title: The human coronavirus 229E superfamily 1 helicase has RNA and DNA duplex-unwinding activities with 5'-to-3' polarity.

text: The human coronavirus 229E replicase gene encodes a protein, p66HEL, that contains a putative zinc finger structure linked to a putative superfamily (SF) 1 helicase. A histidine-tagged form of this protein, HEL, was expressed using baculovirus vectors in insect cells. The purified recombinant protein had in vitro ATPase activity that was strongly stimulated by poly(U), poly(dT), poly(C), and poly(dA), but not by poly(G). The recombinant protein also had both RNA and DNA duplex-unwinding activities with 5'-to-3' polarity. The DNA helicase activity of the enzyme preferentially unwound 5'-oligopyrimidine-tailed, partial-duplex substrates and required a tail length of at least 10 nucleotides for effective unwinding. The combined data suggest that the coronaviral SF1 helicase functionally differs from the previously characterized RNA virus SF2 helicases.


title: Infectious disease survey of lesser prairie chickens in north Texas.

text: Lesser prairie chicken (Tympanuchus pallidicinctus) abundance, like that of most grassland birds, has declined rangewide for decades. Although habitat loss and degradation are likely ultimate causes for this decline, infectious agents, particularly microparasites, could be proximate contributors. No surveys of pathogenic bacteria or viruses have been published for this species. We surveyed 24 free-living lesser prairie chickens from Hemphill County, Texas (USA), for evidence of exposure to Salmonella typhimurium, S. pullorum, Mycoplasma gallisepticum, M. synoviae, Chlamydophila psittaci, and the avian influenza, Newcastle disease, infectious bronchitis, and reticuloendotheliosis viruses. Two of 18, and eight of 17 samples were seropositive for the Massachusetts and Arkansas serotypes of infectious bronchitis virus, respectively. Five of the eight positive individuals were juveniles, two of which were seropositive for both serotypes. All other serologic and genetic tests were negative. Because the ecological significance of these results is unknown, the pathogenesis, transmission, and/or population-level influences of infectious bronchitis and related avian coronaviruses for lesser prairie chickens deserves further study.


title: Rhinovirus and coronavirus infections.

text: Rhinoviruses and coronaviruses cause the majority of common colds and play a part in more serious respiratory illnesses that lead to increased morbidity and mortality. Patients who are infants or elderly, have asthma or chronic obstructive pulmonary disease (COPD), or are immunosuppressed have increased frequency of rhinovirus-related respiratory complications. Newer diagnostic tests such as reverse transcriptase polymerase chain reaction (RT-PCR) have greatly expanded our understanding of the importance of these respiratory viruses. Although there are no currently approved antiviral agents for clinical use, our increased understanding of the virus-host interaction should lead to new intervention strategies.


COVID-19: Lost opportunities and lessons for the future.


title: Surveillance of the emerging enterovirus D68 in Canada: An evaluation.

text: Background In the fall of 2014, in response to outbreaks of an emerging respiratory pathogen enterovirus D68 (EV-D68) which affected mostly children, a rapid time-limited surveillance pilot for hospitalized cases was conducted in seven Canadian jurisdictions. Objective To evaluate whether the goals of the EV-D68 pilot were met and to determine the benefits of and lessons learned from a rapid-response surveillance system for emerging pathogens. Methods An evaluation survey was created and administered via a secure online link. All provinces and territories (PTs) and federal partners involved in the pilot were invited to complete one survey per jurisdiction (N=17). Proportions were calculated for responses to closed-ended questions and recurring themes were identified for open-ended questions. Results Fifty four percent (7/13) of PTs and 50% (2/4) of federal partners completed the survey. All four goals of the pilot were met to some degree. All respondents agreed that there were important benefits to rapid surveillance initiatives for emerging pathogens including the capacity to: better understand the epidemiological and clinical features as well as the public health risk of emerging pathogens (66.7%); inform public health action (66.7%); collaborate and avoid duplication of work (11.1%); test and develop jurisdictional capacity (11.1%); and inform future response efforts (11.1%). Receiving timely case summaries (preferably weekly) was identified as important for 88% of respondents. In terms of lessons learned, more than half of respondents (66.7%) indicated that current processes needed to be improved in order to facilitate rapid surveillance initiatives within and across jurisdictions including the need to develop data-sharing agreements and have pre-existing protocols. Important factors identified for a surveillance data reporting platform included: ease of functionality, data security, jurisdictional control, web-based and flexibility to meet changing surveillance needs. Conclusion Evaluation results from the EV-D68 surveillance pilot will assist with future rapid surveillance initiatives. It is important that lessons learned be addressed prior to the emergence of the next emerging pathogen.


Serological evidence of some bovine viruses in the caribou (Rangifer tarandus caribou) in Quebec.


title: Infection prevention and control measures for acute respiratory infections in healthcare settings: an update.

text: Viruses account for the majority of the acute respiratory tract infections (ARIs) globally with a mortality exceeding 4 million deaths per year. The most commonly encountered viruses, in order of frequency, include influenza, respiratory syncytial virus, parainfluenza and adenovirus. Current evidence suggests that the major mode of transmission of ARls is through large droplets, but transmission through contact (including hand contamination with subsequent self-inoculation) and infectious respiratory aerosols of various sizes and at short range (coined as "opportunistic" airborne transmission) may also occur for some pathogens. Opportunistic airborne transmission may occur when conducting highrisk aerosol generating procedures and airborne precautions will be required in this setting. General infection control measures effective for all respiratory viral infections are reviewed and followed by discussion on some of the common viruses, including severe acute respiratory syndrome (SARS) coronavirus and the recently discovered novel coronavirus.


title: Protease-mediated enhancement of severe acute respiratory syndrome coronavirus infection.

text: A unique coronavirus severe acute respiratory syndrome-coronavirus (SARS-CoV) was revealed to be a causative agent of a life-threatening SARS. Although this virus grows in a variety of tissues that express its receptor, the mechanism of the severe respiratory illness caused by this virus is not well understood. Here, we report a possible mechanism for the extensive damage seen in the major target organs for this disease. A recent study of the cell entry mechanism of SARS-CoV reveals that it takes an endosomal pathway. We found that proteases such as trypsin and thermolysin enabled SARS-CoV adsorbed onto the cell surface to enter cells directly from that site. This finding shows that SARS-CoV has the potential to take two distinct pathways for cell entry, depending on the presence of proteases in the environment. Moreover, the protease-mediated entry facilitated a 100- to 1,000-fold higher efficient infection than did the endosomal pathway used in the absence of proteases. These results suggest that the proteases produced in the lungs by inflammatory cells are responsible for high multiplication of SARS-CoV, which results in severe lung tissue damage. Likewise, elastase, a major protease produced in the lungs during inflammation, also enhanced SARS-CoV infection in cultured cells.


title: Comparing culture and molecular methods for the identification of microorganisms involved in necrotizing soft tissue infections.

text: BACKGROUND Necrotizing soft tissue infections (NSTIs) are a group of infections affecting all soft tissues. NSTI involves necrosis of the afflicted tissue and is potentially life threatening due to major and rapid destruction of tissue, which often leads to septic shock and organ failure. The gold standard for identification of pathogens is culture; however molecular methods for identification of microorganisms may provide a more rapid result and may be able to identify additional microorganisms that are not detected by culture. METHODS In this study, tissue samples (n = 20) obtained after debridement of 10 patients with NSTI were analyzed by standard culture, fluorescence in situ hybridization (FISH) and multiple molecular methods. The molecular methods included analysis of microbial diversity by 1) direct 16S and D2LSU rRNA gene Microseq 2) construction of near full-length 16S rRNA gene clone libraries with subsequent Sanger sequencing for most samples, 3) the Ibis T5000 biosensor and 4) 454-based pyrosequencing. Furthermore, quantitative PCR (qPCR) was used to verify and determine the relative abundance of Streptococcus pyogenes in samples. RESULTS For 70 % of the surgical samples it was possible to identify microorganisms by culture. Some samples did not result in growth (presumably due to administration of antimicrobial therapy prior to sampling). The molecular methods identified microorganisms in 90 % of the samples, and frequently detected additional microorganisms when compared to culture. Although the molecular methods generally gave concordant results, our results indicate that Microseq may misidentify or overlook microorganisms that can be detected by other molecular methods. Half of the patients were found to be infected with S. pyogenes, but several atypical findings were also made including infection by a) Acinetobacter baumannii, b) Streptococcus pneumoniae, and c) fungi, mycoplasma and Fusobacterium necrophorum. CONCLUSION The study emphasizes that many pathogens can be involved in NSTIs, and that no specific "NSTI causing" combination of species exists. This means that clinicians should be prepared to diagnose and treat any combination of microbial pathogens. Some of the tested molecular methods offer a faster turnaround time combined with a high specificity, which makes supplemental use of such methods attractive for identification of microorganisms, especially for fulminant life-threatening infections such as NSTI.


Plaque assay, polypeptide composition and immunochemistry of feline infectious peritonitis virus and feline enteric coronavirus isolates.


title: Methods and protocols for prediction of immunogenic epitopes.

text: T-cell recognition of peptide/major histocompatibility complex (MHC) is a prerequisite for cellular immunity. Recently, there has been an influx of bioinformatics tools to facilitate the identification of T-cell epitopes to specific MHC alleles. This article examines existing computational strategies for the study of peptide/MHC interactions. The most important bioinformatics tools and methods with relevance to the study of peptide/MHC interactions have been reviewed. We have also provided guidelines for predicting antigenic peptides based on the availability of existing experimental data.


title: Extra-articular cartilage affected in collagen-induced, but not pristane-induced, arthritis models.

text: Rheumatoid arthritis (RA) is a chronic inflammatory disease primarily affecting cartilaginous joints but also extra-articular tissues such as the nose and upper respiratory tract. We have investigated extra-articular cartilage involvement in two commonly used animal models for RA, collagen-induced and pristane-induced arthritis, by immunizing rats with different susceptibility to disease (LEW.1 A, LEW.1F and DA rats). We found that nasal and tracheolaryngeal cartilage is affected in LEW.1 A and DA rats to varying degrees in collagen-induced arthritis but not in any strain in the pristane-induced model. Antibodies to matrilin-1, a cartilage-specific protein expressed mainly in tracheolaryngeal and nasal cartilage but not in joints, were positively associated with the presence of inflammation in nasal cartilage. In contrast, no antibody response to matrilin-1 could be detected in pristane-induced arthritis. In addition, nasal vaccination with collagen type II prior to immunization in DA rats significantly decreased the antibody response to matrilin-1 at day 56, but not at earlier time points, indicating a late protective effect on extra-articular cartilage. We conclude that pristane-induced arthritis is a joint-specific model whereas collagen-induced arthritis affect joints as well as extra-articular cartilage. Furthermore, collagen immunization induces an antibody response to matrilin-1.


Voucher specimens for SARS-linked bats.


title: Use of quarantine to prevent transmission of severe acute respiratory syndrome--Taiwan, 2003.

text: On July 5, 2003, Taiwan was removed from the World Health Organization (WHO) list of severe acute respiratory syndrome (SARS)-affected countries. As of July 9, a total of 671 probable cases of SARS had been reported in Taiwan. On February 21, the first identified SARS patient in Taiwan returned from travel to Guangdong Province, mainland China, by way of Hong Kong. Initial efforts to control SARS appeared to be effective; these efforts included isolation of suspect and probable SARS patients, use of personal protective equipment (PPE) for health-care workers (HCWs) and visitors, and quarantine of contacts of known SARS patients. However, beginning in mid-April, unrecognized cases of SARS led to a large nosocomial cluster and subsequent SARS-associated coronavirus transmission to other health-care facilities and community settings. In response to the growing epidemic, additional measures were taken to limit nosocomial and community transmission of SARS, including more widespread use of quarantine. By the end of the epidemic, 131,132 persons had been placed in quarantine, including 50,319 close contacts of SARS patients and 80,813 travelers from WHO-designated SARS-affected areas. This report describes the quarantine measures used in Taiwan and discusses the need for further evaluation of quarantine and other control measures used to prevent SARS.


title: Hypocortisolism in survivors of severe acute respiratory syndrome (SARS).

text: OBJECTIVE Following the severe acute respiratory syndrome (SARS) outbreak, many survivors were observed to suffer from psychosomatic symptoms reminiscent of various endocrine disorders. Hence, we sought to determine the existence of any chronic endocrine sequelae in SARS survivors. DESIGN, PATIENTS, MEASUREMENTS Sixty-one survivors of SARS prospectively recruited were analysed for hormonal derangements 3 months following recovery. Patients with pre-existing endocrine disorders were excluded. Any endocrine abnormalities diagnosed were investigated and treated where indicated up to a year. Serial evaluation facilitated characterization of trends and prognostication of any endocrinological aberrations. RESULTS Twenty-four (39.3%) patients had evidence of hypocortisolism. The hypothalamic-pituitary-adrenal (HPA) axis dysfunction of the majority resolved within a year. Two (3.3%) of the hypocortisolic cohort had transient subclinical thyrotoxicosis. Four (6.7%) were biochemically hypothyroid, being comprised of three with central hypothyroidism and one with primary hypothyroidism. Two of the three with central hypothyroidism had concomitant central hypocortisolism. Eight had subnormal DHEAS levels. CONCLUSIONS These preliminary findings highlight a possible aetiologic role of SARS-associated coronavirus in causing a reversible hypophysitis or direct hypothalamic effect, with the HPA axis affected more frequently than the HPT axis.


From the Centers for Disease Control and Prevention. Updated interim surveillance case definition for severe acute respiratory syndrome (SARS)--United States, April 29, 2003.


title: Door-to-puncture: a practical metric for capturing and enhancing system processes associated with endovascular stroke care, preliminary results from the rapid reperfusion registry.

text: BACKGROUND In 2011, the Brain Attack Coalition proposed door-to-treatment times of 2 hours as a benchmark for patients undergoing intra-arterial therapy (IAT). We designed the Rapid Reperfusion Registry to capture the percentage of stroke patients who meet the target and its impact on outcomes. METHODS AND RESULTS This is a retrospective analysis of anterior circulation patients treated with IAT within 9 hours of symptom onset. Data was collected from December 31, 2011 to December 31, 2012 at 2 centers and from July 1, 2012 to December 31, 2012 at 7 centers. Short “Door-to-Puncture” (D2P) time was hypothesized to be associated with good patient outcomes. A total of 478 patients with a mean age of 68±14 years and median National Institutes of Health Stroke Scale (NIHSS) of 18 (IQR 14 to 21) were analyzed. The median times for IAT delivery were 234 minutes (IQR 163 to 304) for “last known normal-to-groin puncture” time (LKN-to-GP) and 112 minutes (IQR 68 to 176) for D2P time. The overall good outcome rate was 39.7% for the entire cohort. In a multivariable model adjusting for age, NIHSS, hypertension, diabetes, reperfusion status, and symptomatic hemorrhage, both short LKN-to-GP (OR 0.996; 95% CI [0.993 to 0.998]; P<0.001) and short D2P times (OR 0.993, 95% CI [0.990 to 0.996]; P<0.001) were associated with good outcomes. Only 52% of all patients in the registry achieved the targeted D2P time of 2 hours. CONCLUSIONS The time interval of D2P presents a clinically relevant time frame by which system processes can be targeted to streamline the delivery of IAT care nationally. At present, there is much opportunity to enhance outcomes through reducing D2P.


title: Human immunosenescence: is it infectious?

text: Morbidity and mortality due to infectious disease is greater in the elderly than in the young, at least partly because of age-associated decreased immune competence, which renders individuals more susceptible to pathogens. This susceptibility is particularly evident for novel infectious agents such as in severe acute respiratory syndrome but is also all too apparent for common pathogens such as influenza. Many years ago, it was noted that the elderly possessed oligoclonal expansions of T cells, especially of CD8(+) cells. At the same time, it was established that cytomegalovirus (CMV) seropositivity was associated with many of the same phenotypic and functional alterations to T-cell immunity that were being reported as biomarkers associated with aging. It was discovered that CMV was the prime driving force behind most of the oligoclonal expansions and altered phenotypes and functions of CD8 cells. Independently, longitudinal studies of a free-living population of the very old in Sweden over the past decade have led to the emerging concept of an 'immune risk phenotype' (IRP), predicting mortality, which was itself found to be associated with CMV seropositivity. These findings support our hypothesis that the manner in which CMV and the host immune system interact is critical in determining the IRP and hence is predictive of mortality. In this sense, then, we suggest that immunosenescence is contagious.


A need to update and revise the pneumococcal vaccine recommendations for adults.


title: Comparison of immediate postoperative pain after transvaginal versus traditional laparoscopic cholecystectomy.

text: BACKGROUND Transvaginal cholecystectomy (TVC) is the most common natural orifice transluminal surgery (NOTES) performed in women, yet there is a paucity of data on intraoperative and immediate postoperative pain management. Previous studies have demonstrated that NOTES procedures are associated with less postoperative pain and faster recovery times. This study analyzes intraoperative and postoperative opioid use for TVC compared with traditional four-port laparoscopic cholecystectomies (LCs). METHODS This is a retrospective analysis of consecutive TVC and LC female patients between August 2009 and August 2012 in an academic institution. We compared demographics, intraoperative and postoperative opioid use and times in the operating room (OR) and in the post anesthesia care unit (PACU). RESULTS A total of 68 TVC and 67 LC patients were included in this study. The TVC and LC groups were similar in terms of age (both 41 years) and body mass index (29 and 31 kg/m2, respectively). The intraoperative preparation, surgical, and emergence times were significantly longer for the TVC than for the LC (p ≤ 0.01). Compared with the LC group, the intraoperative opioid requirement was significantly greater (TVC 27 mg vs. LC 25 mg; p = 0.003), but after adjusting for anesthesia time, the difference in OR opioid consumption became non-significant (p = 0.08). The PACU opioid requirement (TVC 2.5 vs. LC 5 mg; p = 0.04) was significantly lower for the TVC group, and a greater proportion of patients did not need any pain medications (TVC 38 % vs. LC 21 %; p = 0.04), compared with the LC group. The average PACU pain scores were not significantly different between the groups (p = 0.45). CONCLUSION TVC patients did not experience more pain than LC patients. Although the average pain scores of TVC patients did not differ from those of the LC patients, TVC patients did require less pain medication in the PACU.


title: Exploring genome architecture through GOV: a WWW-based gene order visualizer.

text: MOTIVATION The past decade has seen extension in the methods of sequence analysis from single gene based to analyzing multiple genes and proteins simultaneously. Consequently, there is a need for software tools that will allow mining of these enormous datasets at genome level effectively. A key challenge is to make them user-friendly, available to a larger community and integrate with public domain software without much hassle. RESULTS A web-based interactive computational tool is described for visualization and comparison of gene order from prokaryotic and selected viral genome data. Many intriguing similarities and differences in gene order of multiple genomes can be compared and revealed. The interface facilitates easy extraction of the nucleotide sequence of the gene of interest and BLAST analysis against GenBank at NCBI to provide insights into gene functions and orthologs of the gene in other species.


title: A human neutralizing antibody against a conformational epitope shared by oligomeric SARS S1 protein.

text: An antibody phage-display library was constructed from the B cells of convalescent severe acute respiratory syndrome (SARS) patients and screened using inactivated SARS coronavirus (CoV) virions as antigens. More than 80 positive clones were isolated from the library and one of them, scFv H12, was extensively characterized. scFv H12 bound to SARS-CoV with high affinity (equilibrium dissociation constant, Kd=73.5 nM), and neutralized SARS virions in vitro. The facts that scFv H12 bound to the SARS-S1 protein under non-reducing conditions and that it did not bind to monomeric S1 protein under reducing conditions strongly suggest that scFv H12 recognizes a conformational epitope shared by oligomeric S1 proteins. This study should aid in the manufacture of neutralizing antibody, provide a better understanding the immunological characteristics of SARS protein and facilitate the design of a SARS vaccine.


title: Evolutionary change--patterns and processes.

text: The present review considered: (a) the factors that conditioned the early transition from non-life to life; (b) genome structure and complexity in prokaryotes, eukaryotes, and organelles; (c) comparative human chromosome genomics; and (d) the Brazilian contribution to some of these studies. Understanding the dialectical conflict between freedom and organization is fundamental to give meaning to the patterns and processes of organic evolution.


The evolution of virulence.


title: Office-related antibiotic prescribing for persons aged ≤ 14 years--United States, 1993-1994 to 2007-2008.

text: In 2003, the Institute of Medicine identified antibiotic resistance as a key microbial threat to health in the United States and recommended promoting appropriate antibiotic use as an important strategy to address this threat. Antibiotic use contributes to development of antibiotic resistance on both the individual and country level. To examine trends in pediatric antibiotic prescribing in physician offices, CDC analyzed data from the National Ambulatory Medical Care Survey (NAMCS) for the period 1993-1994 to 2007-2008. This report summarizes the results of that analysis, which found that antibiotic prescribing rates for persons aged ≤ 14 years who had visited physician offices decreased 24% from 300 antibiotic courses per 1,000 office visits in 1993-1994 to 229 antibiotic courses per 1,000 office visits in 2007-2008. Among the five acute respiratory infections (ARIs) examined, antibiotic prescribing rates decreased 26% for pharyngitis and 19% for nonspecific upper respiratory infection (common cold); prescribing rates for otitis media, bronchitis, and sinusitis did not change significantly. Although the overall antibiotic prescribing rate for persons aged ≤ 14 years has decreased, the rate remains inappropriately high. Further efforts are needed to decrease inappropriate antibiotic prescribing for persons aged ≤ 14 years.


title: Surgical Materials: Current Challenges and Nano-enabled Solutions.

text: Surgical adhesive biomaterials have emerged as substitutes to sutures and staples in many clinical applications. Nano-enabled materials containing nanoparticles or having a distinct nanotopography have been utilized for generation of a new class of surgical materials with enhanced functionality. In this review, the state of the art in the development of conventional surgical adhesive biomaterials is critically reviewed and their shortcomings are outlined. Recent advancements in generation of nano-enabled surgical materials with their potential future applications are discussed. This review will open new avenues for the innovative development of the next generation of tissue adhesives, hemostats, and sealants with enhanced functionality for various surgical applications.


title: Learning needs in a medical curriculum in Hong Kong.

text: OBJECTIVE To survey medical graduates from the University of Hong Kong on how well they perceived their learning needs had been fulfilled by the old (before 1997) and the new (after 1997) curricula. DESIGN Retrospective questionnaire survey. SETTING The University of Hong Kong, Hong Kong. PARTICIPANTS Medical graduates from the University of Hong Kong who graduated between 1997 and 2006 were invited to complete a questionnaire online or in paper form; 1997-2001 graduates were trained under the old curriculum, and 2002-2006 graduates under the new curriculum. RESULTS The response rate was 23%. The survey showed that the graduates of both curricula felt that research skills, population health, and ophthalmology were not emphasised enough in the medical programme. In addition, some graduates of the old curriculum mentioned interpersonal skills, ethics and professionalism, and language skills, which were pinpointed in the curriculum reform in 1997. Some graduates of the new curriculum mentioned anatomy, microbiology, and diagnostic radiology. Graduates of both the old and the new curricula perceived the same top five areas as being lacking in their respective curricula, in relationship to their clinical career and personal growth, namely: business administration, law, professional English, life coaching, and humanities. A small percentage of graduates also took courses in these areas after graduation. CONCLUSIONS The survey showed that the curriculum reform in 1997 at the University of Hong Kong had correctly pinpointed some of the learning needs. The survey also identified educational needs in the existing curriculum that need to be dealt with in the forthcoming curriculum reform in 2012.


title: Antiviral activity of morpholino oligomers designed to block various aspects of Equine arteritis virus amplification in cell culture.

text: The antiviral efficacy of ten antisense phosphorodiamidate morpholino oligomers (PMOs) directed against Equine arteritis virus (EAV), a nidovirus belonging to the family Arteriviridae, was evaluated in mammalian (Vero-E6) cells. Peptide-conjugated PMOs (P-PMOs) supplied in cell culture medium at micromolar concentrations were efficiently taken up by Vero-E6 cells and were minimally cytotoxic. The P-PMOs were designed to base pair to RNA sequences involved in different aspects of EAV amplification: genome replication, subgenomic mRNA synthesis, and translation of genome and subgenomic mRNAs. A novel recombinant EAV, expressing green fluorescent protein as part of its replicase polyproteins, was used to facilitate drug screening. A moderate reduction of EAV amplification was observed with relatively high concentrations of P-PMOs designed to anneal to the 3'-terminal regions of the viral genome or antigenome. To determine if the synthesis of subgenomic mRNAs could be specifically reduced, transcription-regulating sequences essential for their production, but not for the production of genomic RNA, were targeted, but these P-PMOs were found to be ineffective at transcription interference. In contrast, all four P-PMOs designed to base pair with targets in the genomic 5' untranslated region markedly reduced virus amplification in a sequence-specific and dose-responsive manner. At concentrations in the low micromolar range, some of the P-PMOs tested completely inhibited virus amplification. In vitro translation assays showed that these P-PMOs were potent inhibitors of translation. The data suggest that these compounds could be useful as reagents for exploring the molecular mechanics of nidovirus translation and have anti-EAV potential at relatively low concentrations.


title: A case of viral neonatal calf diarrhea in a Quebec dairy herd.

text: This report is concerned with a consistent problem of neonatal calf diarrhea (NCD) in a dairy herd in which, for nearly two years, the morbidity had approached 100% and the mortality had varied from 20% to 45%. Generally, diarrhea appeared at three days of age. By the fluorescent antibody tissue section technique the two Nebraska NCD viruses (reo-like and corona-like) were detected in the cytoplasm of many absorptive cells of the small intestine from a calf submitted for necropsy. Reo-like virus antigen was not detected in the absorptive and crypt cells of the colon but coronavirus-like antigen was. An adenovirus was also isolated from the small intestine of this calf. The disease was reproduced experimentally in a two day old colostrum deprived calf with a bacteria free intestinal homogenate obtained from the naturally infected calf. Both Nebraska NCD viruses were demonstrated in this experimental animal. However, the adenovirus was not re-isolated. Histological lesions observed in the small and large intestines of the naturally and experimentally infected calves were similar and because of their good correlation with the immunofluorescent findings, a combination of the two Nebraska NCD viruses was thought to be a major cause of the neonatal calf diarrhea problem afflicting this dairy herd.


title: Epidemiologic study and containment of a nosocomial outbreak of severe acute respiratory syndrome in a medical center in Kaohsiung, Taiwan.

text: OBJECTIVE We conducted an epidemiologic investigation at the beginning of a nosocomial outbreak of severe acute respiratory syndrome (SARS) to clarify the dynamics of SARS transmission, the magnitude of the SARS outbreak, and the impact of the outbreak on the community. METHODS We identified all potential cases of nosocomially acquired SARS, linked them to the most likely infection source, and described the hospital containment measures. SETTING A 2,300-bed medical center in Kaohsiung, Taiwan. RESULTS A total of 55 cases of SARS were identified, and 227 hospital workers were quarantined. The index patient and neighboring patients were isolated. A chest physician team reviewed medical charts and chest radiographs and monitored the development of SARS in patients staying in the ward. The presence of underlying lung disease and immunocompromise in some patients made the diagnosis of SARS difficult. Some cases of SARS were diagnosed after the patients had died. Medical personnel were infected only if they cared for patients with unrecognized SARS, and caretakers played important roles in transmission of SARS to family members. As the number of cases of nosocomial SARS increased, the hospital closed the affected ward and expedited construction of negative-pressure rooms on other vacated floors for patient cohorting, and the last case in the hospital was identified 1 week later. CONCLUSIONS Timely recognition of SARS is extremely important. However, given the limitations of SARS testing, possible loss of epidemic links, and the nonspecific clinical presentations in hospitalized patients, it is very important to establish cohorts of persons with low, medium, and high likelihoods of SARS acquisition. Rapid closure of affected wards may minimize the impact on hospital operations. Establishment of hospitals dedicated to appropriate treatment of patients with SARS might minimize the impact of the disease in future epidemics.


title: A Systematic Review and Qualitative Analysis of Concussion Knowledge amongst Sports Coaches and Match Officials.

text: Sport-related concussion (SRC) is a public health issue of increasing concern. Sports coaches and match officials are important stakeholders in facilitating early recognition, immediate management and appropriate return-to-play following SRC. This systematic review analyses the current evidence on SRC knowledge amongst sports coaches and match officials. The review was conducted in accordance to PRISMA guideline. A qualitative analysis of knowledge on identification, management, prevention and consequences of SRC as well as return-to-play principles was performed. The Appraisal Tool for Cross-sectional Studies was employed to assess the quality and reliability of each study. Searches were conducted on PubMed, Medline Ovid, Web of Science, CINAHL, SPORTDiscus and Psycinfo. Studies included were primary studies in English published in peer-reviewed journals assessing the level of concussion knowledge or education level amongst coaches, officials or both, regardless of sports or competitive level. A total of 20880 studies were identified, from which 27 were included in this review. There were 26 cross-sectional studies and one randomized controlled trial; 20 assessed SRC knowledge amongst coaches, one considered only officials and six studies assessed both groups. Concussion knowledge amongst coaches and match officials was deemed moderate in most studies, although significant knowledge gaps were identified. There is considerable room for further education on SRC amongst coaches and officials, particularly with the less commonly recognized symptoms of SRC and misconceptions about SRC management and prevention. Beyond knowledge assessment, further investigation should explore the translation of concussion knowledge to on-field management of players with SRC.


title: Severe acute respiratory syndrome-associated coronavirus 3a protein forms an ion channel and modulates virus release.

text: Fourteen ORFs have been identified in the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) genome. ORF 3a of SARS-CoV codes for a recently identified transmembrane protein, but its function remains unknown. In this study we confirmed the 3a protein expression and investigated its localization at the surface of SARS-CoV-infected or 3a-cDNA-transfected cells. Our experiments showed that recombinant 3a protein can form a homotetramer complex through interprotein disulfide bridges in 3a-cDNA-transfected cells, providing a clue to ion channel function. The putative ion channel activity of this protein was assessed in 3a-complement RNA-injected Xenopus oocytes by two-electrode voltage clamp. The results suggest that 3a protein forms a potassium sensitive channel, which can be efficiently inhibited by barium. After FRhK-4 cells were transfected with an siRNA, which is known to suppress 3a expression, followed by infection with SARS-CoV, the released virus was significantly decreased, whereas the replication of the virus in the infected cells was not changed. Our observation suggests that SARS-CoV ORF 3a functions as an ion channel that may promote virus release. This finding will help to explain the highly pathogenic nature of SARS-CoV and to develop new strategies for treatment of SARS infection.


title: New insights into viral structure and virus-cell interactions through proteomics.

text: Although genomics techniques such as DNA microarrays have been widely used in virology, much more limited use has been made of proteomics. Although difficult, proteomics can greatly contribute to an understanding of virus-cell interactions, including the ternary structure of viral receptors at the cell surface, post-translational modifications and isoforms of critical viral and cellular proteins and even to the structure of viruses. Proteomics techniques also offer the potential for discovering markers for diagnostic and prognostic tests of viral infections in vivo. This review describes the use of several proteomic approaches for the analysis of HIV-cellular receptor interactions, the molecular mechanisms of transport of herpes simplex virus within neurons, and the structure of the tegument of herpes simplex virus.


title: Virus-provoked rhinitis in patients who have allergies.

text: The most common illnesses in humans are the respiratory tract infections caused by viruses. When limited to the upper respiratory region, these infections often are designated as "a common cold." Viruses commonly associated with these upper respiratory infections (URI) include rhinoviruses (RVs), respiratory syncytial virus, influenza virus, parainfluenza virus, corona virus, and adenoviruses. Clinical observations have suggested that patients with allergic rhinitis and asthma experience more pronounced symptoms during a viral URI than patients who do not have allergies and who are infected with the same virus under similar circumstances. Using an experimental virus infection model in human volunteers with and without allergic rhinitis, several groups of clinical investigators have studied the effects of experimental RV infections. These observations indicate that the experimental virus infection may induce host responses that provoke enhanced immunoglobulin E (IgE) synthesis. Whether this translates into enhanced symptoms has been suggested in one study but not in another. This article will review these studies, which suggest that it is the host response to the virus and not the virus itself that plays the major role in symptom pathogenesis.


title: Analysis of JHM central nervous system infections in rats.

text: Intracerebral inoculation of murine coronavirus JHM into 2- to 3-day-old Wistar Furth rats causes an acute encephalomyelitis, while inoculations at 10 days of age usually result in hind leg paralysis. To examine the distribution of viral antigens within this infected central nervous system (CNS) tissue, we used the avidin-biotin-peroxidase method to detect monoclonal and polyclonal antibodies bound to JHM structural proteins; in addition we used the Western blot technique to detect viral proteins. Our study demonstrated the following characteristics: Infected neuronal and glial cells produced viral nucleocapsid and E2 glycoprotein. The synthesis of these viral structural proteins was not restricted to cells in any particular part of the central nervous system. While JHM E2 proteins could be detected in individual cells of JHM-infected CNS tissue, the relative level of detectable E2 protein in the total CNS tissue of infected rats was reduced by more than 13-fold compared with JHM-infected tissue culture cells. Hippocampus neuronal cells provided a sensitive indication of JHM infection. These cells invariably contained antigens in both acutely and chronically infected animals. The distribution of cells containing viral antigens differed markedly for JHM-induced acute encephalitis and chronic demyelinating disease. Acutely infected brains had large lesions containing low levels of viral antigen scattered throughout the brain. One percent to ten percent of histologically normal cells in many parts of the brain contained viral antigens; in addition, more neuronal cells than glial cells were observed to be antigen-positive. The hippocampus appeared normal with hematoxylin-eosin staining; however, a scattered infection of neuronal cells was apparent.(ABSTRACT TRUNCATED AT 250 WORDS)


title: Levelling the playing field? Sharing of influenza viruses and access to vaccines and other benefits.

text: With the adoption of the Pandemic Influenza Preparedness Framework, including its annexes, by the 64th World Health Assembly, this article investigates the disproportionate burden of risk and benefits between resource-poor countries in the developing South and resource-rich industrialised developed nations of the North in the World Health Organisation's Standard Material Transfer Agreement (SMTA) for accessing and sharing influenza viruses. It concludes that the countries of the South have a unique opportunity to level the playing field through providing timely and affordable access to life-saving vaccine and meaningful benefit-sharing that will deliver technology and economic development. Importantly, the article also demonstrates that SMTAs are not merely a redirection of existing resources from North to South but offer a solution to the ongoing shortage of pandemic influenza vaccine by enabling the South to access technology necessary for sustainable vaccine production and thus increasing global vaccine capacity.


title: Limbic encephalitis after inhalation of a murine coronavirus.

text: The spread of a neurotropic coronavirus, mouse hepatitis virus strain A59, in the mouse central nervous system was studied after intranasal inoculation. Mouse hepatitis virus strain A59 spread during the 3- to 5-day postinoculation period, through the olfactory pathway into the limbic system. Coronavirus particles were detected in the limbic system by electron microscopy. The combination of temporal propagation through an anatomical-physiological central nervous system pathway and anatomical restriction of viral infection suggests that specific interneuronal transport is important in spread of the virus. This experimental system may represent a model for diseases associated with human coronaviruses (common cold viruses) and/or the human limbic system.


Effects of amino acid insertions in the cysteine-rich domain of the MHV-A59 spike protein on cell fusion.


title: Chronic gastroenterocolitis in nine cats.

text: Lesions of a chronic gastroenterocolitis were found in 9 cats of the Persian breed that were euthanized after a prolonged period of bloody diarrhea. Gross lesions consisted of gastrointestinal edema with prominent Payer's patches, multiple grayish nodules, and a few irregular erosions within the colonic mucosa. Microscopically, the changes were composed of degeneration, necrosis, and proliferation of gastric glandular epithelium, dilated intestinal crypts with lymphoplasmacytic cell infiltration of the lamina propria, and in 1 cat, severe transmural necrosis of the colon. With the Giemsa stain, spiral-shaped organisms in the gastrointestinal lumen and intracellularly in the gastric and the colonic epithelium were observed. These organisms could not be cultured. Although the role of these spiral-shaped organisms was not determined, other agents that could explain the disorder were not found.


title: Investigations into shaking mink syndrome: an encephalomyelitis of unknown cause in farmed mink (Mustela vison) kits in Scandinavia.

text: An apparently novel neurological disease clinically characterized by shaking, tremors, seizures, staggering gait, and ataxia was first observed in farmed mink kits in Denmark in 2000 and subsequently in Sweden, Denmark, and Finland in 2001, and again in Denmark in 2002. Lymphoplasmacytic encephalomyelitis was found in the affected kits. The lesions were most severe in the brainstem and cerebellum and consisted of neuronal degeneration and necrosis, neuronophagia, focal and diffuse gliosis, perivascular cuffs formed by lymphocytes, plasma cells and macrophages, and segmental loss of Purkinje cells. Testing was conducted to determine the cause of the disease, including general virological investigations (virus culture, negative-staining electron microscopy, immunoelectron microscopy, polymerase chain reaction for herpesviruses, adenoviruses, pestiviruses, and coronaviruses), tests for specific viral diseases (canine distemper, Borna disease, Louping ill, West Nile virus infection, tick-borne encephalitis, Aleutian disease), tests for protozoa (Toxoplasma gondii, Neospora caninum, Encephalitozoon cuniculi), bacteria (general culture, listeria, Clamydophila psittaci), and intracerebral inoculation of neonatal mice. The results of all these investigations were negative. One group of 3 mink kits inoculated intracerebrally with brain homogenate of affected mink developed clinical signs and histological lesions similar to those observed in naturally infected mink. Based on the histopathological features, it is postulated that the disease is caused by a yet unidentified virus.


Indian COVID-19 Risk Score, Comorbidities and Mortality.


title: Detection of Mycoplasma pneumoniae by two polymerase chain reactions and role of M. pneumoniae in acute respiratory tract infections in pediatric patients.

text: Mycoplasma pneumoniae and viruses in acute respiratory tract infections in children were studied during the winter of 1992-1993 in Antwerp, Belgium. M. pneumoniae was diagnosed in nasopharyngeal aspirates by culture and polymerase chain reaction (PCR). For this, amplification of a fragment of the PI adhesin gene in samples prepared by two methods was compared in two laboratories, and in one laboratory, a fragment of the 16S rRNA gene was amplified. The sensitivity of culture versus PCR was 61.5%. Provided a specific internal control is used, sample preparation by freeze-boiling combined with PCR for the PI gene and amplicon detection by visual inspection of the electrophoresis gel can be recommended, although maximal results are obtained after hybridization. M. pneumoniae was present in 0.5% of patients <2 years old and 6.9% of patients >2. M. pneumoniae was second to respiratory syncytial virus or detected equally in lower respiratory infections.


title: Stent-Retriever Thrombectomy for Acute Anterior Ischemic Stroke with Tandem Occlusion: A Systematic Review and Meta-Analysis.

text: OBJECTIVES To assess the efficacy and safety profile of stent-retriever thrombectomy (SRT) in acute anterior ischemic stroke patients with tandem occlusion. MATERIALS AND METHODS Using the MEDLINE database, we conducted a systematic review and meta-analysis of all studies that included patients with acute ischemic stroke attributable to tandem occlusion who received treatment with SRT between November 2010 and May 2015. RESULTS The literature search identified 11 previous studies involving a total of 237 subjects out of whom 193 (81.4 %) were treated with acute stent placement for the extracranial internal carotid artery occlusion. Mean initial NIHSS score was 17, and median time from onset to recanalization was 283.5 min. Mean intravenous thrombolysis rate was 63.8 %. In the meta-analysis, the recanalization rate reached 81 % (95 % CI, 73-89). Meta-analysis of clinical outcomes showed a pooled estimate of 44 % (95 % CI, 33-55; 10 studies) for favourable outcome, 13 % (95 % CI, 8-20; 10 studies) for mortality, and 7 % (95 % CI, 2-13; eight studies) for symptomatic intracranial haemorrhage. CONCLUSION SRT with emergency carotid stenting is associated with acceptable safety and efficacy in acute anterior stroke patients with tandem occlusion compared to natural history. However, the best modality to treat proximal stenosis is based on an individual case basis. KEY POINTS • Stent retriever thrombectomy of tandem occlusion is efficient and safe. • Emergent carotid stenting during thrombectomy increase symptomatic intracranial haemorrhage without impact mortality. • Thrombectomy of tandem anterior circulation occlusion may be the first therapeutic option.


title: Rescue of IBV D-RNA by heterologous helper virus strains.

text: Coronavirus defective RNA (D-RNA) vectors could be developed to deliver selected genes for the production of recombinant coronavirus vaccines. An IBV D-RNA, CD-61, derived from a naturally occurring IBV Beaudette D-RNA, CD-91, is being developed as a D-RNA vector for IBV. In order to use CD-61 as a vector it will require rescue by heterologous strains in addition to Beaudette. Rescue will be determined by recognition of replication and packaging signals within the D-RNA by the helper virus. The 5' and 3' UTRs are believed to contain sequences involved in replication and transcription. The 5' and 3' UTRs of six strains of IBV have been sequenced and experiments performed using six strains of helper virus for rescue of CD-61 to determine whether rescue correlates with sequence conservation within the 5' and 3' UTRs. Results indicate that all strains of helper virus rescued the D-RNA to varying degrees. Sequence comparisons show a high degree of sequence identity in the UTRs, but enough strain differences exist to be used as markers. The 5' and 3' UTRs of the D-RNAs rescued by the heterologous strains were also sequenced and leader switching between the helper virus and the Beaudette leader on the D-RNAs was observed.


title: Hexachlorophene inhibits Wnt/beta-catenin pathway by promoting Siah-mediated beta-catenin degradation.

text: Aberrant activation of Wnt/beta-catenin signaling and subsequent up-regulation of beta-catenin response transcription (CRT) is a critical event in the development of human colon cancer. Thus, Wnt/beta-catenin signaling is an attractive target for the development of anticancer therapeutics. In this study, we identified hexachlorophene as an inhibitor of Wnt/beta-catenin signaling from cell-based small-molecule screening. Hexachlorophene antagonized CRT that was stimulated by Wnt3a-conditioned medium by promoting the degradation of beta-catenin. This degradation pathway is Siah-1 and adenomatous polyposis colidependent, but glycogen synthase kinase-3beta and F-box beta-transducin repeat-containing protein-independent. In addition, hexachlorophene represses the expression of cyclin D1, which is a known beta-catenin target gene, and inhibits the growth of colon cancer cells. Our findings suggest that hexachlorophene attenuates Wnt/beta-catenin signaling through the Siah-1-mediated beta-catenin degradation.


Data show that SARS is gradually coming under control.


title: A new cell culture tube in diagnostic virology for virus isolation.

text: Virus isolation and accurate characterization plays a crucial role in the rapid identification of the causative agents of infectious disease outbreaks especially if the causative viruses are novel where no pre-existing diagnostic reagents would be available. A new cell culture tube, named Jui Meng (JM) Cell Culture Tube, was developed to reduce the cost and improve the efficiency and biosafety of work pertaining to virus isolation. The design of the tube is based heavily on the principle of practicability, functionality, biosafety and long-term cost saving for diagnostic laboratory work in virus isolation. It is designed to culture an initial inoculum of one milliliter of culture medium containing 1 x 10(4) to 1 x 10(5) cells/ml.


title: Severe acute respiratory syndrome coronavirus entry as a target of antiviral therapies.

text: The identification in 2003 of a coronavirus as the aetiological agent of severe acute respiratory syndrome (SARS) intensified efforts to understand the biology of coronaviruses in general and SARS coronavirus (SARS-CoV) in particular. Rapid progress was made in describing the SARS-CoV genome, evolution and lifecycle. Identification of angiotensin-converting enzyme 2 (ACE2) as an obligate cellular receptor for SARS-CoV contributed to understanding of the SARS-CoV entry process, and helped to characterize two targets of antiviral therapeutics: the SARS-CoV spike protein and ACE2. Here we describe the role of these proteins in SARS-CoV replication and potential therapeutic strategies aimed at preventing entry of SARS-CoV into target cells.


title: Marked depletion of glycosylation sites in HIV-1 gp120 under selection pressure by the mannose-specific plant lectins of Hippeastrum hybrid and Galanthus nivalis.

text: The plant lectins from Hippeastrum hybrid (HHA) and Galanthus nivalis (GNA) are 50,000-D tetramers showing specificity for alpha-(1,3) and/or alpha-(1,6)-mannose oligomers. They inhibit HIV-1 infection at a 50% effective concentration of 0.2 to 0.3 microg/ml. Escalating HHA or GNA concentrations (up to 500 microg/ml) led to the isolation of three HIV-1(III(B)) strains in CEM T cell cultures that were highly resistant to HHA and GNA, several other related mannose-specific plant lectins, and the monoclonal antibody 2G12, modestly resistant to the mannose-specific cyanovirin, which is derived from a blue-green alga, but fully susceptible to other HIV entry inhibitors as well as HIV reverse transcriptase inhibitors. These mutant virus strains were devoid of up to seven or eight of 22 glycosylation sites in the viral envelope glycoprotein gp120 because of mutations at the Asn or Thr/Ser sites of the N-glycosylation motifs. In one of the strains, a novel glycosylation site was created near a deleted glycosylation site. The affected glycosylation sites were predominantly clustered in regions of gp120 that are not involved in the direct interaction with either CD4, CCR5, CXCR4, or gp41. The mutant viruses containing the deleted glycosylation sites were markedly more infectious in CEM T-cell cultures than wild-type virus.


The role of breathing exercises in the treatment of COPD.


The structure and replication of coronaviruses.


title: Nosocomial and community transmission of measles virus genotype D8 imported by a returning traveller from Nepal.

text: Measles is uncommon in Australia due to effective national vaccination strategies. In mid-2003, a cluster of nine cases of measles occurred in western Sydney. The index case was a 29-year-old traveller recently returned from Nepal. The case presented to hospital and transmitted the disease to two others in the Emergency Department. Further cases resulted from both community and nosocomial transmission. The median age of cases was 24 years, with three cases in children aged under four years. Only one person had a documented history of measles vaccination, a child who had received one dose of vaccine overseas. One case was a 2-month-old infant whose mother was immune and two cases were hospital staff members. Molecular analysis of measles virus isolates from four cases revealed the same D8 genotype, a strain previously identified in Nepal. Staff vaccination strategies implemented as a result of the outbreak were poorly patronised despite nosocomial transmission. As diseases such as measles become rare it is important to thoroughly investigate any outbreaks, and to maintain a high index of suspicion of measles, particularly in travellers presenting with a rash having returned from measles-endemic areas. Genetic analysis is important in tracing the origins of an outbreak, and to confirm relatedness between cases. The highly infectious nature of measles virus also underscores the need for appropriate infection control in minimising risk of nosocomial transmission. Such policies are of increasing importance with the emergence of novel viruses or the threat of pandemic influenza.


From the Centers for Disease Control and Prevention. Update: outbreak of severe acute respiratory syndrome--worldwide, 2003.


title: Pasteurella gallinarum: Zimbabwean experience of a versatile pathogen.

text: Pasteurella gallinarum-related outbreaks in chickens and African guinea fowls are described. Four outbreaks were recorded in chickens and one in guinea fowls. Periorbital swelling and keratoconjunctivitis were the consistently present clinical signs in all the diseased birds. In several, swollen hocks and wattles were also discerened. Birds which succumbed to the infection showed petechiation in the internal organs and evidence of airsacculitis. Pasteurella gallinarum was isolated from the lesions and also from conjunctival swabs of the apparently healthy in-contact birds. There was no evidence of concurrent infection with Haemophilus, Mycoplasma or Chlamydia. Quinolone therapy when resorted to on one of the farms resolved the clinical signs. Phenotypes of 28 isolates were studied. The results compared well with the Pasteurella gallinarum isolates reported earlier from elsewhere. It was also found that results of xylose fermentation and ONPG test appear to be a variable character. There is no earlier report of P. gallinarum infection in guinea fowls.


title: An overall picture of SARS coronavirus (SARS-CoV) genome-encoded major proteins: structures, functions and drug development.

text: A severe atypical pneumonia designated as severe acute respiratory syndrome (SARS) by The World Health Organization broke out in China and menaced to more than other 30 countries between the end of the year 2002 and June of the year 2003. A novel coronavirus called severe acute respiratory syndrome coronavirus (SARS-CoV) has been recently identified as the etiological agent responsible for the infectious SARS disease. Based on extensively scientific cooperation and almost two-year's studies, remarkable achievements have been made in the understanding of the phylogenetic property and the genome organization of SARS-CoV, as well as the detailed characters of the major proteins involved in SARS-CoV life cycle. In this review, we would like to summarize the substantial scientific progress that has been made towards the structural and functional aspects of SARS-CoV associated key proteins. The progress focused on the corresponding key proteins' structure-based drug and vaccine developments has been also highlighted. The concerted and cooperative response for the treatment of the SARS disease has been proved to be a triumph of global public health and provides a new paradigm for the detection and control of future emerging infectious disease threats.


title: [Genomic characterization of SARS coronavirus: a novel member of coronavirus].

text: In March 2003, SARS-CoV, a novel coronavirus which has been proved to be a pathogen causing Severe Acute Respiratory Syndrome (SARS). The complete genome of SARS-CoV has been sequenced by international collaboration including China. In the present study, the genome sequences were collected from NCBI and genomic characterization was analyzed. SARS-CoV has a genome of 28-30 kb including 11 ORFs (Open Reading Frames), which is consistent with that of coronavirus family, and its genome organization is similar to those of other coronaviruses as well. SARS-CoV evolutionally closes to other coronavirus in their corresponding proteins, such as spike protein, small membrane protein and nucleocapsid protein. In some regions of the genome, the genomic sequence of SARS-CoV was significantly different from that of other coronavirus, and has a self-conservative genomic sequence. Moreover, its encoding protein sequences were greatly different from those of other coronavirus. The analysis indicated that SARS-CoV has lower redundancy, that is, it has a high variation possibility. It may not be a variant of other coronaviruses but a novel coronavirus, which existed independently in nature and was not recognized by human being before, although SARS-CoV is morphologically similar to other coronavirus and belongs to coronavirus family. The sequences of its genes and encoding proteins are substantially different from those of other coronavirus.


title: Epidemiology and control of SARS in Singapore.

text: Severe acute respiratory syndrome (SARS) was imported into Singapore in late February 2003 by a local resident who returned from a holiday in Hong Kong and started an outbreak in the hospital where she was admitted on 1 March 2003. The disease subsequently spread to 4 other healthcare institutions and a vegetable wholesale centre. During the period between March and May 2003, 238 probable SARS cases, including 8 imported cases and 33 deaths, were reported. Transmission within the healthcare and household settings accounted for more than 90% of the cases. Factors contributing to the spread of infection included the failure to recognise the high infectivity of this novel infection, resulting in a delay in isolating initial cases and contacts and the implementation of personal protective measures in healthcare institutions; and the super-spreading events by 5 index cases, including 3 with co-morbid conditions presenting with atypical clinical manifestations of SARS. Key public health measures were directed at prevention and control within the community and hospitals, and the prevention of imported and exported cases. An isolated laboratory-acquired case of SARS was reported on 8 September 2003. Based on the lessons learnt, Singapore has further strengthened its operational readiness and laboratory safety to respond to SARS, avian flu and other emerging diseases.


title: Development of a semi-nested reverse transcription polymerase chain reaction assay for the retrospective diagnosis of canine distemper virus infection.

text: Formalin-fixed, paraffin-embedded tissue blocks from 14 dogs were used to test the utility of a newly developed semi-nested reverse transcription polymerase chain reaction (RT-PCR) assay for canine distemper virus (CDV). The results from this new test were compared with those of histopathologic examination, fluorescent antibody detection (FA), and immunohistochemistry (IHC). The semi-nested RT-PCR protocol was used to detect CDV RNA in 9 of the 10 cases that were positive by at least 1 of the immunologic (FA and IHC) methods. Sequence data indicated that the amplified strains of CDV are more closely related to a naturally occurring strain than to a vaccine strain. Thus, the semi-nested RT-PCR assay is a useful diagnostic method applicable to the retrospective diagnosis of CDV infection. Sequence determination may yield molecular epidemiologic information regarding vaccine efficacy.


title: Emerging respiratory viruses: challenges and vaccine strategies.

text: The current threat of avian influenza to the human population, the potential for the reemergence of severe acute respiratory syndrome (SARS)-associated coronavirus, and the identification of multiple novel respiratory viruses underline the necessity for the development of therapeutic and preventive strategies to combat viral infection. Vaccine development is a key component in the prevention of widespread viral infection and in the reduction of morbidity and mortality associated with many viral infections. In this review we describe the different approaches currently being evaluated in the development of vaccines against SARS-associated coronavirus and avian influenza viruses and also highlight the many obstacles encountered in the development of these vaccines. Lessons learned from current vaccine studies, coupled with our increasing knowledge of the host and viral factors involved in viral pathogenesis, will help to increase the speed with which efficacious vaccines targeting newly emerging viral pathogens can be developed.


title: Institutional First 100 Case Experience and Outcomes of Robotic Hepatectomy for Liver Tumors.

text: The nascent robotic approach for hepatic resections is gaining momentum in the United States because it offers solutions to the known limitations of laparoscopic approach. Herein, we report our initial experience and short-term outcomes of the first 100 robotic hepatectomies. With Institutional Review Board approval, all patients undergoing robotic hepatectomy were prospectively followed up. Patient demographics, operative outcomes, complications, and 30-day readmissions were collected and analyzed. Data are presented as median (mean ± SD). One hundred consecutive patients underwent robotic hepatectomy. Patients were aged 62 (63 ± 13.6) years, 66 per cent were women, and BMI was 29 (29 ± 6.4) kg/m². In all, 76 per cent of the hepatectomies were undertaken for malignancy [metastatic colorectal cancer (28%), hepatocellular carcinoma (21%), and intrahepatic cholangiocarcinoma (15%)], and 20 per cent for benign lesions; 66 per cent of patients underwent nonanatomical partial hepatectomies, 17 per cent right hepatectomies, 16 per cent left hepatectomies, and 1 per cent trisegmentectomy. Operative time was 233 (268 ± 109.3) minutes, and the estimated blood loss was 123 (269 ± 322.1) mL. Conversion to "open" approach was necessary in one patient. The length of stay was 3 (5 ± 4.6) days. There were no intraoperative complications. Twelve patients experienced postoperative complications. Six patients required readmission to the hospital within 30 days of discharge. Robotic hepatectomy is safe and feasible with favorable short-term outcomes. The robotic system enhances application of minimally invasive surgery for complex hepatobiliary operations.


title: Systematic review of benzodiazepines for anxiety disorders in late life.

text: BACKGROUND Benzodiazepines are currently the most commonly prescribed medication for the treatment of anxiety in older adults, although there is a dearth of good-quality data on this subject. The aim of this review was to systematically review studies examining the efficacy and tolerability of benzodiazepines for the treatment of anxiety disorders among older adults. METHODS The authors conducted a systematic review, searching PubMed, Ovid MEDLINE, Ovid Embase, Web of Science, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials. All searches were limited to English-language articles. The quality of each study was appraised using criteria developed by the Centre for Evidence-Based Medicine for randomized controlled trials. RESULTS A total of 8,785 citations were retrieved and pooled in EndNote and de-duplicated to 3,753. This set was uploaded to Covidence for screening. Two separate screeners (AG and SAF) evaluated the titles, abstracts, and full text of the eligible articles. Five studies met the inclusion criteria. Across all studies, benzodiazepines were associated with decreased anxiety at the end of the study period. The limited tolerability data show mild adverse effects from the benzodiazepines studied. Limitations of the trials included limited data on the long-term use of benzodiazepines for anxiety and a preponderance of trials examining generalized anxiety disorder, with relatively less data on other anxiety disorders. CONCLUSIONS Benzodiazepines are effective for treating anxiety disorders in late life, at least in the short term, but more data is needed to establish tolerability and their long-term benefits.


title: Protocol for the systematic review of the prevention, treatment and public health management of impetigo, scabies and fungal skin infections in resource-limited settings.

text: BACKGROUND Impetigo, scabies, and fungal skin infections disproportionately affect populations in resource-limited settings. Evidence for standard treatment of skin infections predominantly stem from hospital-based studies in high-income countries. The evidence for treatment in resource-limited settings is less clear, as studies in these populations may lack randomisation and control groups for cultural, ethical or economic reasons. Likewise, a synthesis of the evidence for public health control within endemic populations is also lacking. We propose a systematic review of the evidence for the prevention, treatment and public health management of skin infections in resource-limited settings, to inform the development of guidelines for the standardised and streamlined clinical and public health management of skin infections in endemic populations. METHODS The protocol has been designed in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols statement. All trial designs and analytical observational study designs will be eligible for inclusion. A systematic search of the peer-reviewed literature will include PubMed, Excertpa Medica and Global Health. Grey literature databases will also be systematically searched, and clinical trials registries scanned for future relevant studies. The primary outcome of interest will be the clinical cure or decrease in prevalence of impetigo, scabies, crusted scabies, tinea capitis, tinea corporis or tinea unguium. Two independent reviewers will perform eligibility assessment and data extraction using standardised electronic forms. Risk of bias assessment will be undertaken by two independent reviewers according to the Cochrane Risk of Bias tool. Data will be tabulated and narratively synthesised. We expect there will be insufficient data to conduct meta-analysis. The final body of evidence will be reported against the Grades of Recommendation, Assessment, Development and Evaluation grading system. DISCUSSION The evidence derived from the systematic review will be used to inform the development of guidelines for the management of skin infections in resource-limited settings. The evidence derived will be intended for use by clinicians, public health practitioners and policy makers in the treatment of skin infections and the development of skin infection control programmes. The review will identify any gaps in the current evidence to provide direction for future research. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42015029453.


The Great American Smokeout.


title: Differentiation of transmissible gastroenteritis virus from porcine respiratory coronavirus and other antigenically related coronaviruses by using cDNA probes specific for the 5' region of the S glycoprotein gene.

text: Two cDNA clones prepared from the virulent Miller strain of transmissible gastroenteritis virus (TGEV) were identified, and their nucleotide sequences were determined. The clones were nonoverlapping and located in the 5' region of the S glycoprotein gene. Their nucleotide and predicted amino acid sequences were compared with published sequences of the attenuated Purdue strain of TGEV and feline infectious peritonitis virus (FIPV). TGEV clone pE21 contained 381 bp of the S glycoprotein gene and had greater than 98% nucleotide and amino acid sequence homology with Purdue TGEV and over 87% nucleotide and amino acid sequence homology with FIPV. TGEV clone pD24 contained 267 bp of the S glycoprotein gene. It had greater than 98% nucleotide and amino acid sequence homology with Purdue TGEV but only 54% nucleotide sequence homology and 24% amino acid sequence homology with FIPV. A probe prepared from pD24 could differentiate TGEV from porcine respiratory coronavirus and other antigenically related coronaviruses, FIPV, feline enteric coronavirus, and canine coronavirus in a dot blot hybridization assay.


title: Modified vaccinia virus Ankara multiplies in rat IEC-6 cells and limited production of mature virions occurs in other mammalian cell lines.

text: Recombinant viruses based on modified vaccinia virus Ankara (MVA) are vaccine candidates against infectious diseases and cancers. Presently, multiplication of MVA has been demonstrated in chicken embryo fibroblast and baby hamster kidney (BHK-21) cells only. The multiplication and morphogenesis of a recombinant (MVA-HANP) and non-recombinant MVA strain in BHK-21 and 12 other mammalian cell lines have now been compared. Rat IEC-6 cells were fully permissive to MVA infection. The virus yield in IEC-6 cells was similar to that obtained in BHK-21 cells at low as well as high multiplicities of infection. Vero cells were semi-permissive to MVA infection. Mature virions were produced in supposedly non-permissive cell lines. The multiplication and morphogenesis of non-recombinant MVA and MVA-HANP were similar. These results are relevant to the production and biosafety of MVA-vectored vaccines.


title: Update: severe acute respiratory syndrome--United States, June 18, 2003.

text: CDC continues to work with state and local health departments, the World Health Organization (WHO), and other partners to investigate cases of severe acute respiratory syndrome (SARS). This report updates reported SARS cases worldwide and in the United States and summarizes changes in travel recommendations for provinces in China with the exclusion of Beijing, where a travel advisory remains.


title: Animal welfare: the role and perspectives of the meat and livestock sector.

text: Those in the livestock industry involved in rearing animals and in producing milk, meat and eggs, must respond to two demands: one expressed by consumers, and the other by the public. Regarding consumers, demand for food produced by the livestock industry has shown steady growth for a century. Over the last few decades, this growth has been sustained by the developing countries, and is based mainly on pig and poultry production, which provides cheaper products. Regarding the public, society is showing greater concern about the conditions in which livestock is reared, transported and slaughtered. The public demands not only that ill treatment of animals be fought against and penalised, but also that any unnecessary suffering should be avoided and even that animals should be guaranteed a certain degree of 'comfort'. Animal health, the most important aspect of their welfare, has vastly improved, as has the care of sick or injured animals. At the same time, the latest amenities used in livestock rearing, transport and slaughter are helping to eliminate situations involving extreme stress and suffering. Finally, the motivation of industry players and the safety of those who work with livestock must be taken into consideration. Training of personnel and the implementation of guides to good practice or of quality control do as much to improve animal welfare as do overzealous regulations.


title: Urological implications of SARS CoV-19.

text: INTRODUCTION The novel coronavirus disease 2019 (COVID-19), pandemic has afflicted > 3.3 million people around the world since December 2019. Though, more than 1000 publications have appeared in scientific journals addressing a plethora of questions, there is a considerable hiatus in understanding of the behavior and natural history of the virus and its impact on urology. Also, a modified approach is the need of hour in taking care of patients as urologists should safeguard their teams, families, and patients. MATERIAL AND METHODS The authors have used guidelines from USA, Canada, UK, Europe and India for making recommendations to help urologist define their own policies that may have to be fine-tuned on the basis of continued and evolving challenges they would encounter and the local resources at their disposal. RESULTS COVID-19 do effect genitourinary system from kidney to testis. The authors provide scientific basis to urologists to help identify patients by remote consultation who are likely to be harmed by coming to the hospital, and not to miss those who need hospitalization for diagnostic or therapeutic interventions. There is uncompromised need of specific precautions during surgery to safe guard the surgeon and his team along with the patient. CONCLUSIONS Urological operations during COVID-19 pandemic should be limited to emergency cases during the acute phase with an exit strategy planned in a staggered manner, based on the scientific risk stratification. Telemedicine (e-clinics or virtual clinics) would help achieve the goal of risk stratification.


Thoracic CT scan findings in 2009 Influenza A (H1N1) virus pandemic in Isfahan.


title: Protective humoral responses to severe acute respiratory syndrome-associated coronavirus: implications for the design of an effective protein-based vaccine.

text: Some of the structural proteins of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) carry major epitopes involved in virus neutralization and are essential for the induction of protective humoral responses and the development of an effective vaccine. Rabbit antisera were prepared using full-length N and M proteins and eight expressed fragments covering the S protein. Antisera to S and M proteins were found to have different neutralizing titres towards SARS-CoV infection in vivo, ranging from 1:35 to 1:128. Antiserum to the N protein did not contain neutralizing antibodies. Epitopes inducing protective humoral responses to virus infection were located mainly in the M protein and a region spanning residues 13-877 of the S protein. The neutralizing ability of antisera directed against the expressed structural proteins was greater than that of convalescent patient antisera, confirming that, as immunogens, the former induce strong, SARS-CoV-specific neutralizing antibody responses. The in vitro neutralization assay has important implications for the design of an effective, protein-based vaccine preventing SARS-CoV infection.


Screening, the everlasting quest for the needle in the haystack.


Coronavirus receptor specificity.


title: Potential pathogens in feces from unweaned llamas and alpacas with diarrhea.

text: OBJECTIVE To identify potential pathogens in feces from llama and alpaca crias with diarrhea. DESIGN Prospective observational study. ANIMALS 45 unweaned crias with diarrhea. PROCEDURE Fecal samples were evaluated for Eimeria spp, Giardia spp, Cryptosporidium spp, enteric viruses, and Salmonella spp. A questionnaire yielded information concerning herd management and presence of other affected camelids. RESULTS 28 crias were < or = 31 days old, 11 were 32 to 62 days old, and 6 were 63 to 210 days old. Potential pathogens were isolated from feces from 32 of the 45 crias. A total of 39 potential pathogens were obtained, including coronavirus (n = 19 crias; 42%), Giardia spp (8; 18%), Eimeria spp (6; 13%), Cryptosporidium spp (4; 9%), rotavirus (1; 2%), and nematode ova (1; 2%). Salmonella spp were not isolated. Most crias from which potential pathogens were isolated were identified during outbreaks of diarrhea involving other camelids, although only coronavirus was isolated from crias identified during outbreaks involving adult camelids. Coronavirus was detected throughout the year, whereas protozoa were most commonly isolated during the fall and winter. CONCLUSIONS AND CLINICAL RELEVANCE Results suggest that a variety of potential pathogens may be isolated from young crias with diarrhea. Many crias shed coronavirus, which may also have been affecting older camelids. Protozoa were isolated most often during wetter months, suggesting that crias born during these months may have greater exposure to protozoal pathogens.


title: Point-of-care testing for community-acquired pneumonia: do we have all the answers?

text: Point-of-care tests (POCTs) are available for rapid, "bedside" diagnosis of some causes of community-acquired pneumonia. POCTs complement other laboratory investigations for pneumonia. Although their sensitivity and specificity are improving, they are generally less sensitive than nucleic acid amplification and culture techniques. Questions remain as to the most cost-effective use of POCTs in clinical practice. To ensure their maximum value for both individual patients and the public health system, POCTs are probably best used as part of laboratory-designed algorithms for investigating pneumonia. POCTs are a valuable tool for surveillance, for rapid investigation of outbreaks, and for use in laboratories with limited diagnostic facilities.


title: The cytoplasmic tails of Uukuniemi Virus (Bunyaviridae) G(N) and G(C) glycoproteins are important for intracellular targeting and the budding of virus-like particles.

text: Functional motifs within the cytoplasmic tails of the two glycoproteins G(N) and G(C) of Uukuniemi virus (UUK) (Bunyaviridae family) were identified with the help of our recently developed virus-like particle (VLP) system for UUK virus (A. K. Overby, V. Popov, E. P. Neve, and R. F. Pettersson, J. Virol. 80:10428-10435, 2006). We previously reported that information necessary for the packaging of ribonucleoproteins into VLPs is located within the G(N) cytoplasmic tail (A. K. Overby, R. F. Pettersson, and E. P. Neve, J. Virol. 81:3198-3205, 2007). The G(N) glycoprotein cytoplasmic tail specifically interacts with the ribonucleoproteins and is critical for genome packaging. In addition, two other regions in the G(N) cytoplasmic tail, encompassing residues 21 to 25 and 46 to 50, were shown to be important for particle generation and release. By the introduction of point mutations within these two regions, we demonstrate that leucines at positions 23 and 24 are crucial for the initiation of VLP budding, while leucine 46, glutamate 47, and leucine 50 are important for efficient exit from the endoplasmic reticulum and subsequent transport to the Golgi complex. We found that budding and particle generation are highly dependent on the intracellular localization of both glycoproteins. The short cytoplasmic tail of UUK G(C) contains a lysine at position -3 from the C terminus that is highly conserved among members of the Phlebovirus, Hantavirus, and Orthobunyavirus genera. Mutating this single amino acid residue in G(C) resulted in the mislocalization of not only G(C) but also G(N) to the plasma membrane, and VLP generation was compromised in cells expressing this mutant. Together, these results demonstrate that the cytoplasmic tails of both G(N) and G(C) contain specific information necessary for efficient virus particle generation.


[COVID-19 - 2019].


title: Risk factors for SARS-related deaths in 2003, Beijing.

text: OBJECTIVE To study the potential risk factors for severe acute respiratory syndromes (SARS)-related deaths in Beijing. METHODS Epidemiological data were collected among the confirmed SARS patients officially reported by Beijing Centers for Disease Control and Prevention (BCDC), and information was also supplemented by a follow-up case survey. Chi-square test and multivariate stepwise logistic regression analysis were performed. RESULTS Old age (over 60 years) was found to be significantly associated with SARS-related deaths in the univariate analysis. Also, history of contacting SARS patients within 2 weeks prior to the onset of illness, health occupation, and inferior hospital ranking as well as longer interval of clinic consulting (longer than 1 day) were the risk factors for SARS-related deaths. Multivariate stepwise logistic regression analysis found four risk factors for SARS-related deaths. CONCLUSION Old age (over 60 years) is the major risk factor for SARS-related deaths. Moreover, hospital health workers, the designated hospitals for SARS clinical services and the interval of consulting doctors (less than 1 day) are protective factors for surviving from SARS.


title: Amino acids 270 to 510 of the severe acute respiratory syndrome coronavirus spike protein are required for interaction with receptor.

text: A novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV), has recently been identified as the causative agent of severe acute respiratory syndrome (SARS). SARS-CoV appears similar to other coronaviruses in both virion structure and genome organization. It is known for other coronaviruses that the spike (S) glycoprotein is required for both viral attachment to permissive cells and for fusion of the viral envelope with the host cell membrane. Here we describe the construction and expression of a soluble codon-optimized SARS-CoV S glycoprotein comprising the first 1,190 amino acids of the native S glycoprotein (S(1190)). The codon-optimized and native S glycoproteins exhibit similar molecular weight as determined by Western blot analysis, indicating that synthetic S glycoprotein is modified correctly in a mammalian expression system. S(1190) binds to the surface of Vero E6 cells, a cell permissive to infection, as demonstrated by fluorescence-activated cell sorter analysis, suggesting that S(1190) maintains the biologic activity present in native S glycoprotein. This interaction is blocked with serum obtained from recovering SARS patients, indicating that the binding is specific. In an effort to map the ligand-binding domain of the SARS-CoV S glycoprotein, carboxy- and amino-terminal truncations of the S(1190) glycoprotein were constructed. Amino acids 270 to 510 were the minimal receptor-binding region of the SARS-CoV S glycoprotein as determined by flow cytometry. We speculate that amino acids 1 to 510 of the SARS-CoV S glycoprotein represent a unique domain containing the receptor-binding site (amino acids 270 to 510), analogous to the S1 subunit of other coronavirus S glycoproteins.


Staphylococcus aureus and Escherichia hermanii in diabetes patient.


title: [Hypertension, RAAS blockade and risk in COVID-19 patients].

text: SARS-coronavirus 2 (SARS-CoV-2) enters the host-cells by binding the transmembraneous angiotensin converting enzyme 2 (ACE2) when causing coronavirus disease 2019 (COVID-19). The role of angiotensin converting enzyme inhibitors (ACE) and angiotensin II receptor blockers (ARB) in COVID-19 is debated. Several well-conducted observational studies show no increased risk from RAAS blockade in COVID-19 patients and are detailed in this brief review. The Swedish Society of Hypertension, Stroke and Vascular Medicine supports current recommendations that ongoing RAAS blockade should be maintained in patients with COVID-19.


title: Mosaic evolution of the severe acute respiratory syndrome coronavirus.

text: Severe acute respiratory syndrome (SARS) is a deadly form of pneumonia caused by a novel coronavirus, a viral family responsible for mild respiratory tract infections in a wide variety of animals including humans, pigs, cows, mice, cats, and birds. Analyses to date have been unable to identify the precise origin of the SARS coronavirus. We used Bayesian, neighbor-joining, and split decomposition phylogenetic techniques on the SARS virus replicase, surface spike, matrix, and nucleocapsid proteins to reveal the evolutionary origin of this recently emerging infectious agent. The analyses support a mammalian-like origin for the replicase protein, an avian-like origin for the matrix and nucleocapsid proteins, and a mammalian-avian mosaic origin for the host-determining spike protein. A bootscan recombination analysis of the spike gene revealed high nucleotide identity between the SARS virus and a feline infectious peritonitis virus throughout the gene, except for a 200- base-pair region of high identity to an avian sequence. These data support the phylogenetic analyses and suggest a possible past recombination event between mammalian-like and avian-like parent viruses. This event occurred near a region that has been implicated to be the human receptor binding site and may have been directly responsible for the switch of host of the SARS coronavirus from animals to humans.


Novel SARS unique AdoMet-dependent methyltransferase.


Clinical status and its associated early warning per emerging infectious respiratory disease in China.


title: Viral etiology of frequently recurring respiratory tract infections in children.

text: The viral etiology of frequently recurring respiratory tract infection (FRRI) in children aged <2 years was studied. Altogether, 329 children were followed from 2 to 24 months of age in the Finnish Otitis Media Cohort Study. Children with FRRI were defined as having > or =9 episodes of upper respiratory tract infection (URI) and/or > or =4 episodes of acute otitis media during follow-up. Nasopharyngeal aspirates, middle ear fluid specimens, and serum samples were analyzed for 8 common respiratory viruses. Of 1358 URI episodes, 642 (47%) occurred in the 78 children with FRRI. At least 1 virus was associated with 62% of these episodes, whereas the corresponding figure for children without FRRIs was 54%. The frequency of different viruses was similar in both groups, but the relative proportion of rhinovirus infections was slightly higher among children with FRRI. In conclusion, a specific viral etiology does not explain the excess of URI episodes in children with FRRI.


title: Do C-reactive protein and body mass index predict duration of mechanical ventilation in critically ill trauma patients?

text: BACKGROUND The predictive ability of body mass index (BMI) or C-reactive protein (CRP) as a simple, inexpensive, and dynamic marker of critical illness in patients requiring mechanical ventilation (MV) is unknown. This study was thus conducted to determine the incidence and presence of a relationship between the predictors of BMI or CRP and duration of MV in trauma patients admitted to the intensive care unit (ICU). METHODS This prospective observational study included 72 critically ill trauma patients. Admitted patients were categorized by duration of MV to Group A (< or =7 days) and Group B (>7 days). The biological status of patients was assessed by the serial measurement of CRP on admission to the ICU (T1), at 48 and 72 hours after admission, and on the day of beginning (T2) or discontinuation (T3) of MV. Data on BMI, serum albumin, and the Sequential Organ Failure Assessment (SOFA) score were also collected at T2 or T3. RESULTS At T3, the SOFA score, BMI, albumin, and CRP were significantly higher in patients in Group B compared with Group A (p<0.01). The incidence of low BMI (< or =20 kg/m2) or high CRP (>10 mg/L) in patients in Group B was significantly higher at T2 or T3 compared with Group A (p<0.05). At T3, CRP was determined as the most powerful predictor of >7 days of MV followed by BMI. CONCLUSION Both BMI and CRP, comparable with the SOFA score, can be used in estimating the risk of prolonged MV.


title: [Thymus-dependent nature of the antigens of enteropathogenic viruses].

text: The nature of antigens in enteropathogenic animal viruses--coronavirus--an agent of transmissive gastroenteritis of pigs (TGE) and pig enterovirus of serotype VI was studied. Basing on the results of the histomorphometric study of the white spleen pulp under the individual introduction of viruses and in combination with the lymphoid chalone it was established that the developing immune response has a thymus-dependent induction mechanism. The pharmacological stimulation of the T-system of animals suffering from virus gastroenteritis provides a positive therapeutic effect. The selective stimulation of the animal T-system may be considered as a promising trend in therapy of intestinal infections and as one of the possible ways to increase the immune response to the antigens of viral vaccines.


title: Cell- and region-specific expression of biliary glycoprotein and its messenger RNA in normal human colonic mucosa.

text: The localization of biliary glycoprotein (BGP) and its mRNA in normal colonic mucosa was studied by immunohistochemistry and in situ hybridization. BGP mRNA was confined to columnar epithelial cells and expressed abundantly in the superficial mature cells and at low levels in differentiating cells in the upper crypts. Epithelial expression of BGP coincided with that of BGP mRNA. Ultrastructurally, BGP was localized to microfilaments of the fuzzy coat of the columnar cells at the luminal surface and the upper crypts. Additionally, BGP was found in cryptal caveolated cells. The results are consistent with primary transcriptional regulation of BGP production and suggest that BGP synthesis is controlled by the degree of cytodifferentiation. The fuzzy-coat localization of BGP implies a role in nonspecific defense mechanisms against pathogens.


title: [The early warning signs of deterioration of severe acute respiratory syndrome].

text: OBJECTIVE To explore the risk factors related to severe cases of severe acute respiratory syndrome (SARS) in order to find the early warning signs of deterioration of this disease. METHODS Three hundred and fifty-five patients with severe SARS and 841 patients with regular SARS from Beijing were studied. RESULTS Patients with elder age or with comorbid conditions were more likely to develop into severe cases. Data also showed the following characteristics in those severe cases: sustained fever, tachycardia (pulse rate being over 100 per minute), persistent decrease in lymphocytes (< 0.9 x 10(9)/L), increase in neutrophils (> 7.1 x 10(9)/L, 80%), and rapid changes in abnormal chest X-ray. The Cox proportional hazard multi-variable stepwise analysis showed the prediction model of severe SARS included age, comorbid disease, body temperature being still abnormal after 2 days of hospitalization, neutrophil percentage began to increase steadily to more than 80% after 3 days of hospitalization, counts of lymphocytes persisted < 0.9 x 10(9)/L after 4 days of hospitalization. CONCLUSIONS According to patient's age, comorbid conditions, one can effectively predict the development of the severe SARS by closely monitoring temperature, pulse rate, the counts of lymphocytes and percent of neutrophils.


title: Previous bariatric surgery increases postoperative morbidity after sleeve gastrectomy for morbid obesity.

text: OBJECTIVES Sleeve gastrectomy (SG) has been used as the first step of a staged malabsorptive procedure for high-risk patients. More recently SG was proposed as an stand alone procedure in the treatment of morbidly obese patients. The aim of this study is to analyze perioperative outcome of morbid obese patients after SG. METHODS 301 patients, 201 women and 100 men, undergoing SG were retrospectively analyzed. SG was performed by 17 surgeons all member of the Club Coelio. The mean BMI was 44.7kg/m2 (27.4-70.3 kg/m2). 34 patients (11.3%) of our series had SG as revisional surgery. These revisional procedures consisted of 32 conversions from gastric banding, 1 conversion from vertical gastroplasty (VBG) and 1 from transoral endoscopic gastroplasty. Among the 32 patients that had revisional SG after a gastric banding, 13 bands were removed at least 3 months before the revisional SG and 19 bands were removed during the SG procedure. Endpoints were perioperative morbidity and mortality and potential risk factors for complications, mainly per or postoperative bleeding or leakage. RESULTS Overall mortality was 0% and morbidity was 10.3%. Perioperative bleeding occurred in 10 patients (3.3%), leakage in 12 patients (4%) patients and stenosis in 3 patients (1%). The risk of leakage was significantly higher after revisional bariatric surgery and in case of gastric perforation during surgery (p = 0.0001). Previous gastric banding is also associated with a higher risk of postoperative bleeding (p = 0.0006). CONCLUSIONS SG can be safely performed but patients and surgeons must be aware of a higher risk of postoperative complications when SG is proposed as a revisional surgery.


title: Biomechanical testing of epitenon suture strength in Achilles tendon repairs.

text: BACKGROUND Recent evidence that early, active mobilization protocols after Achilles tendon repairs increase recovery speed and strength make operative repair strength critical to positive outcomes after Achilles tendon ruptures. While previous research has focused on core (tendon proper) repair techniques, no previous literature has reported testing of core repairs augmented with epitenon sutures, which have been shown to increase the strength of repairs of flexor tendons of the hand. METHODS Five matched pairs of fresh frozen human Achilles tendons were tested with and without the addition of an epitenon suture to the core repair suture. All specimens were repaired using a No. 2 Ethibond Krakow locking loop core suture. The epitenon suture was added to one tendon randomly chosen from each pair, using a 4-0 nylon suture. All specimens were mounted on an MTS testing machine (MTS Systems Corp., Eden Prairie, MN) and loaded to failure, which was defined as a 1-cm gap formation. RESULTS The addition of epitenon sutures significantly increased the force necessary to produce a 2-mm gap as compared to core sutures alone by 74%, and it increased the average load to failure by 119%. Also, initial tendon stiffness was 173% greater in tendons reinforced with epitenon sutures. CONCLUSIONS This study demonstrates that greater resistance to gap formation, approximation of tissue ends, and tensile strength were achieved by the addition of an epitenon suture. Clinical relevance may improve healing by decreased gap formation at the repair site and a lower risk of adhesion formation.


Kansas state university.


Cell-based tests tackle predicting safety of antibody drugs.


title: Regulation of transport of the dopamine D1 receptor by a new membrane-associated ER protein.

text: Many structural determinants for G protein-coupled receptor (GPCR) functions have been defined, but little is known concerning the regulation of their transport from the endoplasmic reticulum (ER) to the cell surface. Here we show that a carboxy-terminal hydrophobic motif, FxxxFxxxF, which is highly conserved among GPCRs, functions independently as an ER-export signal for the dopamine D1 receptor. A newly identified ER-membrane-associated protein, DRiP78, binds to this motif. Overexpression or sequestration of DRiP78 leads to retention of D1 receptors in the ER, reduced ligand binding, and a slowdown in the kinetics of receptor glycosylation. Our results indicate that DRiP78 may regulate the transport of a GPCR by binding to a specific ER-export signal.