title: Impact of a Transfusion-free Program on Patients Undergoing Pancreaticoduodenectomy.

text: Patients undergoing pancreaticoduodenectomy (PD) often require transfusion. However, transfusion-related complications and decreased blood donation in Korea encourage the development of new treatment strategies for PD patients. Although transfusion-free (TF) operation is thought to be beneficial, results supporting its beneficial effects are lacking. The aim of our study was to demonstrate the impact on PD patients of a TF program. From December 2003 to April 2013, 80 consecutive patients with periampullary lesions underwent PD performed. These patients were divided into two groups as follows: 39 PD patients in the "before TF program" (Group 1) and 41 PD patients in the "after TF program" (Group 2). Among patients in Group 2, patients who agreed with the TF program were enrolled and proceed with the TF program prospectively. Participants in the TF program had perioperative blood augmentation and intraoperative acute normovolemic hemodilution. The perioperative data were compared with the two groups. The mean preoperative hemoglobin, operative times, and operative blood loss showed no significance between two groups. The mean postoperative hemoglobin was lower in Group 2 (11.7 g/dL vs 10.9 g/dL, P = 0.038). The mean amount of blood transfusion was significantly lower in Group 2. (950.8 mL vs 124.9 mL, P = 0.009). The TF program considerably decreases the amount of perioperative blood transfusion. The overall perioperative course and complication rate in the TF group were not inferior to those in the non-TF group. The TF program appears safe and should be considered in PD patients.


title: Persistence of viral RNA in the central nervous system of mice inoculated with MHV-4.

text: In order to study the role that viral persistence may play in chronic central nervous system (CNS) disease induced by murine coronaviruses, we have used the reverse transcriptase-polymerase chain reaction (RT-PCR) to study viral RNA in the brains of mice after intracerebral inoculation of JHM virus (JHMV or MHV-4). Quantitative RT-PCR showed that JHMV RNA decreased from approximately 2 ng/ug total brain RNA at day 6 post-inoculation (PI) to 0.1 pg/ug total brain RNA at 360 days PI. Double-stranded viral RNA could be detected up to day 20 PI. By the selective use of upstream or downstream primers during the RT step, it was possible to measure negative sense and positive sense JHMV RNA respectively, and we found that there was a marked rise in the ratio of positive to negative sense JHMV RNA after day 13 PI. Analysis of amplified products by dideoxy DNA sequencing showed that the characteristic mutation of our input virus (at position 3340 of gene 3) is maintained to at least day 42 PI. Taken together, these results favor a model of JHMV persistence in vivo in which viral RNA is present as double stranded forms initially and predominantly as single stranded, positive sense forms at late timepoints. Further analysis of this model in quantitative terms may contribute to our understanding of the biological significance of coronavirus persistence in the CNS.


title: Evolution of an emergency department screening questionnaire for severe acute respiratory syndrome.

text: OBJECTIVES To describe the screening tool that was used to screen for severe acute respiratory syndrome (SARS), the three revisions that were made, and the factors that led to these revisions. On March 13, 2003, on receiving notification of an outbreak of atypical pneumonia, nurses from the study emergency department (ED) started screening patients for the disease that became known as SARS. METHODS The ED nurses started with a simple screening tool that was incorporated into triage. The screening tool was later revised into a questionnaire. An outdoor screening station was set up and patients were subsequently screened before triage. After the patients were screened, they were assigned to different risk areas, where triage and treatment were rendered. Two further revisions were made to the questionnaire. RESULTS From March 13 to May 31, 11457 patients were screened. Version One of the screening questionnaire was used to screen 72 patients from March 13 to 17, Version Two screened 93 patients from March 18 to 21, Version Three screened 2909 patients from March 22 to April 8, and Version Four screened 8383 patients from April 9 to May 31. There was a significant (p < 0.05) downward trend in the proportion of admissions. Among those discharged from the ED, 0.28% reattended and were later confirmed to have SARS. CONCLUSIONS The screening tool underwent three major revisions in response to new information. By keeping it relatively simple, user-friendly, and regularly updated, nurses were able to screen patients rapidly. Risk categorization ensured that no cross-infection occurred among patients and that no one contracted SARS in the ED.


title: Collaborative colorectal cancer screening: a successful quality improvement initiative.

text: PROBLEM Low screening and referral rates for colorectal cancer at a primary care clinic suggest the need for alternative methods to identify patients and complete the screening process. DESIGN A review of >5000 medical charts established baseline screening and referral data. After a 3-month trial of a screening protocol, the research team conducted a follow-up medical chart review to determine referral levels. BACKGROUND AND SETTING The clinic is an 8-physician primary care facility in Southlake, Texas, and is one of 36 clinics affiliated with HealthTexas Provider Network. KEY MEASURES FOR IMPROVEMENT The goal was to increase referrals for colorectal cancer to at least 85% among patients aged 50 to 75 years. STRATEGIES FOR IMPROVEMENT The entire staff of the primary care clinic and the gastroenterology office became involved in the referral process. The team used simple tools such as chart stickers to draw attention to patients requiring screening, generation of referral forms that were numbered for follow-up and faxed to the gastroenterologists, and patient educational material on colorectal cancer screening. These tools were designed to overcome specific barriers to successful screening that the team had identified. EFFECTS OF CHANGE Referrals for sigmoidoscopy, colonoscopy, and double-contrast barium enema increased from 47% to 86%. Fecal occult blood testing was arranged for additional patients through the primary care office. Revenues related to colonoscopies increased by about 50% for the gastroenterologist group, the hospital, and the pathology group affiliated with Southlake Family Medicine. LESSONS LEARNED This colorectal cancer screening protocol succeeded in its 3-month trial because it was collaborative, opportunistic, simple, and made good business sense. The protocol is now being implemented at other HealthTexas Provider Network offices.


title: Nucleic-acid-based antiviral agents against positive single-stranded RNA viruses.

text: Positive single-stranded RNA viruses constitute a broad and prevalent group of pathogens that threaten human health and life worldwide. While effective vaccines have been developed for some, such as poliovirus and hepatitis A, others such as coxsackievirus, severe acute respiratory syndrome coronavirus (SARS-CoV) and West Nile virus have no accredited drug treatments. Antisense technologies, which encompass small interfering RNA, antisense oligonucleotides, ribozymes and their chemically modified analogs, involve small sequence-specific nucleic-acid-based molecules that inhibit viral replication at the level of translation. Many antisense oligomers are proven antiviral agents in vitro. In this review, iwe provide an overview of the antiviral antisense field, highlighting specific studies of interest over the past several years, using our experience with coxsackievirus B3 as a reference point. Overall, both the challenges and successes of existing antisense therapies for positive single-stranded RNA viruses can be paralleled to those for other virus groups, and vice versa.


title: Reverse transcriptase polymerase chain reaction-based diagnosis and molecular characterization of a new rat coronavirus strain.

text: BACKGROUND AND PURPOSE Rat coronaviruses (RCV) are highly infectious and spread rapidly through laboratory rat colonies, causing sneezing, nasal and ocular discharges, photophobia, and cervical swelling. Current diagnostic methods include serologic testing and histologic examination. During a recent rat coronavirus outbreak, we tested a rapid, noninvasive method of RCV diagnosis that involved use of reverse transcriptase-polymerase chain reaction (RT-PCR) analysis to detect RCV RNA on cages housing infected rats. METHODS The RT-PCR was used to detect RCV RNA in tissues from infected rats and on cages housing infected rats and to amplify portions of the RCV N, M, and S genes for molecular characterization. RESULTS The RT-PCR detected RCV RNA on cages and in tissues from infected rats. The RCV-NJ N gene is most closely related to the MHV-Y N gene. The M proteins of RCV-NJ and RCV-SDA are 99% homologous, and the six RCV S protein fragments are 97 to 100% homologous. CONCLUSIONS Use of RT-PCR with cage-swab specimens was capable of diagnosing RCV infection in and viral excretion from rats. Additionally, molecular characterization of the N, M, and S genes of RCV-NJ provided baseline information that can be used in performing further epidemiologic studies.


docid: jqvnzofi

title: Prevalence and genetic diversity of coronaviruses in bats from China.

text: Coronaviruses can infect a variety of animals including poultry, livestock, and humans and are currently classified into three groups. The interspecies transmissions of coronaviruses between different hosts form a complex ecosystem of which little is known. The outbreak of severe acute respiratory syndrome (SARS) and the recent identification of new coronaviruses have highlighted the necessity for further investigation of coronavirus ecology, in particular the role of bats and other wild animals. In this study, we sampled bat populations in 15 provinces of China and reveal that approximately 6.5% of the bats, from diverse species distributed throughout the region, harbor coronaviruses. Full genomes of four coronavirues from bats were sequenced and analyzed. Phylogenetic analyses of the spike, envelope, membrane, and nucleoprotein structural proteins and the two conserved replicase domains, putative RNA-dependent RNA polymerase and RNA helicase, revealed that bat coronaviruses cluster in three different groups: group 1, another group that includes all SARS and SARS-like coronaviruses (putative group 4), and an independent bat coronavirus group (putative group 5). Further genetic analyses showed that different species of bats maintain coronaviruses from different groups and that a single bat species from different geographic locations supports similar coronaviruses. Thus, the findings of this study suggest that bats may play an integral role in the ecology and evolution of coronaviruses.


title: Essential veterinary education in zoological and wildlife medicine: a global perspective.

text: The current veterinary curriculum leaves graduates ill-equipped for careers in the field of zoological and wildlife medicine. Further postgraduate training is required to be an effective zoo or wildlife veterinarian. However, whether or not students choose to specialise in this field at a later date, the veterinary curriculum should cover several issues that are related to wildlife and zoo animals, including conservation biology, zoology, behaviour, physiology and conservation medicine. These subjects are essential, as we are preparing students to work in a world in which there is a global trade in wild animals, an increasing number of emerging infectious diseases and numerous environmental threats (habitat fragmentation, climate change) linked to anthropogenic change. Veterinary students should also be exposed to new opportunities to identify field and laboratory tools for the management and possible treatment of diseases in captive and wild populations and ecosystems using both in situ and ex situ approaches to conservation.


title: The impact of the Hand Hygiene New Zealand programme on hand hygiene practices in New Zealand's public hospitals.

text: AIM To detail the progress made by Hand Hygiene New Zealand (HHNZ) since 2011 and also describe the challenges experienced along the way and the factors required for delivery of a successful hand hygiene programme at a national level. METHOD HHNZ is a multimodal culture-change programme based on the WHO '5 moments for hand hygiene' approach. The key components of the programme include clinical leadership, auditing of hand hygiene compliance with thrice yearly reporting of improvement in hand hygiene practice, biannual reporting of the outcome marker, healthcare-associated Staphylococcus aureus bacteraemia (HA-SAB), effective communication with key stakeholders and the use of the front-line ownership (FLO) principles for quality improvement. RESULTS The nationally aggregated hand hygiene compliance has increased from 62% in June 2012 to 81% in March 2016. There has been improvement across all 'moments', all healthcare worker groups and a range of different clinical specialties. The rate of HA-SAB has remained stable. CONCLUSION The HHNZ programme has led to significant improvements in hand hygiene practice in DHBs throughout New Zealand. The principles of FLO are now widely used to drive hand hygiene improvement in New Zealand DHBs.


Temporal regulation of RNA synthesis of bovine coronavirus.


docid: xtadsqke

title: Computed tomography screening for lung cancer: where are we now?

text: Low-dose computed tomography (LDCT) screening has been shown to result in detection of earlier-stage lung cancers, with a 20% reduction in cancer-related deaths. LDCT screening offers significant potential benefits to selected patients; however, many questions remain, including questions about the applicability of lung cancer screening in clinical practice.


title: Genetic, geographical and temporal variation of porcine reproductive and respiratory syndrome virus in Illinois.

text: Porcine reproductive and respiratory syndrome virus (PRRSV) ORF5 gene sequences were generated by RT-PCR from 55 field isolates collected in Illinois and eastern Iowa. Spatial and temporal patterns of genetic variation in the virus were examined on a local geographical scale in order to test the hypothesis that the genetic similarity of PRRSV isolates (measured as their percentage pairwise ORF5 nucleotide similarity) was positively correlated with their geographical proximity. Levels of genetic variability in the Illinois/eastern Iowa PRRSV sample were similar to levels of variability seen across broader geographical regions within North America. The genetic similarity of isolates did not correlate with their geographical distance. These results imply that the movement of PRRSV onto farms does not generally occur via distance-limited processes such as wind or wildlife vectors, but more typically occurs via the long-distance transport of animals or semen. Genetic distances between PRRSV isolates collected from the same farms at different times increased as the time separating the collection events increased. This result implies rapid movement of new genetic types of PRRSV into and out of farms. PRRSV ORF5 displayed a pattern of third-codon-position diversity bias that was not evident in a geographically comparable sample of pseudorabies virus (a swine alphaherpesvirus) gC gene sequences. This result provides evidence that PRRSV ORF5 is experiencing stabilizing selection against structural novelty. Despite high genetic variability at all geographical levels, PRRSV ORF5 nevertheless contained potentially antigenic regions that were invariant at the amino acid level. These regions should make effective vaccine targets if they prove to be immunogenic.


title: Incidence of upper respiratory tract Mycoplasma pneumoniae infections among outpatients in Rhône-Alpes, France, during five successive winter periods.

text: In this prospective study, nasal swab samples from patients with acute respiratory infections were evaluated for the presence of Mycoplasma pneumoniae. This PCR-plus-hybridization-based detection was associated with the detection of other viral agents. During the five winter surveillance periods, 3,897 samples were collected by 75 medical practitioners participating in the Groupe Régional d'Observation de la Grippe surveillance network in Rhône-Alpes (France). M. pneumoniae was detected in 283 samples (7.3%); its rate of detection ranged from 10.1 to 2.0% over the five periods, and it was the second most frequently isolated pathogen during the survey, after influenza A. Three high-prevalence winters were observed, yielding an early winter peak of M. pneumoniae infection which was observed in all age groups. No statistically significant difference was detected between rates of infections in the different age groups, but M. pneumoniae infection was significantly related to lower respiratory tract infection during periods of high prevalence. This study defined the frequency of M. pneumoniae detection from nasal swab specimens in patients with acute respiratory infections, confirming its high prevalence and the presence of large outbreaks due to this pathogen.


docid: lnogjdet

title: Efficacy of isolated colostral IgA, IgG, and IgM(A) to protect neonatal pigs against the coronavirus of transmissible gastroenteritis.

text: To ascertain what class of immunoglobulin (Ig; IgA, IgG, or IgM) is most efficacious in protection, a large quantity of colostrum from sows immunized with virulent transmissible gastroenteritis (TGE) virus was fractionated by chromatographic and gel filtration methods. The isolated IgG, IgA, and IgM(A) had specific virus-neutralizing activities of 1:7.6, 1:342, and 1:302 per milligram of protein, respectively. Each Ig was fed to groups of hysterectomy-derived colostrum-deprived neonatal pigs before and after exposure (challenge) with virulent TGE virus. The 7 pigs fed IgG survived the challenge exposure, but 2 of 7 fed IgA and 1 of 7 fed IgM(A) died of TGE. Three of the survivor pigs that had been fed IgG and 2 of the survivor pigs that had been fed IgA had increased serum antibody titers between 8 and 19 days after challenge exposure, but none of the survivor pigs fed IgM(A) had TGE antibody. In contrast, 12 of 14 virus-control pigs died of TGE and the 2 survivors had antibody conversion. The data show that all 3 Ig classes in immune colostrum will protect neonatal pigs against exposure with virulent TGE virus.


title: Specific binding of host cellular proteins to multiple sites within the 3' end of mouse hepatitis virus genomic RNA.

text: The initial step in mouse hepatitis virus (MHV) RNA replication is the synthesis of negative-strand RNA from a positive-strand genomic RNA template. Our approach to begin studying MHV RNA replication is to identify the cis-acting signals for RNA synthesis and the proteins which recognize these signals at the 3' end of genomic RNA of MHV. To determine whether host cellular and/or viral proteins interact with the 3' end of the coronavirus genome, an RNase T1 protection/gel mobility shift electrophoresis assay was used to examine cytoplasmic extracts from mock- and MHV-JHM-infected 17Cl-1 murine cells for the ability to form complexes with defined regions of the genomic RNA. We demonstrated the specific binding of host cell proteins to multiple sites within the 3' end of MHV-JHM genomic RNA. By using a set of RNA probes with deletions at either the 5' or 3' end or both ends, two distinct binding sites were located. The first protein-binding element was mapped in the 3'-most 42 nucleotides of the genomic RNA [3' (+42) RNA], and the second element was mapped within an 86-nucleotide sequence encompassing nucleotides 171 to 85 from the 3' end of the genome (171-85 RNA). A single potential stem-loop structure is predicted for the 3' (+)42 RNA, and two stem-loop structures are predicted for the 171-85 RNA. Proteins interacting with these two elements were identified by UV-induced covalent cross-linking to labeled RNAs followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. The RNA-protein complex formed with the 3'-most 42 nucleotides contains approximately five host polypeptides, a highly labeled protein of 120 kDa and four minor species with sizes of 103, 81, 70, and 55 kDa. The second protein-binding element, contained within a probe representing nucleotides 487 to 85 from the 3' end of the genome, also appears to bind five host polypeptides, 142, 120, 100, 55, and 33 kDa in size, with the 120-kDa protein being the most abundant. The RNA-protein complexes observed with MHV-infected cells in both RNase protection/gel mobility shift and UV cross-linking assays were identical to those observed with uninfected cells. The possible involvement of the interaction of host proteins with the viral genome during MHV replication is discussed.


title: Genome organization and reverse genetic analysis of a type I feline coronavirus.

text: In this study we report the complete sequence and genome organization of the serotype I feline coronavirus (FCoV) strain Black. Furthermore, a reverse genetic system was established for this FCoV strain by cloning a full-length cDNA copy into vaccinia virus. This clone served as basis for the generation of recombinant FCoV (recFCoV) that was shown to bear the same features in vitro as the parental FCoV. Using this system, accessory 3abc genes in the FCoV genome were replaced by green fluorescent protein (recFCoV-GFP) and Renilla luciferase genes (recFCoV-RL). In addition, we showed that feline CD14(+) blood monocytes and dendritic cells can be easily detected after infection with recFCoV-GFP. Thus, our established reverse genetic system provides a suitable tool to study the molecular biology of serotype I FCoV.


title: American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee.

text: OBJECTIVE To update the American College of Rheumatology (ACR) 2000 recommendations for hip and knee osteoarthritis (OA) and develop new recommendations for hand OA. METHODS A list of pharmacologic and nonpharmacologic modalities commonly used to manage knee, hip, and hand OA as well as clinical scenarios representing patients with symptomatic hand, hip, and knee OA were generated. Systematic evidence-based literature reviews were conducted by a working group at the Institute of Population Health, University of Ottawa, and updated by ACR staff to include additions to bibliographic databases through December 31, 2010. The Grading of Recommendations Assessment, Development and Evaluation approach, a formal process to rate scientific evidence and to develop recommendations that are as evidence based as possible, was used by a Technical Expert Panel comprised of various stakeholders to formulate the recommendations for the use of nonpharmacologic and pharmacologic modalities for OA of the hand, hip, and knee. RESULTS Both “strong” and “conditional” recommendations were made for OA management. Modalities conditionally recommended for the management of hand OA include instruction in joint protection techniques, provision of assistive devices, use of thermal modalities and trapeziometacarpal joint splints, and use of oral and topical nonsteroidal antiinflammatory drugs (NSAIDs), tramadol, and topical capsaicin. Nonpharmacologic modalities strongly recommended for the management of knee OA were aerobic, aquatic, and/or resistance exercises as well as weight loss for overweight patients. Nonpharmacologic modalities conditionally recommended for knee OA included medial wedge insoles for valgus knee OA, subtalar strapped lateral insoles for varus knee OA, medially directed patellar taping, manual therapy, walking aids, thermal agents, tai chi, self management programs, and psychosocial interventions. Pharmacologic modalities conditionally recommended for the initial management of patients with knee OA included acetaminophen, oral and topical NSAIDs, tramadol, and intraarticular corticosteroid injections; intraarticular hyaluronate injections, duloxetine, and opioids were conditionally recommended in patients who had an inadequate response to initial therapy. Opioid analgesics were strongly recommended in patients who were either not willing to undergo or had contraindications for total joint arthroplasty after having failed medical therapy. Recommendations for hip OA were similar to those for the management of knee OA. CONCLUSION These recommendations are based on the consensus judgment of clinical experts from a wide range of disciplines, informed by available evidence, balancing the benefits and harms of both nonpharmacologic and pharmacologic modalities, and incorporating their preferences and values. It is hoped that these recommendations will be utilized by health care providers involved in the management of patients with OA.


title: The avian coronavirus infectious bronchitis virus undergoes direct low-pH-dependent fusion activation during entry into host cells.

text: Coronaviruses are the causative agents of respiratory disease in humans and animals, including severe acute respiratory syndrome. Fusion of coronaviruses is generally thought to occur at neutral pH, although there is also evidence for a role of acidic endosomes during entry of a variety of coronaviruses. Therefore, the molecular basis of coronavirus fusion during entry into host cells remains incompletely defined. Here, we examined coronavirus-cell fusion and entry employing the avian coronavirus infectious bronchitis virus (IBV). Virus entry into cells was inhibited by acidotropic bases and by other inhibitors of pH-dependent endocytosis. We carried out fluorescence-dequenching fusion assays of R18-labeled virions and show that for IBV, coronavirus-cell fusion occurs in a low-pH-dependent manner, with a half-maximal rate of fusion occurring at pH 5.5. Fusion was reduced, but still occurred, at lower temperatures (20 degrees C). We observed no effect of inhibitors of endosomal proteases on the fusion event. These data are the first direct measure of virus-cell fusion for any coronavirus and demonstrate that the coronavirus IBV employs a direct, low-pH-dependent virus-cell fusion activation reaction. We further show that IBV was not inactivated, and fusion was unaffected, by prior exposure to pH 5.0 buffer. Virions also showed evidence of reversible conformational changes in their surface proteins, indicating that aspects of the fusion reaction may be reversible in nature.


title: Assessing the quality of a web-based learning system for nurses.

text: Continuing professional education is essential for nurses to update their clinical skills and knowledge to meet the complex demands of current patient care. Compared to traditional in-class continuing education, a web-based learning system is efficient for nurses with a three shift-working schedule and is timely to deliver knowledge about newly emerging epidemics such as Severe Acute Respiratory Syndrome. Many studies reveal the advantages of various web-based learning systems but seldom evaluate them from the perspective of quality. This study develops an instrument to assess the quality of a web-based learning system for nurses' continuing education based on the quality dimensions of a mature information systems success model. The research results show that all indicators of the instrument provide a fit to the quality measurement of a web-based learning system and have high reliability and validity. Based on the research findings, implications and limitations are discussed.


title: Zinc-binding of the cysteine-rich domain encoded in the open reading frame of 1B of the RNA polymerase gene of coronavirus.

text: We cloned and sequenced the second open reading frame of the RNA polymerase gene, ORF1b, of bovine coronavirus. In the region representing nucleotide positions 4919-5677 upstream from the initiation codon of the 32K non-structural protein gene, we identified two putative functional domains. One of these domains contained four leucine residues repeated exactly in every seventh position, and the other domain represented a cluster of cysteine and histidine residues. The DNA sequence representing these domains was cloned and expressed in Escherichia coli as fusion proteins with glutathione S-transferase from Schistosoma japonicum. A high level expression of the cysteine-rich domain was achieved as a fusion protein when the bacterial culture was induced with IPTG. In a solid phase zinc binding assay using the recombinant fusion protein, we found that the protein containing the cysteine-rich domain was able to bind to radioactive zinc in vitro, demonstrating that the polypeptide encoded by the ORF1b of coronavirus is a zinc-binding protein.


title: Profiles of antibody responses against severe acute respiratory syndrome coronavirus recombinant proteins and their potential use as diagnostic markers.

text: A new coronavirus (severe acute respiratory syndrome coronavirus [SARS-CoV]) has been identified to be the etiological agent of severe acute respiratory syndrome. Given the highly contagious and acute nature of the disease, there is an urgent need for the development of diagnostic assays that can detect SARS-CoV infection. For determination of which of the viral proteins encoded by the SARS-CoV genome may be exploited as diagnostic antigens for serological assays, the viral proteins were expressed individually in mammalian and/or bacterial cells and tested for reactivity with sera from SARS-CoV-infected patients by Western blot analysis. A total of 81 sera, including 67 from convalescent patients and seven pairs from two time points of infection, were analyzed, and all showed immunoreactivity towards the nucleocapsid protein (N). Sera from some of the patients also showed immunoreactivity to U274 (59 of 81 [73%]), a protein that is unique to SARS-CoV. In addition, all of the convalescent-phase sera showed immunoreactivity to the spike (S) protein when analyzed by an immunofluorescence method utilizing mammalian cells stably expressing S. However, samples from the acute phase (2 to 9 days after the onset of illness) did not react with S, suggesting that antibodies to N may appear earlier than antibodies to S. Alternatively, this could be due to the difference in the sensitivities of the two methods. The immunoreactivities to these recombinant viral proteins are highly specific, as sera from 100 healthy donors did not react with any of them. These results suggest that recombinant N, S, and U274 proteins may be used as antigens for the development of serological assays for SARS-CoV.


title: Multicenter, Prospective, Longitudinal Study of the Recurrence, Surgical Site Infection, and Quality of Life After Contaminated Ventral Hernia Repair Using Biosynthetic Absorbable Mesh: The COBRA Study.

text: OBJECTIVE The aim of the study was to evaluate biosynthetic absorbable mesh in single-staged contaminated (Centers for Disease Control class II and III) ventral hernia (CVH) repair over 24 months. BACKGROUND CVH has an increased risk of postoperative infection. CVH repair with synthetic or biologic meshes has reported chronic biomaterial infections and high hernia recurrence rates. METHODS Patients with a contaminated or clean-contaminated operative field and a hernia defect at least 9 cm had a biosynthetic mesh (open, sublay, retrorectus, or intraperitoneal) repair with fascial closure (n = 104). Endpoints included overall Kaplan-Meier estimates for hernia recurrence and postoperative wound infection rates at 24 months, and the EQ-5D and Short Form 12 Health Survey (SF-12). Analyses were conducted on the intent-to-treat population, and health outcome measures evaluated using paired t tests. RESULTS Patients had a mean age of 58 years, body mass index of 28 kg/m, 77% had contaminated wounds, and 84% completed 24-months follow-up. Concomitant procedures included fistula takedown (n = 24) or removal of infected previously placed mesh (n = 29). Hernia recurrence rate was 17% (n = 16). At the time of CVH repair, intraperitoneal placement of the biosynthetic mesh significantly increased the risk of recurrences (P ≤ 0.04). Surgical site infections (19/104) led to higher risk of recurrence (P < 0.01). Mean 24-month EQ-5D (index and visual analogue) and SF-12 physical component and mental scores improved from baseline (P < 0.05). CONCLUSIONS In this prospective longitudinal study, biosynthetic absorbable mesh showed efficacy in terms of long-term recurrence and quality of life for CVH repair patients and offers an alternative to biologic and permanent synthetic meshes in these complex situations.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0.


Highlights from the 2019 San Antonio Breast Cancer Symposium.


title: Antigenic variability among North American and European strains of porcine reproductive and respiratory syndrome virus as defined by monoclonal antibodies to the matrix protein.

text: Two hybridoma cell lines producing monoclonal antibodies (Mabs) to the 19-kDa matrix (M) protein of porcine reproductive and respiratory syndrome virus (PRRSV) were obtained from BALB/c mice that were immunized with a reference Quebec tissue culture-adapted strain (strain IAF-Klop). The polypeptide specificities of the MAbs were determined by immunoblotting and immunoprecipitation tests with concentrated and purified preparations of the virus and by determining their reactivities with the Escherichia coli-expressed gene products of open reading frames 5 to 7. The two anti-M protein MAbs (MAbs IAFK3 and IAFK6) and another MAb (MAb IAFK8) directed to the 15-kDa nucleocapsid (N) protein were devoid of virus-neutralizing activity. A library of four anti-N protein MAbs (MAbs IAFK8, SDOW17, VO17, and EP147) and two anti-M protein MAbs (MAbs IAFK6 and IAFK3) was used to investigate, by an indirect fluorescent-antibody assay, the antigenic diversity of 15 Canadian PRRSV isolates, in comparison with those of the U.S. ATCC VR2332 attenuated vaccine strain and two reference European (Lelystad and Weybridge) PRRSV strains. The North American and European PRRSV isolates tested shared the epitopes recognized by anti-N protein MAbs IAFK8 and SDOW17, but three distinct patterns could be identified on the basis of their reactivities with the other anti-PRRSV MAbs. No reactivity to the anti-M protein MAbs was observed by either European PRRSV isolate or the attenuated U.S. vaccine strain.


title: The Risk Factors for Refractory Fistula after Esophagectomy with Gastric Tube Reconstruction in Patients with Esophageal Cancer.

text: BACKGROUND/AIMS Anastomotic leakage (AL) after esophagectomy is associated with high rates of postoperative morbidity and mortality. In cases with leakage, a refractory fistula (RF) is sometimes recognized after esophagectomy. The aim of this study was to evaluate the risk factors for RF after esophagectomy with gastric tube reconstruction. METHODS This study enrolled 244 consecutive esophageal cancer patients who had undergone esophagectomy with gastric tube reconstruction. RF was defined as a noncurative anastomotic site-cutaneous fistula that had been present for more than 2 months. We evaluated the risk factors for RF. RESULTS AL occurred in 30 patients (12.3%). There was one mortality case (0.4%) due to mediastinitis caused by AL in the present series. A multivariate analysis revealed that the subcutaneous route was an independent risk factor for AL (OR 4.42, 95% CI 1.42-13.8, p = 0.01), and that the subcutaneous route was an independent risk factor for RF (OR 13.30, 95% CI 2.50-71.30, p = 0.0024). CONCLUSION The results of this retrospective study suggest that subcutaneous route was associated with an increased risk of RF after esophagectomy with gastric tube reconstruction. The preoperative identification of risk factors may contribute to the prevention of postoperative AL and RF.


title: Characterization of the high Mr glycoprotein (gP300) of equine herpesvirus type 1 as a novel glycoprotein with extensive O-linked carbohydrate.

text: The high Mr glycoprotein (gp300) of equine herpesvirus type 1 was found to have an Mr, estimated by SDS-PAGE, of over 400,000 and was confirmed as being a surface glycoprotein by 125I-labelling. In contrast to [3H]glucosamine, gp300 showed very low levels of [3H]glucosamine, gp300 showed very low levels of [3H]mannose incorporation. The Mr of gp300 showed no detectable change upon treatment of purified virus with N-glycanase, and showed only a small change in virus-infected cells treated with tunicamycin. In addition, gp300 failed to bind the lectin concanavalin A. Taken together, these results indicate a lack of N-linked carbohydrate on gp300. The major carbohydrate species were found to be composed primarily of O-linked chains, as indicated by the sensitivity of the protein to monensin, to exoglycanase enzymes specific for sugars present in O-linked chains and to mild alkaline borohydride treatment, which revealed three species of carbohydrate of Mr of greater than 10,000, 2400 and 1100, respectively. Neuraminidase treatment and binding of Helix pomatia lectin indicated the presence of alpha-N-acetylglucosamine and sialic acid as terminal sugars. Immunological cross-reactivity of gp300 with a high Mr protein of equine herpesvirus type 4 was shown and it also exhibited a marked Mr variation in the vaccine strain Rhinomune.


Sequence and structure of the coronavirus peplomer protein.


title: Rabbit cardiomyopathy associated with a virus antigenically related to human coronavirus strain 229E.

text: A new disease of rabbits is described. Following an acute febrile course, animals die or recover by the 11th day postinoculation. The characteristic pathologic finding is multifocal myocardial degeneration and necrosis. The disease can be transmitted by various routes with tissue filtrates or with infectious sera diluted to 10(-6) and passed through 0.1 micron filters. Virus particles with morphologic features characteristic of a coronavirus are present in infectious but not in normal rabbit serums. The antigen(s) in the infectious serums cross-reacts with the 229E and the OC43 strains of human coronavirus. Antigen cross-reacting with the 229E virus is detectable by immunofluorescent staining in frozen sections of heart tissue from sick but not from healthy animals. Animals surviving infection seroconvert to coronavirus specificity, as demonstrated by the presence in convalescent serums of antibody capable of reacting with the 339E virus. Susceptibility to infection has not been demonstrated in mice, hamsters, or guinea pigs, and the virus was not adapted for growth in tissue culture. It is uncertain whether the agent is a natural pathogen of rabbits or a coronavirus contaminant from another species, possibly human. The name rabbit infectious cardiomyopathy is suggested for this disease.


title: A human RNA viral cysteine proteinase that depends upon a unique Zn2+-binding finger connecting the two domains of a papain-like fold .

text: A cysteine proteinase, papain-like proteinase (PL1pro), of the human coronavirus 229E (HCoV) regulates the expression of the replicase polyproteins, pp1a and ppa1ab, by cleavage between Gly111 and Asn112, far upstream of its own catalytic residue Cys1054. In this report, using bioinformatics tools, we predict that, unlike its distant cellular homologues, HCoV PL1pro and its coronaviral relatives have a poorly conserved Zn2+ finger connecting the left and right hand domains of a papain-like fold. Optical emission spectrometry has been used to confirm the presence of Zn2+ in a purified and proteolytically active form of the HCoV PL1pro fused with the Escherichia coli maltose-binding protein. In denaturation/renaturation experiments using the recombinant protein, its activity was shown to be strongly dependent upon Zn2+, which could be partly substituted by Co2+ during renaturation. The reconstituted, Zn2+-containing PL1pro was not sensitive to 1,10-phenanthroline, and the Zn2+-depleted protein was not reactivated by adding Zn2+ after renaturation. Consistent with the proposed essential structural role of Zn2+, PL1pro was selectively inactivated by mutations in the Zn2+ finger, including replacements of any of four conserved Cys residues predicted to co-ordinate Zn2+. The unique domain organization of HCoV PL1pro provides a potential framework for regulatory processes and may be indicative of a nonproteolytic activity of this enzyme.


title: Bilateral hand-assisted laparoscopic nephrectomy in adult polycystic kidney disease patients: a UK centre experience.

text: PURPOSE We report our experience with bilateral hand-assisted laparoscopic nephrectomy in patients with adult polycystic kidney disease. MATERIALS & METHODS Between November 2009 and November 2010, 3 patients with adult polycystic kidney disease underwent bilateral hand-assisted laparoscopic nephrectomy in our institution. Indications for bilateral nephrectomy included recurrent cyst hemorrhage, impaired gastrointestinal function and early satiety due to direct intestinal compression by large polycystic kidneys, and anatomical lack of space for future renal transplantation. We retrospectively reviewed the records of these patients and we are reporting our experience. RESULTS All three patients successfully underwent bilateral hand-assisted laparoscopic nephrectomy with a mean operating time of 208 minutes (range 195 to 220). There were no conversions to open procedure. Blood loss was less than 100 ml in all cases. Mean renal unit size was of 2037 g (range 1798 to 2214). Hospital stay ranged from 10 to 12 days. One patient developed a chest infection postoperatively and suffered from a prolonged ileus. Another patient developed a retroperitoneal hematoma, which was treated conservatively. CONCLUSIONS Bilateral hand-assisted laparoscopic nephrectomy is a feasible and safe procedure in adult polycystic kidney disease patients, which has potential benefits of a shorter hospital stay and reduced morbidity and mortality in comparison to open procedure.


Detection of Cryptosporidium muris oocysts in the faeces of adult dairy cattle in Scotland.


docid: znnlvsrs

title: Infectious diseases. Early indications point to lab infection in new SARS case.


title: [Assessment of health-related quality of life in cured SARS patients].

text: OBJECTIVE To assess the quality of life in cured patients with severe acute respiratory syndrome (SARS). METHODS One hundred and nineteen SARS outpatients, including 64 men and 55 women, with mean age (34.1 +/- 11.4) years and average days of discharge from hospital (28.0 +/- 12.8) days, were assessed by the St George's respiratory questionnaire (SGRQ), and 72 patients with spirometry test. RESULTS The patients had a moderately degree physiological impairment and increased SGRQ score. Scores of all four part of SGRQ correlated significantly with diffuse capacity of the lung for carbon monoxide/pre (DLco%). The correlation coefficients between the activation, impaction, total score, and diffuse capacity of the lung for carbon monoxide/alveolar ventilation/pre (DLco/Va%) were resembled (r = 0.47-0.54, P < 0.01). There was a significant relationship between the score of SGRQ and patients age, and gender. The time leaving hospital only had a significant relationship with the symptom score of SGRQ. CONCLUSIONS SGRQ is a sensitive tool for assessing quality of life in cured SARS patients. The cured SARS patients' quality of life decrease moderately.


Resources during covid-19.


title: Biotech innovations in the prevention of respiratory infectious diseases.

text: Acute respiratory infections place a huge burden on society in terms of disability, premature mortality, and also direct health service costs (drugs prescriptions) and the indirect costs related to lost production. Therefore, prevention of respiratory infections is an important goal for public health interventions. In this context, silver nanoparticles (AgNPs) represent an interesting perspective for research and development by virtue of their favorable antimicrobial activity against many respiratory pathogens. One of the latest innovations in the biotech field discussed in this review is the creation of a biocompatible, biogel-based nasal filter enriched with AgNPs. Compared to traditional personal protective equipment (PPE), this type of nasal filter has the advantage of combining the antibacterial and antiviral activity of AgNPs with the common filtration capacity shared by other PPEs. This dual mechanism means that AgNP-enriched nasal filters serve to reduce the infecting microbial-load and protect the lower airways, without interfering with the normal respiratory capacity (airflow-resistance <5%). Given their antimicrobial characteristics and performance, AgNP-enriched nasal filters can meet many community and occupational currently unmet needs in the prevention of airborne infectious diseases, by ensuring an excellent respiratory-comfort and a continuous day-use.


title: Design and synthesis of hydroxyferroquine derivatives with antimalarial and antiviral activities.

text: Three ferroquine (FQ) derivatives, closely mimicking the antimalarial drug hydroxychloroquine (HCQ), have been prepared. Whereas these organometallic compounds provide the expected reduced cytotoxic effects compared to FQ, they inhibit in vitro growth of Plasmodium falciparum far better than chloroquine (CQ). Moreover, this new class of bioorganometallic compounds exert antiviral effects with some selectivity toward SARS-CoV infection. These new drugs may offer an interesting alternative for Asia where SARS originated and malaria has remained endemic.


Enteric coronaviruses in primates.


title: Effect of soluble porcine aminopeptidase N on antibody production against porcine epidemic diarrhea virus.

text: A few members of coronavirus group I which includes porcine epidemic diarrhea virus (PEDV) use porcine aminopeptidase N (pAPN) as a cellular receptor. Cellular receptors play an important role in virus attachment and entry. However, the low permissiveness of PEDV to APN-expressing porcine cell lines has made it difficult to elucidate the role of pAPN in vitro. The purpose of this study was to prove whether the treatment of soluble pAPN could enhance the antibody production against PEDV in guinea pigs, rabbits and sows. The animals (20 guinea pigs, 8 rabbits and 20 sows) were divided into 4 groups. Group A was injected intramuscularly (IM) with soluble pAPN at one hour before intramuscular infection of PEDV on the same site, group B for IM simultaneous injection of pAPN and PEDV, and group C for IM injection of PEDV only. Group D served as a control of pAPN treatment or PEDV infection. Antibody production against PEDV was compared among groups at regular intervals. The results suggested that pAPN could enhance the antibody production against PEDV in guinea pigs and rabbits which are free of pAPN, however, the effect of pAPN treatment in sows was not clearly elucidated.


title: Trial of early noninvasive ventilation for ALS: A pilot placebo-controlled study.

text: OBJECTIVE To evaluate the use and tolerability of noninvasive positive pressure ventilation (NIV) in patients with amyotrophic lateral sclerosis (ALS) early in their disease by comparing active NIV and sham NIV in patients not yet eligible for NIV use as recommended by practice guidelines. METHODS This was a single-center, prospective, double-blind, randomized, placebo (sham)-controlled pilot trial. Patients with ALS were randomized to receive either sham NIV or active NIV and underwent active surveillance approximately every 3 months until they reached a forced vital capacity (FVC) <50% or required NIV for clinical symptom management. RESULTS In total, 54 participants were randomized. The mean NIV use was 2.0 hours (95% confidence interval [CI] 1.1-3.0) per day in the sham NIV treatment group and 3.3 hours (CI 2.0-4.6) per day in the active NIV group, which did not differ by treatment group (p = 0.347). The majority of sham NIV participants (88%) and active NIV participants (73%) reported only mild or no problem with NIV use. Difference of change in FVC through the treatment period by group (0.44 per month) favored active NIV (p = 0.049). Survival and changes in maximal inspiratory or expiratory pressure did not differ between treatment groups. CONCLUSIONS The efficacy of early NIV in ALS should be tested in randomized, placebo-controlled trials. The trial is registered on clinicaltrials.gov (NCT00580593). CLASSIFICATION OF EVIDENCE This study provides Class II evidence that for patients with ALS, adherence with NIV and sham NIV are similar.


Dengue research in Singapore marking the inaugural ASEAN Dengue Day.


title: Traumatic cervical internal carotid artery pseudoaneurysm in a child refractory to initial endovascular treatment: case report and technical considerations.

text: PURPOSE Optimal management of extracranial carotid artery dissections (eCAD) in pediatric patients is not well documented, and endovascular interventions are rarely reported. METHODS A 10-year-old girl sustained multiple systemic injuries in a motor vehicle accident, including an eCAD with pseudoaneurysm. She initially failed both aspirin and endovascular stenting with progressive enlargement of a traumatic cervical carotid pseudoaneurysm and stenosis. RESULTS Second-stage endovascular stent placement with coiling resulted in successful occlusion of the pseudoaneurysm. At 30-month imaging follow-up, the parent vessel remained patent with no evidence of the pseudoaneurysm. CONCLUSION In the setting of poly-trauma, management of eCAD can be complex especially in the pediatric population. There is little data on the endovascular treatment of eCAD in children. Failed endovascular therapies are extremely rare. Our report supports surveillance imaging as repeat endovascular treatment may be necessary.


docid: aklxnzos

title: A new perspective on the treatment of complicated giant emphysematous bulla A case report.

text: UNLABELLED We report a case of 31 years-old female suffering from complicated giant bulla in the right upper pulmonary lobe. The patient was admitted to our hospital with a radiologic diagnosis of hydro - pneumothorax treated by chest tube in a first time, and later, for prolonged air leaks, by uniportal VATS with a single 4-cm skin incision. We have observed a giant ruptured bulla in right upper lobe, so we have performed bullectomy and mechanical pleurodesis. This case, in our knowledge, represents the first giant bulla resection performed by uniportal VATS. KEY WORDS Giant bulla, Giant bullous emphysema, Uniportal VATS.


title: Irritable bowel syndrome.

text: Conceptually, the irritable bowel syndrome (IBS) has been considered a brain-gut functional disorder, but this paradigm is under serious challenge. There is increasing evidence that organic disease of the gastrointestinal tract can be identified in subsets of patients who fulfil the Rome criteria for IBS. Evidence for subtle inflammatory bowel disease, serotonin dysregulation, bacterial overgrowth and central dysregulation continue to accumulate. The underlying causes of IBS remain to be adequately identified, but postinfectious IBS is a clear-cut entity. Furthermore, a genetic contribution to IBS also seems likely. Diagnosis continues to be based on the symptom profile and the absence of alarm features. A heightened awareness of coeliac disease masquerading as IBS is becoming accepted. Management remains largely based on symptomatic rather than on disease-modifying therapy, but this is likely to change in the near future. Here, recent advances in the pathophysiology and management of IBS are considered.


title: [Clinical diagnosis, treatment and prognosis of elderly SARS patients].

text: OBJECTIVE To discuss the clinical manifestations, therapeutic strategy and prognosis of patients with severe acute respiratory syndrome (SARS) older than 60 years. METHODS Elderly patients diagnosed as SARS in Peking Union Medical College Hospital were compared with younger patients. RESULTS Twenty-four elderly patients and 53 younger patients were analysed. Elderly patients had more coexisting conditions, such as hypertension, diabetes, coronary heart disease, and renal disease than control group (P < 0.05). Rate of respiratory failure in elderly patients was higher than that in control group (P < 0.05). Elderly patients had more respiratory symptoms, such as cough, sputum, and shortness of breath (P < 0.05). Rate of lymphocytopenia and thrombocytopenia in elderly patients was higher than that in control group. All patients were given ribavirin and antibiotics. More patients in elderly group were given 3rd generation cephalosporin and imipenem. Mortality rate in elderly group was higher than that in control group (33.3% vs 3.8%, P < 0.05). Univariate analysis showed that age, respiratory failure, and thrombocytopenia were risk factors of death, but logistic analysis did not find any independent risk factor. CONCLUSIONS Though the elderly patients have a lower morbidity of SARS, they have more coexisting conditions. The therapy of elderly patients is more difficult than that of control group, and the mortality in elderly patients is high.


title: Thin-Section CT 12 Months After the Diagnosis of Severe Acute Respiratory Syndrome in Pediatric Patients.

text: OBJECTIVE The objective of our study was to report the thin-section CT findings 12 months after the diagnosis of severe acute respiratory syndrome (SARS) in pediatric patients who had recovered clinically but had persistent abnormal CT findings 6 months after the diagnosis. The clinical data for these patients were correlated to identify risk factors that might increase the likelihood of the development of CT abnormalities. SUBJECTS AND METHODS The study involved an extended 12-month thin-section CT follow-up of 16 of 47 pediatrics patients with SARS coronavirus-associated pneumonia proven serologically (21 girls and 26 boys; age range, 1.5-17 years; median age, 13.6 years). Patients' clinical information, the extent of radiographic opacification during the acute phase of illness, and conventional pulmonary function test results on follow-up were obtained for correlation. The clinical parameters were compared with other pediatric SARS patients who had normal CT findings at the 6-month follow-up. RESULTS Fifteen patients still had abnormal CT findings 12 months after diagnosis, all of whom were older than 10 years (age range, 10-17 years). In seven patients with previous residual ground-glass opacification at the 6-month follow-up, two showed persistent changes and three had a reticular pattern in the area of the previously detected abnormality, whereas two showed complete resolution. The extent of air trapping remained similar to that at the 6-month follow-up in nine of 11 patients while two showed a slight increase in the same segments. Parenchymal scars remained unchanged from the 6- to 12-month follow-up in all six patients with that finding. None of our patients showed any evidence of bronchiectasis or bronchial wall thickening. Lymphopenia (p = 0.03), extent of radiographic opacification at acute illness (p = 0.047), and duration of use of ribavirin (p = 0.03) were significant risk factors in predicting whether abnormal CT features persisted 12 months after diagnosis. CONCLUSION We found that 32% of the children (15/47) affected with SARS showed thin-section CT abnormalities up to 12 months after diagnosis despite clinical remission and unremarkable pulmonary function assessment. Persistent CT abnormalities are more likely to develop in patients who are older and who present with more severe disease. The CT changes in children with SARS are, however, minor.


title: Investigation of the second wave (phase 2) of severe acute respiratory syndrome (SARS) in Toronto, Canada. What happened?

text: BACKGROUND Severe acute respiratory syndrome (SARS) was introduced to Toronto on 23 February, 2003. The outbreak was believed to be over in early May after two incubation periods had passed with no newly identified cases. However, on 20 May, 2003 a cluster of respiratory illnesses occurred in a rehabilitation facility in Toronto. These cases were later identified as SARS but not until a community hospital in which one of these cases was previously hospitalized (Hospital X) had already experienced nosocomial transmission. This report describes the outbreak investigation of nosocomial transmission of SARS at Hospital X. METHODS An investigation of 90 probable and suspect cases of SARS associated with a hospital outbreak was performed. The investigation included death record reviews, chart reviews, case finding and contact tracing. Nursing cohorts who worked on the specific ward in which nosocomial transmission occurred had work-shift and patient-assignment records reviewed to determine source of infection. RESULTS The greatest number of cases occurred within hospital employees (42.5%) with an average age of 51 years and 69% being female. The mean incubation period for one time exposure patients was 6.3 days (range 4 to 10 days). Twelve (13.8%) of the cases died. Five of seven nurses who cared for a specific SARS patient during this period acquired SARS. Twelve of 17 (70.6%) nursing staff who developed SARS worked with another nursing staff who was symptomatic for SARS. Staff members who worked the evening shift or the morning shift and therefore likely attended a nursing appreciation breakfast were five times more likely to acquire SARS than those who did not attend. INTERPRETATION What was believed to be the end of the Toronto SARS outbreak led the Provincial Operations Centre (POC) to issue a directive allowing a more relaxed use of infection-control precautions during the beginning of Phase 2 of the outbreak. These relaxations of precautions were temporally associated with the nosocomial transmission of SARS to hospital staff, other patients and visitors at Hospital X. As a result of this outbreak significant changes have been made with respect to infection-control practices within Canada.


title: IL-10 enhances CTL-mediated tumor rejection by inhibiting highly suppressive CD4+ T cells and promoting CTL persistence in a murine model of plasmacytoma.

text: Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine that regulates immune responses. IL-10 has also been shown to enhance antitumor CD8+ T-cell responses in tumor models although the underlying mechanisms are not fully understood. In this study, we used a series of genetic mouse models and the mouse plasmacytoma J558 model to investigate this issue. J558 tumors grew significantly faster in IL-10-/- mice than in wild type (WT) mice, but similarly in IL-10 -/- Rag2 -/- and Rag2 -/- mice. Tumors from IL-10 -/- mice contained fewer IFN-γ-producing CD8+ and CD4+ T cells than tumors from WT mice. Strikingly, depletion of total CD4+ T cells, but not CD25+ cells, resulted in tumor eradication in IL-10 -/- mice. Adoptive transfer studies revealed that CD4+ T cells from IL-10 -/- mice exhibited more potent suppression of cytotoxic T lymphocyte (CTL)-mediated tumor rejection than their WT counterparts, and IL-10-deficient tumor-infiltrating CD4+ T cells expressed higher levels of PD-L1 and CTLA-4 inhibitory molecules. Although IL-10-deficient CD8+ T cells are not defective in activation and initial rejection of tumors, adoptive transfer studies using IL-10-deficient P1CTL transgenic T cells that recognize the tumor rejection antigen P1A reveal that IL-10 is required for long-term persistence of CTLs and control of tumor growth. Thus, we have found that IL-10 enhances antitumor CTL responses by inhibiting highly suppressive CD4+ T cells and promoting CTL persistence. These data have important implications for the design of immunotherapy for human cancer.


title: Re-emergence of Chikungunya and other scourges: the role of globalization and climate change.

text: Globalization and climate change are important phenomena in a changing world. To date, only the effect of globalisation on infectious diseases, from vector-borne to respiratory infections, has been well established. The influence of cyclic natural climatic events and local variations in temperature and precipitation has also been recognised; however, there is still no conclusive evidence of an effect of global warming on infectious disease patterns.


Influence of practicable virus inactivation procedures on tests for frequently measured analytes in plasma.


Astroviruses.


title: Infection and atherosclerosis: potential roles of pathogen burden and molecular mimicry.

text: Infection has been implicated as a cause of atherosclerosis since the first half of the 19th century. Over the years, sporadic publications have appeared in the literature reflecting a persistent but relatively low level of research activity in this area. In the last decade, however, publications relating to this topic have increased markedly. And very recently, new epidemiological and mechanistic data relating infection to several different diseases, including atherosclerosis, have appeared, stimulating the emergence of important paradigm shifts in how we think about the causes of chronic disease. The following article reviews some of these newer concepts as they relate to a possible role of infection in atherosclerosis.


title: Ultrasonographic findings in three cows with chronic ragwort (Senecio alpinus) poisoning.

text: Three cows with regwort (Senecio alpinus) poisoning were examined clinically, haematologically and ultrasonographically, and biopsy specimens of the liver were examined histologically. At the end of the study, the cows were euthanased and examined postmortem. The major clinical signs included severely disturbed general demeanour and behaviour, and severe diarrhoea. One cow was photosensitive. The activities of liver enzymes and the concentration of bilirubin were high in all of the cows. In two of the cows, ultrasonographic examination revealed a heavy accumulation of abdominal fluid, which was diagnosed as non-inflammatory ascites. In all the cows, the liver parenchyma was heterogeneous, and cows 1 and 2 had multiple echogenic foci 5 to 10 mm in diameter. In cow 3, the facies diaphragmatica of the liver appeared irregular in outline owing to the presence of nodules which were approximately 5 cm in diameter. The liver was also greatly enlarged and extended almost to the linea alba ventrally and beyond the reticulum cranially. All the cows had portal hypertension and the portal vein was dilated, resulting in oedema of the walls of the gall bladder, the small intestines and the omentum. The diameter of the caudal vena cava was reduced as a result of the impaired hepatic circulation. Histological examination of liver biopsy specimens revealed severe hepatic fibrosis in all the cows.


title: Intermittent inhaled corticosteroids in infants with episodic wheezing.

text: BACKGROUND We hypothesized that asthma is preceded by a stage of recurrent episodes of wheezing during the first years of life and that inhaled corticosteroid therapy during symptomatic episodes in this early phase may delay progression to persistent wheezing. METHODS We assigned one-month-old infants to treatment with two-week courses of inhaled budesonide (400 mug per day) or placebo, initiated after a three-day episode of wheezing, in this single-center, randomized, double-blind, prospective study of three years' duration. The primary outcome was the number of symptom-free days; key secondary outcomes were the time to discontinuation due to persistent wheezing and safety, as evaluated by height and bone mineral density at the end of the study. RESULTS We enrolled 411 infants and randomly assigned 294 to receive budesonide at a first episode of wheezing. The proportion of symptom-free days was 83 percent in the budesonide group and 82 percent in the placebo group (absolute difference, 1 percent; 95 percent confidence interval, -4.8 to 6.9 percent). Twenty-four percent of children in the budesonide group had persistent wheezing, as compared with 21 percent in the placebo group (hazard ratio, 1.22; 95 percent confidence interval, 0.71 to 2.13)--a finding that was unaffected by the presence or absence of atopic dermatitis. The mean duration of the acute episodes was 10 days in both groups and was independent of respiratory viral status. Height and bone mineral density were not affected by treatment. CONCLUSIONS Intermittent inhaled corticosteroid therapy had no effect on the progression from episodic to persistent wheezing and no short-term benefit during episodes of wheezing in the first three years of life. (ClinicalTrials.gov number, NCT00234390.).


Role of dendritic cells in SARS coronavirus infection.


docid: jerctbyl

title: Identification and characterization of a serine-like proteinase of the murine coronavirus MHV-A59.

text: Gene 1 of the murine coronavirus, MHV-A59, encodes approximately 800 kDa of protein products within two overlapping open reading frames (ORFs 1a and 1b). The gene is expressed as a polyprotein that is processed into individual proteins, presumably by virus-encoded proteinases. ORF 1a has been predicted to encode proteins with similarity to viral and cellular proteinases, such as papain, and to the 3C proteinases of the picornaviruses (A. E. Gorbalenya, A. P. Donchenko, V. M. Blinov, and E. V. Koonin, FEBS Lett. 243:103-114, 1989; A. E. Gorbalenya, E. V. Koonin, A. P. Donchenko, and V. M. Blinov, Nucleic Acids Res. 17:4847-4861, 1989). We have cloned into a T7 transcription vector a cDNA fragment containing the putative 3C-like proteinase domain of MHV-A59, along with portions of the flanking hydrophobic domains. The construct was used to express a polypeptide in a combined in vitro transcription-translation system. Major polypeptides with molecular masses of 38 and 33 kDa were detected at early times, whereas polypeptides with molecular masses of 32 and 27 kDa were predominant after 30 to 45 min and appeared to be products of specific proteolysis of larger precursors. Mutations at the putative catalytic histidine and cysteine residues abolished the processing of the 27-kDa protein. Translation products of the pGpro construct were able to cleave the 27-kDa protein in trans from polypeptides expressed from the noncleaving histidine or cysteine mutants. The amino-terminal cleavage of the 27-kDa protein occurred at a glutamine-serine dipeptide as previously predicted. This study provides experimental confirmation that the coronaviruses express an active proteinase within the 3C-like proteinase domain of gene 1 ORF 1a and that this proteinase utilizes at least one canonical QS dipeptide as a cleavage site in vitro.


Potential Impact of Delay in Cancer Screening due to COVID-19.


title: The benefits of automated suturing devices in gynecologic endoscopic surgeries: the Endo Stitch and SILS Stitch.

text: Traditional laparoscopic suturing and knot tying requires a steep learning curve and is often the rate-limiting step in performing advanced laparoscopic gynecologic surgical procedures. It is particularly challenging due to difficulties with tissue handling and needle control while performing the procedure on a two-dimensional screen, oftentimes at unfavorable suturing angles. Automated suturing devices have greatly simplified the process and allow less-experienced surgeons to safely and efficiently perform laparoscopic suturing and knot tying. The Endo Stitch (Covidien, Mansfield, MA) is a 10-mm single-use suturing device that allows placement of multiple suture types during laparoscopic surgery, and simplifies the process of laparoscopic knot tying. The SILS Stitch (Covidien, Mansfield, MA) is based on the same technology as the Endo Stitch with the added advantage of articulation up to 75 degrees and rotation up to 360 degrees. This enables surgeons to operate in tight spaces during advanced laparoscopic procedures, and to reach tissues in their natural anatomical position rather than pulling or manipulating tissue into the suturing device. Newer technologies in laparoscopic surgery, such as the Endo Stitch and SILS Stitch, may allow gynecologic surgeons to expand their surgical repertoire of advanced laparoscopic procedures.


title: [Serological investigation on close contacts to patients with severe acute respiratory syndrome in an SARS outbreak].

text: OBJECTIVE To study the evidence of severe acute respiratory syndrome (SARS) infection among close contacts to SARS patients and the level of sera IgG antibody in SARS cases. METHODS Specific IgG antibody against SARS-CoV in serum samples from contacts to patients, five months before an SARS outbreak in Beijing. Neutralized test, ELISA and immunity adherence test were studied. Samples were collected after clinical onset of patients or close contacts to patients, for 22 - 24 weeks. 19 close contacts and 13 cases were included in the study. RESULTS In close contacts, all tests were negative on three methods. All SARS cases were positive except one by immunity adherence test. The neutralized antibody levels were from 1:16 to 1:203, with medium level of 1:43. CONCLUSION According to our survey, there was no latent infection among close contacts. IgG antibody in sera continued to be at higher levels among SARS cases 22 - 24 weeks after onset.


title: [Analysis on the SARS-CoV genome of PUMC01 isolate].

text: OBJECTIVE To perform variation and phylogenetics analysis on the SARS-CoV genome sequence (PUMC01) isolated in the Peking Union Medical College Hospital. METHODS The cDNA library of SARS-CoV (PUMC01 isolate) was constructed by means of random-priming strategy. Random selected plasmid was sequenced and the genome sequence of SARS-CoV-PUMC01 was assembled by conventional methods (The Genebank Accession No. of SARS-CoV-PUMC01 is AY350750). The variation and phylogenetics analysis were performed by comparing the PUMC01 sequence with other SARS-CoV isolates. RESULTS Ten variation sites were found by comparing PUMC01 isolate with Tor2 and Urbani isolates. In phylogenetic analysis of 18 SARS-CoV isolates, two classes were observed and there is different differential time between these two classes and the different isolates in each class. CONCLUSIONS The evidence of phylogenetic analysis of different SARS-CoV isolates from different region is instructive for understanding the clinical relations between the different isolates and the transmission chain of SARS-CoV.


title: Severe acute respiratory syndrome coronavirus 3a protein is a viral structural protein.

text: The present study showed the association of a severe acute respiratory syndrome coronavirus (SCoV) accessory protein, 3a, with plasma membrane and intracellular SCoV particles in infected cells. 3a protein appeared to undergo posttranslational modifications in infected cells and was incorporated into SCoV particles, establishing that 3a protein was a SCoV structural protein.


title: Biomarkers of sepsis: clinically useful?

text: PURPOSE OF REVIEW The purpose of this review is to indicate recent developments in biomarkers of sepsis and to evaluate their impact on clinical use. According to the 'surviving sepsis campaign,' diagnosis of sepsis and infection is urgent; early and specific treatment is most effective to reduce complications and to decrease mortality. RECENT FINDINGS A variety of biomarkers of sepsis is presently available. The diagnostic spectrum of the various markers, however, is different. Some primarily indicate severity of inflammation (e.g. interleukin-6), others respond to infection, but do not indicate the host response well (endotoxin, lipoprotein binding protein, triggering receptor on myeloid cells). There are new markers with limited clinical experience, for example triggering receptor on myeloid cells or mid-pro atrial natriuretic peptide (Seristra, Brahms AG, Hennigsdorf, Germany). Procalcitonin is a well-established biomarker of sepsis that fulfills several criteria of clinical needs: it responds both to infection and severity of inflammation and thus has an impact on therapy. Recent studies indicate that antibiotic treatment can also be guided by procalcitonin. Further indications, including diagnosis of invasive bacterial infections and diagnosis of sepsis in neonates and children have been reported recently. SUMMARY Recent data and cumulative analyses indicate that biomarkers of sepsis improve diagnosis of sepsis. However, only a few markers have impact on therapy and fulfill the clinical requirements. Procalcitonin is a well-established marker, indicating infection, sepsis, and progression to the more severe stages of the disease. Today, this biomarker should be in the diagnostic portfolio of an intensive care unit or emergency ward.


title: Fatal peritonitis caused by Pasteurella multocida capsular type F in calves.

text: A fatal case of atypical septicemia of pasteurellosis in veal calves is described. The causative organism was identified as a multiresistant Pasteurella multocida capsular type F isolate. The outbreak was characterized by fibrinous peritonitis and mortality, which are hitherto unreported features of P. multocida capsular type F infections.


title: Clinical features of probable severe acute respiratory syndrome in Beijing.

text: AIM To summarize clinical features of probable severe acute respiratory syndrome (SARS) in Beijing. METHODS Retrospective cases involving 801 patients admitted to hospitals in Beijing between March and June 2003, with a diagnosis of probable SARS, moderate type. The series of clinical manifestation, laboratory and radiograph data obtained from 801 cases were analyzed. RESULTS One to three days after the onset of SARS, the major clinical symptoms were fever (in 88.14% of patients), fatigue, headache, myalgia, arthralgia (25-36%), etc. The counts of WBC (in 22.56% of patients) lymphocyte (70.25%) and CD3, CD4, CD8 positive T cells (70%) decreased. From 4-7 d, the unspecific symptoms became weak; however, the rates of low respiratory tract symptoms, such as cough (24.18%), sputum production (14.26%), chest distress (21.04%) and shortness of breath (9.23%) increased, so did the abnormal rates on chest radiograph or CT. The low counts of WBC, lymphocyte and CD3, CD4, CD8 positive T cells touched bottom. From 8 to 16 d, the patients presented progressive cough (29.96%), sputum production (13.09%), chest distress (29.96%) and shortness of breath (35.34%). All patients had infiltrates on chest radiograph or CT, some even with multi-infiltrates. Two weeks later, patients' respiratory symptoms started to alleviate, the infiltrates on the lung began to absorb gradually, the counts of WBC, lymphocyte and CD3, CD4, CD8 positive T cells were restored to normality. CONCLUSION The data reported here provide evidence that the course of SARS could be divided into four stages, namely the initial stage, progressive stage, fastigium and convalescent stage.


title: Antisense morpholino-oligomers directed against the 5' end of the genome inhibit coronavirus proliferation and growth.

text: Conjugation of a peptide related to the human immunodeficiency virus type 1 Tat represents a novel method for delivery of antisense morpholino-oligomers. Conjugated and unconjugated oligomers were tested to determine sequence-specific antiviral efficacy against a member of the Coronaviridae, Mouse hepatitis virus (MHV). Specific antisense activity designed to block translation of the viral replicase polyprotein was first confirmed by reduction of luciferase expression from a target sequence-containing reporter construct in both cell-free and transfected cell culture assays. Peptide-conjugated morpholino-oligomers exhibited low toxicity in DBT astrocytoma cells used for culturing MHV. Oligomer administered at micromolar concentrations was delivered to >80% of cells and inhibited virus titers 10- to 100-fold in a sequence-specific and dose-responsive manner. In addition, targeted viral protein synthesis, plaque diameter, and cytopathic effect were significantly reduced. Inhibition of virus infectivity by peptide-conjugated morpholino was comparable to the antiviral activity of the aminoglycoside hygromycin B used at a concentration fivefold higher than the oligomer. These results suggest that this composition of antisense compound has therapeutic potential for control of coronavirus infection.


Pedagogy in the time of COVID-19.


COVID-19 Response in Mid-Missouri.


title: Long-term Experience of Magnetic Anal Sphincter Augmentation in Patients With Fecal Incontinence.

text: BACKGROUND Magnetic anal sphincter augmentation is a novel technique for the treatment of patients with fecal incontinence. OBJECTIVE The current study reports the long-term effectiveness and safety of this new treatment modality. DESIGN This was a prospective multicenter pilot study. SETTINGS The study was performed at 4 clinical sites in Europe and the United States. PATIENTS The cohort included patients with severe fecal incontinence for ≥6 months who had previously failed conservative therapy and were implanted with a magnetic anal sphincter device between 2008 and 2011. MAIN OUTCOME MEASURES Adverse events, symptom severity, quality of life, and bowel diary data were collected. RESULTS A total of 35 patients (34 women) underwent magnetic anal sphincter augmentation. The median length of follow-up was 5.0 years (range, 0-5.6 years), with 23 patients completing assessment at 5 years. Eight patients underwent a subsequent operation (7 device explantations) because of device failure or complications, 7 of which occurred in the first year. Therapeutic success rates, with patients who underwent device explantation or stoma creation counted as treatment failures, were 63% at year 1, 66% at year 3 and 53% at year 5. In patients who retained their device, the number of incontinent episodes per week and Cleveland Clinic incontinence scores significantly decreased from baseline, and there were significant improvements in all 4 scales of the Fecal Incontinence Quality of Life instrument. There were 30 adverse events reported in 20 patients, most commonly defecatory dysfunction (20%), pain (14%), erosion (11%), and infection (11%). LIMITATIONS This study does not allow for comparison between surgical treatments and involves a limited number of patients. CONCLUSIONS Magnetic anal sphincter augmentation provided excellent outcomes in patients who retained a functioning device at long-term follow-up. Protocols to reduce early complications will be important to improve overall results.


Diagnosis of peripheral arterial disease of the lower limb.


title: Laparoscopic sleeve gastrectomy: an innovative new tool in the battle against the obesity epidemic in Canada.

text: Obesity can be considered to be one of the most important chronic diseases facing Canadians of all ages. Whereas patients with a very high body mass index may have the most to gain from procedures such as Roux-en-Y gastric bypass or biliopancreatic diversion/duodenal switch, the increased risk of postoperative complications often makes them poor surgical candidates. As a result, several "bridging" procedures have been proposed to impart clinically effective weight loss and reduce the risk of complications and improve outcomes in the definitive weight-loss procedure. In this article, we provide a review of the evidence in support of laparoscopic sleeve gastrectomy as an innovative new surgical procedure used as a bridging procedure in patients with severe obesity and discuss new findings for its possible role as a definitive procedure for some individuals with less severe obesity. Finally, we comment on a possible approach to introduce this innovative new procedure to Canadian bariatric centres.


title: Analysis of genetic mutations in the 7a7b open reading frame of coronavirus of cheetahs (Acinonyx jubatus).

text: OBJECTIVE To analyze the 7a7b genes of the feline coronavirus (FCoV) of cheetahs, which are believed to play a role in virulence of this virus. SAMPLE POPULATION Biologic samples collected during a 4-year period from 5 cheetahs at the same institution and at 1 time point from 4 cheetahs at different institutions. PROCEDURES Samples were first screened for FCoV via a reverse transcription-PCR procedure involving primers that encompassed the 3'-untranslated region. Samples that yielded positive assay results were analyzed by use of primers that targeted the 7a7b open reading frames. The nucleotide sequences of the 7a7b amplification products were determined and analyzed. RESULTS In most isolates, substantial deletional mutations in the 7a gene were detected that would result in aberrant or no expression of the 7a product because of altered reading frames. Although the 7b gene was also found to contain mutations, these were primarily point mutations resulting in minor amino acid changes. The coronavirus associated with 1 cheetah with feline infectious peritonitis had intact 7a and 7b genes. CONCLUSIONS AND CLINICAL RELEVANCE The data suggest that mutations arise readily in the 7a region and may remain stable in FCoV of cheetahs. In contrast, an intact 7b gene may be necessary for in vivo virus infection and replication. Persistent infection with FCoV in a cheetah population results in continued virus circulation and may lead to a quasispecies of virus variants.


title: Development and initial validation of a virtual reality haptically augmented surgical knot-tying trainer for the Autosuture ENDOSTITCH instrument.

text: The Autosuture Endostitch device (Covidien, CT) is difficult to learn. In particular, the handle requires the use of a toggle which is unique in this instrument. We have developed a virtual reality trainer for the device that offers the use of the actual instrument handle while creating a visible virtual instrument tip complete with virtual needle and suture on a monitor. This report represents the development and initial validation experiments for the device.


Identification of a trypsin-like serine proteinase domain encoded by ORF 1a of the coronavirus IBV.


title: Characterization of new variants of avian infectious bronchitis virus in Tunisia.

text: Three infectious bronchitis virus (IBV) strains, isolated from suspected Tunisian broiler flocks, were characterized as variant viruses using genotyping and serotyping techniques. They were compared with commonly used vaccine strains, including 793/B, D274, and Massachusetts types. Reverse transcription-PCR-restriction fragment length polymorphism, nucleotide sequencing, and GenBank BLAST database analyses of the hypervariable region of the S1 subunit of the virus spike gene showed that the three isolates, designated TN20/00, TN200/01, and TN335/01, share from 64% to 82% homologies between each other but are very different from the H120 strain, the only infectious bronchitis vaccine used in Tunisia. In addition, they showed from 57% to 78% similarities with the European genotypes, including D274 and 793/B. Phylogenetic data allowed classification of the three Tunisian isolates as new genotypes placed inside the same genetic group as the CR88121 and D274 genotypes but very distant from the Massachusetts genotype. Cross-virus neutralization tests confirmed the genotyping results and showed that both TN200/01 and TN335/01 isolates are serologically related, whereas the TN20/00 is closer to TN335/01 than to TN200/01. Moreover, all three Tunisian isolates are closely related to the European variant serotypes, including the CR88121 and the D274 strains, but none is serologically related to the H120 vaccine strain. These data demonstrated, for the first time in Tunisia, the cocirculation of IBV variant serotypes along with the Massachusetts type, causing severe clinical diseases and high economic losses to the poultry industry.


title: Impact of COVID-19 in spanish urology residents: Recommendations and perspective.

text: The COVID-19 pandemic has seriously disrupted the day-to-day running of hospitals, affecting the activity of all medical and surgical departments. It has also affected urology residents, depriving them of training at their usual workplaces and forcing them to support COVID units. This has implied not only the loss of daily activities, but also the uncertainty of job opportunities for the final year residents. In addition, the cancellation of numerous events such as congresses, exams,or courses has affected the annual planning of the specialty. A review of the current literature on the impact of the COVID-19 pandemic, as well as the de-escalation process, on resident training has been carried out using web search and PubMed. The situation of the residents has been analyzed, both through the information generated by recent literature and by the personal experience of the authors, from different areas: evaluation systems, educational and surgical aspects, as well as healthcare work. As a result of this review, the negative impact of the crisison urology resident training can be observed, especially in the surgical field, but new learning opportunities or new forms of communication with the patient can also be observed. These educational and healthcare resources invite the urology resident in particular, and the medical society in general, to reinvent themselves. The aim of this article is to analyse the training of the urology resident in the de-escalation phase. Similarly, the emerging educational resources during the pandemic are synthesized, inviting the reader, and especially the urology resident, to continue their training and learningin these times of uncertainty.


title: Do age of onset and course of illness define biologically distinct groups within atypical depression?

text: Illness course separates patients with atypical depression into tricyclic responders and nonresponders as does perceptual asymmetry. The authors therefore investigated whether the course-of-illness parameters would define groups within atypical depression differing in brain laterality. Patients with atypical depression were assessed for illness course and brain laterality. Two patient groups were defined, 1 with onset prior to age 20 plus a very chronic course, and a 2nd group having later onset or less chronic illness. Patients reporting early onset of very chronic dysphoria showed significantly less right-ear (left-hemisphere) accuracy and also differed in characteristic perceptual asymmetry when compared to patients with later onset or less chronicity. Course of illness may usefully define more homogeneous depressive subgroups within atypical depression.


Preface: the role of the epidemiologist in injury prevention and control--an unmet challenge.


title: A Prospective, Single-Arm, Single-Center, Case Series to Determine the Feasibility of Safe Skill Transfer for Transabdominal Preperitoneal (TAPP) Repair Utilizing a Hands-On Mentorship Model.

text: OBJECTIVES It is difficult to introduce laparoscopic surgery in institutions with a small number of patients, and surgical training relies heavily on mentors to produce well-trained surgeons. The aim of this study was to determine whether implementation of a hands-on mentorship model could provide safe skill transfer for transabdominal preperitoneal (TAPP) repair. METHODS A trainee who had no experience with TAPP repair underwent operative tutorials until the mentor judged that the trainee could carry out the operation independently. Ten patients who underwent an elective TAPP repair were prospectively enrolled in this study. RESULTS No cases had over 5 mL of bleeding, intraoperative/postoperative complications, or recurrence. There were significant differences in operation times between the first 4 cases and the later 5 cases, except for a bilateral inguinal hernia case. CONCLUSION A prospective, single-arm, single-center, case series showed the feasibility of safe skill transfer for TAPP repair using a hands-on mentorship model.


title: Infectious bronchitis viruses with a novel genomic organization.

text: A number of novel infectious bronchitis viruses (IBVs) were previously identified in commercial poultry in Australia, where they caused significant economic losses. Since there has been only limited characterization of these viruses, we investigated the genomic and phenotypic differences between these novel IBVs and other, classical IBVs. The 3' 7.5 kb of the genomes of 17 Australian IBV strains were sequenced, and growth properties of 6 of the strains were compared. Comparison of sequences of the genes coding for structural and nonstructural proteins revealed the existence of two IBV genotypes: classical and novel. The genomic organization of the classical IBVs was typical of those of other group III coronaviruses: 5'-Pol-S-3a-3b-E-M-5a-5b-N-untranslated region (UTR)-3'. However, the novel IBV genotype lacked either all or most of the genes coding for nonstructural proteins at the 3' end of the genome and had a unique open reading frame, X1. The gene order was either 5'-Pol-S-X1-E-M-N-UTR-3' or 5'-Pol-S-X1-E-M-5b-N-UTR-3'. Phenotypically, novel and classical IBVs also differed; novel IBVs grew at a slower rate and reached lower titers in vitro and in vivo and were markedly less immunogenic in chicks. Although the novel IBVs induced histopathological lesions in the tracheas of infected chicks that were comparable to those induced by classical strains, they did not induce lesions in the kidneys. This study has demonstrated for the first time the existence of a naturally occurring IBV genotype devoid of some of the genes coding for nonstructural proteins and has also indicated that all of the accessory genes are dispensable for the growth of IBV and that such viruses are able to cause clinical disease and economic loss. The phylogenic differences between these novel IBVs and other avian coronaviruses suggest a reservoir host distinct from domestic poultry.


title: Hospital planning for acts of terrorism and other public health emergencies involving children.

text: In today's world the increased potential of terrorist attacks places unique burdens and consequences on health care workers. Hospitals and hospital personnel must now be prepared to react immediately to such events. They must also implement, in advance, policies to protect their own health care personnel while providing care to victims. In this review, we discuss the four major forms of mass casualty terrorism (biological, chemical, nuclear, and thermomechanical) including clinical signs and symptoms for each, the impact on health care personnel, and special considerations for children. We will then outline key principles of hospital preparation with regard to paediatrics in anticipation of such emergencies.


title: Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2.

text: Monocytes recruited to tissues mediate defense against microbes or contribute to inflammatory diseases. Regulation of the number of circulating monocytes thus has implications for disease pathogenesis. However, the mechanisms controlling monocyte emigration from the bone marrow niche where they are generated remain undefined. We demonstrate here that the chemokine receptor CCR2 was required for emigration of Ly6C(hi) monocytes from bone marrow. Ccr2(-/-) mice had fewer circulating Ly6C(hi) monocytes and, after infection with Listeria monocytogenes, accumulated activated monocytes in bone marrow. In blood, Ccr2(-/-) monocytes could traffic to sites of infection, demonstrating that CCR2 is not required for migration from the circulation into tissues. Thus, CCR2-mediated signals in bone marrow determine the frequency of Ly6C(hi) monocytes in the circulation.


title: High-dose antithrombin III in the treatment of severe sepsis in patients with a high risk of death: efficacy and safety.

text: OBJECTIVE To explore if patients with severe sepsis and with a predicted high risk of death (according to the Simplified Acute Physiology Score II) might have a treatment benefit from high-dose antithrombin III. DESIGN Subgroup analysis of a randomized, placebo-controlled, double-blind, prospective phase III study. SETTING Unifactorial and multifactorial reanalysis of prospectively defined populations from the KyberSept trial. PATIENTS We studied 1,008 patients (43.6% of the overall intention-to-treat population, n = 2,314) with a predicted mortality rate of 30-60% at study entry as defined by the Simplified Acute Physiology Score II. INTERVENTIONS Patients were randomized in a 1:1 fashion to receive either high-dose antithrombin III (30,000 IU intravenously over the period of 4 days) or placebo. MEASUREMENTS AND MAIN RESULTS In a Kaplan-Meier analysis of patients with a predicted mortality of 30-60%, the survival time when followed up for 90 days after admission was increased in the high-dose antithrombin III group compared with placebo (p = .04). If heparin was avoided during the 4-day treatment phase with high-dose antithrombin III (n = 140) or placebo (n = 162), the treatment effect appeared to be even more pronounced: 28-day mortality rate, 35.7% vs. 44.4% (risk ratio, 0.804; 95% confidence interval, 0.607-1.064); 56-day mortality rate, 39.9% vs. 52.2% (risk ratio, 0.764; 95% confidence interval, 0.593-0.984); 90-day mortality rate, 42.8% vs. 55.1% (risk ratio, 0.776; 95% confidence interval, 0.614-0.986). Like in the overall population, the percentage with any bleeding was increased in patients receiving high-dose antithrombin III compared with placebo. Survival rates were in favor of high-dose antithrombin III in patients both with and without bleeding complications. CONCLUSIONS Treatment with high-dose antithrombin III may increase survival time up to 90 days in patients with severe sepsis and high risk of death. This benefit may even be stronger when concomitant heparin is avoided.


title: CAUSATIVE AGENTS OF SEVERE COMMUNITY ACQUIRED VIRAL PNEUMONIA AMONG CHILDREN IN EASTERN THAILAND.

text: Pneumonia is a leading cause of morbidity and mortality among infants and young children. The most common causes of pneumonia in children are respiratory viruses. In Thailand, the epidemiology of the viruses causing community-acquired pneumonia (CAP) among children is poorly defined. In this cross sectional study we used nasopharyngeal samples collected from hospitalized children diagnosed with severe CAP in accordance with WHO criteria between June 2013 and May 2014 to determine the causes of infection. The samples were analyzed for respiratory syncytial virus (RSV), parainfluenza viruses (PIV) types 1,2 and 3, adenovirus, rhinovirus, influenza viruses types A and B and coronavirus by polymerase chain reaction (PCR) and reverse transcriptase-polymerase chain reaction (RT-PCR). Of 102 cases of severe CAP, samples were obtained in 91 cases and 48 (52.7%) were positive for respiratory viruses. The most common viruses were RSV (n = 22; 45.8%), rhinovirus (n = 11; 22.9%) and adenovirus (n = 9; 18.7%). Patients were aged 1 month to 4 years 5 months, with a median age of 1 year 1 month. Thirty-seven (77.1%) were male. Asthma was the most common co-morbidity affecting 5 (10.4%) of the 48 cases with an identified virus. The peak prevalence occurred during October (n = 17). All patients required oxygen therapy and 17 (35.4%) required mechanical ventilation. The median length of hospitalization was 11 days. Preterm infants had a significantly higher rate of RSV infection than other respiratory viruses (8 of 21; 38% vs 3 of 27; 11.1%) (p = 0.02). Viruses were most commonly associated with severe CAP among children aged less than 1 year. The peak prevalence occurred during the rainy season. Our findings suggest that young and preterm infants with CAP should be monitored closely due to their high risk for developing serious complications.


title: Mapping of the Tobacco mosaic virus movement protein and coat protein subgenomic RNA promoters in vivo.

text: The Tobacco mosaic virus movement protein (MP) and coat protein (CP) are expressed from 3'-coterminal subgenomic RNAs (sgRNAs). The transcription start site of the MP sgRNA, previously mapped to positions 4838 (Y. Watanabe, T. Meshi, and Y. Okada (1984), FEBS Lett. 173, 247-250) and 4828 (K. Lehto, G. L. Grantham, and W. O. Dawson (1990), Virology 174, 145-157) for the TMV OM and U1 strains, respectively, has been reexamined and mapped to position 4838 for strain U1. Sequences of the MP and CP sgRNA promoters were delineated by deletion analysis. The boundaries for minimal and full MP sgRNA promoter activity were localized between -35 and +10 and -95 and +40, respectively, relative to the transcription start site. The minimal CP sgRNA promoter was mapped between -69 and +12, whereas the boundaries of the fully active promoter were between -157 and +54. Computer analysis predicted two stem-loop structures (SL1 and SL2) upstream of the MP sgRNA transcription start site. Deletion analysis and site-directed mutagenesis suggested that SL1 secondary structure, but not its sequence, was required for MP sgRNA promoter activity, whereas a 39-nt deletion removing most of the SL2 region increased MP sgRNA accumulation fourfold. Computer-predicted folding of the fully active CP sgRNA promoter revealed one long stem-loop structure. Deletion analysis suggested that the upper part of this stem-loop, located upstream of the transcription start site, was essential for transcription and that the lower part of the stem had an enhancing role.


title: SARS-CoV-2 infection virological diagnosis.

text: SARS-CoV-2 infection has to be confirmed by virological diagnosis. Multiple diagnostic tests are available without enough perspective on their reliability. Therefore, it is important to choose the most suitable test according to its sensitivity and specificity but also to the stage of the disease. Currently, the RT-PCR detection of the viral genome in respiratory samples is the most reliable test to confirm the diagnosis of an acute SARS-CoV-2 infection. It has to be done in Class II biological safety laboratory. However, it may lack sensitivity, particularly in the advanced phase of infection, and depends closely on the samples' quality. Rapid PCR by cartridge system reduces response times but is not suitable for laboratories with high throughput of requests. Detection of virus antigens on respiratory samples is a quick and easy to use technique; however it has not good specificity and sensitivity and cannot be used for diagnosis and patient management. The detection of specific antibodies against SARS-CoV-2 is better used for epidemiological analyses. Research should be encouraged to overcome the limits of the currently available diagnostic tests.