title: Secondary hemophagocytic lymphohistiocytosis in zoonoses. A systematic review.

text: BACKGROUND Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome that is often fatal despite treatment. It is caused by a dysregulation in natural killer T-cell function, resulting in activation and proliferation of histiocytes with uncontrolled hemophagocytosis and cytokines overproduction. The syndrome is characterized by fever, hepatosplenomegaly, cytopenias, liver dysfunction, and hyperferritinemia. HLH can be either primary, with a genetic aetiology, or secondary, associated with malignancies, autoimmune diseases, or infections. AIM To focus on secondary HLH complicating zoonotic diseases. MATERIALS AND METHODS PubMed search of human cases of HLH occurring during zoonotic diseases was performed combining the terms (haemophagocytic or haemophagocytosis or hemophagocytosis or hemophagocytic or erythrophagocytosis or macrophage activation syndrome) with each one of the etiological agents of zoonoses. RESULTS Among bacterial diseases, most papers reported cases occurring during brucellosis, rickettsial diseases and Q fever. Regarding viral diseases, most of the cases were reported in patients with avian influenza A subtype H5N1. Among the protozoan zoonoses, most of the cases were reported in patients with visceral leishmaniasis. Regarding zoonotic fungi, most of the cases were reported in AIDS patient with histoplasmosis. No cases of secondary HLH were reported in patient with zoonotic helminthes. CONCLUSIONS Zoonotic diseases are an important cause of HLH. Secondary HLH can delay the correct diagnosis of the zoonotic disease, and can contribute to an adverse outcome.


title: [Spread of infectious agents through refuse by domestic, community and field parasites with special reference to human health].

text: The accumulation of refuse in urban and agricultural areas provides parasitic vermin with new feeding sources and also creates for them partly entirely new biotopes. Vermin transmit both mechanically and biologically the most varied species of pathogens to man, domestic animals and work animals. With respect to the spread of pathogens by vermin via the refuse route, we must distinguish between vermin infesting either the human body, the houses, communities or our environment. Among the human vermin and house species, cockroaches, house gnats and house flies are the most important genera for the spread of pathogens via refuse. Cockroaches transmit bacteria (e.g. Salmonella), viruses (e.g. enterovirus, rota and corona viruses), fungi (e.g. Trichophyton and Candida) and worm eggs (e.g. Ascaris lumbricoides). House flies and house gnats take up all infection carriers from refuse and transmit the pathogens, as a rule, purely mechanically. Rats and mice are the most important species among community vermin. These rodents act both as mechanical and biological vehicles of infectious diseases. A case in point is lymphocytic chorio-meningitis and three different types of hemorrhagic fever in man. Among the vermin infesting our environment, the diptera are the most important carriers. Gnats, especially, often act as intermediate hosts (biological transmission) and, as a result, represent an inexhaustible reservoir of pathogen transmitters. More than 50 diseases caused by arbovirus in man and animal are known. Beside the viruses, the field diptera transmit bacteria (e.g. Rickettsiosis) and protozoa (e.g. Leishmaniasis, Trypanosomiasis).(ABSTRACT TRUNCATED AT 250 WORDS)


Non-contact infrared thermal imagers may still be useful for mass fever screening.


title: Pattern of Colon Cancer Lymph Node Metastases in Patients Undergoing Central Mesocolic Lymph Node Excision: A Systematic Review.

text: BACKGROUND Extended mesocolic lymph node dissection in colon cancer surgery seems to improve oncological outcome. A possible reason might be related to metastases in the central mesocolic lymph nodes. OBJECTIVE The purpose of this study was to describe the pattern of mesocolic lymph node metastases, particularly in central lymph nodes, and the risk of skip, aberrant, and gastrocolic ligament metastases as the argument for performing extended lymph node dissection. DATA SOURCES EMBASE and PubMed were searched using the terms colon or colorectal with sentinel node, lymph node mapping, or skip node; lymph node resection colon; and complete or total and mesocolic excision. STUDY SELECTION Studies describing the risk of metastases in central, skip, aberrant, and gastrocolic ligament lymph node metastases from colon adenocarcinomas in 10 or more patients were included. No languages were excluded. MAIN OUTCOME MEASURES The risk of metastases in the central mesocolic lymph nodes was measured. RESULTS A total of 2052 articles were screened, of which 277 underwent full-text review. The 47 studies fulfilling the inclusion criteria were very heterogeneous, and meta-analyses were not considered appropriate. The risk of central mesocolic lymph node metastases for right-sided cancers varies between 1% and 22%. In sigmoid cancer, the risk is reported in ≤12% of the patients and is associated with advanced T stage. LIMITATIONS The retrospective design and heterogeneity, in terms of definitions of lymph node location, tumor sites, stage, morphology, pathology assessment, and inclusion criteria (selection bias), of the included studies were limitations. Also, anatomic definitions were not uniform. CONCLUSIONS The present literature cannot give a theoretical explanation of a better oncological outcome after extended lymph node dissection. Consensus for a standardization of anatomical definitions and surgical and pathological assessments is warranted for future mapping studies.


title: Establishment of a canine cell line: derivation, characterization, and viral spectrum.

text: A cell line, designated A-72, for virus studies was established from a tumor surgically removed from a female, 8-year-old Golden Retriever dog. Following explant culture, the cells were serially passaged 135 times. The A-72 cells maintained a fibroblastic appearance and, at the 123rd passage, had a population doubling time of approximately 27 hours. Karyotypic analysis of the high passage cells showed the modal 2n chromosome number was 92 to 93. Using starch gel electrophoresis for enzyme characterization, the electrophoretic mobilities of enzymes extracted from A-72 cells were identical with those of canine peritoneal fibroblasts and primary canine kidney cells. The A-72 cells were susceptible to infection with infectious canine hepatitis virus, canine adenovirus type II, canine herpesvirus, canine parainfluenza virus, and canine coronavirus, but were not susceptible to canine distemper virus or the minute virus of canines. These cells have been particularly useful for studies of the fastidious canine coronaviruses, as the commonly used primary canine kidney cells exhibit varied susceptibility to these viruses.


title: Antimicrobial and antiparasitic activity of lectins.

text: Antibiotic resistance is a major problem in current contemporary medicine and it has become a major concern of the 21st century. New resistance mechanisms developed by microorganisms spread greatly, threatening the ability to treat numerous infectious diseases, and increasing the number of nosocomial infections. Besides the role in immunology and glycobiology where they are used as hemaglutinine and identification of complex carbohydrates and glycoconjugates, lectins proved to mediate diversified biological functions like cytotoxicity, complement activation, cell-to-cell and host-pathogen communications, innate immune response, and cell-to-cell signalling. Recently, great interest has been developed for the research and applications of lectins in agriculture and medicine due to their antiparasitic and antimicrobial potentials. This review focuses on the recent data regarding the antimicrobial and antiparasitic activities of lectins, by presenting the role of lectins in host-pathogen interaction and also the cytotoxic effects on microorganisms and parasites. Identification and characterisation of new lectins with antimicrobial activity could serve as a natural alternative for the treatment of infections caused by antibiotic-resistant microorganisms and parasites.


title: Bovine coronavirus mRNA replication continues throughout persistent infection in cell culture.

text: The existence of viral mRNA replicons was demonstrated in cells infected with the bovine coronavirus by showing a minus-strand counterpart and a corresponding replicative intermediate for each subgenomic mRNA species. mRNA replication is thus a universal property of coronaviruses, since this is now the third coronavirus for which it has been demonstrated. During the acute phase of infection (first 48 h), minus and plus strands accumulated at the same rate initially, but maximal accumulation of minus strands peaked earlier than that for plus strands, indicating that minus- and plus-strand levels are differentially regulated. In addition, packaged (input) mRNAs appeared to serve as templates for their own early replication. mRNA replication continued throughout establishment and maintenance of persistent infection (studied for 120 days), which is consistent with our hypothesis that mRNA replication contributes mechanistically to virus persistence. A replication-defective (potentially interfering) species of RNA existed transiently (beginning at day 2 and ending before day 76 postinfection), but because of its transient nature it cannot be considered essential to the long-term maintenance of virus persistence.


title: Processing of the equine arteritis virus replicase ORF1b protein: identification of cleavage products containing the putative viral polymerase and helicase domains.

text: The replicase open reading frame lb (ORF1b) protein of equine arteritis virus (EAV) is expressed from the viral genome as an ORF1ab fusion protein (345 kDa) by ribosomal frameshifting. Processing of the ORF1b polyprotein was predicted to be mediated by the nsp4 serine protease, the main EAV protease. Several putative cleavage sites for this protease were detected in the ORF1b polyprotein. On the basis of this tentative processing scheme, peptides were selected to raise rabbit antisera that were used to study the processing of the EAV replicase ORF1b polyprotein (158 kDa). In immunoprecipitation and immunoblotting experiments, processing products of 80, 50, 26, and 12 kDa were detected. Of these, the 80-kDa and the 50-kDa proteins contain the putative viral polymerase and helicase domains, respectively. Together, the four cleavage products probably cover the entire ORF1b-encoded region of the EAV replicase, thereby representing the first complete processing scheme of a coronaviruslike ORF1b polyprotein. Pulse-chase analysis revealed that processing of the ORF1b polyprotein is slow and that several large precursor proteins containing both ORF1a- and ORF1b-encoded regions are generated. The localization of ORF1b-specific proteins in the infected cell was studied by immunofluorescence. A perinuclear staining was observed, which suggests association with a membranous compartment.


title: Use of gastrointestinal anastomosis stapler for harvest of gracilis muscle and securing it in the face for facial reanimation: a novel technique.

text: BACKGROUND The primary objective of this study is to report a novel technique that uses the gastrointestinal anastomosis (GIA) stapler for harvesting and securing the gracilis muscle in facial reanimation surgery. METHODS We conducted a retrospective chart review with 18 consecutive patients who underwent gracilis muscle flap transfer with or without the use of a GIA stapler. RESULTS Of 11 operations with the GIA stapler, one patient developed a hematoma (donor site) and another required drainage of an abscess (recipient site). Of 8 operations without the use of the stapler, one patient had total flap failure and three required drainage of an abscess (2 recipient sites and 1 donor site). These differences trended toward improvement but were not statistically different. CONCLUSIONS The use of the GIA stapler is a fast, safe technique. Larger studies are, however, warranted to further examine this novel approach in order to test precisely what factors of increased efficiency occur, the amount of suture pull-through, and overall tension capable of being applied to the secured staple line.


title: Designing a biocontainment unit to care for patients with serious communicable diseases: a consensus statement.

text: In spite of great advances in medicine, serious communicable diseases are a significant threat. Hospitals must be prepared to deal with patients who are infected with pathogens introduced by a bioterrorist act (e.g., smallpox), by a global emerging infectious disease (e.g., avian influenza, viral hemorrhagic fevers), or by a laboratory accident. One approach to hazardous infectious diseases in the hospital setting is a biocontainment patient care unit (BPCU). This article represents the consensus recommendations from a conference of civilian and military professionals involved in the various aspects of BPCUs. The role of these units in overall U.S. preparedness efforts is discussed. Technical issues, including medical care issues (e.g., diagnostic services, unit access); infection control issues (e.g., disinfection, personal protective equipment); facility design, structure, and construction features; and psychosocial and ethical issues, are summarized and addressed in detail in an appendix. The consensus recommendations are presented to standardize the planning, design, construction, and operation of BPCUs as one element of the U.S. preparedness effort.


Controversies and uncertainties in managing SARS.


title: Mycoplasma-induced hydrocephalus in rats and hamsters.

text: Mycoplasma pulmonis, a pathogen of the respiratory tract in rats, was inoculated intracerebrally into neonate rats and hamsters to determine if it would induce lesions in the ependyma. Hydrocephalus was induced in 116 of 120 rats and in 23 of 28 hamsters. The severity of hydrocephalus was greater in the rats than in the hamsters. Hydrocephalus induction occurred only subsequent to inoculation of viable M. pulmonis. At 2 weeks of age, rats became refractory to induction of hydrocephalus. Light microscopy indicated that the hydrocephalus was communicating without an inflammatory response in the ventricles and meninges. Preliminary electron microscopy revealed that amorphous material covered portions of the ependymal surface and that cilia were sometimes matted together. It was suggested that the hydrocephalus was due to ciliary dysfunction or to an imbalance of cerebrospinal fluid secretion and absorption. This M. pulmonis-induced hydrocephalus may be a useful model for elucidating the pathogenesis of certain types of congenital hydrocephalus in humans.


title: Research gaps in protecting healthcare workers from SARS and other respiratory pathogens: an interdisciplinary, multi-stakeholder, evidence-based approach.

text: OBJECTIVE To identify priorities for further research in protecting healthcare workers (HCWs) from severe acute respiratory syndrome (SARS) and other respiratory pathogens by summarizing the basic science of infectious bioaerosols and the efficacy of facial protective equipment; the organizational, environmental, and individual factors that influence the success of infection control and occupational health programs; and factors identified by HCWs as important. METHOD An extensive literature review was conducted and 15 focus groups held, mostly with frontline HCWs in Toronto. Critical gaps in knowledge were identified and prioritized. RESULTS Highest priority was given to organizational factors that create a climate of safety. Other priority areas included understanding aerosolization risks and practical measures to control bioaerosols at the source. CONCLUSIONS Further research is warranted to improve safety climate in health care and, specifically, to provide greater protection against respiratory pathogens.


title: Epimedium-derived phytoestrogen exert beneficial effect on preventing steroid-associated osteonecrosis in rabbits with inhibition of both thrombosis and lipid-deposition.

text: OBJECTIVES This study tested the effect of Epimedium-derived phytoestrogen (PE) on preventing steroid-associated osteonecrosis (ON) in rabbit model. METHODS Thirty 28-week-old male New-Zealand white rabbits were divided into control group (CON; n=14) and PE group (PE; n=16; 5 mg/kg body weight/day) after receiving an established inductive protocol for inducing steroid-associated ON. Before and after inductive protocol, Dynamic-MRI was employed on bilateral femora for local intra-osseous perfusion, blood samples were examined for coagulation, fibrinolysis and lipid-transportation, and marrow samples were quantified for adipogenesis-gene mRNA expression. Six weeks later, bilateral femora were dissected for Micro-CT-based micro-angiography, and then ON lesion, intravascular thrombosis and extravascular fat-cell-size were examined histopathologically. RESULTS The incidence of ON in the PE group (31%) was significantly lower than that in the CON group (93%). Compared to the CON group, local intra-osseous perfusion was maintained in the PE group. Blocked trunk vessels were seldom found in micro-angiography of the PE-treated rabbits. Thrombosis incidence and fat-cell-size were both significantly lower in the PE group than those in the CON group. During the early period after induction, indicator of coagulation, fibrinolysis, lipid-transportation and adipogenesis-gene expression were found with significantly changing pattern in the PE group compared to the CON group. CONCLUSION PE was able to exert beneficial effect on preventing steroid-associated ON in rabbits with inhibition of both thrombosis and lipid deposition.


title: Communicating public health advice after a chemical spill: results from national surveys in the United Kingdom and Poland.

text: OBJECTIVE The aim of this study was to enhance public health preparedness for incidents that involve the large-scale release of a hazardous substance by examining factors likely to influence public responses to official guidance on how to limit their exposure. METHODS An online demographically representative survey was conducted in the United Kingdom (n = 601) and Poland (n = 602) to test the strength of association of trust in authorities, anxiety, threat, and coping appraisals with the intention to comply with advice to shelter in place following a hypothetical chemical spill. The impact of ease of compliance and style of message presentation were also examined. RESULTS Participants were more likely to comply if at home when the incident happened, but message presentation had little impact. Coping appraisals and trust were key predictors of compliance, but threat appraisals were associated with noncompliance. Anxiety was seen to promote behavioral change. UK participants were more likely to comply than Polish participants. CONCLUSIONS Successful crisis communications during an emergency should aim to influence perceptions regarding the efficacy of recommended behaviors, the difficulties people may have in following advice, and perceptions about the cost of following recommended behaviors. Generic principles of crisis communication may need adaptation for national contexts.


title: RNA-dependent RNA polymerase activity in murine coronavirus-infected cells.

text: The multiplication of murine coronavirus strains A59 or JHM in Sac(-) cells was unaffected by the presence of alpha-amanitin at concentrations which inhibited the host cell DNA-dependent RNA polymerase activity. In cells infected with the A59 virus strain, actinomycin D-resistant RNA synthesis could readily be detected by pulse-labelling with [3H]uridine; this virus-specific RNA synthesis was not induced in the presence of the protein synthesis inhibitor anisomycin. A new RNA-dependent RNA polymerase activity was detected in the large particle fraction of A59 virus-infected cells. Optimal conditions for enzyme activity in vitro were established. Maximum activity occurred 5 h after infection, coincident with the peak of virus-specific RNA synthesis detected by pulse-labelling in vivo.


title: Data from 11 years of molecular typing infectious bronchitis virus field isolates.

text: In 1993, a new molecular typing method for infectious bronchitis virus (IBV) was introduced. This method uses reverse transcriptase-polymerase chain reaction (RT-PCR) and restriction fragment length polymorphism (RFLP) analysis of the spike gene to obtain RFLP patterns that correlate with serotype. Using that test at the Poultry Diagnostic and Research Center (PDRC, University of Georgia, Athens, GA), we have identified a total of 1523 IBV isolates in the past 11 yr. The data were obtained from clinical samples submitted to our laboratory from birds with clinical signs characteristic of IBV infection. The samples are primarily from the southeastern United States but are also from many other states as well as from outside the United States. Most of the isolations occurred during July, followed by May, April, November, October, and January. The fewest number of isolates identified on an annual basis was 20 in 2003. An unusually high number of isolations occurred in 1997 (318 isolations) and 1999 (246 isolations), which coincided with the GAV variant virus and GA98 variant virus outbreaks respectively. By far, the Ark-DPI strain was the most frequently identified type of IBV and ranged from 23% to 65% of total isolations per year. Ark-like isolates, defined as having a similar but unique RFLP pattern from the Ark-DPI vaccine strain were identified every year of the study except in 1996. In addition, new Ark-like isolates continued to emerge each year (except in the year 2000) beginning in 1997, reflecting the ability of that IBV type to undergo genetic drift. Eighty-two different variant viruses were identified although only two (GAV and GA98) became persistent and caused widespread disease. Some viruses tended to be geographically restricted to a given area (CAV in California and MX97-8147 in Mexico), whereas others were widespread (Ark-DPI, Conn, DE072, and Mass). The Florida, Gray, Holte, Iowa, and JMK types were not detected during the 11-yr period, and no foreign virus types were detected in the United States. These data show that IBV variant viruses are consistently circulating in commercial poultry and are capable of causing disease outbreaks. Our observations highlight the importance of constantly monitoring IBV as well as other coronaviruses like severe acute respiratory syndrome-coronavirus that have the ability to change and emerge to cause disease in a susceptible host.


Treatment of severe acute respiratory syndrome with convalescent plasma.


title: Myocarditis associated with reovirus in turkey poults.

text: Myocarditis associated with reovirus was diagnosed in 17-day-old, male turkey poults, based on virus isolation, reverse transcriptase-polymerase chain reaction (RT-PCR), demonstration of reovirus antigen in the cytoplasm of mononuclear inflammatory cells and myocytes in the heart by immunohistochemistry (IHC), and reovirus particles in the endoplasmic reticulum of myocytes by transmission electron microscopy (TEM). Clinical signs in the poults included anorexia, growth depression, and increased mortality. Gross lesions in the six poults examined were increased pericardial fluid, mild-to-moderate dilation of right ventricles, pale-yellow myocardium, and ascites. Other lesions in a few birds included mild pulmonary edema, congestion, and pale serosa of the small intestine that had watery contents in their lumens. Microscopically, in the heart, there was mild-to-severe necrosis of myocytes and infiltration of primarily lymphocytes mixed with a few heterophils, macrophages, and occasionally, plasma cells and multinucleated giant cells. There was mild-to-moderate lymphoid depletion in the bursa of Fabricius. Reovirus was isolated from the heart of the turkey poults in chicken-embryo liver cells and was confirmed by RT-PCR, IHC, and TEM. A retrospective search of the laboratory database for cases of myocarditis associated with reovirus in turkeys revealed that this condition has occurred sporadically in California turkey flocks since 1991. This is the first documentation of myocarditis in turkey poults associated with reovirus.


Incomplete Kawasaki Disease in a Child with Covid-19.


title: Development of real-time polymerase chain reaction assays for rapid detection and differentiation of wild-type pseudorabies and gene-deleted vaccine viruses.

text: The successful eradication of pseudorabies in U.S. domestic swine was accomplished through the use of glycoprotein E (gE) deleted modified live virus vaccines and an accompanying gE differential enzyme-linked immunosorbent assay (ELISA). Yet, pseudorabies virus (PRV) was established in feral swine in the United States, becoming a potential reservoir of PRV for infection of domestic swine and other native wildlife. A critical need for the current PRV surveillance program in the United States is the rapid detection of PRV infection. For this reason, a set of 2 real-time polymerase chain reaction (PCR) assays by using TaqMan chemistry was developed and evaluated for their capability in the detection and differentiation of field and vaccine strains of PRV. PCR primers and probes were designed for gB and gE genes of PRV, respectively. The newly developed PRV-specific real-time PCR assays could detect all wild-type PRV isolates from diagnostic submissions and differentiate them from vaccine strains. The analytical sensitivity of the assays was approximately 0.1 plaque-forming units per reaction. The assays were highly specific for PRV, because no positive results were obtained from testing other common swine viral pathogens and other animal herpesviruses. The results of testing samples from domestic and feral swine and from bovine showed that the real-time PCR assays are more sensitive than gel-based PCR. These results demonstrated the potential application of the developed real-time PCR assays as a differential test for rapid and specific detection of PRV in domestic and feral swine, as well as nonporcine species that can be infected with PRV and serve as carriers.


title: Prospective multicenter study of children with bronchiolitis requiring mechanical ventilation.

text: OBJECTIVE To identify factors associated with continuous positive airway pressure (CPAP) and/or intubation for children with bronchiolitis. METHODS We performed a 16-center, prospective cohort study of hospitalized children aged <2 years with bronchiolitis. For 3 consecutive years from November 1 until March 31, beginning in 2007, researchers collected clinical data and a nasopharyngeal aspirate from study participants. We oversampled children from the ICU. Samples of nasopharyngeal aspirate were tested by polymerase chain reaction for 18 pathogens. RESULTS There were 161 children who required CPAP and/or intubation. The median age of the overall cohort was 4 months; 59% were male; 61% white, 24% black, and 36% Hispanic. In the multivariable model predicting CPAP/intubation, the significant factors were: age <2 months (odds ratio [OR] 4.3; 95% confidence interval [CI] 1.7-11.5), maternal smoking during pregnancy (OR 1.4; 95% CI 1.1-1.9), birth weight <5 pounds (OR 1.7; 95% CI 1.0-2.6), breathing difficulty began <1 day before admission (OR 1.6; 95% CI 1.2-2.1), presence of apnea (OR 4.8; 95% CI 2.5-8.5), inadequate oral intake (OR 2.5; 95% CI 1.3-4.3), severe retractions (OR 11.1; 95% CI 2.4-33.0), and room air oxygen saturation <85% (OR 3.3; 95% CI 2.0-4.8). The optimism-corrected c-statistic for the final model was 0.80. CONCLUSIONS In this multicenter study of children hospitalized with bronchiolitis, we identified several demographic, historical, and clinical factors that predicted the use of CPAP and/or intubation, including children born to mothers who smoked during pregnancy. We also identified a novel subgroup of children who required mechanical respiratory support <1 day after respiratory symptoms began.


title: Outbreaks of human metapneumovirus in two skilled nursing facilities -West Virginia and Idaho, 2011-2012.

text: During January and February 2012, state and local public health agencies in West Virginia and Idaho, with assistance from facility staff members and CDC, investigated outbreaks of unexplained respiratory illness characterized by high proportions of lower respiratory tract infections (LRTIs) at two skilled nursing facilities (SNFs). Investigations were conducted to determine the extent and etiology of each outbreak and make recommendations to prevent further spread. During both outbreaks, influenza was initially suspected; however, human metapneumovirus (hMPV) was identified as the etiologic agent. Among 57 cases of respiratory illness from both facilities, 45 (79%) patients had evidence of LRTI, of whom 25 (56%) had radiologically confirmed pneumonia; five (9%) had evidence of upper respiratory tract infection (URTI), and seven (12%) could not be classified. Six patients (11%) died. These outbreaks demonstrate that hMPV, a recently described pathogen that would not have been detected without the use of molecular diagnostics in these outbreaks, is associated with severe LRTI and should be considered as a possible etiology of respiratory outbreaks in SNFs.


title: The effect of RNA secondary structures on RNA-ligand binding and the modifier RNA mechanism: a quantitative model.

text: RNA-ligand binding often depends crucially on the local RNA secondary structure at the binding site. We develop here a model that quantitatively predicts the effect of RNA secondary structure on effective RNA-ligand binding activities based on equilibrium thermodynamics and the explicit computations of partition functions for the RNA structures. A statistical test for the impact of a particular structural feature on the binding affinities follows directly from this approach. The formalism is extended to describing the effects of hybridizing small "modifier RNAs" to a target RNA molecule outside its ligand binding site. We illustrate the applicability of our approach by quantitatively describing the interaction of the mRNA stabilizing protein HuR with AU-rich elements. We discuss our model and recent experimental findings demonstrating the effectivity of modifier RNAs in vitro in the context of the current research activities in the field of non-coding RNAs. We speculate that modifier RNAs might also exist in nature; if so, they present an additional regulatory layer for fine-tuning gene expression that could evolve rapidly, leaving no obvious traces in the genomic DNA sequences.


title: Deficiencies in gut NK cell number and function precede diabetes onset in BB rats.

text: Defects in the intestinal immune system may contribute to the pathogenesis of autoimmune diseases. Intraepithelial lymphocytes represent a substantial fraction of gut-associated lymphocytes, but their function in mucosal immunity is unclear. A newly described population of NK cells that spontaneously secrete IL-4 and IFN-gamma is present in the intraepithelial lymphocyte compartment of the rat. We hypothesized that defects in the number or function of these cells would be present in rats susceptible to autoimmunity. We report that the number of NKR-P1A(+)CD3(-) intraepithelial NK (IENK) cells is deficient before onset of spontaneous autoimmune diabetes in diabetes-prone BB (BBDP) rats. The absolute number of recoverable IENK cells was only approximately 8% of that observed in WF rats. Bone marrow transplantation from histocompatible WF donors reversed the IENK cell deficiency (and prevented diabetes) in these animals, suggesting a hemopoietic origin for their IENK cell defect. Analysis of diabetes-resistant BB rats, which develop autoimmune diabetes only after perturbation of the immune system, revealed IENK cell numbers intermediate between that of BBDP and WF rats. IENK cells were selectively depleted during treatment to induce diabetes. Prediabetic BBDP and diabetes-resistant BB animals also exhibited defective IENK cell function, including decreased NK cell cytotoxicity and reduced secretion of IL-4 and IFN-gamma. IENK functional defects were also observed in LEW and BN rats, which are susceptible to induced autoimmunity, but not in WF, DA, or F344 rats, which are resistant. Defects in IENK cell number and function may contribute to the pathogenesis of autoimmune diseases including type 1 diabetes.


title: Tracking the emergence of pandemic Influenza A/H1N1/2009 and its interaction with seasonal influenza viruses in Singapore.

text: INTRODUCTION Since the emergence of the pandemic influenza A/H1N1/2009 virus in April 2009, diagnostic testing in many countries has revealed the rapid displacement and then replacement of circulating seasonal influenza viruses by this novel virus. MATERIALS AND METHODS In-house seasonal and pandemic influenza-specific polymerase chain reaction assays were introduced and/or developed at the Molecular Diagnosis Centre (MDC) at the National University Hospital (NUH), Singapore. These assays have been used to test all samples received from in-patients, out-patients, staff and visitors for suspected pandemic influenza A/H1N1/2009 infection. RESULTS Prior to the arrival of the pandemic A/H1N1/2009 virus in Singapore at the end of May 2009, seasonal influenza A/H3N2 predominated in this population, with very little seasonal influenza A/H1N1 and B viruses detected. Within about 1 month of its arrival in Singapore (mainly during June to July 2009), this pandemic virus rapidly displaced seasonal influenza A/H3N2 to become the predominant strain in the Singaporean population served by MDC/NUH. CONCLUSIONS Realtime molecular techniques have allowed the prompt detection of different influenza subtypes during this current pandemic, which has revealed the displacement/replacement of previously circulating seasonal subtypes with A/H1N1/2009. Although some of this may be explained by immunological cross-reactivity between influenza subtypes, more studies are required.


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title: Burden of infectious diseases in South Asia.


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title: An RNA stem-loop within the bovine coronavirus nsp1 coding region is a cis-acting element in defective interfering RNA replication.

text: Higher-order cis-acting RNA replication structures have been identified in the 3'- and 5'-terminal untranslated regions (UTRs) of a bovine coronavirus (BCoV) defective interfering (DI) RNA. The UTRs are identical to those in the viral genome, since the 2.2-kb DI RNA is composed of only the two ends of the genome fused between an internal site within the 738-nucleotide (nt) 5'-most coding region (the nsp1, or p28, coding region) and a site just 4 nt upstream of the 3'-most open reading frame (ORF) (the N gene). The joined ends of the viral genome in the DI RNA create a single continuous 1,635-nt ORF, 288 nt of which come from the 738-nt nsp1 coding region. Here, we have analyzed features of the 5'-terminal 288-nt portion of the nsp1 coding region within the continuous ORF that are required for DI RNA replication. We observed that (i) the 5'-terminal 186 nt of the nsp1 coding region are necessary and sufficient for DI RNA replication, (ii) two Mfold-predicted stem-loops within the 186-nt sequence, named SLV (nt 239 to 310) and SLVI (nt 311 to 340), are supported by RNase structure probing and by nucleotide covariation among closely related group 2 coronaviruses, and (iii) SLVI is a required higher-order structure for DI RNA replication based on mutation analyses. The function of SLV has not been evaluated. We conclude that SLVI within the BCoV nsp1 coding region is a higher-order cis-replication element for DI RNA and postulate that it functions similarly in the viral genome.


title: Evaluation of tongue as a complementary sample for the diagnosis of parvoviral infection in dogs and cats.

text: Diagnosis of canine parvovirus type 2 and feline panleukopenia virus infection in dogs and cats may be hampered by the severity of enteric lesions, secondary bacterial overgrowth, and rapid onset of autolysis. In contrast to small intestine, tongue epithelium is less sensitive to postmortem changes. Sections of tongue and small intestine from 11 dogs and 11 cats with a clinical history and gross and microscopic lesions compatible with canine and feline parvoviral infection were examined for parvoviral infection using real-time polymerase chain reaction (PCR), immunohistochemistry (IHC), and direct fluorescent antibody testing (FA). Parvoviral DNA was detected by PCR in both small intestine and tongue of all but 1 dog. Nineteen of 22 animals (86%) with suspect or positive FA staining in the small intestine also had positive FA and IHC staining in the tongue. Three of 3 dogs (100%) whose carcasses had been frozen and thawed prior to necropsy had more consistently positive staining in tongue than in small intestine by FA and IHC. These data confirm tongue as an excellent complementary sample for parvoviral testing in dogs and cats, especially in cases in which postmortem autolysis has occurred.


Obturator hernia: an uncommon cause of thigh pain: a difficult diagnosis.


title: [Maternal and neonatal consequences of coronavirus COVID-19 infection during pregnancy: a scoping review].

text: BACKGROUND Coronavirus disease 2019 (COVID-19) is a new pathology, declared a public health emergency by the World Health Organization, which can have negative consequences for pregnant women and their newborns. The aim of this study was to explore the available knowledge on the consequences of developing COVI-19 in pregnant women and their neonates. METHODS Scoping Review, in which the search for articles was conducted using DeCS ("pregnancy", "coronavirus", "health") and MeSH ("pregnan*", "pregnant women", "coronavirus"), linking the terms with the Boolean AND operator. Databases used were Web of Science, Scopus, BVS, Scielo and CUIDEN. In addition, the PRISMA methodology was applied. RESULTS Ten studies were identified that assessed maternal and neonatal health after maternal COVID-19 infection. Pregnant women seem to had no serious symptoms. Neonates appeared to be affected to a greater extent. A death was reported in a premature newborn whose mother had COVID-19 pneumonia. There did not appear to be vertical transmission from mother to child. Nevertheless, this information was not conclusive. CONCLUSIONS COVID-19 appears to be more benign with pregnant women than with their neonates.


title: The radiologic manifestations of H5N1 avian influenza.

text: Avian influenza is caused by the H5N1 subtype of the influenza A virus. Human transmission is either directly through close contact with infected birds usually poultry or their secretions. To date 178 people throughout South East Asia have been infected with 85 deaths. Patients usually present with a rapidly progressive pneumonia that can result in respiratory failure and acute respiratory distress syndrome. The chest radiograph therefore remains the most convenient and accessible imaging modality. Studies have shown that most radiographs are abnormal at the time of presentation with multifocal consolidation the commonest radiographic finding. During the course of disease, pleural effusions and cavitation can also develop. Consolidation that involves > or = 4 zones on presentation or at day 7 after the onset of symptoms and subsequent development of acute respiratory distress syndrome are generally associated with an adverse outcome. Chest CT examinations performed during the convalescent period have demonstrated persistent ground glass attenuation and segmental consolidation. Additional features included pseudocavitation, pneumatocoele formation, lymphadenopathy, and centrilobular nodules. Overall the appearances are suggestive of mild fibrosis.


title: [Expression and significance of severe acute respiratory syndrome associated coronavirus (SARS-CoV)-X4 protein in lungs of SARS patients].

text: OBJECTIVE To investigate the significance of severe acute respiratory syndrome associated coronavirus (SARS-CoV)-X4 protein expression in lungs of patients with SARS. METHODS Pathological features of the lungs from 4 SARS patients were examined and the expression of SARS-CoV-X4 protein in the lungs was evaluated with immunohistochemical staining using specific antibodies against protein X4. RESULTS Microscopically, all lungs from 4 cases showed edema, erythrocyte and fibrin exudates in the alveoli, hyperplasia of alveolar epithelium, necrosis, hyaline membrane formation and fibroblast foci. Immunohistochemical stains showed a strong positivity of X4 protein in denudation cells, vascular endothelial cells and also erythrocytes and neutrophils in the alveoli of the lung tissues from the 4 cases. CONCLUSIONS Expression of SARS-CoV-X4 protein in the lungs may be involved in the pathogenesis and progression of SARS.


title: Genetic analysis and attribution of microbial forensics evidence.

text: Because of the availability of pathogenic microorganisms and the relatively low cost of preparing and disseminating bioweapons, there is a continuing threat of biocrime and bioterrorism. Thus, enhanced capabilities are needed that enable the full and robust forensic exploitation and interpretation of microbial evidence from acts of bioterrorism or biocrimes. To respond to the need, greater resources and efforts are being applied to the burgeoning field of microbial forensics. Microbial forensics focuses on the characterization, analysis and interpretation of evidence for attributional purposes from a bioterrorism act, biocrime, hoax or inadvertent agent release. To enhance attribution capabilities, a major component of microbial forensics is the analysis of nucleic acids to associate or eliminate putative samples. The degree that attribution can be addressed depends on the context of the case, the available knowledge of the genetics, phylogeny, and ecology of the target microorganism, and technologies applied. The types of genetic markers and features that can impact statistical inferences of microbial forensic evidence include: single nucleotide polymorphisms, repetitive sequences, insertions and deletions, mobile elements, pathogenicity islands, virulence and resistance genes, house keeping genes, structural genes, whole genome sequences, asexual and sexual reproduction, horizontal gene transfer, conjugation, transduction, lysogeny, gene conversion, recombination, gene duplication, rearrangements, and mutational hotspots. Nucleic acid based typing technologies include: PCR, real-time PCR, MLST, MLVA, whole genome sequencing, and microarrays.


Vaccines: all things considered.


title: Antagonistic effects of atipamezole, yohimbine and prazosin on medetomidine-induced diuresis in healthy cats.

text: This study aimed to investigate and compare the antagonistic effects of atipamezole, yohimbine and prazosin on medetomidine-induced diuresis in healthy cats. Five cats were repeatedly used in each of the 9 groups. One group was not medicated. Cats in the other groups received 40 µg/kg medetomidine intramuscularly and saline (as the control), 160 µg/kg prazosin, or 40, 160 or 480 µg/kg atipamezole or yohimbine intravenously 0.5 hr later. Volume, pH and specific gravity of urine; plasma arginine vasopressin (AVP) level; and creatinine, osmolality and electrolyte levels in both urine and plasma were measured. Both atipamezole and yohimbine, but not prazosin, antagonized medetomidine-induced diuresis. The antidiuretic effect of atipamezole was more potent than that of yohimbine, but was not dose dependent, in contrast to the effect of yohimbine at the tested doses. Both atipamezole and yohimbine reversed medetomidine-induced decreases in both urine specific gravity and osmolality and increases in plasma osmolality and free-water clearance. Antidiuresis of either atipamezole or yohimbine was not related to the area under the curve for AVP level, although the highest dose of both atipamezole and yohimbine initially and temporarily increased plasma AVP levels, suggesting that this may partly influence the antidiuretic effects of both agents. The diuretic effect of medetomidine in cats may be mediated by α2-adrenoceptors, but not α1-adrenoceptors. Atipamezole and yohimbine can be used as antagonistic agents against medetomidine-induced diuresis in healthy cats.


docid: hqzfczim

title: Induction of the membrane alanyl aminopeptidase gene and surface expression in human T-cells by mitogenic activation.

text: The metal-dependent membrane alanyl aminopeptidase (amino-peptidase N, APN, CD13; EC 3.4.11.2) is a well-established marker of normal and malignant cells of the myelo-monocytic lineage. It is also expressed by leukaemic blasts of a small group of patients suffering from acute or chronic lymphoid leukaemia. CD13-specific monoclonal antibodies do not bind to the surface of normal B lymphocytes, and APN mRNA was not detectable by Northern analysis in normal lymphocytes or in T-cell lines. Recently the expression of the APN gene in T-cell lines as well as the ability of these cells to cleave chromogenic substrates preferred by APN have been demonstrated [Lendeckel, Wex, Kähne, Frank, Reinhold and Ansorge (1994) Cell. Immunol. 153, 214-226]. Here, by means of dot-blot hybridization and RNase protection assay, evidence is provided that human peripheral T-cells as well as derived cell lines contain significant amounts of APN mRNA, comparable to that in the promyeloic cell line U937, and that mitogenic activation of peripheral human T-cells leads to a more than 4-fold increase in their APN mRNA content. In the course of activation, T-cells increase their total alanine p-nitroanilide-hydrolysing activity to approx. 7-fold that of resting cells. Furthermore these cells become immunoreactive towards CD13 to a significant extent (up to 51%) as shown by surface staining and confirmed by activity staining and immunostaining after isoelectric focusing (pI of T-cell APN = 4.6). In addition it is demonstrated by fluorescence microscopy that viable, activated T-cells effectively cleave the fluorogenic aminopeptidase substrate bis-glycyl-rhodamine 110 and that the corresponding aminopeptidase activity is associated with the cell surface. We show that specific inhibitors of APN, probestin and actinonin, strongly decrease DNA synthesis in phytohaemagglutinin (PHA)-stimulated T-cells. In summary, evidence is presented that in the course of mitogenic activation human peripheral T-cells increase the expression of APN both at the transcriptional level and at the cell surface. This has been demonstrated both at the APN mRNA level and at the protein level with respect to aminopeptidase enzymic activity and CD13 immunoreactivity.


title: Bioinformatic approaches for predicting substrates of proteases.

text: Proteases have central roles in "life and death" processes due to their important ability to catalytically hydrolyze protein substrates, usually altering the function and/or activity of the target in the process. Knowledge of the substrate specificity of a protease should, in theory, dramatically improve the ability to predict target protein substrates. However, experimental identification and characterization of protease substrates is often difficult and time-consuming. Thus solving the "substrate identification" problem is fundamental to both understanding protease biology and the development of therapeutics that target specific protease-regulated pathways. In this context, bioinformatic prediction of protease substrates may provide useful and experimentally testable information about novel potential cleavage sites in candidate substrates. In this article, we provide an overview of recent advances in developing bioinformatic approaches for predicting protease substrate cleavage sites and identifying novel putative substrates. We discuss the advantages and drawbacks of the current methods and detail how more accurate models can be built by deriving multiple sequence and structural features of substrates. We also provide some suggestions about how future studies might further improve the accuracy of protease substrate specificity prediction.


The severe acute respiratory syndrome.


title: Passage of classical swine fever virus in cultured swine kidney cells selects virus variants that bind to heparan sulfate due to a single amino acid change in envelope protein E(rns).

text: Infection of cells with Classical swine fever virus (CSFV) is mediated by the interaction of envelope glycoprotein E(rns) and E2 with the cell surface. In this report we studied the role of the cell surface glycoaminoglycans (GAGs), chondroitin sulfates A, B, and C (CS-A, -B, and -C), and heparan sulfate (HS) in the initial binding of CSFV strain Brescia to cells. Removal of HS from the surface of swine kidney cells (SK6) by heparinase I treatment almost completely abolished infection of these cells with virus that was extensively passaged in swine kidney cells before it was cloned (clone C1.1.1). Infection with C1.1.1 was inhibited completely by heparin (a GAG chemically related to HS but sulfated to a higher extent) and by dextran sulfate (an artificial highly sulfated polysaccharide), whereas HS and CS-A, -B, and -C were unable to inhibit infection. Bound C1.1.1 virus particles were released from the cell surface by treatment with heparin. Furthermore, C1.1.1 virus particles and CSFV E(rns) purified from insect cells bound to immobilized heparin, whereas purified CSFV E2 did not. These results indicate that initial binding of this virus clone is accomplished by the interaction of E(rns) with cell surface HS. In contrast, infection of SK6 cells with virus clones isolated from the blood of an infected pig and minimally passaged in SK6 cells was not affected by heparinase I treatment of cells and the addition of heparin to the medium. However, after one additional round of amplification in SK6 cells, infection with these virus clones was affected by heparinase I treatment and heparin. Sequence analysis of the E(rns) genes of these virus clones before and after amplification in SK6 cells showed that passage in SK6 cells resulted in a change of an Ser residue to an Arg residue in the C terminus of E(rns) (amino acid 476 in the polyprotein of CSFV). Replacement of the E(rns) gene of an infectious DNA copy of C1.1.1 with the E(rns) genes of these virus variants proved that acquisition of this Arg was sufficient to alter an HS-independent virus to a virus that uses HS as an E(rns) receptor.


title: Severe acute respiratory syndrome coronavirus persistence in Vero cells.

text: BACKGROUND Several coronaviruses establish persistent infections in vitro and in vivo, however it is unknown whether persistence is a feature of the severe acute respiratory syndrome coronavirus (SARS-CoV) life cycle. This study was conducted to investigate viral persistence. METHODS We inoculated confluent monolayers of Vero cells with SARS-CoV at a multiplicity of infection of 0.1 TCID50 and passaged the remaining cells every 4 to 8 days for a total of 11 passages. Virus was titrated at each passage by limited dilution assay and nucleocapsid antigen was detected by Western blot and immunofluoresence assays. The presence of viral particles in passage 11 cells was assessed by electron microscopy. Changes in viral genomic sequences during persistent infection were examined by DNA sequencing. RESULTS Cytopathic effect was extensive after initial inoculation but diminished with serial passages. Infectious virus was detected after each passage and viral growth curves were identical for parental virus stock and virus obtained from passage 11 cells. Nucleocapsid antigen was detected in the majority of cells after initial inoculation but in only 10%-40% of cells at passages 2-11. Electron microscopy confirmed the presence of viral particles in passage 11 cells. Sequence analysis at passage 11 revealed fixed mutations in the spike (S) gene and ORFs 7a-8b but not in the nucleocapsid (N) gene. CONCLUSIONS SARS-CoV can establish a persistent infection in vitro. The mechanism for viral persistence is consistent with the formation of a carrier culture whereby a limited number of cells are infected with each round of virus replication and release. Persistence is associated with selected mutations in the SARS-CoV genome. This model may provide insight into SARS-related lung pathology and mechanisms by which humans and animals can serve as reservoirs for infection.


title: [Epidemiology of acute upper and lower respiratory tract infections in children].

text: More than 200 antigenically distinct viruses have been documented as causes of sporadic or epidemic respiratory infections in infants and children. The lung itself is rarely sampled directly, and sputum representing lower-airway secretions can rarely be obtained from children. In addition culture of secretions from upper respiratory tract is not useful since the normal flora includes the bacteria commonly responsible for pneumonia. Clinical and radiology data only suggest the diagnosis. The development of techniques to detect antigens of the causative agent in nasopharyngeal secretions, nucleic acid by means of the polymerise-chain reaction assays has significantly improved the identification of the responsible pathogen and the choice of appropriate treatment. Since more 30 years rhinovirus, coronavirus, enterovirus, parainfluenza virus and respiratory syncytial virus were added to influenza, adenovirus and measles virus as causes of respiratory tract infections. This list of pathogens was extended last years with the discovery of human metapneumovirus, bocavirus, polyomavirus. In restricted patient groups, such as the immunocompromised, members of the family of herpesvirus have also been associated with respiratory disease.


Legal power and legal rights--isolation and quarantine in the case of drug-resistant tuberculosis.


title: Aurintricarboxylic acid inhibits the early stage of vaccinia virus replication by targeting both cellular and viral factors.

text: Aurintricarboxylic acid (ATA) has been shown to inhibit the replication of viruses from several different families, including human immunodeficiency virus, vesicular stomatitis virus, and the coronavirus causing severe acute respiratory syndrome. This study characterizes the inhibitory effect of ATA on vaccinia virus replication in HeLa, Huh7, and AD293 cells. Vaccinia virus replication is significantly abrogated upon ATA treatment, which is associated with the inhibition of early viral gene transcription. This inhibitory effect may be attributed to two findings. First, ATA blocks the phosphorylation of extracellular signal-regulated kinase 1/2, an event shown to be essential for vaccinia virus replication. Second, ATA inhibits the phosphatase activity of the viral enzyme H1L, which is required to initiate viral transcription. Thus, ATA inhibits vaccinia virus replication by targeting both cellular and viral factors essential for the early stage of replication.


Poliomyelitis (Heine-Medin disease).


title: Nonfatal dog bite-related injuries treated in hospital emergency departments--United States, 2001.

text: In 1994, the most recent year for which published data are available, an estimated 4.7 million dog bites occurred in the United States, and approximately 799,700 persons required medical care. Of an estimated 333,700 patients treated for dog bites in emergency departments (EDs) in 1994, approximately 6,000 (1.8%) were hospitalized. To estimate the number of nonfatal dog bite-related injuries treated in U.S. hospital EDs, CDC analyzed data from the National Electronic Injury Surveillance System-All Injury Program (NEISS-AIP). This report summarizes the results of the analysis, which indicate that in 2001, an estimated 368,245 persons were treated in U.S. hospital EDs for nonfatal dog bite-related injuries. Injury rates were highest among children aged 5-9 years. To reduce the number of dog bite-related injuries, adults and children should be educated about bite prevention, and persons with canine pets should practice responsible pet ownership.


title: Analysis of the overdispersed clock in the short-term evolution of hepatitis C virus: Using the E1/E2 gene sequences to infer infection dates in a single source outbreak.

text: The assumption of a molecular clock for dating events from sequence information is often frustrated by the presence of heterogeneity among evolutionary rates due, among other factors, to positively selected sites. In this work, our goal is to explore methods to estimate infection dates from sequence analysis. One such method, based on site stripping for clock detection, was proposed to unravel the clocklike molecular evolution in sequences showing high variability of evolutionary rates and in the presence of positive selection. Other alternatives imply accommodating heterogeneity in evolutionary rates at various levels, without eliminating any information from the data. Here we present the analysis of a data set of hepatitis C virus (HCV) sequences from 24 patients infected by a single individual with known dates of infection. We first used a simple criterion of relative substitution rate for site removal prior to a regression analysis. Time was regressed on maximum likelihood pairwise evolutionary distances between the sequences sampled from the source individual and infected patients. We show that it is indeed the fastest evolving sites that disturb the molecular clock and that these sites correspond to positively selected codons. The high computational efficiency of the regression analysis allowed us to compare the site-stripping scheme with random removal of sites. We demonstrate that removing the fast-evolving sites significantly increases the accuracy of estimation of infection times based on a single substitution rate. However, the time-of-infection estimations improved substantially when a more sophisticated and computationally demanding Bayesian method was used. This method was used with the same data set but keeping all the sequence positions in the analysis. Consequently, despite the distortion introduced by positive selection on evolutionary rates, it is possible to obtain quite accurate estimates of infection dates, a result of especial relevance for molecular epidemiology studies.


title: The severe acute respiratory syndrome coronavirus in tears.

text: BACKGROUND Severe acute respiratory syndrome (SARS) is a new infectious disease that caused a global outbreak in 2003. Research has shown that it is caused by a novel coronavirus. A series of cases is reported where polymerase chain reaction (PCR) testing on tears had demonstrated the presence of the virus. Detection of ocular infection from tears using the PCR technique has been widely used by ophthalmologists to diagnose infections for other viruses. METHODS This is a case series report from cases classified as probable or suspect SARS cases. Tear samples were collected from 36 consecutive patients who were suspected of having SARS in Singapore over a period of 12 days (7-18 April 2003), and analysed by PCR using protocols developed by the WHO network of laboratories. RESULTS Three patients with probable SARS (one female and two male patients) had positive results from their tear samples. Tear samples were used to confirm SARS in the female patient, who was positive only from her tears. The positive specimens were found in cases sampled early in their course of infection. CONCLUSIONS This is the first case series reported with the detection of the SARS coronavirus from tears, and has important implications for the practice of ophthalmology and medicine. The ability to detect and isolate the virus in the early phase of the disease may be an important diagnostic tool for future patients and tear sampling is both simple and easily repeatable. Many healthcare workers are in close proximity to the eyes of patients and this may be a source of spread among healthcare workers and inoculating patients. Ophthalmic practices may need to change as more stringent barrier methods, appropriate quarantine, and isolation measures are vital when managing patients with SARS.


title: Lung pathology and infectious agents in fatal feedlot pneumonias and relationship with mortality, disease onset, and treatments.

text: This study charted 237 fatal cases of bovine respiratory disease (BRD) observed from May 2002 to May 2003 in a single Oklahoma feed yard. Postmortem lung samples were used for agent identification and histopathology. Late in the study, 94 skin samples (ear notches) were tested for Bovine viral diarrhea virus (BVDV) by immunohistochemistry (IHC). Bovine respiratory disease morbidity was 14.7%, and the mortality rate of all causes was 1.3%, with more than half (53.8%) attributed to BRD (0.7% total of all causes). The agents isolated were the following: Mannheimia haemolytica (25.0%), Pasteurella multocida (24.5%), Histophilus somni (10.0%), Arcanobacterium pyogenes (35.0%), Salmonella spp. (0.5%), and Mycoplasma spp. (71.4%). Viruses recovered by cell culture were BVDV-1a noncytopathic (NCP; 2.7%), BVDV-1a cytopathic (CP) vaccine strain (1.8%), BVDV-1b NCP (2.7%), BVDV-2a NCP (3.2%), BVDV-2b CP (0.5%), and Bovine herpesvirus 1 (2.3%). Gel-based polymerase chain reaction (PCR) assays were 4.6% positive for Bovine respiratory syncytial virus and 10.8% positive for Bovine coronavirus. Bovine viral diarrhea virus IHC testing was positive in 5.3% of the animals. The mean values were determined for the treatment data: fatal disease onset (32.65 days), treatment interval (29.15 days), number of antibiotic treatments (2.65), number of different antibiotics (1.89), and day of death (61.81 days). Lesions included the following: 1) duration: acute (21%), subacute (15%), chronic (40.2%), healing (2.8%), normal (18.1%), and autolyzed (2.8%); 2) type of pneumonia: lobar bronchopneumonia (LBP; 27.1%), LBP with pleuritis (49.1%), interstitial pneumonia (5.1%), bronchointerstitial pneumonia (1.4%), septic (0.9%), embolic foci (0.5%), other (2.8%), normal (10.3%), and autolyzed (2.8%); and 3) bronchiolar lesions: bronchiolitis obliterans (39.7%), bronchiolar necrosis (26.6%), bronchiolitis obliterans/bronchiolar necrosis (1.4%), other bronchiolar lesions (6.5%), and bronchiolar lesion negative (25.7%). Statistically significant relationships were present among the agents, lesions, and the animal treatment, disease onset, and mortality data. Clinical illnesses observed in this study were lengthier than those reported 16-20 years ago, based on fatal disease onset, treatment interval, and day of death.


title: Tick-borne viruses in Norway.

text: The purpose of the investigation was to chart the existence and extent of arboviruses in Norway and provide information on their possible significance. Virus isolations have been attempted from ticks (I. ricinus, I. trianguliceps, I. uriae) and host animal blood from selected locations. Serological screenings have been performed with bird, small mammal, cattle and human blood. Five virus strians have been identified to date. Three of them are related to Uukuniemi virus group. Two identical strains from I. uriae demonstrate the morphology of coronaviruses and no antigenic relationship to major arbovirus groups. Within the distribution areas of I. ricinus, antibodies to tick-borne encephalitis virus are prevalent in cattle. Antibodies to Uukuniemi viruses are found in passerine birds, small mammals, cattle and man. Antibodies to the coronavirus like agents have been demonstrated in seabirds.


Home ventilators for invasive ventilation of patients with COVID-19.


Celebrating the past; awakening the future: the NSW Public Health Forum highlights public health successes in NSW.


Protein microarrays: a literature survey.


title: Emotional and deliberative reactions to a public crisis: Mad Cow disease in France.

text: Although most theories of choice are cognitive, recent research has emphasized the role of emotions. We used a novel context--the Mad Cow crisis in France--to investigate how emotions alter choice even when consequences are held constant. A field study showed that individuals reduced beef consumption in months after many newspaper articles featured the emotional label "Mad Cow," but beef consumption was unaffected after articles featured scientific labels for the same disease. The reverse pattern held for the disease-related actions of a government bureaucracy. A lab study showed that the Mad Cow label induces people to make choices based solely on emotional reactions, whereas scientific labels induce people to consider their own probability judgments. Although the Mad Cow label produces less rational behavior than scientific labels, it is two to four times more common in the environment.


title: Identification and characterization of viral structural proteins of infectious salmon anemia virus.

text: Infectious salmon anemia virus (ISAV) is an unclassified Orthomyxovirus that has been shown to contain a segmented genome with eight single-stranded RNA species coding for 10 viral proteins. Four major structural proteins were characterized in the present study: two glycosylated proteins with estimated molecular masses of 42 and 50 kDa, one 66-kDa phosphoprotein, and one 22-kDa protein. Examination of lysed virions revealed the two glycoproteins and the 22-kDa protein in the soluble fraction, while the 66-kDa phosphoprotein and a minor part of the 22-kDa protein were found in the pelleted fraction. Immunofluorescence staining of infected cells demonstrated that the 22-kDa protein was a late protein accumulating in the nucleus. We conclude that the 66-kDa protein is the nucleoprotein, the 22-kDa protein is the matrix protein, and the 42- and 50-kDa proteins are the surface proteins. Radioimmunoprecipitation analysis of the 42-kDa glycoprotein, which was previously shown to represent the ISAV hemagglutinin, indicated that this protein exists at least as dimers. Further, by labeling of purified ISAV with [1,3-(3)H]diisopropyl fluorophosphate, it was also demonstrated that the viral esterase is located with the hemagglutinin. This finding was confirmed by demonstration of acetylesterase activity in affinity-purified hemagglutinin preparations. Finally, the active-site serine residue could be tentatively identified at position 32 within the amino acid sequence of the hemagglutinin of ISAV strain Glesvaer/2/90. It is proposed that the ISAV vp66 protein be termed nucleoprotein, the gp42 protein be termed HE protein, and the vp22 protein be termed matrix protein.


docid: ndncrfjt

title: Resistance to fatal central nervous system disease by mouse hepatitis virus, strain JHM. II. Adherent cell-mediated protection.

text: Resistance of SJL/J mice to intracranial inoculation with the JHM strain of mouse hepatitis, a coronavirus, is dependent upon the age of the animals at inoculation. Animals 12 weeks of age or older are resistant, whereas those 6 weeks or younger are uniformly susceptible to viral infection. Spleen cells or thioglycolate elicited peritoneal exudate cells can transfer resistance from 12-week-old to 6-week-old recipients. Removal of the adherent cells from either spleen or peritoneal cells ablated protection. Adherent cells from 12-week-old mice were protective even after depletion of Ia- and Thy-1-bearing cells. Antiviral antibody, thioglycolate injection into 6-week-old animals, and nylon wool-purified T cells were ineffective in mediating resistance. Adherent cells transferred 4 days before virus challenge, but not after challenge, were protective. Thus, there is an age-related change in SJL mice that protects from acute central nervous system disease, which may be due to maturation of a specialized adherent cell population.


Echocardiographic changes following rabbit coronavirus infection.


docid: yiiqcita

title: Coronavirus and dermatology: a resident's perspective.


title: A comparison of three oral electrolyte solutions in the treatment of diarrheic calves.

text: Thirty-six diarrheic calves infected with rota- and coronaviruses were randomly allocated to one of three oral electrolyte treatments: Ion-Aid (Syntex Agribusiness), Life-Guard (Norden Inc), or Revibe (Langford Inc). The calves were also allowed voluntary access to milk which was offered at the rate of 5% of body weight per feeding in two feedings daily. There were significant differences in recovery rate among calves treated with the different electrolytes. Only 33% of Ion-Aid-treated calves recovered; Revibe- and Life-Guard-treated calves had high recovery rates of 92% and 83%, respectively. The much higher recovery rates with Life-Guard and Revibe were attributed to the presence of an alkalizing agent in these preparations. Life-Guard uses bicarbonate to counteract acidosis and there was some evidence that this may have interfered with milk digestion. Revibe uses acetate; this was effectively metabolized within the calves' tissues and produced alkalization without interference with milk digestion.


title: Physiological functions and clinical implications of fibrinogen-like 2: A review.

text: Fibrinogen-like 2 (FGL2) encompasses a transmembrane (mFGL2) and a soluble (sFGL2) form with differential tertiary structure and biological activities. Typically, mFGL2 functions as prothrombinase that is capable of initiating coagulation in tissue without activation of the blood clotting cascade, whereas sFGL2 largely acts as an immunosuppressor that can repress proliferation of alloreactive T lymphocytes and maturation of bone marrow dendritic cells. Protein sequences of FGL2 exhibit evolutionary conservation across wide variety of species, especially at the carboxyl terminus that contains fibrinogen related domain (FRED). The FRED of FGL2 confers specificity and complexity in the action of FGL2, including receptor recognition, calcium affiliation, and substrate binding. Constitutive expression of FGL2 during embryogenesis and in mature tissues suggests FGL2 might be physiologically important. However, excessive induction of FGL2 under certain medical conditions (e.g., pathogen invasion) could trigger complement activation, inflammatory response, cellular apoptosis, and immune dysfunctions. On the other hand, complete absence of FGL2 is also detrimental as lack of FGL2 can cause autoimmune glomerulonephritis and acute cellular rejection of xenografts. All these roles involve mFGL2, sFGL2, or their combination. Although it is not clear how mFGL2 is cleaved off its host cells and secreted into the blood, circulating sFGL2 has been found correlated with disease severity and viral loading among patients with human hepatitis B virus or hepatitis C virus infection. Further studies are warranted to understand how FGL2 expression is regulated under physiological and pathological conditions. Even more interesting is to determine whether mFGL2 can fulfill an immunoregulatory role through its FRED at carboxyl end of the molecule and, and vice versa, whether sFGL2 is procoagulant upon binding to a target cell. Knowledge in this area should shed light on development of sFGL2 as an alternative immunosuppressive agent for organ transplantation or as a biomarker for predicting disease progression, monitoring therapeutic effects, and targeting FGL2 for repression in ameliorating fulminant viral hepatitis.


title: [Benign prostatic hyperplasia management during COVID-19 pandemia.]

text: OBJECTIVES The pandemic caused by the new SARS / Cov-2 Coronavirus represents an unprecedented scenario in modern medicine that affects many aspects of daily healthcare. Lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH) has a high prevalence and is related to high consumption of health resources. For this reason, we performed a revision of the management of LUTS and HBP during and after COVID-19 pandemic. MATERIAL AND METHODS A group of experts in benign prostatic hyperplasia from different regions of Spain were selected to design a strategy to reorganize the management of benign prostatic hyperplasia and lower urinary tract symptoms during the pandemic. A comprehensive review of the literature was undertaken and a set of recommendations are generated. RESULTS Recommendations for the management of LUTS-BPH during and after the SARS/CoV2 coronavirus pandemic outbreak consist of promoting telemedicine and developing joint protocols with Primary Care Attention .Clear diagnostic and treatment criteria and referral criteria must be established. Referral of patients for risk complications such as kidney failure, recurrent hematuria and obstructive uropathy are a priority. Surgeries due to BPH are generally potentially delayed until phases I and II of the pandemic, in which the percentage of hospitalized patients with COVID-19 does not exceed 25%, and it is necessary to determine COVID19 negativity. The surgical technique that associates the least complications and the shortest stay should be selected. CONCLUSIONS The diagnosis and prescription of treatment for BPH during the COVID-19 pandemic should be based on telemedicine and joint protocols for primary care attention and urology. Elective surgical treatment can be delayed until we are in phases I or II, individualizing the surgical and anaesthetic technique of choice to minimize risks.


title: Severe acute respiratory syndrome coronavirus protein 6 accelerates murine coronavirus infections.

text: One or more of the unique 3'-proximal open reading frames (ORFs) of the severe acute respiratory syndrome (SARS) coronavirus may encode determinants of virus virulence. A prime candidate is ORF6, which encodes a 63-amino-acid membrane-associated peptide that can dramatically increase the lethality of an otherwise attenuated JHM strain of murine coronavirus (L. Pewe, H. Zhou, J. Netland, C. Tangudu, H. Olivares, L. Shi, D. Look, T. Gallagher, and S. Perlman, J. Virol. 79:11335-11342, 2005). To discern virulence mechanisms, we compared the in vitro growth properties of rJ.6, a recombinant JHM expressing the SARS peptide, with isogenic rJ.6-KO, which has an inactive ORF containing a mutated initiation codon and a termination codon at internal position 27. The rJ.6 infections proceeded rapidly, secreting progeny about 1.5 h earlier than rJ.6-KO infections did. The rJ.6 infections were also set apart by early viral protein accumulation and by robust expansion via syncytia, a characteristic feature of JHM virus dissemination. We found no evidence for protein 6 operating at the virus entry or assembly stage, as virions from either infection were indistinguishable. Rather, protein 6 appeared to operate by fostering viral RNA and protein synthesis, as RNA quantifications by reverse transcription-quantitative PCR revealed viral RNA levels in the rJ.6 cultures that were five to eight times higher than those lacking protein 6. Furthermore, protein 6 coimmunoprecipitated with viral RNAs and colocalized on cytoplasmic vesicles with replicating viral RNAs. The SARS coronavirus encodes a novel membrane protein 6 that can accelerate replication of a related mouse virus, a property that may explain its ability to increase in vivo virus virulence.


title: [Coronavirus disease 2019 and hypertension in 2 children].

text: This article reports the diagnosis and treatment of two children with coronavirus disease 2019 (COVID-19) and hypertension. Case 1 was a boy aged 13 years and 3 months, with the main manifestations of fever and dry cough; chest CT showed ground-glass opacities, and the nucleic acid test of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) yielded a positive result. Case 2 was a boy aged 13 years and 8 months and had no clinical symptoms; chest CT showed no abnormality, while the nucleic acid test of SARS-CoV-2 yielded a positive result. Both cases were shown with family aggregation of SARS-CoV-2 infection. They had obesity and a family history of hypertension. Continuous blood pressure monitoring in the resting state during hospitalization showed that blood pressure was above the 95% reference interval of normal value for children of the same age, and the two boys were given calcium channel blockers or β-receptor blockers and were then recovered. It is concluded that comprehensive management of children with COVID-19 and underlying cardiovascular diseases, including hypertension, should be taken seriously during the epidemic.


docid: lnywraqz

title: Survey of feline leukemia virus and feline coronaviruses in captive neotropical wild felids from Southern Brazil.

text: A total of 57 captive neotropical felids (one Leopardus geoffroyi, 14 Leopardus pardalis, 17 Leopardus wiedii, 22 Leopardus tigrinus, and three Puma yagouaroundi) from the Itaipu Binacional Wildlife Research Center (Refúgio Bela Vista, Southern Brazil) were anesthetized for blood collection. Feces samples were available for 44 animals, including one L. geoffroyi, eight L. pardalis, 14 L. wiedii, 20 L. tigrinus, and one P. yagouaroundi. Total DNA and RNA were extracted from blood and feces, respectively, using commercial kits. Blood DNA samples were evaluated by polymerase chain reaction (PCR) for feline leukemia virus (FeLV) proviral DNA, whereas reverse transcriptase-PCR was run on fecal samples for detection of coronavirus RNA. None of the samples were positive for coronaviruses. A male L. pardalis and a female L. tigrinus were positive for FeLV proviral DNA, and identities of PCR products were confirmed by sequencing. This is the first evidence of FeLV proviral DNA in these species in Southern Brazil.


title: Eight cases of severe acute respiratory syndrome presenting as round pneumonia.

text: OBJECTIVE The purpose of this study was to describe the radiographic findings and evolution of round pneumonia found in eight patients with confirmed severe acute respiratory syndrome (SARS). CONCLUSION SARS may present as round pneumonia on chest radiographs initially or during the treatment course. It may remain unchanged for up to 9 days before evolution to ill-defined air-space opacities. Radiologists and physicians should consider the possibility of "SARS pneumonia" when spherical air-space opacities are noted on chest radiographs of febrile patients.


Transanal endoscopic microsurgery (TEM)


title: Late-stage adult respiratory distress syndrome caused by severe acute respiratory syndrome: abnormal findings at thin-section CT.

text: PURPOSE To evaluate thin-section computed tomographic (CT) abnormalities in patients in the intensive care unit during the late stage of adult respiratory distress syndrome (ARDS) caused by severe acute respiratory syndrome (SARS). MATERIALS AND METHODS Eight patients in the late stage of ARDS (ie, more than 2 weeks after onset) were imaged with thin-section CT. Images were evaluated for ground-glass opacification, consolidation, interstitial thickening, evidence of fibrosis, and any other abnormalities. Patient records were reviewed, and relevant respiratory and ventilatory parameters, total steroid dose, and outcome were recorded. RESULTS All patients received high-dose pulse methylprednisolone (minimum, 2.5 g total), and all patients who received ventilation received low-pressure, low-volume ventilation. Five patients received prolonged mechanical ventilation (for more than 14 days), one received ventilation for 72 hours, and two patients did not receive ventilation. Three patients died, four were discharged from the hospital, and one continued to require ventilation. Ground-glass opacification and interstitial thickening were present at CT in all eight patients. Consolidation was present in six patients. Three patients had evidence of fibrosis. Patients who received long-term ventilation, those who received short-term ventilation, and those who did not receive ventilation had similar pulmonary changes at CT. Pulmonary cysts, most of which were small (<1 cm), were present in five patients. Cysts were present in one patient who received only short-term low-pressure and low-volume ventilation and in one patient who received no mechanical ventilation. CONCLUSION The CT features of late-stage ARDS caused by SARS are similar to those seen in late-stage ARDS of other causes, with no apparent differences between patients who do and patients who do not receive prolonged mechanical ventilation. The presence of cysts in one patient who received short-term and one patient who received no mechanical ventilation suggests that severe SARS-induced ARDS may independently result in cyst formation.


Psoriasis-COVID 19 Infection: Treatment Options.


title: Chronic nose-only inhalation study in rats, comparing room-aged sidestream cigarette smoke and diesel engine exhaust.

text: Nose-only exposure of male and female Wistar rats to a surrogate for environmental tobacco smoke, termed room-aged sidestream smoke (RASS), to diesel engine exhaust (DEE), or to filtered, fresh air (sham) was performed 6 hours/day, 7 days/week for 2 years, followed by a 6-month post-exposure period. The particulate concentrations were 3 and 10 mg/m3. Markers of inflammation in bronchoalveolar lavage showed that DEE (but not RASS) produced a dose-related and persistent inflammatory response. Lung weights were increased markedly in the DEE (but not RASS) groups and did not decrease during the 6-month post-exposure period. Bulky lung DNA adducts increased in the RASS groups, but not in the DEE groups. Cell proliferation in the lungs was unaffected by either experimental treatment. Histopathological responses in the RASS groups were minimal and almost completely reversible; lung tumors were similar in number to those seen in the sham-exposed groups. Rats exposed to DEE showed a panoply of dose-related histopathological responses: largely irreversible and in some cases progressive. Malignant and multiple tumors were seen only in the DEE groups; after 30 months, the tumor incidence (predominantly bronchiolo-alveolar adenomas) was 2% in the sham-exposed groups, 5%in the high RASS groups, and 46% in the high DEE groups (sexes combined). Our results suggest that in rats exposed to DEE, but not to RASS, the following series of events occurs: particle deposition in lungs --> lung "overload" --> pulmonary inflammation --> tumorigenesis, without a significant modifying role of cell proliferation or DNA adduct formation.


title: Implications of SARS: medical geography and surveillance in disease detection.

text: OBJECTIVE To expose pharmacy educators and practitioners to concepts of medical geography and medical surveillance. Severe acute respiratory syndrome (SARS) is used as a case example because it is an emerging infection and a prime example of the type of disease that pharmacists may encounter in daily practice (e.g., easily transmitted, resembles the common cold). DATA SOURCES We retrieved data from publications related to medical geography, medical surveillance, and SARS. Data on current SARS cases in Hong Kong were obtained from the Hong Kong Department of Health Web site. STUDY SELECTION AND DATA EXTRACTION Variables regarding new cases and deaths due to SARS were evaluated. DATA SYNTHESIS Background information on medical geography and medical surveillance was reviewed. Descriptive statistics were calculated for incidence, prevalence, and the number of deaths due to SARS in Hong Kong from March 14 to May 31, 2003. CONCLUSIONS Emerging infections are a serious concern for both the public and healthcare practitioners. The recent global diffusion of SARS highlights the ease in which diseases can diffuse from place to place. Understanding concepts related to medical geography and medical surveillance can help pharmacists be better prepared to anticipate disease diffusion and to evaluate signs of emerging infections. In turn, this can help pharmacists be better prepared to provide information and care to their patients. The long-term benefit of understanding how diseases spread and the specific activities related to disease detection is an opportunity for expanding the scope of pharmacy practice.


title: [Rotavirus and other viruses of diarrhea].

text: Rotaviruses represent 80% of recognized viral etiologies and 140 million cases of diarrhea per year. They strike young children with similar frequency throughout the world, but the mortality rate is high in developing countries only, with some 870,000 deaths per year (WHO, 1997). Rotaviruses belong to the family of Reoviridae; they are segmented bicatenary RNA viruses, which explains their genetic variability, the presence of mixed infections, the establishment for some time already of a molecular epidemiology by electrophore types. The viruses are "naked" and thus resistant to the outside environment; their massive elimination, 10(8) to 10(10)viral particles per gram of faeces, begins with the first day of diarrhea. They are found in used water and can also be concentrated by shellfish; the environment thus constitutes a notable reservoir for the virus. Oral-faecal transmission is facilitated by deficient sanitary conditions. The 11 fragments of the genome each codify for 1 viral protein; 2 surface proteins, VP4 and VP7, bring about the formation of neutralizing antibodies, which are important for the protection and determination of different serotypes. A non structural protein--NSP4--would seem to intervene in the cytopathogenic effect and may act as a veritable viral enterotoxine. Numerous animal species are infected by rotaviruses which are district from the human ones. The pathology as it affects animals is of economic importance and of interest as an experimental and vaccinal model. Between human and animal rotaviruses there can be genetic rematchings and the VP6 protein is an antigen common to the group. The description of the other viruses responsible for diarrhea has benefited from widespread use of electronic microscopes from the very first years of study of rotaviruses. These other viruses belong to 6 different types: adenovirus, calcivirus, astrovirus, Norwalk agent and related viruses, coronavirus, enterovirus. They therefore have a structural and antigenic polymorphism but, except for the coronavirus, they are all "naked" virions with resistance in outside environments and means of transmission analogous to the rotaviruses. Clinical signs of viral gastroenterites, the age of the patient and epidemiological circumstances help in making an etiological diagnosis; the biological diagnosis has been simplified for the rotaviruses and the adenoviruses. Epidemics related to food, or of hydric and nosocomial origin, especially those due to the Norwalk agent, are under-declared and more frequent than those of bacterial origin. The prevention of dangers related to faeces, the improvement of sanitary conditions, health education, and better nutrition contribute to rotavirus prevention, but rotavirus diarrheas, the incidence of which is similar in developed and developing countries, would be more efficiently controlled through vaccination.


title: [Drugs that aggravate the course of COVID-19 : really ?]

text: The safety of NSAIDs, corticosteroids and renin-angiotensin inhibitors in COVID-19 is challenged. NSAIDs may interfere with the defense process against viral infection and are best avoided. Systemic corticosteroids have not shown benefit in viral infection, including other coronavirus; thus they should be avoided, unless prescribed for another indication. The benefit-risk ratio is however clearly in favor of continuing inhaled corticosteroids in patients with asthma or COPD. ACE inhibitors and sartans upregulate the expression of angiotensin-converting enzyme 2 (ACE2), the pulmonary receptor for SARS-CoV-2. Any possible clinical impact of these treatments on COVID-19 infection remains to be clarified; in the meantime, they should be continued.


title: Both spike and background genes contribute to murine coronavirus neurovirulence.

text: Various strains of mouse hepatitis virus (MHV) exhibit different pathogenic phenotypes. Infection with the A59 strain of MHV induces both encephalitis and hepatitis, while the highly neurovirulent JHM strain induces a fatal encephalitis with little, if any, hepatitis. The pathogenic phenotype for each strain is determined by the genetic composition of the viral genome, as well as the host immune response. Using isogenic recombinant viruses with A59 background genes differing only in the spike gene, we have previously shown that high neurovirulence is associated with the JHM spike protein, the protein responsible for attachment to the host cell receptor (J. J. Phillips, M. M. Chua, G. F. Rall, and S. R. Weiss, Virology 301:109-120, 2002). Using another set of isogenic recombinant viruses with JHM background genes expressing either the JHM or A59 spike, we have further investigated the roles of viral genes in pathogenesis. Here, we demonstrate that the high neurovirulence of JHM is associated with accelerated spread through the brain and a heightened innate immune response that is characterized by high numbers of infiltrating neutrophils and macrophages, suggesting an immunopathogenic component to neurovirulence. While expression of the JHM spike is sufficient to confer a neurovirulent phenotype, as well as increased macrophage infiltration, background genes contribute to virulence as well, at least in part, by dictating the extent of the T-cell immune response.


title: G-quadruplex DNA aptamers and their ligands: structure, function and application.

text: Highly specific and tight-binding nucleic acid aptamers have been selected against a variety of molecular targets for over 20 years. A significant proportion of these oligonucleotides display G-quadruplex structures, particularly for DNA aptamers, that enable molecular recognition of their ligands. G-quadruplex structures couple a common scaffold to varying loop motifs that act in target recognition. Here, we review DNA G-quadruplex aptamers and their ligands from a structural and functional perspective. We compare the diversity of DNA G-quadruplex aptamers selected against multiple ligand targets, and consider structure with a particular focus on dissecting the thrombin binding aptamer - thrombin interaction. Therapeutic and analytical applications of DNA G-quadruplex aptamers are also discussed. Understanding DNA G-quadruplex aptamers carries implications not only for therapeutics and diagnostics, but also in the natural biochemistry of guanine-rich nucleic acids.


docid: febnswpe

title: Cloning and identification of lpsH, a novel gene playing a fundamental role in symbiotic nitrogen fixation of Mesorhizobium huakuii.

text: Mesorhizobium huakuii 7653R forms a symbiotic relationship with Astragalus sinicus to produce nitrogen-fixing root nodules under nitrogen-limiting conditions. By screening its transposon-inserted mutant library, a mutation in the lpsH gene was found to form pseudonodules on A. sinicus. Its effect was further confirmed by double-crossover mutant HK242. DNA sequence analysis revealed that the lpsH gene encodes a deduced protein of 397 amino acids with a predicted molecular mass of 43.6 kD. LpsH contains a putative signal peptide, 11 transmembrane helices, and an O-antigen polymerase domain, which locates on the periplasmic membrane and is necessary to lipopolysaccharide synthesis. Plant studies showed that the lpsH gene mutant formed ineffective nodules, and this symbiotic phenotype was linked to abnormal nodule development.


title: Prognostic score in gastric cancer: the importance of a conjoint analysis of clinical, pathologic, and therapeutic factors.

text: BACKGROUND This study was designed to establish a prognostic score for gastric cancer that takes into account factors related to the tumor, the patient, and the treatment. METHODS Two hundred thirty patients with gastric adenocarcinoma admitted t o the Department of Abdominal Surgery at Hospital do Câncer A. C. Camargo (São Paulo) and treated by gastrectomy from January 1992 until December 1996 were included in this retrospective cohort. The prognostic score was created according to the variables identified in the multivariate analysis and by using the regression coefficients generated by the Cox regression. RESULTS The 5-year overall survival rate was 44.5%. The final multivariate model identified six variables with a significant and independent effect on survival: sex, weight loss, lymphocyte count, tumor-node-metastasis staging, lymphadenectomy, and lymph node ratio. Patients were divided into four groups according to their scores, as follows: group 1, 0 to 3.0; group 2, 3.5 to 5.5; group 3, 6.0 to 8.5; and group 4, 9.0 to 14.0. The 5-year survival rates were 91.5%, 49.3%, 20.3%, and .0% for the score groups 1, 2, 3, and 4, respectively (P<.001). The score was superior in the assessment of prognosis when compared with tumor-node-metastasis staging alone. CONCLUSIONS It is possible to create a prognostic score that simultaneously includes factors related to the tumor, patient, and treatment, thus generating a more effective system in predicting the prognosis than the morphology-based staging systems.


title: Mobile device use while driving--United States and seven European countries, 2011.

text: Road traffic crashes are a global public health problem, contributing to an estimated 1.3 million deaths annually. Known risk factors for road traffic crashes and related injuries and deaths include speed, alcohol, nonuse of restraints, and nonuse of helmets. More recently, driver distraction has become an emerging concern. To assess the prevalence of mobile device use while driving in Belgium, France, Germany, the Netherlands, Portugal, Spain, the United Kingdom (UK), and the United States, CDC analyzed data from the 2011 EuroPNStyles and HealthStyles surveys. Prevalence estimates for self-reported talking on a cell phone while driving and reading or sending text or e-mail messages while driving were calculated. This report describes the results of that analysis, which indicated that, among drivers ages 18-64 years, the prevalence of talking on a cell phone while driving at least once in the past 30 days ranged from 21% in the UK to 69% in the United States, and the prevalence of drivers who had read or sent text or e-mail messages while driving at least once in the past 30 days ranged from 15% in Spain to 31% in Portugal and the United States. Lessons learned from successful road safety efforts aimed at reducing other risky driving behaviors, such as seat belt nonuse and alcohol-impaired driving, could be helpful to the United States and other countries in addressing this issue. Strategies such as legislation combined with high-visibility enforcement and public education campaigns deserve further research to determine their effectiveness in reducing mobile device use while driving. Additionally, the role of emerging vehicle and mobile communication technologies in reducing distracted driving-related crashes should be explored.


[DIABETES AND SURGERY].


title: An efficient method for the synthesis of peptide aldehyde libraries employed in the discovery of reversible SARS coronavirus main protease (SARS-CoV Mpro) inhibitors.

text: A method for the parallel solid-phase synthesis of peptide aldehydes has been developed. Protected amino acid aldehydes obtained by the racemization-free oxidation of amino alcohols with Dess-Martin periodinane were immobilized on threonyl resins as oxazolidines. Following Boc protection of the ring nitrogen to yield the N-protected oxazolidine linker, peptide synthesis was performed efficiently on this resin. A peptide aldehyde library was designed for targeting the SARS coronavirus main protease, SARS-CoV M(pro)(also known as 3CL(pro)), on the basis of three different reported binding modes and supported by virtual screening. A set of 25 peptide aldehydes was prepared by this method and investigated in inhibition assays against SARS-CoV M(pro). Several potent inhibitors were found with IC(50) values in the low micromolar range. An IC(50) of 7.5 muM was found for AcNSTSQ-H and AcESTLQ-H. Interestingly, the most potent inhibitors seem to bind to SARS-CoV M(pro) in a noncanonical binding mode.


docid: lzvmpyks

title: Occurrence and frequency of coronavirus infections in humans as determined by enzyme-linked immunosorbent assay.

text: The occurrence of human coronavirus (HCV) infections was analyzed by using sequential sera taken between 1976 and 1981 from adults working in the London area. Antibody rises to HCV 229E and HCV OC43 group viruses were measured in serum samples from these subjects by enzyme-linked immunosorbent assay. HCV infections were found throughout the year, although most occurred during two periods, from June through September and from December through February. There were no marked seasonal differences in either the range of antibody rises obtained or in the HCV groups to which these antibody rises were directed. However, there were more HCV antibody rises during the summer than in the winter. The antibody duration varied considerably, but had a mean of 3.5 months. Finally, the frequency of HCV infection per person was calculated to be 1 per 7.8 months.


Linking bats to emerging diseases.


Survey of public understanding regarding SARS-CoV-2.