijing could be divided into five phases: import and spreading-from 1 to 31 in March, rising-from April 1 to April 15, peak-from April 16 to May 4, declining-from 5 to 18 in May, terminating-from 19 to 28 in May. The proportions of portable cases of SARS in each phase were 2.7%, 13.6%, 71.0%, 11.6% and 1.1%, respectively. Totally, 2 521 portable cases were diagnosed and verified according to the diagnostic criteria of SARS issued by the Ministry of Health. Among them, 192 died from SARS. The incidence and mortality rates of SARS were 18.57 per 100,000 and 1.41 per 100,000 with the fatality of 7.6%. The ratio of male to female with SARS was 1:0.97. The highest incidence rate of SARS was in the group of 20 - 29 years (30.85 per 100,000), and the lowest was in the group of 0 - 14 years (2.54 per 100,000). People aged 20 - 49 accounted for 72.3% of all SARS cases. The incidence rates in urban, suburb and far-suburb were 32.25/100,000, 20.57/100,000 and 8.90/100,000, respectively, decreasing according to the population density. Health care providers (17.3%), staff (12.9%), retirees (11.4%), workers (9.7%) and house-hold unemployees (8.8%) appeared to be at the five top risk populations being infected. The fatality increased significantly with age. CONCLUSION Beijing was the most severe epidemic region of SARS in the world, but the fatality was the lowest.


title: Modulation of the suppressive effect of corticosterone on adult rat hippocampal cell proliferation by paroxetine.

text: OBJECTIVE The literature has shown that cognitive and emotional changes may occur after chronic treatment with glucocorticoids. This might be caused by the suppressive effect of glucocorticoids on hippocampal neurogenesis and cell proliferation. Paroxetine, a selective serotonin reuptake transporter, is a commonly used antidepressant for alleviation of signs and symptoms of clinical depression. It was discovered to promote hippocampal neurogenesis in the past few years and we wanted to investigate its interaction with glucocorticoid in this study. METHODS Adult rats were given vehicle, corticosterone, paroxetine, or both corticosterone and paroxetine for 14 d. Cell proliferation in the dentate gyrus was quantified using 5-bromo-2-deoxyuridine (BrdU) immunohistochemistry. RESULTS The corticosterone treatment suppressed while paroxetine treatment increased hippocampal cell proliferation. More importantly, paroxetine treatment could reverse the suppressive effect of corticosterone on hippocampal cell proliferation. CONCLUSION This may have clinic application in preventing hippocampal damage after glucocorticoid treatment.


title: Sequence of the spike protein of the porcine epidemic diarrhoea virus.

text: The complete sequence of the spike (S) gene of the Br1/87 isolate of porcine epidemic diarrhoea virus (PEDV) was determined from cDNA clones. The predicted polypeptide was 1383 amino acids long, contained 29 potential N-linked glycosylation sites and showed structural features similar to those of the coronavirus spike protein. The PEDV S protein, like that of the members of the transmissible gastroenteritis virus (TGEV)-related subset, lacks a proteolytic site to yield cleaved amino and carboxy subunits S1 and S2. Viral polypeptide species of the expected M(r), i.e. 170K/190K, were observed in PEDV-infected cells. Sequence comparison confirmed that, within the subset, PEDV was most closely related to the human respiratory coronavirus HCV 229E. However, PEDV S protein has an additional 250 residue N-terminal domain which is absent from HCV 229E and porcine respiratory coronavirus, the respiratory variant of TGEV. Alignment of the S1 regions revealed a second domain of about 90 residues with increased sequence divergence which might possibly express virus-specific determinants.


title: The causes and diagnosis of influenza-like illness.

text: BACKGROUND Influenza and other respiratory viruses circulate between spring and autumn in temperate climates and all year in tropical climates. These viruses cause symptoms often referred to as influenza-like illness (ILI), but are not generally distinguishable on clinical grounds alone. OBJECTIVE This article provides a brief review of the surveillance, viral causes and current diagnostic methods used to identify viruses causing ILI. DISCUSSION Influenza-like illness surveillance with laboratory support, conducted in most Australian stats and territories, aims to define the impact of influenza seasons in the community and provide virus strains that may be used in future vaccine formulations. Surveillance may also be useful in the early stages of an influenza pandemic. In addition to influenza, viruses known to cause ILI include respiratory syncytial virus, rhinovirus, adenovirus, parainfluenza viruses, human coronaviruses (including the virus that causes severe acute respiratory syndrome) and the recently recognised human metapneumovirus. Polymerase chain reaction assays are the most common diagnostic tests now used for the differential diagnosis of ILI.


Medical considerations for supporting elite athletes during the post-peak phase of the New Zealand COVID-19 pandemic: a New Zealand sporting code consensus.


docid: rawxxcia

title: [Viral zoonoses].

text: In different areas of the World, whether in industrialized or developing countries, zoonoses represent an emerging Public Health concern either as known agents appear in areas or species in which they had not been reported or as new pathogens parasite Human as consequence of successful host switching. Epidemiological data outlined that vectorborne viral zoonoses are of particular relevance. This paper review the changes in epidemiology of bat rabies and arbovirus encephalitis.


docid: cvditdnn

title: Case management of ill travelers with infectious diseases.

text: Recent increase of international travelers raises awareness of travel-related infections. Travelers' diarrhea is the most common and caused by diarrheagenic E. coli and other patho- gens. Undifferentiated fever challenges physicians to correctly diagnose and includes ma- laria, dengue, and enteric fever. The pre-test probability for a disease which causes undiffer- entiated fever largely depends on the travel destination. Malaria is most common in travelers returning from sub-Saharan Africa while dengue is most common those returning from Southeast Asia and Latin America. Screening for asymptomatic travelers is not generally rec- ommended, but for long-term travelers and immigrants. Following outbreaks of highly infectious diseases in the past decades, hospital prepared- ness for travel-related infections focuses on infection prevention and control. Emerging viral pneumonias such as Middle East respiratory syndrome (MERS) and avian influenza H7N9 are major concerns. As seen in the largest outbreak of Ebola virus disease in West Africa, imported viral hemorrhagic fever such as Lassa fever is another concern. Since multidrug resistant bacteria silently spread globally by infected travelers, it would be of help to install appropriate isolation precaution for travelers with history of hospital admission abroad.


title: Ostrich diseases.

text: Scientific knowledge of ostrich diseases is incomplete and very fragmented, with specific details on technical aspects of diagnostic and/or screening tests completely absent in most cases. Salmonella Typhimurium is common in multispecies collections and causes mortality in chicks younger than three months on commercial farms, but is rarely found in chicks older than six months, or slaughter birds of twelve to fourteen months in southern Africa. Campylobacter jejuni and Chlamydia psittaci are occasionally reported, mainly in young ostriches, but both remain a diagnostic challenge. Crimean-Congo haemorrhagic fever is transmitted to domestic animals including ostriches, principally by ticks of the genus Hyalomma. In the ostrich, the disease causes no clinical symptoms during a viraemia of approximately four days. Spongiform encephalopathy has not been reliably reported in ostriches, while anthrax has occurred rarely in modern times but was reportedly an important cause of death approximately 100 years ago in South Africa. Salmonella Gallinarum and S. Pullorum are unknown in ostriches. Pasteurella multocida occurs but is easily contained with antibiotics. Mycoplasma spp. are regularly found in an upper respiratory disease syndrome complicated by opportunistic bacterial pathogens. Ostriches of all ages are susceptible to challenge by velogenic Newcastle disease virus (NDV), but standard inactivated La Sota poultry vaccines can stimulate protective immunity lasting over six months. The viraemic period in vaccinated slaughter ostriches is between nine and eleven days and there are no indications of a carrier state or presence of the virus in the meat or any other tissues after this period, with peak immunoglobulin G response reached on day fourteen post infection. Haemagglutination inhibition tests are significantly less sensitive and less specific than enzyme-linked immunosorbent assays. Cloacal and choanal swabs used for direct virological screening in clinically affected cases (field and experimental) could not detect NDV. All avian influenza isolates reported from ostriches have been non-pathogenic to poultry, even the H5 and H7 subtypes. Some of the latter have been associated with mortality of ostrich chicks in localised outbreaks during periods of inclement weather and with significant wild bird (waterfowl) contact. Borna disease causes a nervous syndrome in ostrich chicks, but to date, has only been reported in Israel. Eastern and Western equine encephalomyelitides cause fatal disease in ostriches and other ratites, with mortality ranging from less than 20% to over 80% in affected flocks. These diseases are present in North, Central and South America where the associated ornithophilic mosquito vectors occur. Equine and human vaccines are apparently safe and efficacious in ratites. Wesselsbron disease, infectious bursal disease (type 2), adenovirus and coronavirus infections have been reported from ostriches but the significance of these diseases is unclear. Due to the paucity of data regarding ostrich diseases and the unvalidated state of most poultry tests in this unique group of birds, strict observation of a pre-slaughter quarantine of thirty days is strongly advised, whilst live exports and fertile eggs should be screened through the additional use of sentinel chickens and/or young ostriches.


title: [Simultaneous multiple assay (Luminex xTAG respiratory viral panel FAST assay) efficacy in human respiratory virus detection].

text: Luminex xTAG respiratory viral panel FAST (RVP FAST) assay detects 17 human respiratory virus strains per measurement. Studying RVP FAST efficacy in detecting respiratory viruses in 67 aspirate samples from the nasal cavities of children with acute respiratory infection, we compared RVP FAST results to those of conventional nucleic acid amplification tests (NAT), e.g., real-time PCR, targeting 8 strains. RVP FAST assay detected 13 strains (98 isolates) in 59 of 67 samples. Of these, 8--influenza virus (Inf.V)-AH1, Inf. V-AH3, novel Inf.V-AH1, and Inf.V-B, and adenovirus, RS virus, metapneumovirus, and bocavirus--were compared to NAT results. RVP FAST showed higher sensitivity (83.3-100%) and specificity (98.2-100%) than NAT. RVP FAST also detected coronavirus (CoV) 229E, OC43, NL63, and HKU1 from 10 virus strain samples and enterovirus and/or rhinovirus from 35. RVP FAST assay thus comprehensively detects clinically important viruses in a single measurement, making RVP FAST assay useful in detecting causative respiratory tract viruses.


Extensively overlapping reading frames in a second mammalian gene.


title: Increased epitope-specific CD8+ T cells prevent murine coronavirus spread to the spinal cord and subsequent demyelination.

text: CD8+ T cells are important for clearance of neurotropic mouse hepatitis virus (MHV) strain A59, although their possible role in A59-induced demyelination is not well understood. We developed an adoptive-transfer model to more clearly elucidate the role of virus-specific CD8+ T cells during the acute and chronic phases of infection with A59 that is described as follows. C57BL/6 mice were infected with a recombinant A59 virus expressing the gp33 epitope, an H-2Db-restricted CD8+ T-cell epitope encoded in the glycoprotein of lymphocytic choriomeningitis virus, as a fusion with the enhanced green fluorescent protein (RA59-gfp/gp33). P14 splenocytes (transgenic for a T-cell receptor specific for the gp33 epitope) were transferred at different times pre- and postinfection (p.i.). Adoptive transfer of P14 splenocytes 1 day prior to infection with RA59-gfp/gp33, but not control virus lacking the gp33 epitope, RA59-gfp, reduced weight loss and viral replication and spread in the brain and to the spinal cord. Furthermore, demyelination was significantly reduced compared to that in nonrecipients. However, when P14 cells were transferred on day 3 or 5 p.i., no difference in acute or chronic disease was observed compared to that in nonrecipients. Protection in mice receiving P14 splenocytes prior to infection correlated with a robust gp33-specific immune response that was not observed in mice receiving the later transfers. Thus, an early robust CD8+ T-cell response was necessary to reduce virus replication and spread, specifically to the spinal cord, which protected against demyelination in the chronic phase of the disease.


title: Vacuum-assisted closure increases ICAM-1, MIF, VEGF and collagen I expression in wound therapy.

text: Severe traumatic wounds are challenging to manage during surgery. The introduction of vacuum-assisted closure (VAC) is a breakthrough in wound management. The aim of the present study was to investigate the effect of VAC on cytokines in wounds during the management of severe traumatic wounds following initial debridement. VAC and conventional wound care (CWC) were independently applied to severe traumatic wounds on pigs. The expression levels of intercellular adhesion molecule-1 (ICAM-1), migration inhibitory factor (MIF), vascular endothelial growth factor (VEGF), basic fibroblast growth factor, collagen I and human fibroblast collagenase 1 were detected by quantitative polymerase chain reaction and western blotting. VAC significantly increased the expression of ICAM-1, MIF, VEGF and collagen I compared with that induced by CWC at the protein and mRNA levels. Therefore, the results of the present study indicate that VAC therapy is an effective method for treating severe traumatic wounds, as it increases the expression of cytokines in wounds. VAC significantly increases the expression of ICAM-1, MIF, VEGF and collagen I to manage severe traumatic wounds.


title: Plasma proteome of severe acute respiratory syndrome analyzed by two-dimensional gel electrophoresis and mass spectrometry.

text: We have investigated the plasma proteome by using 2D gel electrophoresis and MS from patients with severe acute respiratory syndrome (SARS). A complete proteomic analysis was performed on four patients with SARS in different time courses, and a total of 38 differential spots were selected for protein identification. Most of the proteins identified are acute phase proteins, and their presence represents the consequence of serial cascades initiated by SARS-coronavirus infection. There are several proteins that have never been identified in plasma before using 2D gel electrophoresis, among which peroxiredoxin II was chosen for further study by analyzing additional 20 plasma samples from patients with probable and suspected SARS and patients with fever, respectively. The results showed that the level of plasma peroxiredoxin II in patients with SARS is significantly high and could be secreted by T cells. Taken together, our findings indicate that active innate immune responses, along with the oxidation-associated injuries, may play a major role in the pathogenesis of SARS.


title: In vivo and in vitro interferon (IFN) studies with the porcine reproductive and respiratory syndrome virus (PRRSV).

text: Some of the interactions between the porcine reproductive and respiratory syndrome virus (PRRSV) and the porcine interferon-alpha (IFN-alpha) system were studied. In a first experiment, it was shown that pretreatment of primary porcine alveolar macrophages (AMs) with recombinant porcine (rPo) IFN-alpha 1 resulted in significant reductions of PRRSV yield and numbers of antigen expressing cells. In a second experiment, sensitivity of PRRSV to IFN-alpha was confirmed in vivo. In pigs inoculated with porcine respiratory coronavirus (PRCV)--a potent inducer of endogenous IFN-alpha in the lungs of pigs--followed 2 days later by PRRSV--lung PRRSV titers were 1.7 to 2.9 log10 TCID50 reduced compared to those in singly PRRSV inoculated pigs. It was concluded therefore that PRRSV has a fairly good sensitivity to the antiviral effects of IFN-alpha. A third experiment documented that in vivo PRRSV infection generally does not affect PRCV-induced IFN-alpha production in the lungs of pigs. In addition, it was shown that the IFN-inducing capacity of PRRSV is at least 159 times lower than that of PRCV. This finding suggests that cells other than AMs may be responsible for IFN production in the lungs of pigs.


title: The pharmacology of topical analgesics.

text: Pain management of patients continues to pose challenges to clinicians. Given the multiple dimensions of pain--whether acute or chronic, mild, moderate, or severe, nociceptive or neuropathic--a multimodal approach may be needed. Fortunately, clinicians have an array of nonpharmacologic and pharmacologic treatment choices; however, each modality must be chosen carefully, because some often used oral agents are associated with safety and tolerability issues that restrict their use in certain patients. In particular, orally administered nonsteroidal antiinflammatory drugs, opioids, antidepressants, and anticonvulsants are known to cause systemic adverse effects in some patients. To address this problem, a number of topical therapies in various therapeutic classes have been developed to reduce systemic exposure and minimize the risks of patients developing adverse events. For example, topical nonsteroidal anti-inflammatory drug formulations produce a site-specific effect (ie, cyclo-oxygenase inhibition) while decreasing the systemic exposure that may lead to undesired effects in patients. Similarly, derivatives of acetylsalicylic acid (ie, salicylates) are used in topical analgesic formulations that do not significantly enter the patient's systemic circulation. Salicylates, along with capsaicin, menthol, and camphor, compose the counterirritant class of topical analgesics, which produce analgesia by activating and then desensitizing epidermal nociceptors. Additionally, patches and creams that contain the local anesthetic lidocaine, alone or co-formulated with other local anesthetics, are also used to manage patients with select acute and chronic pain states. Perhaps the most common topical analgesic modality is the cautious application of cutaneous cold and heat. Such treatments may decrease pain not by reaching the target tissue through systemic distribution, but by acting more directly on the affected tissue. Despite the tolerability benefits associated with avoiding systemic circulation, topically applied analgesics are associated with application-site reactions in patients, such as dryness, erythema, burning, and discoloration. Furthermore, some adverse events that have been observed in patients may be suggestive of some degree of systemic exposure. This article reviews the mechanisms of action, pharmacokinetics, and tolerability of topical treatments for the management of patient pain.


Severe acute respiratory syndrome: imported cases of severe acute respiratory syndrome to Singapore had impact on national epidemic.


title: In vivo and in vitro models of demyelinating disease: activation of the adenylate cyclase system influences JHM virus expression in explanted rat oligodendrocytes.

text: The specificity of JHM virus (JHMV) tropism for rat oligodendrocytes, as one of the primary host cells in the central nervous system, is maintained after explanation (S. Beushausen and S. Dales, Virology 141:89-101, 1985). The temporal correlation between onset of resistance to JHMV infection in vivo, completion of myelination, and maturation of the central nervous system can be simulated in vitro by inducers of oligodendrocyte differentiation (Beushausen and Dales, Virology, 1985). Stimulation of differentiation through the elevation of intracellular cyclic AMP (cAMP) levels suggests a possible connection between activation of the adenylate cyclase system and coronavirus expression. Chromatographic analysis of cAMP-dependent protein kinase activity in cytosol extracts prepared from astrocytes or oligodendrocytes revealed that both glial cell types were deficient in protein kinase I, indicating that expression of coronavirus in differentiated cells was not contingent upon the presence of protein kinase I. However, treatment with N6,2'-O-dibutyryladenosine-3',5'-cyclic monophosphate (dbcAMP) resulted in a severalfold enhancement of the free regulatory subunit (RI) in oligodendrocytes but not in astrocytes. The RII subunit in both neural cell types was relatively unaffected. Rapid increase in RI due to dbcAMP treatment was correlated with inhibition of JHMV expression. Other differentiation inducers, including 8-Br cAMP and forskolin which, by contrast, caused a decrease in detectable RI, also blocked JHMV expression. This apparent anomaly can be attributed to an increased turnover of RI due to destabilization of the molecule which occurs upon site-specific binding of the cyclic nucleotides. On the basis of these observations, we conclude that the state of oligodendrocyte differentiation manifested with the modulation of RI regulates JHMV expression. The differentiation process did not affect either virus adsorption or sequestration but appeared to inhibit the expression of viral RNA and proteins, implying that replication was inhibited at some step between penetration and initiation of genomic functions, perhaps at the stage of uncoating. We therefore examined the possibility that protein kinases and phosphatases, which influence cellular regulation during cAMP-induced differentiation, may be responsible for the phenomenon of coronavirus suppression in oligodendrocytes. Evidence was obtained indicating that normal processing of the phosphorylated nucleocapsid protein is inhibited in differentiated oligodendrocytes, consistent with the notion that JHMV replication might be arrested during uncoating.


docid: cwzhxzps

title: Opening data to the world: why health numbers matter.


title: Amino acid substitutions within the leucine zipper domain of the murine coronavirus spike protein cause defects in oligomerization and the ability to induce cell-to-cell fusion.

text: The murine coronavirus spike (S) protein contains a leucine zipper domain which is highly conserved among coronaviruses. To assess the role of this leucine zipper domain in S-induced cell-to-cell fusion, the six heptadic leucine and isoleucine residues were replaced with alanine by site-directed mutagenesis. The mutant S proteins were analyzed for cell-to-cell membrane fusion activity as well as for progress through the glycoprotein maturation process, including intracellular glycosylation, oligomerization, and cell surface expression. Single-alanine-substitution mutations had minimal, if any, effects on S-induced cell-to-cell fusion. Significant reduction in fusion activity was observed, however, when two of the four middle heptadic leucine or isoleucine residues were replaced with alanine. Double alanine substitutions that involved either of the two end heptadic leucine residues did not significantly affect fusion. All double-substitution mutant S proteins displayed levels of endoglycosidase H resistance and cell surface expression similar to those of the wild-type S. However, fusion-defective double-alanine-substitution mutants exhibited defects in S oligomerization. These results indicate that the leucine zipper domain plays a role in S-induced cell-to-cell fusion and that the ability of S to induce fusion may be dependent on the oligomeric structure of S.


title: [Protease-dependent cell entry mechanism of coronaviruses].

text: Previous studies have demonstrated that the SARS-CoV S protein requires proteolytic cleavage by elastase, cathepsin or TMPRSS2 for S-mediated cell-cell or virus-cell membrane fusion. Activation of viral glycoprotein (GP) by protease also has been reported for influenza virus. The most distinctive difference between influenza virus and SARS-CoV is the stage during virus replication in which viral glycoproteins are cleaved by proteases. In influenza virus, the protease makes a simple cut in the GP during maturation. In contrast, SARS-CoV S protein is cleaved by the protease following receptor-induced conformational changes. The protease cleavage site in S protein is thought to be exposed only after receptor binding. In support of this model, we reported that the S protein of mouse hepatitis virus type 2 (MHV-2), which is highly similar to the S protein of SARS-CoV, requires two-step conformational changes mediated by sequential receptor binding and proteolysis to be activated for membrane fusion. Such a mechanism allows for tight temporal control over fusion by protecting the activating cleavage site from premature proteolysis yet allowing efficient cleavage upon binding to the receptor on target cells.


docid: wvkvatnh

title: Neutralizing epitopes of the SARS-CoV S-protein cluster independent of repertoire, antigen structure or mAb technology.

text: Neutralizing antibody responses to the surface glycoproteins of enveloped viruses play an important role in immunity. Many of these glycoproteins, including the severe acute respiratory syndrome-coronavirus (SARS-CoV) spike (S) protein form trimeric units in the membrane of the native virion. There is substantial experimental and pre-clinical evidence showing that the S protein is a promising lead for vaccines and therapeutics. Previously we generated a panel of monoclonal antibodies (mAbs) to whole inactivated SARS-CoV which neutralize the virus in vitro. Here, we define their specificity and affinity, map several of their epitopes and lastly characterise chimeric versions of them. Our data show that the neutralizing mAbs bind to the angiotensin-converting enzyme 2 (ACE2) receptor-binding domain (RBD) of the SARS S protein. Three of the chimeric mAbs retain their binding specificity while one conformational mAb, F26G19, lost its ability to bind the S protein despite high level expression. The affinity for recombinant S is maintained in all of the functional chimeric versions of the parental mAbs. Both parental mAb F26G18 and the chimeric version neutralize the TO R2 strain of SARS-CoV with essentially identical titres (2.07 and 2.47 nM, respectively). Lastly, a comparison with other neutralizing mAbs to SARS-CoV clearly shows that the dominance of a 33 amino acid residue loop of the SARS-CoV RBD is independent of repertoire, species, quaternary structure, and importantly, the technology used to derive the mAbs. In cases like this, the dominance of a compact RBD antigenic domain and the central role of the S protein in pathogenesis may inherently create immunoselection pressure on viruses to evolve more complex evasion strategies or die out of a host species. The apparent simplicity of the mechanism of SARS-CoV neutralization is in stark contrast to the complexity shown by other enveloped viruses.


title: A comparison of bovine coronavirus strains using monoclonal antibodies.

text: Eight monoclonal antibodies (MAbs) were raised against a bovine coronavirus (B.C.V.) which had been isolated in Scotland and was designated S2. The MAbs were divided into two groups on the basis of their reactions with S2 virus in indirect immunofluorescence (I.F.), neutralisation and haemagglutination inhibition (H.A.I.) tests. Five of the MAbs were positive by all three tests but failed to bind to proteins in Western immunoblotting experiments. The remaining three MAbs were positive in I.F. tests only, two of which were shown to bind to the 52K nucleocapsid protein by Western immunoblotting. Different patterns of antigen distribution within infected cells were demonstrated when the MAbs were used in the I.F. test. However only minor strain variations were detected by I.F. and H.A.I. tests when the MAbs were tested against each of five cell culture adapted strains of B.C.V. Twenty-nine isolates of B.C.V. have been grown in neonatal calf tracheal organ cultures: attempts are being made to further characterize these isolates.


title: [Clinical detection of polymerase gene of SARS-associated coronavirus].

text: OBJECTIVE To analyze the heterogeneity of polymerase gene fragment of SARS-associated coronavirus from SARS patients, and establish a RT-PCR method for detecting SARS-associated coronavirus. METHODS RT-PCR was performed using SARS coronavirus-specific primers to amplify the polymerase gene fragment of SARS-associated coronavirus from specimens of suspected and established SARS cases. The amplicons were cloned and sequenced. All the obtained sequences were compared with the sequence of published SARS-associated coronavirus, and alignment was proceeded with other coronavirus sequences. RESULTS Specific amplicons can be amplified from the sputum samples, throat swab and plasma of most SARS patients, and 8 were random selected and sequenced. All of them possessed 100% homology with the published SARS-associated coronavirus sequence, while all the negative controls were RT-PCR negative. Nucleotide-sequence and amino acid-sequence alignment of the fragment BNI109 with other six known coronavirus show that the fragment BNI109 is more close to bovine coronavirus(BCV) and murine hepatitis virus(MHV). The BNI109 fragment showed 75% homology with BCV and MHV at amino acid level. CONCLUSION The polymerase fragment BNI109 of SARS coronavirus is highly conservative and is suitable for detecting SARS-associated coronavirus using RT-PCR method.


title: Consequences of the COVID-19 Pandemic on Cancer Clinical Trials.

text: The battle against cancer is formidable even in normal circumstances and the COVID-19 selectively cancer patients with an increased risk of mortality by three times higher than those without cancer but also forced us to shut down the clinical trials in cancer patients to deal with the present crisis. We discuss here the disruptions on research in cancer with its immediate and delayed consequences and offer some suggestions to modify our practices, strategies and rationalization to help succeed the cancer treatment and research after the crisis is over.


docid: rwypqzqu

title: Detection and quantitation of the etiologic agents of ventilator-associated pneumonia in endotracheal tube aspirates from patients in Iran.


title: Molecular mimicry revisited: gut bacteria and multiple sclerosis.

text: Molecular mimicry is a possible explanation for autoimmune side effects of microorganism infections. Protein sequences from a particular microorganism are compared to known autoimmune immunogens. For diseases such as multiple sclerosis (MS), where the infectious agent is unknown, guesses to its identity are made. Mimics are assumed to be rare. This study takes a radically different approach. Reported sequences from all known human bacterial and viral agents were searched for autoimmune immunogen mimics. Three encephalitogenic peptides, whose autoimmune requirements have been studied extensively, were selected for comparison. Mimics were seen in a wide variety of organisms. For each immunogen, the mimics were found predominantly in nonpathogenic gut bacteria. Since the three immunogens used in this study are related to MS, it is suggested that a microorganism responsible for autoimmune activity in MS could be a normally occurring gut bacterium. This would explain many of the peculiar MS epidemiological data and why no infective agent has been identified for MS and supports recently found MS gut metabolism abnormalities.


title: Identification of a putative cellular receptor 150 kDa polypeptide for porcine epidemic diarrhea virus in porcine enterocytes.

text: Porcine epidemic diarrhea virus (PEDV) causes an acute enteritis in pigs of all ages, often fatality for neonates. PEDV occupies an intermediate position between two well characterized members of the coronavirus group I, human coronavirus (HCoV-229E)and transmissible gastroenteritis virus (TGEV) which uses aminopeptidase N (APN), a 150 kDa protein, as their receptors. However, the receptor of the PEDV has not been identified yet. A virus overlay protein binding assay (VOPBA) was used to identify PEDV binding protein in permissive cells. The binding ability of PEDV to porcine APN (pAPN) and the effects of pAPN on infectivity of PEDV in Vero cells were also investigated. VOPBA identified a 150 kDa protein, as a putative PEDV receptor in enterocytes and swine testicle (ST) cells. Further the PEDV binding to pAPN was blocked by anti-pAPN and pAPN enhanced PEDV infectivity in Vero cells. In conclusion, these results suggested that pAPN may act as a receptor of PEDV.


Health Care System and Pharmacy Practice in Hong Kong.


title: The "delay effect" of donning a gown during cardiopulmonary resuscitation in a simulation model.

text: OBJECTIVE We sought to determine whether the use of currently issued gowns delays initiation of chest compressions and ventilations during cardiopulmonary resuscitation and whether simple gown modifications can reduce this delay. METHODS Firefighter defibrillation instructors were allocated into pairs and videotaped while performing standardized cardiac arrest scenarios. Three scenarios were compared: "no gown," "standard gown" and "modified gown." Key time intervals were extracted from videotaped data. RESULTS Ninety-five scenarios were analyzed. Mean time interval to chest compression was 39 seconds (95% confidence interval [CI] 34-43) for "no gown" scenarios, 71 seconds (95% CI 66-77) for "standard gown" scenarios and 59 seconds (95% CI 54-63) for "modified gown" scenarios (p < 0.001). Time to first ventilation was 146 seconds (95% CI 134-158), 238 seconds (95% CI 224-253) and 210 seconds (95% CI 198-223) in the 3 groups, respectively (p < 0.001). Post hoc testing showed that the time differences between all groups were statistically significant. CONCLUSION Standard gowns protect front-line care providers but cause significant delays to chest compressions and ventilations, potentially increasing patient morbidity and mortality. Minor gown modifications, including pre-tied neck straps and longer waist ties that tie in front, allow for easier use and shorter delays to time-critical interventions. Future research is required to reduce care delays while maintaining adequate protection of emergency medical service providers from infectious disease.


docid: tpdkdeha

title: Clinical decision making during public health emergencies: ethical considerations.

text: Recent public health emergencies involving anthrax, the severe acute respiratory syndrome (SARS), and shortages of influenza vaccine have dramatized the need for restrictive public health measures such as quarantine, isolation, and rationing. Front-line physicians will face ethical dilemmas during public health emergencies when patients disagree with these measures. Patients might request interventions that are not recommended or for which they are not eligible, or they might object to intrusive or restrictive measures. The physician's primary responsibility in such emergencies is to the public rather than to the individual patient. In public health emergencies, physicians need to address the patient's needs and concerns, recognize their changed roles, and work closely with public health officials. Physicians can still work on behalf of patients by advocating for changes in policies and exceptions when warranted and by mitigating the adverse consequences of public health measures. Before an emergency occurs, physicians should think through how they will respond to foreseeable dilemmas arising when patients disagree with public health recommendations.


title: Impact of SARS on an emergency department in Hong Kong.

text: OBJECTIVE To report on the impact of a Severe Acute Respiratory Syndrome (SARS) outbreak on the attendances of a major teaching hospital ED. METHODS Two periods were studied. The first was prior to the closure of the ED due to SARS and the second was after re-opening of the ED. Data on attendances, discharge against medical advice, triage categories, trauma and ambulance cases were retrieved from the computer and compared with the data in the same periods in 2002. RESULTS In the first period, when compared with 2002 there was a significant decrease in the mean daily attendance (397 vs 524), trauma cases (68 vs 111), minor cases (category 4: 283 vs 361, and category 5: 20 vs 43). In the second period, there was a significant decrease in the mean daily attendance (265 vs 545), trauma cases (40 vs 111), minor cases (category 4:181 vs 376, and category 5: 12 vs 45), discharge against medical advice (4 vs 6 daily) and ambulance cases (70 vs 86 daily). Patients requiring immediate care however, remained similar. CONCLUSION There was a significant drop in the overall ED attendance, trauma cases and minor cases after the outbreak of SARS. Possible causes include changes in community behaviour, resulting in a lower incidence of trauma and disease and fear of presenting to hospital and contracting SARS.


title: Infection with a new porcine respiratory coronavirus in Denmark: serologic differentiation from transmissible gastroenteritis virus using monoclonal antibodies.

text: In 1984 neutralizing antibodies against transmissible gastroenteritis virus (TGEV) were detected in pig herds in a small geographical area in the southern part of Denmark. No clinical symptoms were observed and accumulating epidemiological evidence gradually pointed towards a respiratory infection. In 1986 a TGE-like virus, tentatively named porcine respiratory coronavirus (PRCV), was isolated from the lungs of swine. The virus was partially characterized using monoclonal antibodies against TGEV and this showed that some (mainly nonneutralizing) epitopes of the peplomer glycoprotein E2 were absent in PRCV, whereas the major neutralizing domains were conserved. These findings allowed the design of competitive antibody immunoassays either discriminating or not discriminating the immune responses against the two viruses. However, the discriminating epitopes studied so far have shown minor immunodominance and some steric interference from nondiscriminating epitopes.


The new Clostridium difficile--what does it mean?


title: Central failures of lightweight monofilament polyester mesh causing hernia recurrence: a cautionary note.

text: INTRODUCTION Uncoated, lightweight, macroporous,monofilament mesh has been shown to demonstrate improved bacterial clearance, better tissue integration,reduced foreign body response, and less chronic pain with equivalent durability for hernia repair. These findings led us to use a new lightweight monofilament polyester mesh (Parietex TCM, Covidien). Here, we report our experience with this mesh in open incisional hernia repair. METHODS Patients undergoing incisional hernia repair with Parietex TCM were retrospectively identified within our prospectively maintained database. Patient demographics,operative characteristics, and follow-up were reviewed. Outcome parameters included 90-day wound morbidity and hernia recurrence. RESULTS In 2011, 36 patients (mean age 56.8; mean BMI32.4 kg/m2) underwent open incisional hernia repair with retrorectus mesh placement by two surgeons (MJR, YWN) at Case Medical Center. Anterior and posterior fascial closure was achieved in all cases. Wound morbidity included seven surgical site occurrences: four superficial infections that resolved with antibiotics, one wound dehiscence requiring wet-to-dry packing, and two seromas that resolved without intervention. With a mean follow-up of 13 months, 8 (22%) recurrences have occurred. On reoperation, 7 (19%) of these patients had mechanical failure or fracturing of the mesh. No confounding variables were identified by univariate analysis of patient demographics,operative characteristics, or wound morbidity. CONCLUSION Lightweight monofilament polyester mesh (Parietex TCM) appears to have a high incidence of mechanical failure in the context of open incisional hernia repair. While this limitation may ultimately be revealed asa weakness of all lightweight mesh, surgeons should be aware that these failures have already been documented.


title: Severe acute respiratory syndrome coronavirus papain-like protease: structure of a viral deubiquitinating enzyme.

text: Replication of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) requires proteolytic processing of the replicase polyprotein by two viral cysteine proteases, a chymotrypsin-like protease (3CLpro) and a papain-like protease (PLpro). These proteases are important targets for development of antiviral drugs that would inhibit viral replication and reduce mortality associated with outbreaks of SARS-CoV. In this work, we describe the 1.85-A crystal structure of the catalytic core of SARS-CoV PLpro and show that the overall architecture adopts a fold closely resembling that of known deubiquitinating enzymes. Key features, however, distinguish PLpro from characterized deubiquitinating enzymes, including an intact zinc-binding motif, an unobstructed catalytically competent active site, and the presence of an intriguing, ubiquitin-like N-terminal domain. To gain insight into the active-site recognition of the C-terminal tail of ubiquitin and the related LXGG motif, we propose a model of PLpro in complex with ubiquitin-aldehyde that reveals well defined sites within the catalytic cleft that help to account for strict substrate-recognition motifs.


title: Preparing for pandemic influenza and its aftermath: mental health issues considered.

text: In November of 2005, President George W Bush requested $7.1 billion dollars for a global influenza epidemic preparedness initiative (Brown, 2005). Preparation measures for a biological threat or influenza pandemic focus on rapid quarantine, vaccines, developing antiviral treatments, and economic concerns (Brown, 2005; Ferguson et al., 2006; Reina, 2008). Although these public health measures are vital, they do not consider the acute mental health consequences that could develop during a pandemic and its aftermath. The most recent H1N1 swine flu has now spread to more than 70 countries (CDC, June 2009), and as of June 11, 2009, is considered a Phase 6 pandemic by the World Health Organization, indicative of ongoing community level outbreaks in multiple parts of the globe. Following recent cases of swine flu, global concern of an influenza pandemic has risen, and it is critical that metal health considerations become an integrated part of the pandemic response. Here, potential mental health consequences and high risk populations are identified and reviewed. Mental health professionals, communities, businesses, and organizations can create an infrastructure to help mitigate mental health consequences. These issues, as well as familial stressors and coping methods, are reviewed.


Why are antibiotic-resistant nosocomial infections spiraling out of control?


title: How the COVID-19 Overcomes the Battle? An Approach to Virus Structure.

text: Coronaviruses primarily cause zoonotic infections, however in the past few decades several interspecies transmissions have occurred, the last one by SARS-CoV-2, causing COVID-19 pandemic, posing serious threat to global health. The SARS-CoV-2 spike (S) protein plays an important role in viral attachment, fusion and entry. However, other structural and non-structural SARS-CoV-2 proteins are potential influencers in virus pathogenicity. Among these proteins; Orf3, Orf8, and Orf10 show the least homology to SARSCoV proteins and therefore should be further studied for their abilities to modulate antiviral and inflammatory responses. Here, we discuss how SARS-COV-2 interacts with our immune system.


title: Molecular dynamics simulations of various coronavirus main proteinases.

text: In this study, two homology models (denoted as MproST and MproSH) of main proteinase (Mpro) from the novel coronavirus associated with severe acute respiratory syndrome (SARS-CoV) were constructed based on the crystal structures of Mpro from transmissible gastroenteritis coronavirus (TGEV) (MproT) and human coronavirus HcoV-229E (MproH), respectively. Both MproST and MproSH exhibit similar folds as their respective template proteins. These homology models reveal three distinct functional domains as well as an intervening loop connecting domains II and III as found in both template proteins. A catalytic cleft containing the substrate binding sites S1 and S2 between domains I and II are also observed. S2 undergoes more significant structural fluctuation than S1 during the 400 ps molecular dynamics simulations because it is located at the open mouth of the catalytic cleft, while S1 is situated in the very bottom of this cleft. The thermal unfolding of these proteins begins at domain III, where the structure is least conserved among these proteins. Mpro may still maintain its proteolytic activity while it is partially unfolded. The electrostatic interaction between Arg40 and Asp186 plays an important role in maintaining the structural integrity of both S1 and S2.


title: Cinanserin is an inhibitor of the 3C-like proteinase of severe acute respiratory syndrome coronavirus and strongly reduces virus replication in vitro.

text: The 3C-like proteinase (3CLpro) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is one of the most promising targets for anti-SARS-CoV drugs due to its crucial role in the viral life cycle. In this study, a database containing structural information of more than 8,000 existing drugs was virtually screened by a docking approach to identify potential binding molecules of SARS-CoV 3CLpro. As a target for screening, both a homology model and the crystallographic structure of the binding pocket of the enzyme were used. Cinanserin (SQ 10,643), a well-characterized serotonin antagonist that has undergone preliminary clinical testing in humans in the 1960s, showed a high score in the screening and was chosen for further experimental evaluation. Binding of both cinanserin and its hydrochloride to bacterially expressed 3CLpro of SARS-CoV and the related human coronavirus 229E (HCoV-229E) was demonstrated by surface plasmon resonance technology. The catalytic activity of both enzymes was inhibited with 50% inhibitory concentration (IC50) values of 5 microM, as tested with a fluorogenic substrate. The antiviral activity of cinanserin was further evaluated in tissue culture assays, namely, a replicon system based on HCoV-229E and quantitative test assays with infectious SARS-CoV and HCoV-229E. All assays revealed a strong inhibition of coronavirus replication at nontoxic drug concentrations. The level of virus RNA and infectious particles was reduced by up to 4 log units, with IC50 values ranging from 19 to 34 microM. These findings demonstrate that the old drug cinanserin is an inhibitor of SARS-CoV replication, acting most likely via inhibition of the 3CL proteinase.


title: Epidemiologic factors and isotype-specific antibody responses in serum and mucosal secretions of dairy calves with bovine coronavirus respiratory tract and enteric tract infections.

text: Blood, feces, and nasal swabs specimens were collected 12 to 24 hours after birth and then 3 times/week (blood only once per week) from one group of 10 calves until they were 10 weeks old and from a second group of 10 calves until they were 10 to 20 weeks old. Colostrum was collected from all calves' dams and tears from 5 randomly selected calves in the first group. All fecal and nasal specimens were assayed for bovine coronavirus (BCV) antigens by ELISA. Nasal epithelial cells were examined for BCV antigens by direct immunofluorescence. Isotype antibody titers to BCV in all samples from 5 calves in group 1 were evaluated by ELISA. Zinc sulfate turbidity (ZST) values were determined on the first serum samples taken from all calves in group 1. To determine whether any correlation existed between ZST values, isotype antibody titers to BCV (12 to 24 hours after birth), number of respiratory sick days, number of enteric sick days, or days to first shedding of virus, a Spearman rank order correlation coefficient was done. Bovine coronavirus respiratory tract and enteric tract infections were common on this farm. Most initial infections developed when calves were 1 to 3 weeks old; however, there were also multiple incidences of shedding of viral antigens or seroconversions at later times during the study. Persistence of infection or reinfection of the upper respiratory tract with BCV was common. Colostral antibody titers to BCV (IgG1) were in all cows at moderate amounts; however, calf serum antibody titers and ZST values (12 to 24 hours after birth) were highly variable.(ABSTRACT TRUNCATED AT 250 WORDS)


title: Viral expression of CCL2 is sufficient to induce demyelination in RAG1-/- mice infected with a neurotropic coronavirus.

text: Mouse hepatitis virus strain JHM causes a chronic demyelinating disease in susceptible strains of rodents. Demyelination does not develop in infected RAG1-/- (recombination activation gene-deficient) mice but can be induced by several experimental interventions, including adoptive transfer of virus-specific T cells or antibodies. A common feature of demyelination in these models is extensive infiltration of macrophages/microglia into the white matter. The data obtained thus far do not indicate whether macrophage/microglia infiltration, in the absence of T cells or antibody, is sufficient to mediate demyelination. To determine whether the expression of a single macrophage chemoattractant, in the context of virus infection, could initiate the demyelinating process, we engineered a recombinant coronavirus that expressed the chemokine CCL2/monocyte chemoattractant protein-1. CCL2 has been implicated in macrophage infiltration into the central nervous system and is involved in demyelination in many experimental models of demyelination. Extensive macrophage/microglia infiltration and demyelination has developed in RAG1-/- mice infected with this recombinant virus. Thus, these results suggest that the minimal requirement for demyelination is increased expression of a single macrophage-attracting chemokine in the context of an inflammatory milieu, such as that induced by a viral infection.


title: Epidemiological and genetic correlates of severe acute respiratory syndrome coronavirus infection in the hospital with the highest nosocomial infection rate in Taiwan in 2003.

text: Taiwan experienced a series of outbreaks of nosocomial severe acute respiratory syndrome (SARS) infections in 2003. Two months after the final outbreak, we recruited 658 employees from the hospital that suffered the first and most severe SARS infections to help us investigate epidemiological and genetic factors associated with the SARS coronavirus (SARS-CoV). SARS-CoV infections were detected by using enzyme immunoassays and confirmed by a combination of Western blot assays, neutralizing antibody tests, and commercial SARS tests. Risk factors were analyzed via questionnaire responses and sequence-specific oligonucleotide probes of human leukocyte antigen (HLA) alleles. Our results indicate that 3% (20/658) of the study participants were seropositive, with one female nurse identified as a subclinical case. Identified SARS-CoV infection risk factors include working in the same building as the hospital's emergency room and infection ward, providing direct care to SARS patients, and carrying a Cw*0801 HLA allele. The odds ratio for contracting a SARS-CoV infection among persons with either a homozygous or a heterozygous Cw*0801 genotype was 4.4 (95% confidence interval, 1.5 to 12.9; P = 0.007).


title: Influenza and the challenge for immunology.

text: The continued westward dissemination of H5N1 influenza A viruses in avian populations and the nearly 50% mortality rate of humans infected with H5N1 are a source of great international concern. A mutant H5N1 virus with the capability to spread rapidly between humans could cause a global catastrophe. Governments have reacted by developing national response plans, stockpiling antiviral drugs and speeding up the development and approval of vaccines. Here we summarize what is known about the interaction between influenza A viruses and the mammalian host response, specifically emphasizing issues that might be of interest to the broader immunology community.


Echinococcosis, Ningxia, China.


title: The United Kingdom public health response to an imported laboratory confirmed case of a novel coronavirus in September 2012.

text: On 22 September 2012, a novel coronavirus, very closely related to that from a fatal case in Saudi Arabia three months previously, was detected in a previously well adult transferred to intensive care in London from Qatar with severe respiratory illness. Strict respiratory isolation was instituted. Ten days after last exposure, none of 64 close contacts had developed severe disease, with 13 of 64 reporting mild respiratory symptoms. The novel coronavirus was not detected in 10 of 10 symptomatic contacts tested.


title: [Report on the investigation of lower extremity osteonecrosis with magnetic resonance imaging in recovered severe acute respiratory syndrome in Guangzhou].

text: OBJECTIVE To report the occurrence of lower extremity avascular abnormalities in 124 cases of recovered severe acute respiratory syndrome (SARS) health care workers of four hospitals in Guangzhou and preliminary investigate the correlation with the treatment of steroid. METHODS 124 health care workers with recovered SARS from four hospitals in Guangzhou were examined with MR imaging of the lower extremity including bilateral hips and knees. In 124 health care workers, 38 cases have not treated with steroid, while 86 cases have treated with varied dosage. The imaging protocol was consisted of screening and full examination. Coronal T1-weighted imaging and short tau inversion recovery sequence were defined as the screening examination. The full examination was defined as images from the screening examination plus three additional imaging sequences: transverse and coronal T2-weighted imaging and short tau inversion recovery sequence. RESULTS In 86 health care workers, 5 cases were found positive in the lower extremity. Osteonecrosis was found in 3 cases. One was involved in bilateral femoral head, and another was unilateral femoral head, and the remaining one was bilateral femoral heads and unilateral femoral condyle and tibial condyle. Bilateral femoral and tibial marrow edema were found in one case. Femoral infarction with significant calcification occurred in one health care worker. Logistic regression analysis indicated that the presence of avascular abnormalities was related with maximum daily dosage. CONCLUSION Osteonecrosis definitely exists in the minority of health care workers with recovered SARS in Guangzhou, who had treated with steroid. The maximum daily dosage of steroid may significantly influence on the occurrence of avascular abnormalities.


Susceptibility to mouse hepatitis virus strain 3 in BALB/cJ mice: failure of immune cell proliferation and interleukin 2 production.


title: Laboratory Tests for COVID-19: A Review of Peer-Reviewed Publications and Implications for Clinical UIse.

text: Diagnostic tests for the coronavirus infection 2019 (COVID-19) are critical for prompt diagnosis, treatment and isolation to break the cycle of transmission. A positive real-time reverse-transcriptase polymerase chain reaction (RT-PCR), in conjunction with clinical and epidemiologic data, is the current standard for diagnosis, but several challenges still exist. Serological assays help to understand epidemiology better and to evaluate vaccine responses but they are unreliable for diagnosis in the acute phase of illness or assuming protective immunity. Serology is gaining attention, mainly because of convalescent plasma gaining importance as treatment for clinically worsening COVID-19 patients. We provide a narrative review of peer-reviewed research studies on RT-PCR, serology and antigen immune-assays for COVID-19, briefly describe their lab methods and discuss their limitations for clinical practice.


title: Investigation of a nosocomial outbreak of severe acute respiratory syndrome (SARS) in Toronto, Canada.

text: BACKGROUND Severe acute respiratory syndrome (SARS) was introduced into Canada by a visitor to Hong Kong who returned to Toronto on Feb. 23, 2003. Transmission to a family member who was later admitted to a community hospital in Toronto led to a large nosocomial outbreak. In this report we summarize the preliminary results of the epidemiological investigation into the transmission of SARS between 128 cases associated with this hospital outbreak. METHODS We collected epidemiologic data on 128 probable and suspect cases of SARS associated with the hospital outbreak, including those who became infected in hospital and the next generation of illness arising among their contacts. Incubation periods were calculated based on cases with a single known exposure. Transmission chains from the index family to hospital contacts and within the hospital were mapped. Attack rates were calculated for nurses in 3 hospital wards where transmission occurred. RESULTS The cases ranged in age from 21 months to 86 years; 60.2% were female. Seventeen deaths were reported (case-fatality rate 13.3%). Of the identified cases, 36.7% were hospital staff. Other cases were household or social contacts of SARS cases (29.6%), hospital patients (14.1%), visitors (14.1%) or other health care workers (5.5%). Of the 128 cases, 120 (93.8%) had documented contact with a SARS case or with a ward where there was a known SARS case. The remaining 8 cases without documented exposure are believed to have had exposure to an unidentified case and remain under investigation. The attack rates among nurses who worked in the emergency department, intensive care unit and coronary care unit ranged from 10.3% to 60.0%. Based on 42 of the 128 cases with a single known contact with a SARS case, the mean incubation period was 5 days (range 2 to 10 days). INTERPRETATION Evidence to date suggests that SARS is a severe respiratory illness spread mainly by respiratory droplets. There has been no evidence of further transmission within the hospital after the elapse of 2 full incubation periods (20 days).


docid: elburiqv

title: Communicating risk: from crisis to calm.


docid: jjwcldwt

title: The ultrastructure of feline infectious peritonitis virus in feline embryonic lung cells.

text: The ultrastructure of feline infectious peritonitis virus in cultured feline embryonic lung cells is reported. Feline embryonic lung cells were infected with feline infectious peritonitis virus and studied by transmission electron microscopy. The virus was not apparent in the cultured cells until 24 h after infection when it occurred in the endoplasmic reticulum, perinuclear space, Golgi apparatus, free in the cytoplasm, in large vacuoles in the cytoplasm and outside the cell membrane. The virus possessed typical coronavirus morphology and was produced by budding into the endoplasmic reticulum. There was no evidence to indicate that this virus budded through the cell membrane. Multinucleate giant cells were formed by infection of the cultured cells with the virus. The host cells were destroyed by the virus and phagocytosed by apparently healthy cells.


title: Serosurveillance of viral diseases in Korean native goats (Capra hircus).

text: A total of 804 goat sera were collected from 144 goat farms in five regions of South Korea during a period between 2005 and 2006 and screened for the antibodies of viral pathogens in ruminants. The individual seropositive rates for each virus were 13.7% (110/804) for bovine herpesvirus-1 (BHV-1), 9.5% (76/804) for bovine parainfluenza type-3 virus (PI-3V), 5.5% (44/804) for Akabane virus (AKAV), 13.3% (107/804) for Aino virus (AINV), 2.0% (16/804) for Chuzan virus (CHUV) and 1.0% (8/804) for bovine coronavirus (BCoV). Compared with other areas, Chungcheong Province showed higher seropositive rates of 13.6% for PI-3V, 22.3% for AKAV and 28.2% for AINV. The results indicate that among the six viral diseases, BHV-1 infection is quite prevalent, while BCoV infection is less prevalent on domestic goat farms in Gyeongsang and Jeonla Provinces.


title: Fractional Flow in Cerebrovascular Disorders.

text: There is an urgent need for stroke experts to advance the care of their patients, yet current approaches are outmoded and have not been successful. The traditional emphasis on anatomical identification of disease, using percent luminal stenosis, results in suboptimal identification of lesions likely to produce recurrent ischemia and, consequently, results in poor patient selection and hampers the development of new aggressive treatments. The traditional emphasis on time since symptom onset and alleged need to achieve complete revascularization in patients with acute ischemic stroke ignores the very nature and degree of the underlying culprit lesion and hampers our understanding of the relationships between the patient's original ischemic state, revascularization, reperfusion, reperfusion injury and hemorrhagic transformation. The trajectory for the study and care of cerebrovascular patients needs to adapt, as it has in cardiology, employing hemodynamics and pathophysiology as the new guideposts for advancement. We introduce fractional flow as one hemodynamic parameter to be utilized to set a course on this new path for the care of stroke patients.


title: Reproducibility of step tests in patients with bronchiectasis.

text: BACKGROUND The step test has been used to assess exercise capacity in patients with chronic respiratory disease; however, its use has not been described with regard to patients with bronchiectasis (BCT). OBJECTIVE This study assessed the reliability of the Chester step test (CST) and the modified incremental step test (MIST) and also correlated these tests with pulmonary function, heart rate (HR), and distance walked during the 6-min walk test (6-MWT). METHOD On separate days, 17 patients randomly underwent two CSTs, two MISTs, and two 6-MWTs. Number of steps (NOSs), HR, and perceived exertion were recorded immediately before and after these tests. RESULTS NOSs were similar across CSTs (124±65 and 125±67) and MISTs (158±83 and 156±76). Differences were not found across the CSTs and MISTs with regard to HR (138±25 bpm and 136±27 bpm), SpO2 (91±5% and 91±3%), perceived exertion (dyspnea=4 [3-5] and 4 [2-4.5]) and fatigue (4 [2-6] and 4 [3-5]). The CST was significantly briefer than the MIST (6.0±2.2 min and 8.6±3.0 min) and had fewer associated NOS (125±67 and 158±83). NOSs were correlated with FEV1, the 6-MWD, and HR for both tests. CONCLUSIONS The CST and MIST are reliable in patients with BCT. Patients tolerated the MIST more than the CST. Better lung function and 6-MWT scores predicted the greater NOSs and greater peak HR.


title: Proteins specified by swine transmissible gastroenteritis virus: identification of non-structural proteins by two-dimensional electrophoresis.

text: Four virus-induced non-structural proteins with apparent molecular weights of 11-14 kilodaltons (kDa) were identified by two-dimensional electrophoresis in cells infected by TGEV. Differences in the number of non-structural proteins were observed among virulent and attenuated TGEV strains as well as with two antigenically related feline and canine coronaviruses.


title: Fecal immunoglobulin A antibodies in dogs infected or vaccinated with canine coronavirus.

text: Fecal secretory immunoglobulin A (IgA) antibodies in dogs infected or vaccinated with canine coronavirus (CCV) were evaluated by an enzyme-linked immunosorbent assay. The study was carried out with 32 fecal samples collected just before inoculation and at 28 days postinoculation. Five groups were studied: naturally infected dogs, experimentally infected dogs, dogs inoculated with a modified live (ML) CCV vaccine by the intramuscular route, dogs inoculated with an ML CCV vaccine by the oronasal route, and dogs given an inactivated CCV vaccine. Both the naturally and the experimentally infected dogs developed high levels of fecal IgAs. Interestingly, dogs inoculated with the ML CCV vaccine by the oronasal route developed levels of fecal IgA that were higher than those observed in the dogs inoculated with the same CCV vaccine by the intramuscular route or those observed in dogs inoculated with the inactivated vaccine. A relationship between the level of fecal IgAs to CCV and the degree of protection against CCV infection was observed.


title: Two distinct size classes of immature and mature subviral particles from tick-borne encephalitis virus.

text: Flaviviruses assemble in the endoplasmic reticulum by a mechanism that appears to be driven by lateral interactions between heterodimers of the envelope glycoproteins E and prM. Immature intracellular virus particles are then transported through the secretory pathway and converted to their mature form by cleavage of the prM protein by the cellular protease furin. Earlier studies showed that when the prM and E proteins of tick-borne encephalitis virus are expressed together in mammalian cells, they assemble into membrane-containing, icosahedrally symmetrical recombinant subviral particles (RSPs), which are smaller than whole virions but retain functional properties and undergo cleavage maturation, yielding a mature form in which the E proteins are arranged in a regular T = 1 icosahedral lattice. In this study, we generated immature subviral particles by mutation of the furin recognition site in prM. The mutation resulted in the secretion of two distinct size classes of particles that could be separated by sucrose gradient centrifugation. Electron microscopy showed that the smaller particles were approximately the same size as the previously described mature RSPs, whereas the larger particles were approximately the same size as the virus. Particles of the larger size class were also detected with a wild-type construct that allowed prM cleavage, although in this case the smaller size class was far more prevalent. Subtle differences in endoglycosidase sensitivity patterns suggested that, in contrast to the small particles, the E glycoproteins in the large subviral particles and whole virions might be in nonequivalent structural environments during intracellular transport, with a portion of them inaccessible to cellular glycan processing enzymes. These proteins thus appear to have the intrinsic ability to form alternative assembly products that could provide important clues about the role of lateral envelope protein interactions in flavivirus assembly.


COVID-19: Transforming Global Health.


title: Structure of the N-terminal RNA-binding domain of the SARS CoV nucleocapsid protein.

text: The severe acute respiratory syndrome (SARS) virus belongs to the Coronaviridea family of viruses. Its virion encodes several proteins including a replicase and four structural proteins. Here we describe the three-dimensional structure of the N-terminal domain of the SARS coronavirus (CoV) nucleocapsid protein. The protein consists of a five-stranded beta sheet with a folding topology distinct from other RNA-binding proteins. Single-stranded RNAs bind to the protein surface at the junction between a flexible, positively charged beta hairpin and the core structure. NMR-based screening was used to identify low molecular weight compounds that bind to this site.


title: Molecular epidemiology of nosocomial rotavirus infection.

text: The molecular epidemiology of nosocomial rotavirus infection in children admitted to the paediatric ward of a large hospital in southern India was studied by transmission electron microscopy and RNA electrophoresis on stool samples. Six hundred and twenty-six samples were collected and rotaviruses were detected in 35 of them. A predominant electropherotype was found in all the samples, and there was no seasonal variation in the incidence of infection. The predominant electropherotype pattern in this study was different from the electropherotype patterns of strains isolated elsewhere in the country and also from the pattern of the strains isolated earlier from children with acute diarrhoea at the same hospital.


title: Early experience with barbed sutures for abdominal closure in deep inferior epigastric perforator flap breast reconstruction.

text: OBJECTIVE Barbed sutures have recently been introduced for closure of surgical incisions. These self-anchoring sutures incorporate evenly spaced barbs in a circumferential distribution along their length, facilitating knotless wound closure and even distribution of tension along the suture line. In this study, we evaluated postoperative complications associated with the use of unidirectional barbed sutures compared with standard sutures for closure of the abdominal incision in deep inferior epigastric perforator flap breast reconstruction. METHODS A consecutive series of 142 patients undergoing deep inferior epigastric perforator flap breast reconstruction were identified at a single institution. The abdominal closure in the first 71 patients was performed using standard suture materials. In the subsequent 71 patients, closure was performed using unidirectional barbed sutures. Patient demographics, complications, procedure time, and costs were compared between standard and barbed suture groups. RESULTS Demographic characteristics and comorbidity profiles were similar between the 2 groups. Overall, there was a significantly higher incidence of complications in the standard suture group (17 vs 7 complications,P = .0423). Similar rates of wound infection (P = .4412), wound dehiscence (P = .4934), and seroma (P = .1157) were recorded in both groups. Barbed sutures were $ 15.58 more expensive than standard sutures. No significant difference in total length of operation was observed. CONCLUSION In this study, the utility of unidirectional barbed sutures in deep inferior epigastric perforator flap breast reconstruction has been demonstrated. Barbed sutures may be useful in a broad range of plastic surgery procedures, not only because of their convenience but also based on favorable clinical outcomes.


title: An update on aspects of viral gastrointestinal diseases of dogs and cats.

text: Viruses commonly cause gastrointestinal illnesses in dogs and cats that range in severity from mild diarrhoea to malignant neoplasia. Perpetual evolution of viruses is reflected in changing disease patterns, so that familiar viruses are sometimes discovered to cause new or unexpected diseases. For example, canine parvovirus (CPV) has regained the ability to infect felids and cause a panleucopenia-like illness. Feline panleucopenia virus (FPV) has been shown to cause fading in young kittens and has recently been implicated as a possible cause of feline idiopathic cardiomyopathy. Molecular scrutiny of viral diseases sometimes permits deeper understanding of pathogenesis and epizootiology. Feline gastrointestinal lymphomas have not, in the past, been strongly associated with retroviral infections, yet some of these tumours harbour retroviral proviruses. Feline leukaemia virus (FeLV) may play a role in lymphomagenesis, even in cats diagnosed as uninfected using conventional criteria. There is strong evidence that feline immunodeficiency virus (FIV) can also be oncogenic. The variant feline coronaviruses that cause invariably-fatal feline infectious peritonitis (FIP) arise by sporadic mutation of an ubiquitous and only mildly pathogenic feline enteric coronavirus (FECV); a finding that has substantial management implications for cat breeders and veterinarians. Conversely, canine enteric coronavirus (CECV) shows considerable genetic and antigenic diversity but causes only mild, self-limiting diarrhoea in puppies. Routine vaccination against this virus is not recommended. Although parvoviruses, coronaviruses and retroviruses are the most important known viral causes of canine and feline gastrointestinal disease, other viruses play a role. Feline and canine rotaviruses have combined with human rotaviruses to produce new, reassortant, zoonotic viruses. Some companion animal rotaviruses can infect humans directly. Undoubtedly, further viral causes of canine and feline gastrointestinal disease await discovery.


title: Evaluation of different irrigating solutions on smear layer removal of primary root dentin.

text: AIM To evaluate the efficacy of ethanolic extract of Salvadora persica (S. persica) and BioPure MTAD (a mixture of a tetracycline isomer, an acid, and a detergent) in removing the intracanal smear layer of primary teeth. MATERIALS AND METHODS The root canal of 40 extracted human primary anterior teeth were cleaned, shaped and grouped into experimental (n = 30) and control (n = 10). The root canals of the positive (n = 5) and the negative control (n = 5) were irrigated for 3 minutes with 5 ml of 17% ethylenediaminetetraacetic acid (EDTA) or saline respectively. The canals in the experimental groups were irrigated for 3 minutes with 5 ml of 1 mg/ml ethanolic extract of S. persica (n = 15) or BioPure MTAD (n = 15) and then flushed with 2 ml of saline. The presence or absence of smear layer at the coronal and middle portion of each canal were examined under a scanning electron microscope (SEM). RESULTS A significant difference (p = 0.004) in smear layer removal between S. persica and MTAD at the middle third of the canal was observed. MTAD solution was as effective as 17% EDTA in removing the smear layer. CONCLUSION MTAD was significantly more effective in smear layer removal than S. persica solution at the middle third of the canal wall. CLINICAL SIGNIFICANCE Both tested irrigant solutions have the ability to remove the intracanal smear from primary root dentin following cleaning and shaping of the root canal and could be an alternative to EDTA.


title: Progress toward global eradication of dracunculiasis, January 2005-May 2007.

text: The World Health Assembly first adopted a resolution calling for the eradication of dracunculiasis (Guinea worm disease) in 1986, when an estimated 3.5 million cases were reported in 20 countries, and 120 million persons were at risk for the disease. This report describes the continued progress of the dracunculiasis eradication program worldwide during July 2005-May 2007. As of May 2007, dracunculiasis was still endemic in nine of the 20 countries cited in 1986; in 2006, approximately 98% of dracunculiasis cases worldwide were reported from Ghana and Sudan, and five other countries reported fewer than 30 cases each. The number of dracunculiasis cases increased from 10,674 in 2005 to 25,217 cases in 2006, with nearly all of the increase reported in Sudan, before decreasing from 9,510 during January-May 2006 to 4,460 cases during January-May 2007. Continued intensification of interventions against transmission of dracunculiasis will be necessary to eradicate dracunculiasis in the nine countries where the disease remains endemic.


title: "What does this mean?" How Web-based consumer health information fails to support information seeking in the pursuit of informed consent for screening test decisions.

text: PURPOSE The authors analyzed online consumer health information related to screening tests to see how well this information meets known standards for supporting the understanding of test uncertainty. SETTING/SUBJECTS MedlinePlus documents regarding maternal serum screening (6), prostate-specific antigen testing (6), and screening mammography (6) were analyzed. METHODOLOGY The content of the documents was analyzed. RESULTS This study showed that most sites conscientiously report that tests are less than 100% accurate, but few provide important details about the level of uncertainty associated with test results. In particular, few resources give information about the predictive value of screening tests and have little mention of the fact that predictive value is influenced by the a priori likelihood of having the condition. DISCUSSION/CONCLUSION These results suggest that online consumer health information does not adequately support decisions about medical screening. We suggest a potential solution to the problem: metadata harvesting coupled with optimized presentation techniques to format personalized information about screening tests. Using these techniques, the empowerment of personal choice in matters of health decisions could become the de facto standard.


title: Monoclonal antibodies to bovine coronavirus glycoproteins E2 and E3: demonstration of in vivo virus-neutralizing activity.

text: Six monoclonal antibodies (MAbs) to bovine coronavirus (BCV, Quebec isolate) E2 and E3 glycoproteins which were found previously to be neutralizing in vitro were examined for virus-neutralizing activity in vivo. Surgically ligated intestinal loops of newborn colostrum-deprived calves were virus-inoculated, mock-infected or inoculated with a mixture of virus and antibody. Of the six BCV-specific MAbs, four were found to be protective against a virulent field isolate of BCV, as indicated by a reduction in villous atrophy. These MAbs were specific to antigenic domain A and antigenic domains A1 and A2 on the E2 and E3 glycoproteins respectively. MAbs to antigenic domains B and C on the E2 and E3 glycoproteins, respectively, were not protective.


title: Detection of feline panleukopenia virus using a commercial ELISA for canine parvovirus.

text: Feline panleukopenia virus (FPV) is a significant pathogen of cats. Rapid virus detection is critical for treatment and management, especially in populations in which spread may occur. This study investigated the ability of the SNAP Canine Parvovirus Antigen Test Kit (SNAP Parvo, IDEXX Laboratories) to detect FPV with confirmation of viral identity by polymerase chain reaction (PCR) assay and genetic sequencing on fecal samples (n = 97) from cats with suspected FPV infection. Fifty-five samples were positive by SNAP Parvo; 54 of 55 were also positive by conventional PCR assay and were identified as FPV by genetic sequencing. This study demonstrates that SNAP Parvo can detect FPV in clinical samples.


title: [Integration of mental health and chronic non-communicable diseases in Peru: challenges and opportunities for primary care settings].

text: In this article, the relationship between mental health and chronic non-communicable diseases is discussed as well as the possibility to address them in a comprehensive manner in the Peruvian health system. First, the prevalence estimates and the burden of chronic non-communicable diseases and mental disorders worldwide and in Peru are reviewed. Then, the detrimental impact of depression in the early stages as well as the progress of diabetes and cardiovascular diseases is described. Additionally, the gap between access to mental health care in Peru is analyzed. Lastly, the alternatives to reduce the gap are explored. Of these alternatives, the integration of mental health into primary care services is emphasized; as a feasible way to meet the care needs of the general population, and people with chronic diseases in particular, in the Peruvian context.


title: [The community health team: roles and responsibilities in infection control].

text: Over the past three decades, chronic disease has replaced communicable disease as the leading collective cause of death in Taiwan. As a result, medical and public healthcare manpower and budgets dedicated to communicable diseases have been reduced. The 2003 outbreak of Severe Acute Respiratory Syndrome (SARS) changed government epidemic prevention policies and marked a renewed focus on preventing and controlling communicable diseases. This study introduces Taiwan's communicable disease control system and reforms, the domestic status of communicable diseases, the infection control policies of Japanese colonial authorities in the early 20th century, and national / community-level communicable disease control mechanisms in place before and after 2003. This paper further examines the actual health management conditions in a county in southern Taiwan to show how the public health system is rooted in communities, how infection control strategies are promoted, and how social organizations influence community life and mores.