title: Astroviruses as causative agents of poultry enteritis: genetic characterization and longitudinal studies on field conditions.

text: Astroviruses (AstVs) are nonenveloped RNA small round viruses (SRVs) with a genome of 6.8-7.9 kb. Known avian AstVs are spread worldwide; they have been associated with poult enteritis and mortality syndrome in the United States and reported in Italy in intensive turkey and guinea fowl flocks. Nevertheless, their real prevalence and their pathogenic role in avian enteritis affecting Italian flocks is far from clear. Negative staining electron microscopy (nsEM) is used for the routine diagnosis of avian enteric SRVs, although it cannot distinguish morphologically similar particles. Enzyme-linked immunosorbent assay (ELISA), reverse-transcription PCR (RT-PCR), and genomic sequencing are now used for this specific purpose. We analyzed 329 samples of chicken, turkey, and guinea fowl intestinal contents from Italian poultry flocks. Most samples were from enteritis outbreaks, but we also included samples from three longitudinal studies (one on 11 broiler flocks and the other two on a guinea fowl flock). We first examined the samples with nsEM. SRVs, including AstVs, are often associated with rotaviruses and were the most commonly detected morphotypes in avian enteric diseases. We then analyzed 124 of the samples with an RT-PCR targeting the open reading frame (ORF)-1b of AstV. This gene codes for an RNA-dependent polymerase. We then sequenced and genetically analyzed the RT-PCR positive samples. Phylogenetic analysis distinguished three defined clusters: the first included guinea fowl AstVs and turkey AstVs-2; the second, chicken AstVs; and the third was formed by avian nephritis viruses (ANVs). No strains clustered with turkey AstVs-1. The results indicate that ORF-1b presents certain genetic variability, even among AstVs from the same species. In longitudinal studies, samples retrieved from the same shed were homogeneous, with some exceptions suggesting possible coexistence of different genetic types in the same unit. The finding of ANV-like viruses in commercial guinea fowls underlines the genetic variability of AstVs and strengthens the hypothesis of a varied intraherd situation.


title: Comprehensive review of mask utility and challenges during the COVID-19 pandemic.

text: Masks are widely discussed during the course of the ongoing COVID-19 pandemic. Most hospitals have implemented universal masking for their healthcare workers, and the Center for Disease Control currently advises even the general public to wear cloth masks when outdoors. The pertinent need for masks arises from plausible dissemination of the SARS-CoV-2 through close contacts, as well as the possibility of virus transmission from asymptomatic, pre-symptomatic, and mildly symptomatic individuals. Given current global shortages in personal protective equipment, the efficacy of various types of masks: N95 respirators, surgical masks, and cloth masks are researched. To accommodate limited supplies, techniques for extended use, reuse, and sterilization of masks are strategized. However, masks alone may not greatly slow down the COVID-19 pandemic unless they are coupled with adequate social distancing, diligent hand hygiene, and other proven preventive measures.


title: Thoracic anaesthesia.

text: The uniqueness of thoracic anaesthesia is that it is conducted concurrently with operative surgery on, or in the vicinity of, those very organs which are receiving the anaesthetic gases. Although some procedures do not directly involve the lungs, e.g. oesophageal surgery, all consist of breaches in the integrity of one or both pleural cavities, whether in open thoracotomies or thoracoscopic procedures. Thus, hypoxia and hypercarbia are a constant threat. This is compounded by the fact that the patients are frequently elderly with chronic health problems and, consequently, poor anaesthetic risks. In view of this, an overview of respiratory anatomy and physiology will be given, followed by consideration of some of the anaesthetic strategies applied to meet the particular challenges of this surgical specialty.


title: Clinical, virologic and immunologic profiles of a young infant with severe acute respiratory syndrome.

text: The clinical findings, plasma viral load, cytokines and chemokines of a 4-month-old infant with severe acute respiratory syndrome (SARS) were assessed at different phases of the disease. Ribavirin failed to inhibit SARS coronavirus (SARS-CoV) replication. One-step real time reverse transcription-polymerase chain reaction for plasma SARS-CoV RNA quantification was useful for early diagnosis and monitoring viremia.


First public health measures for the containment of COVID-19: a hotel in quarantine.


A SHORT STUDY OF THE COMPLICATIONS OF CATARACT EXTRACTION IN EGYPT WITH SOME PRACTICAL SUGGESTIONS.


title: Three distinct suppressors of RNA silencing encoded by a 20-kb viral RNA genome.

text: Viral infection in both plant and invertebrate hosts requires a virus-encoded function to block the RNA silencing antiviral defense. Here, we report the identification and characterization of three distinct suppressors of RNA silencing encoded by the approximately 20-kb plus-strand RNA genome of citrus tristeza virus (CTV). When introduced by genetic crosses into plants carrying a silencing transgene, both p20 and p23, but not coat protein (CP), restored expression of the transgene. Although none of the CTV proteins prevented DNA methylation of the transgene, export of the silencing signal (capable of mediating intercellular silencing spread) was detected only from the F(1) plants expressing p23 and not from the CP- or p20-expressing F(1) plants, demonstrating suppression of intercellular silencing by CP and p20 but not by p23. Thus, intracellular and intercellular silencing are each targeted by a CTV protein, whereas the third, p20, inhibits silencing at both levels. Notably, CP suppresses intercellular silencing without interfering with intracellular silencing. The novel property of CP suggests a mechanism distinct to p20 and all of the other viral suppressors known to interfere with intercellular silencing and that this class of viral suppressors may not be consistently identified by Agrobacterium coinfiltration because it also induces RNA silencing against the infiltrated suppressor transgene. Our analyses reveal a sophisticated viral counter-defense strategy that targets the silencing antiviral pathway at multiple steps and may be essential for protecting CTV with such a large RNA genome from antiviral silencing in the perennial tree host.


title: Neurally adjusted ventilatory assist as an alternative to pressure support ventilation in adults: a French multicentre randomized trial.

text: PURPOSE Neurally adjusted ventilatory assist (NAVA) is a ventilatory mode that tailors the level of assistance delivered by the ventilator to the electromyographic activity of the diaphragm. The objective of this study was to compare NAVA and pressure support ventilation (PSV) in the early phase of weaning from mechanical ventilation. METHODS A multicentre randomized controlled trial of 128 intubated adults recovering from acute respiratory failure was conducted in 11 intensive care units. Patients were randomly assigned to NAVA or PSV. The primary outcome was the probability of remaining in a partial ventilatory mode (either NAVA or PSV) throughout the first 48 h without any return to assist-control ventilation. Secondary outcomes included asynchrony index, ventilator-free days and mortality. RESULTS In the NAVA and PSV groups respectively, the proportion of patients remaining in partial ventilatory mode throughout the first 48 h was 67.2 vs. 63.3 % (P = 0.66), the asynchrony index was 14.7 vs. 26.7 % (P < 0.001), the ventilator-free days at day 7 were 1.0 day [1.0-4.0] vs. 0.0 days [0.0-1.0] (P < 0.01), the ventilator-free days at day 28 were 21 days [4-25] vs. 17 days [0-23] (P = 0.12), the day-28 mortality rate was 15.0 vs. 22.7 % (P = 0.21) and the rate of use of post-extubation noninvasive mechanical ventilation was 43.5 vs. 66.6 % (P < 0.01). CONCLUSIONS NAVA is safe and feasible over a prolonged period of time but does not increase the probability of remaining in a partial ventilatory mode. However, NAVA decreases patient-ventilator asynchrony and is associated with less frequent application of post-extubation noninvasive mechanical ventilation. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02018666.


title: The critically ill avian influenza A (H5N1) patient.

text: OBJECTIVE This review examines perspectives of human infection with avian influenza A H5N1 (AI H5N1), specifically focusing on the presentation, diagnosis, and management of those critically ill with AI H5N1. DATA SOURCE PubMed (1966-2006), PubMed "related articles," publications and Web sites of the World Health Organization and the Centers for Disease Control and Prevention, personal files, abstract proceedings, and reference lists. STUDY SELECTION We reviewed English-language publications pertaining to clinical presentation, diagnosis, and management of AI H5N1 and infection control expressly relating to the intensive care setting. DATA SYNTHESIS The majority of reported patients with AI H5N1 are critically ill and require intensive care management. These patients progress rapidly to severe acute respiratory distress syndrome. Multiorgan failure occurs in a large proportion. Because of the nonspecific clinical, laboratory, and radiologic features, it is critical to seek a history of exposure to poultry or wild birds in suspected cases. Reverse transcription polymerase chain reaction performed on nasopharyngeal aspirate is the most reliable method for the laboratory diagnosis of AI H5N1. Treatment includes starting neuraminidase inhibitor oseltamivir as early as possible in addition to the standard supportive management. Aerosol generating procedures should be minimized to avoid nosocomial transmission. Strict infection control procedures are paramount to staff safety, although human-to-human transmission is rare as of this time. CONCLUSIONS Many patients with AI H5N1 are critically ill either at presentation or shortly thereafter. Intensivists and intensive care units are therefore at the front line for this new cause of severe lung injury. Practitioners must be familiar with the nonspecific presentation of AI H5N1 and its diagnostic and therapeutic options. Although treating the infected patient with AI H5N1 is a priority, safeguarding healthcare workers and other patients must be considered of equal priority.


954: OPTIMAL VENTILATOR STRATEGY FOR ACUTE RESPIRATORY DISTRESS SYNDROME PATIENTS UNDERGOING ECMO THERAPY.


title: Pharmacotherapy of Ebola hemorrhagic fever: a brief review of current status and future perspectives.

text: The 2014 outbreak clearly showed that Ebola viruses (EBOV) remain a substantial threat for public health. The mainstay of management of patients with Ebola disease is isolation of patients and use of strict barrier nursing procedures; the present treatment strategies are mainly symptomatic and supportive (fluid resuscitation, antypyretics, antidiarrheal drugs). Currently, there is no approved therapy for Ebola hemorrhagic fever (EHF), however several advanced treatment options were tested in animal models (on non-human primates or rodents). They include use of both symptomatic (e.g. use of tissue factor inhibitors - rhNAPc2, rhAPC - to abolish coagulopathy) and specific antiviral approaches: e.g. monoclonal anti EBOV antibodies (ZMapp, MB-003), phosphorodiamidate morpholino oligomers (PMOs), liposomes containing siRNA (LNP-siRNA:TKM-Ebola) and small molecule inhibitors (e.g. BCX4430, favipiravir). The scope of this article is to briefly review the most promising therapeutics for EHF, based on the data coming from rare clinical reports, studies on animals and results from in vitro models.


title: Cost-effectiveness of New Surgical Treatments for Hemorrhoidal Disease: A Multicentre Randomized Controlled Trial Comparing Transanal Doppler-guided Hemorrhoidal Artery Ligation With Mucopexy and Circular Stapled Hemorrhoidopexy.

text: OBJECTIVE To compare Doppler-guided hemorrhoidal artery ligation (DGHAL) with circular stapled hemorrhoidopexy (SH) in the treatment of grade II/III hemorrhoidal disease (HD). BACKGROUND DGHAL is a treatment option for symptomatic HD; existing studies report limited risk and satisfactory outcomes. DGHAL has never before been compared with SH in a large-scale multi-institutional randomized clinical trial. METHODS Three hundred ninety-three grade II/III HD patients recruited in 22 centers from 2010 to 2013 were randomized to DGHAL (n = 197) or SH (n = 196). The primary endpoint was operative-related morbidity at 3 months (D.90) based on the Clavien-Dindo surgical complications grading. Total cost, cost-effectiveness, and clinical outcome were assessed at 1 year. RESULTS At D.90, operative-related adverse events occurred after DGHAL and SH, respectively, in 47 (24%) and 50 (26%) patients (P = 0.70). DGHAL resulted in longer mean operating time (44±16 vs 30±14 min; P < 0.001), less pain (postoperative and at 2 wks visual analogic scale: 2.2 vs 2.8; 1.3 vs 1.9; P = 0.03; P = 0.013) and shorter sick leave (12.3 vs 14.8 d; P = 0.045). At 1 year, DGHAL led to more residual grade III HD (15% vs 5%) and a higher reoperation rate (8% vs 4%). Patient satisfaction was >90% for both procedures. Total cost at 1 year was greater for DGHAL [&OV0556;2806 (&OV0556;2670; 2967) vs &OV0556;2538 (&OV0556;2386; 2737)]. The D.90, incremental cost-effectiveness ratio (ICER) was &OV0556;7192 per averted complication. At 1 year DGHAL strategy was dominated. CONCLUSIONS DGHAL and SH are viable options in grade II/III HD with no significant difference in operative-related risk. Although resulting in less postoperative pain and shorter sick leave, DGHAL was more expensive, took longer, and provided a possible inferior anatomical correction suggesting an increased risk of recurrence.


title: [Morphology of coronaviruses-- electron microscopic demonstration by negative contrast technic of the transmissible gastroenteritis virus of swine].

text: This contribution to the morphology of corona virus is based on the use of electron microscopy in a negative contrast investigation of the virus of transmissible gastroenteritis of swine. Viruses of transmissible gastro-enteritis are spherical or, in rare cases, pleomorphous particles of typical corona virus structure. The viruses investigated by the authors were 132 nm in diameter. The surface projections, consisting of a flattened knob and conical shaft, are 18 nm in length. Internal bodies, 50 +/- 2 nm in diameter, occur as "filled" or "empty" particles. The thickness of all internal bodies and virus membranes is 8 +/- 1 nm. Differences were found to exist between virus of transmissible gastro-enteritis and particles similar to corona virus and isolated from faecal samples. A first comparison had been made for that purpose. Those differences were relating to shape and size of individual particles and to morphological setup of surface projections.


title: Rotavirus and coronavirus-like particles in aboriginal and non-aboriginal neonates in Kalgoorlie and Alice Springs.

text: In a series of six-month surveys carried out in Kalgoorlie and Alice Springs Hospitals, rotavirus was infrequently detected both in Aboriginal and in non-Aboriginal neonates. Coronavirus-like particles were also detected infrequently, but they were found more often in Aboriginal than in non-Aboriginal neonates. The surveys did not detect any 28-nm virus-like particles.


docid: guiorfty

title: Comparison of two different circular-stapler techniques for creation of gastrojejunostomy anastomosis in bariatric Roux-en Y gastric bypass.

text: BACKGROUND Circular-stapled anastomosis with trans-oral anvil insertion is one of the most commonly used methods for the creation of the gastrojejunostomy in laparoscopic Roux-en-Y gastric bypass (LRYGB). We present a retrospective analysis of laparoscopic gastric bypass by comparing 2 techniques of circular-stapled gastrojejunostomy; Orvil(TM) and hand-made Orvil. METHODS Patients who were subjected to LRYGB without any concomitant procedures were observed over a 13-months period at the "Obesity clinic of a University". A total of 94 patients with morbid obesity were subjected to LRYGB. Gastrojejunostomy with circular-stapler and Orvil(TM) (CS-O) was performed to 58 patients and 36 patients underwent through the surgery with circular-stapler and hand-made Orvil (CS-HMO). Demographics, clinic, intraoperative data, postoperative complications, and the length of hospital stay were evaluated. RESULTS Ninety-four patients with mean age of 37.2 years and average body mass index of 58.1 kg/m(2) underwent laparoscopic Roux-en-Y gastric bypass. Laparoscopic surgeries of all patients were successful and major intraoperative complications were not reported. Demographic data and complication rates were similar in both groups. The operative time in group CS-HMO was significantly higher (P=0.03) when compared to group CS-O. There was no anastomotic leak in both groups. CONCLUSION The use of hand-made Orvil is a technically feasible and safe method for performing the gastrojejunostomy. This technique can be successfully used in case of difficulties for obtaining the Orvil(TM) or reducing the operational costs.


docid: zobzviti

title: Current strategies for protein production and purification enabling membrane protein structural biology.

text: Membrane proteins are still heavily under-represented in the protein data bank (PDB), owing to multiple bottlenecks. The typical low abundance of membrane proteins in their natural hosts makes it necessary to overexpress these proteins either in heterologous systems or through in vitro translation/cell-free expression. Heterologous expression of proteins, in turn, leads to multiple obstacles, owing to the unpredictability of compatibility of the target protein for expression in a given host. The highly hydrophobic and (or) amphipathic nature of membrane proteins also leads to challenges in producing a homogeneous, stable, and pure sample for structural studies. Circumventing these hurdles has become possible through the introduction of novel protein production protocols; efficient protein isolation and sample preparation methods; and, improvement in hardware and software for structural characterization. Combined, these advances have made the past 10-15 years very exciting and eventful for the field of membrane protein structural biology, with an exponential growth in the number of solved membrane protein structures. In this review, we focus on both the advances and diversity of protein production and purification methods that have allowed this growth in structural knowledge of membrane proteins through X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and cryo-electron microscopy (cryo-EM).


title: Treatment of severe acute respiratory syndrome with lopinavir/ritonavir: a multicentre retrospective matched cohort study.

text: OBJECTIVES To investigate the possible benefits and adverse effects of the addition of lopinavir/ritonavir to a standard treatment protocol for the treatment of severe acute respiratory syndrome. DESIGN Retrospective matched cohort study. SETTING Four acute regional hospitals in Hong Kong. PATIENTS AND METHODS Seventy-five patients with severe acute respiratory syndrome treated with lopinavir/ritonavir in addition to a standard treatment protocol adopted by the Hospital Authority were matched with controls retrieved from the Hospital Authority severe acute respiratory syndrome central database. Matching was done with respect to age, sex, the presence of co-morbidities, lactate dehydrogenase level and the use of pulse steroid therapy. The 75 patients treated with lopinavir/ritonavir were divided into two subgroups for analysis: lopinavir/ritonavir as initial treatment, and lopinavir/ritonavir as rescue therapy. These groups were compared with matched cohorts of 634 and 343 patients, respectively. Outcomes including overall death rate, oxygen desaturation, intubation rate, and use of pulse methylprednisolone were reviewed. RESULTS The addition of lopinavir/ritonavir as initial treatment was associated with a reduction in the overall death rate (2.3%) and intubation rate (0%), when compared with a matched cohort who received standard treatment (15.6% and 11.0% respectively, P<0.05) and a lower rate of use of methylprednisolone at a lower mean dose. The subgroup who had received lopinavir/ritonavir as rescue therapy, showed no difference in overall death rate and rates of oxygen desaturation and intubation compared with the matched cohort, and received a higher mean dose of methylprednisolone. CONCLUSION The addition of lopinavir/ritonavir to a standard treatment protocol as an initial treatment for severe acute respiratory syndrome appeared to be associated with improved clinical outcome. A randomised double-blind placebo-controlled trial is recommended during future epidemics to further evaluate this treatment.


title: Balance and gait abnormalities of a child with West Nile virus infection.

text: We describe a case of a previously healthy 2-year-old female patient with rash, fever and vomiting for 10 days who presented for medical attention with acute profound balance and gait disturbances and intentional movement dysmetria. West Nile virus-specific IgM and IgG antibodies were detected in the patient's cerebrospinal fluid.


title: How the American Society for Virology was founded.

text: The American Society for Virology, the very first such Society to be formed anywhere, was founded at a meeting of some 40 virologists at Chicago O'Hare International airport on June 9, 1981. They met after a decade and a half of intense discussion that originated at the 9th International Congress of Microbiology in Moscow in 1966 when a small group of virologists requested the International Association of Microbiological Societies to form a Virology Section within IAMS, and this request was rejected. Virologists therefore held their own First International Congress of Virology in Helsinki in 1968 which was very successful and generated intense informal discussion among leading virologists in this country as to the desirability of founding an American society for virologists. Proposals were circulated and discussed which resulted in the informal Chicago meeting that created the mechanism for founding the ASV and organizing its 1st Annual Meeting at Cornell in Ithaca in August 1982.


title: Identification of an immunodominant linear neutralization domain on the S2 portion of the murine coronavirus spike glycoprotein and evidence that it forms part of complex tridimensional structure.

text: Numerous studies have demonstrated that the spike glycoprotein of coronaviruses bears major determinants of pathogenesis. To elucidate the antigenic structure of the protein, a panel of monoclonal antibodies was studied by competitive ELISA, and their reactivities were assayed against fragments of the murine coronavirus murine hepatitis virus strain A59 S gene expressed in prokaryotic vectors. An immunodominant linear domain was localized within the predicted stalk, S2, of the peplomer. It is recognized by several neutralizing antibodies. Other domains were also identified near the proteolytic cleavage site, in the predicted globular head, S1, and in another part of the stalk. Furthermore, competition results suggest that the immunodominant functional domain forms part of a complex three-dimensional structure. Surprisingly, some antibodies which have no antiviral biological activities were shown to bind the immunodominant neutralization domain.


title: Intravenous Amide Anesthetics to Treat Pain Associated with Renal Colic in the Emergency Department: a Systematic Review.

text: Introduction Renal colic affects 12% of the U.S. population, accounting for nearly 1% of emergency department (ED) visits. Current recommendations advocate narcotic-limiting multimodal analgesia regimens. The objective of this review is to determine if in patients with renal colic (Population), intravenous (IV) amide anesthetics (Intervention) result in better pain control, lower requirements for rescue analgesia, or less adverse medication effects (outcome) compared to placebo, non-steroidal anti-inflammatory drugs (NSAIDs), or opiates (Comparisons). Methods Scholarly databases and relevant bibliographies were searched using a pre-designed systematic review protocol and registered with PROSPERO. Inclusion criteria were: (1) randomized clinical trial (RCT), (2) age ≥ 18 years, (3) confirmed or presumed renal colic, (4) amide anesthetic administered IV. Eligible comparison groups included: placebo, conventional therapy, acetaminophen, NSAID, or opiate. The primary outcome was pain intensity at baseline, 30, 60, and 120 minutes. Trial quality was graded, and risk-of-bias was assessed. Results Of the 3930 identified references, 4 RCTs (479 participants) were included. One trial (n=240) reported improved analgesia with IV lidocaine (LidoIV) plus metoclopramide, compared to morphine. All other trials reported unchanged or less analgesia compared to placebo, ketorolac, or fentanyl. Very severe heterogeneity (I2= 88%) precluded pooling data. Conclusion Current evidence precludes drawing a firm conclusion on the efficacy or superiority of LidoIV over traditional therapies for ED patients with renal colic. Evidence suggests LidoIV may be an effective non-opiate analgesic alliterative; however, it's efficacy may not exceed that of NSAIDs or opiates. Further study is needed to validate the potential improved efficacy of LidoIV plus metoclopramide.


title: Current status and future directions for Laribacter hongkongensis, a novel bacterium associated with gastroenteritis and traveller's diarrhoea.

text: PURPOSE OF REVIEW Despite extensive investigations, a microbiological cause cannot be found in about half of the patients with infectious disease. Throughout the years, scientists have spent tremendous efforts in looking for microorganisms associated with these "unexplained infectious disease syndromes". Recently, a novel bacterium, Laribacter hongkongensis, was discovered and shown to be associated with gastroenteritis and traveller's diarrhoea. This review summarizes the current status, and shares with the readers the authors' experience in the microbiology, classification, epidemiology, clinical disease, laboratory diagnosis, antibiotic resistance and treatment of L. hongkongensis. It also discusses the importance and perspective of describing novel pathogenic bacterial species. RECENT FINDINGS L. hongkongensis was shown to be associated with gastroenteritis and traveller's diarrhoea. Consumption of fish was associated with recovery of L. hongkongensis. Freshwater fish was a reservoir of L. hongkongensis. Genotypic typing revealed the possibility of virulent clones of L. hongkongensis. The class C beta-lactamase of L. hongkongensis has been cloned and characterized. SUMMARY In 2001, L. hongkongensis, a novel genus and species, was first discovered in Hong Kong from the blood and empyema pus of a patient with alcoholic cirrhosis. Subsequently, it was isolated from patients in other parts of the world. Recently, this bacterium was found to be associated with community-acquired gastroenteritis and traveller's diarrhoea using cefoperazone MacConkey agar as the selective medium. Further studies, including setting up of animal and tissue culture models and characterization of virulence factors, should be performed. For pathogenic microbes, even one strain of a novel species should be described, so that global concerted efforts can be drawn to look for more cases associated with such a pathogen.


title: Is there a dysfunction in the visual system of depressed patients?

text: BACKGROUND: The aim of the current study was to identify a possible locus of dysfunction in the visual system of depressed patients. MATERIALS AND METHODS: Fifty Major Depressive patients aged 21-60 years and 15 age-matched controls took part in the study The diagnosis was obtained with the SCAN v 2.0. The psychometric assessment included the HDRS, the HAS, the Newcastle Scales, the Diagnostic Melancholia Scale and the GAF scale. Flash Electroretinogram and Electrooculogram were performed in all subjects. The statistical analysis included ANCOVA, Student's t-test and Pearson Product Moment Correlation Coefficient were used. RESULTS: The Electro-oculographic findings suggested that all subtypes of depressed patients had lower dark trough and light peak values in comparison to controls (p < 0.001), while Arden ratios were within normal range. Electroretinographic recordings did not reveal any differences between patients and controls or between subtypes of depression. DISCUSSION: The findings of the current study provide empirical data in order to assist in the understanding of the international literature and to explain the mechanism of action of therapies like sleep deprivation and light therapy.


title: Severe acute respiratory syndrome: an update.

text: PURPOSE OF REVIEW An international outbreak of severe acute respiratory syndrome, a recently recognized syndrome caused by the newly identified severe acute respiratory syndrome-associated coronavirus, began in November 2002 and ended in July 2003. Since then, a large body of research on the syndrome has been published; the most updated developments are summarized here. RECENT FINDINGS Recent findings suggest that animal severe acute respiratory syndrome-like coronaviruses may have been transmitted to humans without detection for years before the recent outbreak, and that such transmission may be continuing today. The 2002-2003 outbreak probably originated from similar animal-to-human transmission, but selection and purification of the animal severe acute respiratory syndrome-like virus appears to have occurred, creating the more virulent severe acute respiratory syndrome-associated coronavirus. Recent studies have documented that severe acute respiratory syndrome-associated coronavirus is primarily transmitted via contact and/or respiratory droplets and that the combination of standard, contact, and droplet precautions is generally effective for its control. It has been shown that severe acute respiratory syndrome-associated coronavirus is typically relatively inefficiently transmitted, with the notable exception of transmission during superspreading events. Insights into the pathogenesis of severe acute respiratory syndrome have been made: one study suggests that human leukocyte antigen HLA-B*4601 is a possible risk factor for more severe disease, while another identifies angiotensin-converting enzyme 2 as a cellular receptor for severe acute respiratory syndrome-associated coronavirus. Promising treatments have been identified, including interferons, an anti-spike monoclonal antibody, and fusion inhibitors. In addition, many promising vaccines are currently in development. SUMMARY New findings regarding severe acute respiratory syndrome are continuing to be discovered at an unprecedented pace, permitting a better understanding of the disease and enabling better preparation for its possible return.


docid: pnicobgd

title: Dynamic Modeling COVID-19 for Comparing Containment Strategies in a Pandemic Scenario.

text: The emergence of coronavirus disease 2019 (COVID-19) in the United States has forced federal and local governments to implement containment measures. Moreover, the severity of the situation has sparked engagement by both the research and clinical community with the goal of developing effective treatments for the disease. This article proposes a time dynamic prediction model with competing risks for the infected individual and develops a simple tool for policy makers to compare different strategies in terms of when to implement the strictest containment measures and how different treatments can increase or suppress infected cases. Two types of containment strategies are compared: (1) a constant containment strategy that could satisfy the needs of citizens for a long period; and (2) an adaptive containment strategy whose strict level changes across time. We consider how an effective treatment of the disease can affect the dynamics in a pandemic scenario. For illustration we consider a region with population 2.8 million and 200 initial infectious cases assuming a 4% mortality rate compared with a 2% mortality rate if a new drug is available. Our results show compared with a constant containment strategy, adaptive containment strategies shorten the outbreak length and reduce maximum daily number of cases. This, along with an effective treatment plan for the disease can minimize death rate.


title: Computer-assisted functional assessment and documentation.

text: Occupational therapy personnel spend considerable time on functional assessment and documentation. The rapid and error-free information processing ability of computers offers methods for data collection, clinical decision making, and reporting of functional assessment results, which may be more effective and efficient than the current paper-and-pencil methods. Computers can provide assistance throughout the many steps of the functional assessment and reporting process. Software is available to assist in direct data collection, data reduction, and analysis, or to assess complex data systems and databases. Additionally, computers can use assessment techniques, such as dynamic question sets and expert systems, which have not been possible with paper-and-pencil methods. Furthermore, data collected on computers are readily available to be integrated in computer-assisted report writing and can be compiled into large databases for analysis. These databases can be used for program evaluation, continuous quality improvement exercises, and other research objectives. This paper provides a snapshot of these computer uses in the assessment process.


docid: uaecfjsk

title: CT features of coronavirus disease 2019 (COVID-19) pneumonia: experience of a single center in Southern Italy.

text: PURPOSE The aim of this study was to report the radiological features of chest CT scan of patients with coronavirus disease 2019 (COVID-19) living in a town in Southern Italy where a significant outbreak of the disease occurred. METHODS We revised the CT scan of 62 patients (34 male, 28 female, mean age 71 +/- 14 years) with clinical and laboratory signs of COVID-19, as assessed by positive SARS-CoV-2 RT-PCR testing. All patients underwent chest CT at the time of admission to the hospital. A semi-quantitative scoring system was used to evaluate the extension of the disease. RESULTS Out of the 62 patients the main radiological findings were reticular pattern (29%), ground-glass opacities (24%), crazy paving pattern (11%) and consolidation (35%). Most of the lesions were bilateral (97%), posterior (95%) and located near pleura (50%) or lung fissures (45%), mainly involving the lower right lobe (56%) and lower left lobe (23%). Pleural thickening was observed in 72.6% of patients and pleural effusion in 18%. Median value of the score was 7.0 and was significantly higher in male than female (8.5 vs 6.0, p=0.03) and in patients with pleural thickening compared to those without this finding (8.0 vs 5.0, p=0.03).


title: [A modification of the ABC method (avidin-biotin-peroxidase complex) for the detection of viral antigens in coronavirus infections in cats (FIP) and parvovirus type 2 infections in dogs].

text: A modified ABC-method (avidin-biotin-peroxidase complex) is established to demonstrate viral antigens in paraffin sections of tissues of coronavirus (FIP) infected cats and parvovirus type 2 infected dogs using monoclonal antibodies. The pros and cons and potential sources of error are described and discussed.


title: Synthesis, antiviral and cytotoxic investigation of 2-phenyl-3-substituted quinazolin-4(3H)-ones.

text: OBJECTIVES A series of 3(benzylideneamino)-2-phenyl quinazoline-4(3H)-ones was synthesized by reaction of 3-amino-2-phenyl-3H-quinazoline-4-one with various carbonyl compounds. MATERIALS AND METHODS Chemical structures of the synthesized compounds were confirmed by IR, 1H-NMR and mass spectral analysis. Title compounds were investigated for cytotoxicity and antiviral activity against herpes simplex virus-1 (KOS), herpes simplex virus-2 (G), vaccinia virus, vesicular stomatitis virus, herpes simplex virus-1 TK-KOS ACVr, para influenza-3 virus, reovirus-1, Sindbis virus, Coxsackie virus B4, Punta Toro virus, feline corona virus (FIPV), feline herpes virus, respiratory syncytial virus, influenza A H1 N1 subtype, influenza A H3N2 subtype, influenza B and vesicular stomatitis virus. RESULTS AND CONCLUSION Compound 3d was found inhibit viral replication of para influenza-3virus, reovirus-1, Sindbis virus, Coxsackie virus B4, Punta Toro virus in Vero cell cultures.


PEDV leader sequence and junction sites.


title: The laboratory diagnosis of severe acute respiratory syndrome: emerging laboratory tests for an emerging pathogen.

text: The 2003 pandemic of Severe Acute Respiratory Syndrome (SARS) profiled the ability of modern diagnostic microbiology and molecular biology to identify, isolate and characterize, within weeks, a previously unknown viral infectious pathogen. The culprit, SARS coronavirus (SARS-CoV), was detected in patient specimens by traditional cell culture using an unusual cell line for respiratory viruses, Vero E6, and by reverse transcriptase polymerase chain reaction (RT-PCR) targeting the polymerase 1 B region of the genome. In addition, serologic assays were rapidly developed, and the genome of this large virus was sequenced within one month of its spread to North America. At the present time, diagnostics have progressed to the point that RT-PCR has a sensitivity approaching 80% within the first few days of onset of illness, while serology has a sensitivity close to 100% on convalescent sera taken >21 days after illness onset. Viral culture remains a method confined to biosafety level III laboratories. The specificity of RT-PCR and serology remains to be conclusively defined, but in most studies to date seems to be >90%. Serologic cross-reactivity with human coronaviruses causing the common cold may be a problem with some serologic assays. The early development of SARS-CoV diagnostics is now being replaced by refinement and optimization of these assays. Although at the present time we do not have a test that will definitively rule in or rule out SARS at the time of initial presentation of a patient with a respiratory infection, modifications of existing assays will hopefully result in our ability to make this diagnosis with a high degree of accuracy in the future.


title: Evaluation of right versus left laparoscopic donor nephrectomy.

text: OBJECTIVES With the advent of laparoscopic donor nephrectomy, there has been a general underuse of right laparoscopic donor nephrectomy versus left because of concerns regarding higher complication rates and poorer outcomes. We performed a retrospective analysis of our laparoscopic donor nephrectomy series with an emphasis on the side of the kidney retrieved and the outcomes of donors and recipients. MATERIALS AND METHODS Data on 94 consecutive donor-recipient pairs (188 patients) were reviewed. All donor nephrectomies were performed by pure laparoscopy. There were 74 left laparoscopic donor nephrectomies and 20 right laparoscopic donor nephrectomies. Intraoperative parameters and graft outcome were recorded and the data were analyzed to compare right laparoscopic donor nephrectomy versus left laparoscopic donor nephrectomy using a computer software system. Follow-up ranged from 1 to 6 years (mean, 3.4 y). RESULTS There were no significant differences in any intraoperative or postoperative parameters, except in a slightly higher warm ischemia time in right laparoscopic donor nephrectomy versus left laparoscopic donor nephrectomy, but this did not translate into an adverse effect on renal recovery. Acute graft rejection was observed in 2 of 74 patients who had a left laparoscopic donor nephrectomy (2.7%) and none of the patients who had a right laparoscopic donor nephrectomy. Chronic graft loss was observed in 2 of 74 patients who had a left laparoscopic donor nephrectomy (2.7%); 1 of recurrent pyelonephritis and sepsis and 1 renal oxalosis. No graft losses were observed in any patient who had a right laparoscopic donor nephrectomy. Mean serum creatinine levels in recipients at 1, 3, 6, 9, and 12 months were equivalent for right laparoscopic donor nephrectomy versus left laparoscopic donor nephrectomy; they were 120, 110, 110, 110, 110 µmol/L, versus 110, 110, 110, 110, 110 µmol/L. (1.35, 1.21, 1.24, 1.21, 1.26 mg/dL versus 1.22, 1.17, 1.17, 1.17, 1.23 mg/dL). CONCLUSIONS This single center study demonstrates equivalent results with left laparoscopic donor nephrectomy and right laparoscopic donor nephrectomy with no adverse effects of right laparoscopic donor nephrectomy on donor-recipient outcome or renal function.


title: [Prokaryotic expression and characterization of two recombinant receptor-binding domain(RBD) proteins of human coronavirus NL63(HcoV-NL63)].

text: The receptor-binding domain(RBD) protein of HCoV-NL63 is a major target in the development of diagnostic assay and vaccine, it has a pivotal role in receptor attachment, viral entry and membrane fusion. In this study, we prepared 2 purified recombinant HCoV-NL63 RBD proteins using in E. coli system and identified the proteins by Western blotting. We first optimized codon and synthesized the RL (232-684aa)coding gene, then amplified the RL or RS(476-616aa) coding gene via PCR using different primers . The RL or RS coding gene was cloned into the pM48 expression vector fused with TrxA tag. The RBD (RL and RS) of HCoV-NL63 were expressed majorly as inclusion body when expressed in E. coli BL21pLys S under different conditions. The expressed products were purified by affinity chromatography then analyzed by SDS-PAGE and Western blotting. Our results showed that the recombinant RBD proteins were maximally expressed at 37 degrees C with 0. 8mM IPTG induction for 4h. RL or RS protein with 95 % purity was obtained and reacted positively with anti-sera from mice immunized with the recombinant vaccinia virus (Tiantan strain) in which HCoV-NL63 RL or RS protein was expressed. In conclusion, the purified recombinant RBD proteins(RL and RS)derived from E. coli were first prepared in China and they might provide a basis for further exploring biological role and vaccine development of HCoV-NL63.


title: Drug targets for COVID-19 therapeutics: Ongoing global efforts.

text: The current global pandemic COVID-19 caused by the SARS-CoV-2 virus has already inflicted insurmountable damage both to the human lives and global economy. There is an immediate need for identification of effective drugs to contain the disastrous virus outbreak. Global efforts are already underway at a war footing to identify the best drug combination to address the disease. In this review, an attempt has been made to understand the SARS-CoV-2 life cycle, and based on this information potential druggable targets against SARS-CoV-2 are summarized. Also, the strategies for ongoing and future drug discovery against the SARSCoV- 2 virus are outlined. Given the urgency to find a definitive cure, ongoing drug repurposing efforts being carried out by various organizations are also described. The unprecedented crisis requires extraordinary efforts from the scientific community to effectively address the issue and prevent further loss of human lives and health.


title: Absence of porcine interferon alpha secreting cells in severe combined immunodeficiency (SCID) mice inoculated with porcine leukocytes.

text: A low frequency leukocyte subpopulation, referred to as natural interferon producing cells (NIPC) is able to produce high amounts of interferon alpha (IFN-alpha) following contact with noninfectious viral structures. In order to examine the possible leukocytic nature and bone marrow origin of NIPC, severe combined immunodeficiency (SCID) mice were reconstituted with porcine leukocyte populations, including bone marrow cells. At different times after reconstitution, enriched CD4 and CD45 positive porcine cells were isolated from various mouse organs and tested for the presence of porcine NIPC by porcine IFN-alpha specific ELISPOT assay, after in vitro stimulation by UV inactivated transmissible gastroenteritis virus (TGEV). Although engraftment of porcine cells in SCID mice was shown by flow cytometry and by the production of pig immunoglobulins, no IFN-alpha secreting cells could be detected. This result suggests that NIPC do not derive from bone marrow precursor cells, or that growth factors needed for in vivo expansion of porcine NIPC were absent in mice.


title: Factors affecting perceived risk of contracting severe acute respiratory syndrome among academic physicians.

text: SARS disproportionately affects healthcare providers. A physician survey was administered within three hospitals providing care to SARS patients. Knowing a colleague who contracted SARS and previous occupational exposure to infectious agents were significantly predictive of greater perceived risk, whereas perceived effectiveness of precautions and provision of direct care were not.


Challenges and opportunities of public health research in Nepal.


APIC guide highlights role of ambulatory care in disaster response.


title: Guidelines for preventing health-care--associated pneumonia, 2003: recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee.

text: This report updates, expands, and replaces the previously published CDC "Guideline for Prevention of Nosocomial Pneumonia". The new guidelines are designed to reduce the incidence of pneumonia and other severe, acute lower respiratory tract infections in acute-care hospitals and in other health-care settings (e.g., ambulatory and long-term care institutions) and other facilities where health care is provided. Among the changes in the recommendations to prevent bacterial pneumonia, especially ventilator-associated pneumonia, are the preferential use of oro-tracheal rather than naso-tracheal tubes in patients who receive mechanically assisted ventilation, the use of noninvasive ventilation to reduce the need for and duration of endotracheal intubation, changing the breathing circuits of ventilators when they malfunction or are visibly contaminated, and (when feasible) the use of an endotracheal tube with a dorsal lumen to allow drainage of respiratory secretions; no recommendations were made about the use of sucralfate, histamine-2 receptor antagonists, or antacids for stress-bleeding prophylaxis. For prevention of health-care--associated Legionnaires disease, the changes include maintaining potable hot water at temperatures not suitable for amplification of Legionella spp., considering routine culturing of water samples from the potable water system of a facility's organ-transplant unit when it is done as part of the facility's comprehensive program to prevent and control health-care--associated Legionnaires disease, and initiating an investigation for the source of Legionella spp. when one definite or one possible case of laboratory-confirmed health-care--associated Legionnaires disease is identified in an inpatient hemopoietic stem-cell transplant (HSCT) recipient or in two or more HSCT recipients who had visited an outpatient HSCT unit during all or part of the 2-10 day period before illness onset. In the section on aspergillosis, the revised recommendations include the use of a room with high-efficiency particulate air filters rather than laminar airflow as the protective environment for allogeneic HSCT recipients and the use of high-efficiency respiratory-protection devices (e.g., N95 respirators) by severely immunocompromised patients when they leave their rooms when dust-generating activities are ongoing in the facility. In the respiratory syncytial virus (RSV) section, the new recommendation is to determine, on a case-by-case basis, whether to administer monoclonal antibody (palivizumab) to certain infants and children aged <24 months who were born prematurely and are at high risk for RSV infection. In the section on influenza, the new recommendations include the addition of oseltamivir (to amantadine and rimantadine) for prophylaxis of all patients without influenza illness and oseltamivir and zanamivir (to amantadine and rimantadine) as treatment for patients who are acutely ill with influenza in a unit where an influenza outbreak is recognized. In addition to the revised recommendations, the guideline contains new sections on pertussis and lower respiratory tract infections caused by adenovirus and human parainfluenza viruses and refers readers to the source of updated information about prevention and control of severe acute respiratory syndrome.


title: Localization and membrane topology of coronavirus nonstructural protein 4: involvement of the early secretory pathway in replication.

text: The coronavirus nonstructural proteins (nsp's) derived from the replicase polyproteins collectively constitute the viral replication complexes, which are anchored to double-membrane vesicles. Little is known about the biogenesis of these complexes, the membrane anchoring of which is probably mediated by nsp3, nsp4, and nsp6, as they contain several putative transmembrane domains. As a first step to getting more insight into the formation of the coronavirus replication complex, the membrane topology, processing, and subcellular localization of nsp4 of the mouse hepatitis virus (MHV) and severe acute respiratory syndrome-associated coronavirus (SARS-CoV) were elucidated in this study. Both nsp4 proteins became N glycosylated, while their amino and carboxy termini were localized to the cytoplasm. These observations imply nsp4 to assemble in the membrane as a tetraspanning transmembrane protein with a Nendo/Cendo topology. The amino terminus of SARS-CoV nsp4, but not that of MHV nsp4, was shown to be (partially) processed by signal peptidase. nsp4 localized to the endoplasmic reticulum (ER) when expressed alone but was recruited to the replication complexes in infected cells. nsp4 present in these complexes did not colocalize with markers of the ER or Golgi apparatus, while the susceptibility of its sugars to endoglycosidase H indicated that the protein had also not traveled trough the latter compartment. The important role of the early secretory pathway in formation of the replication complexes was also demonstrated by the inhibition of coronaviral replication when the ER export machinery was blocked by use of the kinase inhibitor H89 or by expression of a mutant, Sar1[H79G].


title: The formation and function of extracellular enveloped vaccinia virus.

text: Vaccinia virus produces four different types of virion from each infected cell called intracellular mature virus (IMV), intracellular enveloped virus (IEV), cell-associated enveloped virus (CEV) and extracellular enveloped virus (EEV). These virions have different abundance, structure, location and roles in the virus life-cycle. Here, the formation and function of these virions are considered with emphasis on the EEV form and its precursors, IEV and CEV. IMV is the most abundant form of virus and is retained in cells until lysis; it is a robust, stable virion and is well suited to transmit infection between hosts. IEV is formed by wrapping of IMV with intracellular membranes, and is an intermediate between IMV and CEV/EEV that enables efficient virus dissemination to the cell surface on microtubules. CEV induces the formation of actin tails that drive CEV particles away from the cell and is important for cell-to-cell spread. Lastly, EEV mediates the long-range dissemination of virus in cell culture and, probably, in vivo. Seven virus-encoded proteins have been identified that are components of IEV, and five of them are present in CEV or EEV. The roles of these proteins in virus morphogenesis and dissemination, and as targets for neutralizing antibody are reviewed. The production of several different virus particles in the VV replication cycle represents a coordinated strategy to exploit cell biology to promote virus spread and to aid virus evasion of antibody and complement.


title: Deformation of the Femoropopliteal Segment: Effect of Stent Length, Location, Flexibility, and Curvature.

text: PURPOSE To quantify the deformation behavior of the diseased femoropopliteal segment and assess the change to deformation behavior due to various stent placements. METHODS The length and curvature changes of 6 femoropopliteal segments (the right and left superficial femoral and popliteal arteries) from 3 cadavers were measured in 3-dimensional space based on rotational angiography image data in straight leg and flexed hip/knee (50°/90°) positions before and after placement of nitinol stents of varying type (EverFlex, Misago, and BioMimics 3D) and length (60, 100, and 200 mm) in different locations along the arteries. Three-dimensional centerline data were extracted for the measurements. RESULTS All 6 femoropopliteal cadaver segments displayed signs of peripheral artery disease. Hip/knee flexion resulted in vessel shortening and increases in the mean and maximum vessel curvatures in all cases. Location-specific results of the unstented arteries showed that magnitudes of vessel length and curvature change vary as a function of vessel length. The average shortening of the entire femoropopliteal segment due to flexion was observed at 10.7%±0.7%, which was reduced to 8.1%±0.9% after stent deployment. Average and maximum curvatures of the unstented segment increased due to flexion (average: 0.008±0.002 mm-1 to 0.019±0.006 mm-1, maximum: 0.030±0.009 mm-1 to 0.091±0.045 mm-1). After stent deployment, average and maximum curvatures of the flexed stented segments increased compared with the flexed unstented segments (average: 0.019±0.006 mm-1 to 0.022±0.004 mm-1, maximum: 0.091±0.045 mm-1 to 0.103±0.025 mm-1). The most flexurally stiff stent demonstrated the least ability to axially shorten during flexion of the leg at the knee joint. CONCLUSION The deformation characteristics of the femoropopliteal segment change in the presence of a stent, with the change to the deformation behavior dependent on stent type, stent length, location, flexibility, and intrinsic centerline curvature.


The coronaviruslike superfamily.


title: Evaluation of antibiotic-loaded calcium phosphate bone cement in an cranium-infected experimental model.

text: Treatment of calvarial defects has remained a challenge in reconstruction surgery, especially because of infection at these sites. We produced a bactericidal biomaterial for treating infected bone defects by using calcium phosphate bone cement mixed with antibiotics. We evaluated the usefulness of this material mixed with the antibiotic vancomycin in a cranium-infected rat model. The concentration of vancomycin used was 5.0 wt%, as reported in our previous study. In order to establish the rat model, a cranium defect (diameter, 5 mm) was made that was infected with methicillin-resistant Staphylococcus aureus (MRSA). Thirty-six rats were divided into 6 groups depending on whether an autologous graft or bone cement with or without antibiotic was used for the defect. After 1 and 4 weeks, abscess formation was checked, tissue bacterial counts were determined, and pathological examination was performed. At both 1 and 4 weeks, no MRSA was detected on tissue bacterial culture or pathological examination in groups that received bone cement with antibiotics. In groups that received bone cement without antibiotic, MRSA was detected, and the bone cement had compromised and disintegrated into several slices. In conclusion, bone cement that contains antibiotics appears to be effective not only for reconstruction in cases of cranial defect, but also in terms of preventing infection.


PETITION FOR A WRIT OF CERTIORARI.


title: Exacerbated viral hepatitis in IFN-gamma receptor-deficient mice is not suppressed by IL-12.

text: Both IL-12 and IFN-gamma have been implicated as principal inducers of type 1 immune responses required for the elimination of intracellular pathogens, such as viruses. We examined the in vivo antiviral role of both cytokines during coronavirus-induced hepatitis in a mouse hepatitis virus (MHV) model. The absence of IFN-gamma function in mice with a targeted disruption of the IFN-gamma R alpha-chain gene (IFN-gamma R -/-) resulted in increased susceptibility to coronaviral hepatitis associated with augmented viral replication and increased hepatocellular injury. The mutant mice showed a type 1 lymphokine response characterized by the normal high IFN-gamma and low IL-4 production. Unlike MHV-infected wild-type mice, however, the mutant IFN-gamma R -/- mice showed no increase in IL-12 p4O gene expression, similar to that in naive animals. IL-12 treatment failed to restore host resistance in IFN-gamma R -/- mice, but significantly protected MHV-susceptible C57BL/6 mice against lethal infection, although less than IFN-gamma treatment. Mice protected by IL-12 or IFN-gamma showed resistance against an otherwise lethal second MHV infection. Our data demonstrate that despite reduced IL-12 gene expression and defective IFN-gamma R function, virus-induced IFN-gamma production can occur. Furthermore, they emphasize the pivotal antiviral role of IFN-gamma in protection against acute coronavirus-induced hepatitis.


title: Human rhinovirus 3C protease: generation of pharmacophore models for peptidic and nonpeptidic inhibitors and their application in virtual screening.

text: Three-dimensional pharmacophore models for peptidic and small organic nonpeptidic inhibitors of the human rhinovirus 3C protease were generated in a structure-based as well as in a ligand-based approach, using the software package Catalyst. The inhibitors possess an electrophilic moiety, often a Michael acceptor function, which covalently binds to a cysteine in the active site of the enzyme. Since this process presents the key step for virus inactivation, the creation of a new function in Catalyst was required in order to include this decisive functionality into the pharmacophore models. In the present study we focus on this feature definition process because it presents an innovative strategy to expand the pharmacophore description ability of the Catalyst software to also include covalent bonds between ligand and binding site. The resulting hypotheses were then used for virtual screening of 3D databases in order to verify their quality and to search for structurally diverse, possible new lead substances.


title: Identification of contaminant sources in enclosed spaces by a single sensor.

text: UNLABELLED To protect occupants from infectious diseases or possible chemical/biological agents released by a terrorist in an enclosed space, such as an airliner cabin, it is critical to identify gaseous contaminant source locations and strengths. This paper identified the source locations and strengths by solving inverse contaminant transport with the quasi-reversibility (QR) and pseudo-reversibility (PR) methods. The QR method replaces the second-order diffusion term in the contaminant transport equation with a fourth-order stabilization term. By using the airflow pattern calculated by computational fluid dynamics (CFD) and the time when the peak contaminant concentration was measured by a sensor in downstream, the QR method solves the backward probability density function (PDF) of contaminant source location. The PR method reverses the airflow calculated by CFD and solves the PDF in the same manner as the QR method. The position with the highest PDF is the location of the contaminant source. The source strength can be further determined by scaling the nominal contaminant concentration computed by CFD with the concentration measured by the sensor. By using a two-dimensional and a three-dimensional aircraft cabin as examples of enclosed spaces, the two methods can identify contaminant source locations and strengths in the cabins if the sensors are placed in the downstream location of the sources. The QR method performed slightly better than the PR method but with a longer computing time. PRACTICAL IMPLICATIONS The paper presents a method that can be used to find a gaseous contaminant source location and determine its strength in enclosed spaces with the data of contaminant concentration measured by one sensor. The method can be a very useful tool to find where, what, and how the contamination has happened. The method is also useful for optimally placing sensors in enclosed spaces. The results can be applied to develop appropriate measures to protect occupants in enclosed environments from infectious diseases or chemical/biological warfare agents released by a terrorist.


title: Subgenomic RNA synthesis directed by a synthetic defective interfering RNA of mouse hepatitis virus: a study of coronavirus transcription initiation.

text: We have used a full-length cDNA clone of a mouse hepatitis virus strain A59 defective interfering (DI) RNA, pMIDI-C, and cassette mutagenesis to study the mechanism of coronavirus subgenomic mRNA synthesis. Promoter sequences closely resembling those of subgenomic mRNAs 3 and 7 were inserted into MIDI-C. Both subgenomic RNA promoters gave rise to the synthesis of a subgenomic DI RNA in virus-infected and DI RNA-transfected cells. From a mutagenic analysis of the promoters we concluded the following. (i) The extent of base pairing between the leader RNA and the intergenic promoter sequence does not control subgenomic RNA abundance. (ii) Promoter recognition does not rely on base pairing only. Presumably, transcription initiation requires recognition of the promoter sequence by the transcriptase. (iii) Fusion of leader and body sequences takes place at multiple--possibly random--sites within the intergenic promoter sequence. A model is presented in which, prior to elongation, the leader RNA is trimmed by a processive 3'-->5' nuclease.


title: Highlights from the 13th European Congress of Clinical Microbiology and Infectious Diseases in Glasgow, Scotland, May 10-13, 2003. The complex world of infectious diseases.

text: At the 13th European Congress of Clinical Microbiology and Infectious Diseases, held in Glasgow, Scotland, May 10-13, 2003, the latest developments in clinical microbiology and the treatment of infectious diseases were presented alongside recent progress on molecular aspects of diagnosis and emerging patterns of infection. Around 5,000 delegates from more than 80 countries attended the congress, which saw the presentation of more than 400 oral communications and 1,700 posters. In addition to a historical session looking at Scotland's own contribution to the control of infectious diseases, the meeting involved up to six parallel sessions a day, looking at all the major aspects of infectious diseases, treatment, surveillance, epidemiology and drug pharmacodynamics and pharmacokinetics. The organizers also organized a Late Breaker symposium on severe acute respiratory syndrome. The topics likely to be of most interest to Drug News and Perspectives readers are described here.


title: [Initial division of the left renal vein before dissection of left renal vein occluded by intracaval tumor thrombus].

text: Between November 2008 and March 2010, we performed initial division of the left renal vein occluded by the tumor thrombus in six cases of left renal cancer at Toranomon Hospital. The left renal vein was completely occluded by the tumor thrombus in all cases. In order to ligate the left renal artery first behind the dilated left renal vein, we must dissect the left kidney with arterial blood flow. Massive bleeding from the numerous engorged collateral veins around the left kidney is inevitable. Furthermore, access to the left renal artery is difficult because of the large tumor. We therefore initially divided the left renal vein without arterial blood flow followed by division of the left renal artery. After nephrectomy by dissecting the tumor without blood flow we extirpated the intracaval tumor thrombus. The median time of the operation was 7 hours 35 minutes and the median amount of blood loss was 2,869 ml. The tumor stage was pT3b in four cases and pT3c in two cases. No complications were observed during and after surgery except for one case of lymphocele and another case of chylous ascites. The initial division of the left renal vein is considered to be a useful surgical approach in left renal cancer with occluded left renal vein, especially when the tumor is large.


title: Mathematical modeling of subgenomic hepatitis C virus replication in Huh-7 cells.

text: Cell-based hepatitis C virus (HCV) replicon systems have provided a means for understanding HCV replication mechanisms and for testing new antiviral agents. We describe here a mathematical model of HCV replication that assumes that the translation of the HCV polyprotein occurs in the cytoplasm, that HCV RNA synthesis occurs in vesicular-membrane structures, and that the strategy of replication involves a double-stranded RNA intermediate. Our results shed light on the intracellular dynamics of subgenomic HCV RNA replication from transfection to steady state within Huh-7 cells. We predict the following: (i) about 6 x 10(3) ribosomes are involved in generating millions of HCV NS5B-polymerase molecules in a Huh-7 cell, (ii) the observed 10:1 asymmetry of plus- to minus-strand RNA levels can be explained by a higher-affinity (200-fold) interaction of HCV NS5B polymerase-containing replication complexes with HCV minus-strand RNA over HCV plus-strand RNA in order to initiate synthesis, (iii) the latter higher affinity can also account for the observed approximately 6:1 plus-strand/minus-strand ratio in vesicular-membrane structures, and (iv) the introduction of higher numbers of HCV plus-strand RNA by transfection leads to faster attainment of steady-state but does not change the steady-state HCV RNA level. Fully permissive HCV replication systems have been developed, and the model presented here is a first step toward building a comprehensive model for complete HCV replication. Moreover, the model can serve as an important tool in understanding HCV replication mechanisms and should prove useful in designing and evaluating new antivirals against HCV.


title: [Respiratory complications of sickle cell anemia in children: the acute chest syndrome].

text: The acute chest syndrome (ACS) is one of the most frequent complications of sickle cell disease. It affects mostly young children and counts for one quarter of mortality in the young sickle cell disease (SCD) population. This retrospective study evaluates the impact of ACS among hospitalizations for other complications of SCD in patients at the University Childrens' Hospital Reine Fabiola (Brussels, Belgium) in order to isolate clinical conditions associated with a high risk of ACS development. The medical records of all SCD patients aged up to 18 years admitted for all SCD related acute complications over a period of 13 month have been reviewed. Two patient groups have been formed based on the presence of an ACS within the study period. Epidemiologic data, medical history, the clinical presentation at admission but also blood counts in steady state, at admission and along the hospital stay were compared for a total of 96 hospital stays. There is no difference for age or hemoglobin phenotype between the two major patient groups. Male sex and having had a previous ACS episode in the past were significantly more important in the group of patients hospitalized for ACS. Thoracic pain in an SCD patient who doesn't show typical ACS symptoms should be interpreted as a risk factor for ACS. In conclusion, male sex, medical history of at least one ACS and thoracic pain at hospital admission are associated with high risk of developing ACS.


title: Cancer-specific viruses and the development of ONYX-015.

text: Viruses can be engineered to replicate in cancer cells selectively. This can be achieved using regulatory elements with tumor-selectivity, or using deletions of viral genes that are essential in normal cells but dispensable in tumor cells. The latter approach has been used to make viruses that depend on loss of RB or loss of p53. However, redundancy of function of viral proteins and cellular pathways has complicated this approach and required further viral engineering or a better understanding of cellular pathways to increase effectiveness. In spite of these complicating factors, ONYX-015, a prototype of this new class of therapeutic agents, has undergone extensive testing in the clinic, and has proven safe with promising signs of efficacy. Here, I summarize issues relating to selectivity of this agent and its clinical potential. Based on clinical data and new basic discoveries, several approaches are suggested to improve the efficacy of this agent in the clinic.


Prepare for Post-COVID-Pandemic Polio Problems.


Use of chaperones by general practitioners.


Evidence against rapid emergence of praziquantel resistance in Schistosoma haematobium, Kenya.


docid: gsssbiqm

title: Sensitive and specific monoclonal antibody-based capture enzyme immunoassay for detection of nucleocapsid antigen in sera from patients with severe acute respiratory syndrome.

text: A rapid antigen test for the diagnosis of severe acute respiratory syndrome (SARS) is essential for control of this disease at the point of management. The nucleocapsid (N) protein of SARS-associated coronavirus (SARS-CoV) is abundantly expressed in infected-cell culture filtrate as demonstrable by Western blotting using convalescent-phase sera from patients with SARS. We used monoclonal antibodies specifically directed against N protein to establish a sensitive antigen capture sandwich enzyme-linked immunosorbent assay (ELISA) for the detection of SARS-CoV. The assay employed a mixture of three monoclonal antibodies for capture and rabbit polyclonal antibodies for detection of serum antigen in 32 cases of clinically probable SARS as defined by the World Health Organization during the epidemic in Guangzhou, China. Recombinant N protein was used as a standard to establish a detection sensitivity of approximated 50 pg/ml. The linear range of detection in clinical specimens was from 100 pg/ml to 3.2 ng/ml. Using a panel of sera collected at different points in time, the amount of circulating N antigen was found to peak 6 to 10 days after the onset of symptoms. The sensitivity of the assay was 84.6% in 13 serologically confirmed SARS patients with blood taken during the first 10 days after the onset of symptoms (11 of 13). The specificity of the assay was 98.5% in 1,272 healthy individuals (1,253 of 1,272). There was no cross-reaction with other human and animal coronaviruses in this assay. In conclusion, a sensitive and quantitative antigen capture ELISA was established for the early diagnosis and disease monitoring of SARS-CoV infection.


title: First experimental evidence of recombination in infectious bronchitis virus. Recombination in IBV.

text: A high frequency of recombination has been shown to occur during replication of the coronavirus mouse hepatitis virus (MHV) in vitro as well as in vivo. Although sequencing of field strains of coronavirus infectious bronchitis virus (IBV) has indicated that IBV strains also undergo recombination, there has been no experimental evidence to support this deduction. To investigate whether recombination occurs in IBV, embryonated eggs were coinfected with IBV-Beaudette and IBV-M41. Potential recombinants were detected by strain-specific polymerase chain reaction (PCR) amplifications, using oligonucleotides corresponding to regions in the 3' end of the genome. Sequencing of the PCR products confirmed that a number of recombinations had occurred between the two strains.


docid: jsjqfwcz

title: Early evolution and the origin of eukaryotes.

text: Our understanding of evolutionary relationships in the eukaryotic world has been revolutionized by molecular systematics. Phylogenies based upon comparisons of rRNAs define five major eukaryotic assemblages plus a series of paraphyletic protist lineages. Comparison of conserved genes that were duplicated prior to the divergence of eubacteria, archaebacteria, and eukaryotes, positions the root of the universal tree within the eubacterial line of descent. In this review a novel model is presented which uses the rRNA and protein based phylogenies to describe the evolutionary origins of eukaryotes.


Neurovirulence for mice of soluble receptor-resistant mutants of murine coronavirus JHMV.


title: Crystal structure of the severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein dimerization domain reveals evolutionary linkage between corona- and arteriviridae.

text: The causative agent of severe acute respiratory syndrome (SARS) is the SARS-associated coronavirus, SARS-CoV. The nucleocapsid (N) protein plays an essential role in SARS-CoV genome packaging and virion assembly. We have previously shown that SARS-CoV N protein forms a dimer in solution through its C-terminal domain. In this study, the crystal structure of the dimerization domain, consisting of residues 270-370, is determined to 1.75A resolution. The structure shows a dimer with extensive interactions between the two subunits, suggesting that the dimeric form of the N protein is the functional unit in vivo. Although lacking significant sequence similarity, the dimerization domain of SARS-CoV N protein has a fold similar to that of the nucleocapsid protein of the porcine reproductive and respiratory syndrome virus. This finding provides structural evidence of the evolutionary link between Coronaviridae and Arteriviridae, suggesting that the N proteins of both viruses have a common origin.


title: Swollen-head syndrome in broiler chickens.

text: Swollen-head syndrome is a disease seen in broiler chickens between 4 and 6 weeks of age in Southern Africa. It appears to be caused by a mixed coronavirus and Escherichia coli infection. The coronavirus appears to be of a hitherto unrecorded serotype. The disease is controlled by an attenuated live-virus vaccine and antibacterial medication.


title: A Qualitative Evaluation of Language Models on Automatic Question-Answering for COVID-19.

text: COVID-19 has resulted in an ongoing pandemic and as of 12 June 2020, has caused more than 7.4 million cases and over 418,000 deaths. The highly dynamic and rapidly evolving situation with COVID-19 has made it difficult to access accurate, on-demand information regarding the disease. Online communities, forums, and social media provide potential venues to search for relevant questions and answers, or post questions and seek answers from other members. However, due to the nature of such sites, there are always a limited number of relevant questions and responses to search from, and posted questions are rarely answered immediately. With the advancements in the field of natural language processing, particularly in the domain of language models, it has become possible to design chatbots that can automatically answer consumer questions. However, such models are rarely applied and evaluated in the healthcare domain, to meet the information needs with accurate and up-to-date healthcare data. In this paper, we propose to apply a language model for automatically answering questions related to COVID-19 and qualitatively evaluate the generated responses. We utilized the GPT-2 language model and applied transfer learning to retrain it on the COVID-19 Open Research Dataset (CORD-19) corpus. In order to improve the quality of the generated responses, we applied 4 different approaches, namely tf-idf, BERT, BioBERT, and USE to filter and retain relevant sentences in the responses. In the performance evaluation step, we asked two medical experts to rate the responses. We found that BERT and BioBERT, on average, outperform both tf-idf and USE in relevance-based sentence filtering tasks. Additionally, based on the chatbot, we created a user-friendly interactive web application to be hosted online.


title: Why examining the desirability of health technology matters.

text: Although technology is ubiquitous in healthcare, its impact on people's perceptions and lives is poorly understood. Fresh insights are required to meet current and future technology-related policy challenges. Keeping a population healthy requires considering not only technologies that are used in clinical settings (diagnostic, therapeutic, palliative), but also those used in the community (home care, self-care, technical aids) and those that affect health more broadly (health promotion technologies, occupational health technologies). At the policy making level, understanding the desirability of health technology may prove to be more important than simply appraising its affordability.


The acute respiratory distress syndrome.


title: Progress in computational approach to drug development against SARS.

text: Since the outbreak of SARS (severe acute respiratory syndrome) in November 2002 in Southern China's Guangdong Province, considerable progress has been made in the development of drugs for SARS therapy. The present mini review is focused on the area of computer-aided drug discovery, i.e., the advances achieved mainly from the approaches of structural bioinformatics, pharmacophore modeling, molecular docking, peptide-cleavage site prediction, and other computational means. It is highlighted that the compounds C(28)H(34)O(4)N(7)Cl, C(21)H(36(O)5)N(6) and C(21)H(36)O(5)N(6) (Wei et al., Amino Acids, 2006, 31: 73-80), as well as KZ7088 (Chou et al. Biochem. Biophys. Res. Commun., 2003, 308: 148-151), a derivative of AG7088, might be the promising candidates for further investigation, and that the octapeptides ATLQAIAS and ATLQAENV, as well as AVLQSGFR, might be converted to effective inhibitors against the SARS enzyme. Meanwhile, how to modify these octapeptides based on the "distorted key" theory to make them become potent inhibitors is explicitly elucidated. Finally, a brief introduction is given for how to use computer-generated graphs to rapidly diagnose SARS coronavirus.


title: Diagnosis of Babesia caballi infections in horses by enzyme-linked immunosorbent assay (ELISA) and western blot.

text: From Babesia caballi in vitro cultures a preparation of 100% infected erythrocytes was obtained. From this, B. caballi antigens were extracted with the detergent 3-[(3-Cholamidopropyl)-dimethylammonio]-1-propane-sulfonate (CHAPS) and used as ELISA antigens. A control antigen of normal erythrocytes from the same donor horse was prepared in an identical manner. The ELISA and Western blot were validated by testing of sera from horses experimentally infected with B. caballi or B. equi or not infected with Babesia spp. ELISA and Western blot results were compared with those obtained by the immunofluorescence antibody test (IFAT) and complement fixation test (CFT). The sensitivity of the ELISA of 98.3% obtained for sera from day 14 after infection was superior to the Western blot (94.9%), the IFAT (96.6%) and the CFT (28.8%). No positive results were obtained in the ELISA and Western blot with 106 sera from horses not infected with Babesia spp. resulting in a calculated specificity of 100% for both tests. Cross reactions of B. equi-positive sera did occur to a larger extent in the ELISA (20%) than in the IFAT (4%). No cross reactions were observed with the Western blot and the CFT. The higher sensitivity of the ELISA was also demonstrated by testing of 132 field sera: more positive results were obtained by ELISA (112) as compared to IFAT (92) or CFT (41). The validity of these results was confirmed by testing of sera by Western blot. The ELISA as the most sensitive test provides the best method for the identification of carrier horses to prevent the introduction into non-endemic areas (export testing).(ABSTRACT TRUNCATED AT 250 WORDS)


title: The effect of antioxidant supplementation on bacterial translocation after intestinal ischemia and reperfusion.

text: The intestine is highly sensitive to ischemia/reperfusion (I/R) injury. Intestinal I/R may cause local tissue injury and disruption of the intestinal mucosal barrier, allowing the passage of viable bacteria and endotoxins from the gastrointestinal lumen to distant organs. This phenomenon, known as bacterial translocation (BT), may lead to systemic disorders with high morbidity and mortality. Oxidative stress mediators such as reactive oxygen species, polymorphonuclear neutrophils and nitric oxide are believed to contribute to the intestinal I/R injury. Many antioxidants have shown protective effects against I/R injury of various organs. The present article provides an overview of studies investigating the effect of antioxidant supplementation on BT after intestinal I/R.


Vet nurse consultations could help financial recovery from Covid-19.


title: Enterotropic mouse hepatitis virus.

text: Mouse hepatitis virus [MHV], the coronavirus of the mouse, is the most common viral pathogen in contemporary laboratory mouse colonies throughout the world. It is highly contagious with variable clinical manifestations. The majority of infections are subclinical, but can still significantly influence biological responses, thus interfering with research, mainly in the field of immunology. MHV has been intensively studied from a number of research perspectives and has become the prototype for studying the molecular biology of coronaviruses. MHV contains a single-stranded, positive-sense RNA genome ranging from 27 to 31 kb, which is divided into seven genes. Virions consist of four to five structural proteins. There are many MHV strains that vary in virulence, organotropism and cell tropism, and are constantly evolving by naturally occurring mutation and recombination. Based on pathogenesis studies MHV strains are usually grouped according to their primary tissue tropism into two biotypes: polytropic and enterotropic. Enterotropic strains of MHV replicate in the intestinal mucosa and only rarely spread to other tissues. No morphological structure of the virion has as yet been identified that is responsible for enterotropism. The course of an MHV infection is dependent on the virus strain and host factors. Generally, MHV causes an acute, self-limiting infection which is inapparent in adult mice. Neonates are highly susceptible to disease and show high mortality. In an enzootically infected colony, however, they are protected by maternally derived passive immunity. Detection of MHV infections depends on serological screening of colonies. MHV is controlled by culling and rederivation of the affected colony using hysterectomy or embryo transfer or by elimination through cessation of breeding.


title: Laparoscopic right colectomy with transvaginal extraction in a patient with prior pancreaticoduodenectomy.

text: INTRODUCTION Previous complicated abdominal surgeries such as pancreaticoduodenectomy with large abdominal incisions may keep the surgeons away from major laparoscopic procedures. To the best of our knowledge, there is no published study that shows the feasibility of major laparoscopic surgery in a patient with previous pancreaticoduodenectomy. CASE REPORT A 68-year-old female (BMI 27 kg/m2, ASA II), was admitted for anemia. Her medical history included an open pancreaticoduodenectomy four years ago for chronic pancreatitis. She had an abdominal Mercedes incision. Computed tomography and colonoscopy showed a 5-cm cecal mass with a histological diagnosis of adenocarcinoma. We performed a totally laparoscopic right hemicolectomy and intracorporeal ileotransverse anastomosis. The specimen was extracted through the vagina. The operating time was 500 minutes and the blood loss was 400 ml. The patient was uneventfully discharged on postoperative day four. CONCLUSIONS Laparoscopic colon surgery can be feasible and safe despite previous extensive abdominal surgeries such as pancreaticoduodenectomy. Moreover, laparoscopic surgery in these cases can also be completed with intracorporeal anastomosis and specimen extraction through a natural orifice.


docid: hiwtouvd

title: Gene 5 of the avian coronavirus infectious bronchitis virus is not essential for replication.

text: The avian coronavirus Infectious bronchitis virus (IBV), like other coronaviruses, expresses several small nonstructural (ns) proteins in addition to those from gene 1 (replicase) and the structural proteins. These coronavirus ns genes differ both in number and in amino acid similarity between the coronavirus groups but show some concordance within a group or subgroup. The functions and requirements of the small ns gene products remain to be elucidated. With the advent of reverse genetics for coronaviruses, the first steps in elucidating their role can be investigated. We have used our reverse genetics system for IBV (R. Casais, V. Thiel, S. G. Siddell, D. Cavanagh, and P. Britton, J. Virol. 75:12359-12369, 2001) to investigate the requirement of IBV gene 5 for replication in vivo, in ovo, and ex vivo. We produced a series of recombinant viruses, with an isogenic background, in which complete expression of gene 5 products was prevented by the inactivation of gene 5 following scrambling of the transcription-associated sequence, thereby preventing the expression of IBV subgenomic mRNA 5, or scrambling either separately or together of the translation initiation codons for the two gene 5 products. As all of the recombinant viruses replicated very similarly to the wild-type virus, Beau-R, we conclude that the IBV gene 5 products are not essential for IBV replication per se and that they are accessory proteins.


title: Aspirin combined with mechanical measures to prevent venous thromboembolism after total knee arthroplasty: a randomized controlled trial.

text: BACKGROUND Venous thromboembolism (VTE) is an important complication after major orthopedic surgery. Pharmaceutical methods represent the main strategy of VTE prevention. The use of aspirin in VTE prevention is still controversial worldwide, especially in China. The purpose of this study was to evaluate the role of aspirin combined with mechanical measures in the prevention of VTE after total knee arthroplasty (TKA). METHODS Between January 2012 and May 2013 and in accordance with the inclusion criteria, 120 patients undergoing TKA were randomly allocated to two groups. To prevent VTE, patients in group A received aspirin combined with mechanical measures postoperatively, while patients in group B received low-molecular-weight heparin (LMWH) sodium and rivaroxaban sequentially in combination with mechanical measures postoperatively. All surgeries were performed by one surgeon using a posterior-stabilized cemented prosthesis. The two groups were followed up and compared for the incidence of deep vein thrombosis (DVT) by duplex ultrasound scan and clinical VTE events. The adverse events, the blood loss index, and the cost of VTE prevention were also compared. RESULTS DVT was detected in 10 of 60 patients in group A (16.7%, 95% CI: 7.3%-26.1%) compared with 11 of 60 in group B (18.3%, 95% CI: 8.5%-27.8%) (P = 0.500). There is no statistical evidence supporting the inferior effect of aspirin in preventing DVT as compared with the other medications. There were no cases of symptomatic VTE or death during the follow-up period. Area of ecchymosis was lower in group A than in group B, and the differences were statistically significant. Patients in group A had the lower blood loss index as compared with patients in group B. No transfusion cases were found in both groups. The differences were statistically significant. The cost of VTE prevention analysis indicated a cost reduction using aspirin in group A compared with using LMWH and rivaroxaban in group B. CONCLUSION Aspirin combined with mechanical measures had a good effect on prevention of VTE after TKA and resulted in lower cost, less blood loss, and less subcutaneous ecchymosis.


Lessons from the SARS crisis--more relevant than ever.


title: Two genotypes of canine coronavirus simultaneously detected in the fecal samples of dogs with diarrhea.

text: Sixty-nine fecal samples from diarrheic puppies were examined by reverse transcription-PCR assays for the M and the S genes of canine coronaviruses (CCoVs). The isolates in 10 samples were recognized as CCoV type I, and the isolates in 6 samples were recognized as CCoV type II, while isolates of both genotypes were simultaneously detected in 53 samples.


title: Detection of influenza antigen with rapid antibody-based tests after intranasal influenza vaccination (FluMist).

text: Rapid tests for influenza antigen detection are frequently used, but it is not known how receipt of intranasal influenza vaccine affects results of these tests. We tested healthy adults who received either intranasal or intramuscular influenza vaccine. Of the 14 intranasal vaccine recipients, 7 (50%) had a direct fluorescent antibody test (DFA) result and 2 (14%) had an enzyme immunoassay (EIA) result that was positive for influenza antigen within 7 days after vaccination. No subjects had positive EIA results on day 12 or 13 after vaccination. For some intranasal vaccine recipients, rapid influenza-antigen detection tests yield positive results within 1 week after vaccination.


HIV vaccine research a shot in the arm for immunologists.


docid: bdgelrhu

title: Ultrastructural telepathology--remote EM-diagnostic via Internet.

text: New collaboratory opportunities in ultrastructural research and diagnostics are now available on the Internet through the combination of digital image acquisition, remote operation of modern digitally controlled and automated electron microscopes, and the development of software specifically tailored for collaboratory needs. Remote experts can examine samples directly, and unique instruments can be utilized from anywhere. In the case of diagnostic dilemmas, the second-opinion expert is no longer constrained by problems inherent in the interpretation of preselected images. The remote examiner can independently choose the area of interest on the sample as well as select the appropriate magnification for an accurate diagnosis. With these capabilities and together with teleconferencing tools and securely accessible databases on-line, telepathology can provide increased effectiveness and support for diagnostics, research, and teaching in many areas. The authors report their experience with remote electron microscope diagnoses of pathological samples using two different dynamic imaging systems and discuss the main technical issues encountered. It appears that only minor technical issues need to be resolved before ultrastructural telepathology can be promoted for routine use in areas with high-speed Internet access.


NIH response to open letter.


title: Infection of AtT20 murine pituitary tumour cells by mouse hepatitis virus strain A59: virus budding is restricted to the Golgi region.

text: AtT20 cells, a line of murine pituitary tumour cells that secrete adrenocorticotropic hormone (ACTH), have been infected with the coronavirus mouse hepatitis virus strain A59 (MHV-A59). Between 5% and 10% of AtT20 cells are susceptible to the infection. Unlike infections of fibroblastic sac- and 17Cl 1 cells, the infection of AtT20 cells does not lead to cell fusion, despite the production of the fusogenic E2 viral spike glycoprotein. Within infected AtT20 cells the second viral envelope glycoprotein, E1, is located in a perinuclear region; at least until very late in the infection it fails to accumulate to detectable levels in the rough endoplasmic reticulum (RER). By contrast to infection of sac- and 17Cl 1 cells, where the RER is a major site of assembly of progeny virions, in AtT20 cells budding of progeny virions is restricted to the Golgi cisternae, which eventually vesiculate, and peri-Golgi smooth membraned vesicles. Apparently, therefore, the intracellular compartments into which wild-type MHV-A59 buds are determined not by the virus but by the host cells. MHV-A59 infected cultures of AtT20 cells can be serially passaged without loss of the infection or increase in the proportion of infected cells; they become persistently infected carrier cultures. The progeny virus from serially passaged, infected AtT20 cells is apparently wild-type. It infects sac- cells and induces them to form syncitia. Within the sac- syncitia the viral E1 glycoprotein accumulates in the RER and many virions assemble there.


title: Biomarker variation in patients successfully treated with tocilizumab for severe coronavirus disease 2019 (COVID-19): results of a multidisciplinary collaboration.

text: OBJECTIVES Acute respiratory distress syndrome (ARDS) related to SARS-CoV-2 is likely due to a cytokine storm characterised by a major release of pro-inflammatory cytokines, including interleukin-6 (IL-6). Blocking excessive IL-6 production might be the key to the COVID-19-ARDS treatment. Beneficial effects of IL-6 blockade using a humanised anti-IL-6 receptor antibody, tocilizumab (TCZ) were previously reported in patients with COVID-19 related ARDS. The aim of the study was to study the variation over time of several biomarkers, demonstrated to be predictors of poor prognostic, in subjects successfully treated with TCZ for severe COVID-19. METHODS Retrospective analysis of a case series of patients with COVID-19-ARDS, evidenced by RT-PCR and lung CT-scan. Patients with increasing O2 requirements, within the window of opportunity for TCZ treatment (Day 7 to Day 17 after onset of symptoms) were treated with TCZ (2 infusions of 8 mg/kg). Demographic, biological and clinical data were collected from the patients' files. Serum levels of CRP, ferritin, fibrinogen, lymphocytes, platelets, creatinine, D-dimer and liver enzymes were assayed at the time of the first TCZ administration, then every two days for 8 days. RESULTS 40 patients were treated with TCZ. Most of them had several comorbidities, and all had multiple biological abnormalities (lymphopenia, increased CRP, ferritin, fibrinogen, D-dimer, liver enzymes). 30 patients (75%) benefited from TCZ and 10 patients died. In the survivors, following TCZ administration CRP decreased dramatically as early as day 4 (-86.7%, p<0.0001) and returned to normal at day 6. Fibrinogen and lymphocyte count returned to normal values at day 6. Ferritin also decreased significantly. No significant change was observed for D-dimer (p=0.68) and other studied biomarkers (haemoglobin, leucocyte count, AST). CONCLUSIONS In patients with COVID-19 acute respiratory distress syndrome, treatment with TCZ resulted in favourable evolution in 75% of the cases. Biomarkers of inflammation (CRP, ferritin, fibrinogen) decreased dramatically as early as the 4th day after TCZ injection. Lymphopenia, a predictor of poor prognostic, was reversed 6 days after TCZ injection.


title: Antiidiotypic vaccination against murine coronavirus infection.

text: Rabbit polyclonal antiidiotypic antibodies were generated against a neutralizing mAb specific for a conformational epitope on the S glycoprotein of murine hepatitis virus, strain A59 (MHV-A59). These anti-Id were directed predominantly against an Id that was undetectable in rabbit and rat anti-MHV-A59 sera and weakly represented in syngeneic and allogeneic antiviral sera. However, some partial idiotypic sharing was observed between the Id-bearing antibody and a mAb with a similar antigenic site specificity. The anti-Id inhibited the virus-binding and neutralizing activities of the immunizing antibody, demonstrating that they recognize paratope-associated idiotopes. Mice immunized with affinity-purified anti-Id developed MHV-A59-specific antibodies that neutralized viral infectivity to high titers. Moreover, these animals survived an otherwise lethal challenge with viral murine hepatitis virus, unlike control mice immunized with normal rabbit Ig. These results indicate that at least a subpopulation of the polyclonal anti-Id could induce a protective immune response directed toward a biologically important MHV-A59 epitope, and demonstrate the feasibility of antiidiotypic vaccination against a coronavirus infection.


ABC of chronic obstructive pulmonary disease. Acute exacerbations.


title: FELASA recommendations for the health monitoring of mouse, rat, hamster, guinea pig and rabbit colonies in breeding and experimental units.

text: The microbiological quality of experimental animals can critically influence animal welfare and the validity and reproducibility of research data. It is therefore important for breeding and experimental facilities to establish a laboratory animal health monitoring (HM) programme as an integrated part of any quality assurance system. FELASA has published recommendations for the HM of rodent and rabbit colonies in breeding and experimental units (Nicklas et al. Laboratory Animals, 2002), with the intention of harmonizing HM programmes. As stated in the preamble, these recommendations need to be adapted periodically to meet current developments in laboratory animal medicine. Accordingly, previous recommendations have been revised and shall be replaced by the present recommendations. These recommendations are aimed at all breeders and users of laboratory mice, rats, Syrian hamsters, guinea pigs and rabbits as well as diagnostic laboratories. They describe essential aspects of HM, such as the choice of agents, selection of animals and tissues for testing, frequency of sampling, commonly used test methods, interpretation of results and HM reporting. Compared with previous recommendations, more emphasis is put on the role of a person with sufficient understanding of the principles of HM, opportunistic agents, the use of sentinel animals (particularly under conditions of cage-level containment) and the interpretation and reporting of HM results. Relevant agents, testing frequencies and literature references are updated. Supplementary information on specific agents and the number of animals to be monitored and an example of a HM programme description is provided in the appendices.


title: Non-small cell lung cancer, version 2.2013.

text: These NCCN Guidelines Insights focus on the diagnostic evaluation of suspected lung cancer. This topic was the subject of a major update in the 2013 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer. The NCCN Guidelines Insights focus on the major updates in the NCCN Guidelines and discuss the new updates in greater detail.


Companion animals as reservoirs of eaeA+ Escherichia coli.