title: Prevalence of various enteropathogens in the feces of diarrheic and healthy calves.

text: The presence of various enteropathogens was examined in the feces of homebred dairy calves reared in a restricted geographical area of France (North West of County of Indre-et-Loire) during winter 1983-1984. Two distinct surveys were carried on: a case-control study including 32 diarrheic calves and 21 healthy calves bred in 53 different farms; and a separate study on nine diarrheic calves in another farm. The following infectious agents were looked for, by specific methods of detection: Escherichia coli K99 and E. coli lethal for mice, Salmonella species, Yersinia enterocolitica, Campylobacter jejuni, enterotoxigenic Clostridium perfringens, Chlamydia psittaci, rotaviruses, coronaviruses, Cryptosporidium. In the case-control survey, no enterotoxigenic E. coli (K99+) was detected in either group of calves. Four agents were more often detected in diarrheic calves than in healthy calves, i.e. rotavirus (12/32 vs 1/21), lethal E. coli (6/32 vs 1/21), Cryptosporidium (2/32 vs 0/21) and Salmonella typhimurium (1/32 vs 0/21). One at least of these four agents was present in 16 diarrheic calves (50%) vs only 2 healthy calves (10%) (P less than 0.01). On the other hand, the occurrence of Campylobacter jejuni and of C. perfringens, enterotoxin was similar in both groups of calves, accounting respectively for about 20% and 10% of total calves. Moreover, coronavirus-like particles were significatively associated with healthy calves (7/32 vs 11/21; P less than 0.05). In the other study, all the main categories of enteropathogens were detected throughout the period of observation in the same farm with the exception of enterotoxigenic E. coli. But each calf taken individually was rarely shedding more than two agents at a time. In addition, specific antibodies against C. perfringens enterotoxin, as tested in an ELISA test, were present in the serum of all the calves examined in both surveys. This study confirms the primary role of rotavirus and Cryptosporidium as agents of diarrhea in calves under three weeks. It also suggests the possible participation of E. coli strains that are lethal for mice and underlines the potential hazard for human health of bovine reservoirs of Campylobacter jejuni and enterotoxigenic C. perfringens.


title: [Apnea as a presenting symptom in human metapneumovirus infection].

text: Human metapneumovirus (hMPV), a recently described pathogen of lower respiratory tract infections (LRTI), has been detected in 5,4% of Chilean infants hospitalized for LRTI whom are negative for adenovirus, respiratory syncytial virus, influenza and parainfluenza viruses. hMPV may cause bronchiolitis or pneumonia in hospitalized patients, and ocassionally require admission to intensive care units and mechanical ventilation. The infection has been associated with apnea, especially in preterm infants. Nosocomial dissemination has also been described. We present the case of a one-month-of age premature infant with apnea, and infection caused by hMPV of probable nosocomial aquisition. Clinical features of hMPV infection are reviewed and its association with apnea and nosocomial transmission is discussed. hMPV should be included in the routine diagnosis of respiratory viruses in infants with apnea and should be considered among the respiratory pathogens associated with nosocomial transmission.


title: Cell biology of virus entry, replication, and pathogenesis.

text: The Keystone Symposium on Cell Biology of Virus Entry, Replication, and Pathogenesis held in Taos, New Mexico February 29 to March 5, 2000 to a large degree fulfilled its purpose to facilitate interdisciplinary exchange of information. The Keynote Address by Sir John J. Skehel (National Institute for Medical Research, London) initiated discussion on the antigenic analyses of influenza virus hemagglutinins. Subsequent topics covered the earliest events in viral receptor-mediated entry through membrane fusion to virus assembly, genetics, pathogenesis, and immunology. While a significant number of taxonomically different viruses was discussed, several common themes emerged from plenary sessions and poster workshops. A few selected topics are highlighted below.


Products of the polymerase-encoding region of the coronavirus IBV.


title: SARS-CoV-2 Entry Genes Are Most Highly Expressed in Nasal Goblet and Ciliated Cells within Human Airways.

text: The SARS-CoV-2 coronavirus, the etiologic agent responsible for COVID-19 coronavirus disease, is a global threat. To better understand viral tropism, we assessed the RNA expression of the coronavirus receptor, ACE2, as well as the viral S protein priming protease TMPRSS2 thought to govern viral entry in single-cell RNA-sequencing (scRNA-seq) datasets from healthy individuals generated by the Human Cell Atlas consortium. We found that ACE2, as well as the protease TMPRSS2, are differentially expressed in respiratory and gut epithelial cells. In-depth analysis of epithelial cells in the respiratory tree reveals that nasal epithelial cells, specifically goblet/secretory cells and ciliated cells, display the highest ACE2 expression of all the epithelial cells analyzed. The skewed expression of viral receptors/entry-associated proteins towards the upper airway may be correlated with enhanced transmissivity. Finally, we showed that many of the top genes associated with ACE2 airway epithelial expression are innate immune-associated, antiviral genes, highly enriched in the nasal epithelial cells. This association with immune pathways might have clinical implications for the course of infection and viral pathology, and highlights the specific significance of nasal epithelia in viral infection. Our findings underscore the importance of the availability of the Human Cell Atlas as a reference dataset. In this instance, analysis of the compendium of data points to a particularly relevant role for nasal goblet and ciliated cells as early viral targets and potential reservoirs of SARS-CoV-2 infection. This, in turn, serves as a biological framework for dissecting viral transmission and developing clinical strategies for prevention and therapy.


title: Discovering severe acute respiratory syndrome coronavirus 3CL protease inhibitors: virtual screening, surface plasmon resonance, and fluorescence resonance energy transfer assays.

text: An integrated system has been developed for discovering potent inhibitors of severe acute respiratory syndrome coronavirus 3C-like protease (SARS-CoV 3CL(pro)) by virtual screening correlating with surface plasmon resonance (SPR) and fluorescence resonance energy transfer (FRET) technologies-based assays. The authors screened 81,287 small molecular compounds against SPECS database by virtual screening; 256 compounds were subsequently selected for biological evaluation. Through SPR technology-based assay, 52 from these 256 compounds were discovered to show binding to SARS-CoV 3CL(pro). The enzymatic inhibition activities of these 52 SARS-CoV 3CL(pro) binders were further applied to FRET-based assay, and IC(50) values were determined. Based on this integrated assay platform, 8 new SARS-CoV 3CL(pro) inhibitors were discovered. The fact that the obtained IC(50) values for the inhibitors are in good accordance with the discovered dissociation equilibrium constants (K(D)s) assayed by SPR implied the reliability of this platform. Our current work is hoped to supply a powerful approach in the discovery of potent SARS-CoV 3CL(pro) inhibitors, and the determined inhibitors could be used as possible lead compounds for further research.


title: Current use and development of vaccines for Japanese encephalitis.

text: BACKGROUND Japanese encephalitis (JE) is a significant cause of human morbidity and mortality throughout Asia. Vaccines for JE have been available for many years and their use has been effective in reducing the incidence of JE disease in several countries but, as disease incidence has decreased, concerns regarding adverse events following immunisation have increased. OBJECTIVE To review existing JE vaccines and new candidates in advanced preclinical or clinical evaluation. METHODS The review primarily covers published and some unpublished literature from the past decade describing current use of approved JE vaccines in various parts of the world, and advanced development and clinical testing of alternative vaccine candidates. RESULTS/CONCLUSION There is a clear need for additional licensing of existing or new JE vaccines. Several promising candidates are currently in use or completing clinical trials.


title: Viruses and virus-like particles detected during examination of feces from calves and piglets with diarrhea.

text: A total of 763 fecal or intestinal samples from diarrheic calves and piglets were examined for viral content by immunofluorescence, electron microscopy or cell culture. Routine fluorescent antibody and cultural tests detected rotavirus (n=126), coronavirus (n=80) and bovine viral diarrhea virus (n=13). Electron microscopy detected rotaviruses (n=24) and coronaviruses (n=17) not identified by standard fluorescent antibody tests. Other viruses detected by electron microscopy included Breda virus-like particles (n=49), astroviruses (n=1), caliciviruses (n=1), rhabdoviruses (n=1), parvoviruses (n=2), enteroviruses (n=3), togavirus-like particles (n=2), and "chained" particles (n=5). Mixtures of several of the viruses were detected in a number of fecal samples.The survey emphasized the value of electron microscopy as a broad-spectrum diagnostic tool.


Isolation and genome characterization of porcine reproductive and respiratory syndrome virus in P.R. China.


TRICHOMONAS.


title: Impact of a severe acute respiratory syndrome outbreak in the emergency department: an experience in Taiwan.

text: OBJECTIVES To evaluate the impact of a severe acute respiratory syndrome (SARS) outbreak in the emergency department (ED). METHODS Computerised records of all ED visits in January and May 2003 were analysed and compared, representing before and during the SARS epidemic respectively. Data were grouped into two categories. Group 1 was the indicators of impact on patients, including visitor's condition classification, number of patients that died on arrival (DOA), received cardiopulmonary resuscitation, underwent endotracheal intubation, needed mechanical ventilation, discharged against medical advice (AAD), died in the ED, and the admission rate to wards. Group 2 was the indicators of impact on the quality of medical care, including number of visits that returned within 72 hours (early returns), underwent chest radiography, upper abdomen sonography or computed tomography, and the length of stay. RESULTS There were 6650 and 3901 consecutive encounters in January and May 2003 respectively. There were significant differences on condition classifications (p = 0.000), increased rate of patients that underwent endotracheal intubation (p = 0.003), needed mechanical ventilation (p = 0.020), and admission (p = 0.000). The rate of AAD decreased significantly (p = 0.024). There was no significant difference on early returns, although the length of stay in the ED increased (p = 0.043). The number of visits that underwent chest radiological examination increased (p = 0.000) and upper abdomen sonography (p = 0.007) decreased significantly in May. CONCLUSIONS SARS had an impact on the medical service system and decreased visits by 40% in the ED. Patients visiting the ED had more severe conditions than before. The impact of SARS on quality of medical care can be minimised when adequate infection control measures are applied.


Coronavirus cell-associated RNA-dependent RNA polymerase.


title: Air cleaning technologies: an evidence-based analysis.

text: OBJECTIVE This health technology policy assessment will answer the following questions: When should in-room air cleaners be used?How effective are in-room air cleaners?Are in-room air cleaners that use combined HEPA and UVGI air cleaning technology more effective than those that use HEPA filtration alone?What is the Plasmacluster ion air purifier in the pandemic influenza preparation plan?The experience of severe acute respiratory syndrome (SARS) locally, nationally, and internationally underscored the importance of administrative, environmental, and personal protective infection control measures in health care facilities. In the aftermath of the SARS crisis, there was a need for a clearer understanding of Ontario's capacity to manage suspected or confirmed cases of airborne infectious diseases. In so doing, the Walker Commission thought that more attention should be paid to the potential use of new technologies such as in-room air cleaning units. It recommended that the Medical Advisory Secretariat of the Ontario Ministry of Health and Long-Term Care evaluate the appropriate use and effectiveness of such new technologies. Accordingly, the Ontario Health Technology Advisory Committee asked the Medical Advisory Secretariat to review the literature on the effectiveness and utility of in-room air cleaners that use high-efficiency particle air (HEPA) filters and ultraviolet germicidal irradiation (UVGI) air cleaning technology. Additionally, the Ontario Health Technology Advisory Committee prioritized a request from the ministry's Emergency Management Unit to investigate the possible role of the Plasmacluster ion air purifier manufactured by Sharp Electronics Corporation, in the pandemic influenza preparation plan. CLINICAL NEED Airborne transmission of infectious diseases depends in part on the concentration of breathable infectious pathogens (germs) in room air. Infection control is achieved by a combination of administrative, engineering, and personal protection methods. Engineering methods that are usually carried out by the building's heating, ventilation, and air conditioning (HVAC) system function to prevent the spread of airborne infectious pathogens by diluting (dilution ventilation) and removing (exhaust ventilation) contaminated air from a room, controlling the direction of airflow and the air flow patterns in a building. However, general wear and tear over time may compromise the HVAC system's effectiveness to maintain adequate indoor air quality. Likewise, economic issues may curtail the completion of necessary renovations to increase its effectiveness. Therefore, when exposure to airborne infectious pathogens is a risk, the use of an in-room air cleaner to reduce the concentration of airborne pathogens and prevent the spread of airborne infectious diseases has been proposed as an alternative to renovating a HVAC system. Airborne transmission is the spread of infectious pathogens over large distances through the air. Infectious pathogens, which may include fungi, bacteria, and viruses, vary in size and can be dispersed into the air in drops of moisture after coughing or sneezing. Small drops of moisture carrying infectious pathogens are called droplet nuclei. Droplet nuclei are about 1 to 5μm in diameter. This small size in part allows them to remain suspended in the air for several hours and be carried by air currents over considerable distances. Large drops of moisture carrying infectious pathogens are called droplets. Droplets being larger than droplet nuclei, travel shorter distances (about 1 metre) before rapidly falling out of the air to the ground. Because droplet nuclei remain airborne for longer periods than do droplets, they are more amenable to engineering infection control methods than are droplets. Droplet nuclei are responsible for the airborne transmission of infectious diseases such as tuberculosis, chicken pox (varicella), measles (rubeola), and dessiminated herpes zoster, whereas close contact is required for the direct transmission of infectious diseases transmitted by droplets, such as influenza (the flu) and SARS. THE TECHNOLOGY In-room air cleaners are supplied as portable or fixed devices. Fixed devices can be attached to either a wall or ceiling and are preferred over portable units because they have a greater degree of reliability (if installed properly) for achieving adequate room air mixing and airflow patterns, which are important for optimal effectiveness. Through a method of air recirculation, an in-room air cleaner can be used to increase room ventilation rates and if used to exhaust air out of the room it can create a negative-pressure room for airborne infection isolation (AII) when the building's HVAC system cannot do so. A negative-pressure room is one where clean air flows into the room but contaminated air does not flow out of it. Contaminated room air is pulled into the in-room air cleaner and cleaned by passing through a series of filters, which remove the airborne infectious pathogens. The cleaned air is either recirculated into the room or exhausted outside the building. By filtering contaminated room air and then recirculating the cleaned air into the room, an in-room air cleaner can improve the room's ventilation. By exhausting the filtered air to the outside the unit can create a negative-pressure room. There are many types of in-room air cleaners. They vary widely in the airflow rates through the unit, the type of air cleaning technology used, and the technical design. Crucial to maximizing the efficiency of any in-room air cleaner is its strategic placement and set-up within a room, which should be done in consultation with ventilation engineers, infection control experts, and/or industrial hygienists. A poorly positioned air cleaner may disrupt airflow patterns within the room and through the air cleaner, thereby compromising its air cleaning efficiency. The effectiveness of an in-room air cleaner to remove airborne pathogens from room air depends on several factors, including the airflow rate through the unit's filter and the airflow patterns in the room. Tested under a variety of conditions, in-room air cleaners, including portable or ceiling mounted units with either a HEPA or a non-HEPA filter, portable units with UVGI lights only, or ceiling mounted units with combined HEPA filtration and UVGI lights, have been estimated to be between 30% and 90%, 99% and 12% and 80% effective, respectively. However, and although their effectiveness is variable, the United States Centers for Disease Control and Prevention has acknowledged in-room air cleaners as alternative technology for increasing room ventilation when this cannot be achieved by the building's HVAC system with preference given to fixed recirculating systems over portable ones. Importantly, the use of an in-room air cleaner does not preclude either the need for health care workers and visitors to use personal protective equipment (N95 mask or equivalent) when entering AII rooms or health care facilities from meeting current regulatory requirements for airflow rates (ventilation rates) in buildings and airflow differentials for effective negative-pressure rooms. The Plasmacluster ion technology, developed in 2000, is an air purification technology. Its manufacturer, Sharp Electronics Corporation, says that it can disable airborne microorganisms through the generation of both positive and negative ions. (1) The functional unit is the hydroxyl, which is a molecule comprised of one oxygen molecule and one hydrogen atom. Plasmacluster ion air purifier uses a multilayer filter system composed of a prefilter, a carbon filter, an antibacterial filter, and a HEPA filter, combined with an ion generator to purify the air. The ion generator uses an alternating plasma discharge to split water molecules into positively and negatively charged ions. When these ions are emitted into the air, they are surrounded by water molecules and form cluster ions which are attracted to airborne particles. The cluster ion surrounds the airborne particle, and the positive and negative ions react to form hydroxyls. These hydroxyls steal the airborne particle's hydrogen atom, which creates a hole in the particle's outer protein membrane, thereby rendering it inactive. Because influenza is primarily acquired by large droplets and direct and indirect contact with an infectious person, any in-room air cleaner will have little benefit in controlling and preventing its spread. Therefore, there is no role for the Plasmacluster ion air purifier or any other in-room air cleaner in the control of the spread of influenza. Accordingly, for purposes of this review, the Medical Advisory Secretariat presents no further analysis of the Plasmacluster. REVIEW STRATEGY The objective of the systematic review was to determine the effectiveness of in-room air cleaners with built in UVGI lights and HEPA filtration compared with those using HEPA filtration only. The Medical Advisory Secretariat searched the databases of MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, INAHATA (International Network of Agencies for Health Technology Assessment), Biosis Previews, Bacteriology Abstracts, Web of Science, Dissertation Abstracts, and NIOSHTIC 2. A meta-analysis was conducted if adequate data was available from 2 or more studies and where statistical and clinical heterogeneity among studies was not an issue. Otherwise, a qualitative review was completed. The GRADE system was used to summarize the quality of the body of evidence comprised of 1 or more studies. SUMMARY OF FINDINGS There were no existing health technology assessments on air cleaning technology located during the literature review. The literature search yielded 59 citations of which none were retained. (ABSTRACT TRUNCATED)


title: Colostrum deficiency in mule deer fawns: identification, treatment and influence on neonatal mortality.

text: Glutaraldehyde coagulation test, zinc sulfate turbidity test, and total protein refractometry were adapted for use in detecting failure of passive transfer of colostral immunoglobulins to mule deer fawns (Odocoileus hemionus). The results of all three tests were similar. Serum total protein concentration was directly correlated to gamma globulin concentration and gave the best indication of morbidity and mortality. Thirteen of 13 fawns with serum total protein concentrations of 5 g/dl or less at 1 to 7 days of age developed diarrhea and died before 17 days of age. Only 1 of 14 fawns having a serum protein concentration above this level became sick and died. Seven of 13 fawns that had serum total protein concentrations of 5 g/dl or less, and that had already developed diarrhea, were given 20 ml of plasma per kg body weight. Although this increased their serum gamma globulin concentrations 0.3 g/dl, none survived. Administration of bovine colostrum to one fawn increased its serum gamma globulin concentration suggesting that mule deer fawns are able to absorb gamma globulins from bovine colostrum.


title: Epidemiology of coronavirus-associated respiratory tract infections and the role of rapid diagnostic tests: a prospective study.

text: 1. Coronaviruses accounted for 1.6% (98/6272) of respiratory tract infections based on nasopharyngeal aspirate samples. 2. HCoV-OC43 was the most common coronavirus detected,followed by HCoV-NL63, CoVHKU1,and HCoV-229E. 3. Although CoV-HKU1 infections were most often associated with the upper respiratory tract, more severe illness (pneumonia,acute bronchiolitis, and asthmatic exacerbation) may occur, especially in those with underlying disease. In young children, CoV-HKU1 infection is associated with a high rate of febrile seizures (50%). 4. CoV-HKU1 and HCoV-OC43 infections peaked in winter, in contrast to HCoV-NL63, which mainly occurred in early summer and autumn, but was absent in winter. 5. Reverse transcriptase polymerase chain reaction is useful for the rapid diagnosis of coronavirus infections.


title: Development of novel electrospun absorbable polycaprolactone (PCL) scaffolds for hernia repair applications.

text: INTRODUCTION Permanent/nonresorbable hernia repair materials rely on profibrotic wound healing, and repair sites are commonly composed of disorganized tissue with inferior mechanical strength and risk of reherniation. Resorbable electrospun scaffolds represent a novel class of biomaterials, which may provide a unique platform for the design of advanced soft tissue repair materials. These materials are simple, inexpensive, nonwoven materials composed of polymer fibers that readily mimic the natural extracellular matrix. The primary goal of the present study was to evaluate the physiomechanical properties of novel electrospun scaffolds to determine their suitability for hernia repair. Based on previous experimentation, scaffolds possessing ≥ 20 N suture retention strength, ≥ 20 N tear resistance, and ≥ 50 N/cm tensile strength are appropriate for hernia repair. METHODS Six novel electrospun scaffolds were fabricated by varying combinations of polymer concentration (10-12 %) and flow rate (3.5-10 mL/h). Briefly, poly(ε-caprolactone) (PCL) was dissolved in a solvent mixture and electrospun onto a planar metal collector, yielding sheets with randomly oriented fibers. Physiomechanical properties were evaluated through scanning electron microscopy, laser micrometry, and mechanical testing. RESULTS Scanning electron micrographs demonstrated fiber diameters ranging from 1.0 ± 0.1 μm (10 % PCL, 3.5 mL/h) to 1.5 ± 0.2 μm (12 % PCL, 4 mL/h). Laser micrometry demonstrated thicknesses ranging from 0.72 ± 0.07 mm (12 % PCL, 10 mL/h) to 0.91 ± 0.05 mm (10 % PCL, 3.5 mL/h). Mechanical testing identified two scaffolds possessing suture retention strengths ≥ 20 N (12 % PCL, 10 mL/h and 12 % PCL, 6 mL/h), and no scaffolds possessing tear resistance values ≥ 20 N (range, 4.7 ± 0.9 N to 10.6 ± 1.8 N). Tensile strengths ranged from 35.27 ± 2.08 N/cm (10 % PCL, 3.5 mL/h) to 81.76 ± 15.85 N/cm (12 % PCL, 4 mL/h), with three scaffolds possessing strengths ≥ 50 N/cm (12 % PCL, 10 mL/h; 12 % PCL, 6 mL/h; 12 % PCL, 4 mL/h). CONCLUSIONS Two electrospun scaffolds (12 % PCL, 10 mL/h and 12 % PCL, 6 mL/h) possessed suture retention and tensile strengths appropriate for hernia repair, justifying evaluation in a large animal model. Additional studies examining advanced methods of fabrication may further improve the unique properties of these scaffolds, propelling them into applications in a variety of clinical settings.


Laparoscopic Roux-en-Y gastric bypass with single transumbilical incision--GelPoint®.


title: Nasal plugs for preventing respiratory infections.

text: Nasal plugs were made from an N-95 respirator, surgical mask or a cotton ball and inserted into the nares of volunteer healthcare workers for 30 min. Initial and persistent respiratory resistance, choking sensation, and discomfort in the mouth and nose areas were recorded for the three different nasal plugs, the N-95 respirator and a surgical mask. Nasal plugs were more convenient and better tolerated than the masks. The ability of the nasal plug material to prevent infection by droplet transmission was also tested. A piece of each material was placed on a blood agar plate, the volunteer coughed onto the plate and the material was removed. Bacterial colonies only grew in the areas not previously covered by the nasal plug material. The cotton ball nasal plug is probably as effective as the N-95 respirator or surgical masks at preventing infection, and is much cheaper.


title: Immunisation registers in Canada: progress made, current situation, and challenges for the future.

text: Immunisation registers have the capacity to capture data on the administration of vaccine doses at the individual level within the population and represent an important tool in assessing immunisation coverage and vaccine uptake. In 1999, the National Advisory Committee on Immunization recommended that a network of immunisation registers be established in Canada. The Canadian Immunization Registry Network (CIRN) was established to coordinate the development of standards and facilitate the sharing of knowledge and experience to develop a national network of such registers. In 2003, the National Immunization Strategy identified immunisation registers as an important component in improving national immunisation surveillance. In addition, there has been consistent public and professional interest in a national immunisation register being available and considerable progress has been made in developing technologies to facilitate the capture of immunisation-related data. More specifically, the automated identification of vaccines, through the use of barcodes on vaccines, will facilitate collection of data related to administered vaccine doses. Nevertheless, challenges remain in the implementation of immunisation registers in all Canadian provinces and territories such that Canada still does not currently have a fully functional network of immunisation registers with the capacity to be interoperable between jurisdictions and to allow for data to be captured at the national level.


title: Coronavirus-like Particles in the Feces of a Cat with Diarrhea.

text: Coronavirus-like particles were visualized in the feces of a young domestic shorthair female cat with diarrhea. On the surface projections, these particles could be distinguished from the enteric coronavirus-like particles of human, dog, cattle and monkey origin. They appeared morphologically similar to a feline enteric coronavirus recently described by other authors. A precipitin antigen was detected in the cat feces by counterimmunoelectroosmophoresis using a rabbit antibovine coronavirus serum.


title: Cryptosporidiosis in neonatal calves: 277 cases (1986-1987).

text: From January 1986 through December 1987, 277 cases of cryptosporidiosis in calves were diagnosed by the South Dakota State University Diagnostic Laboratory. Cryptosporidium sp was the only pathogen identified in 142 (51.3%) of the calves. Concurrent infections with rotavirus, coronavirus, Escherichia coli, Salmonella sp, bovine viral diarrhea virus, or other pathogens were identified in the remaining 135 calves. After elimination of cases involving autolyzed specimens or calves with chronic diarrhea, records of 11 calves with acute, severe cryptosporidiosis were identified in which Cryptosporidium sp was the only pathogen.


title: [Occupational health recommendations for lifeguards in aquatic emergencies in the Covid-19 era: prevention, rescue and resuscitation.]

text: Severe acute respiratory syndrome (SARS-CoV-2), which causes coronavirus disease 2019 (Covid-19), is highly contagious. Lifeguards are the first line of response in aquatic emergencies and they will suffer a strong exposure to risk this first summer of the Covid-19 era, so their occupational health must be rethought in their professional practice during the new normal. The main public health measure to prevent drowning is prevention, but when this fails and assistance or rescue is required, in most interventions, distancing will not be possible. The limitation of personal protective equipment (PPE) for rescue is a reality that must be known and that can affect the health of the lifeguard. A review of the current literature aimed at avoiding or minimizing the risk of contagion in the interventions carried out by rescuers in the Covid-19 era was performed. This article provides structured information on the prevention of contagion in lifeguards, the potential risks, the available PPE, and the recommendations for its proper use during rescue or prehospital care in aquatic settings.


Deubiquitination, a new function of the severe acute respiratory syndrome coronavirus papain-like protease?


title: Neutralizing test of hemagglutinating encephalomyelitis virus (HEV) in FS-L3 cells cultured without serum.

text: FS-L3 cells, originating from porcine kidney, were used for propagation of Hemagglutinating encephalomyelitis virus (HEV) and development of a virus neutralizing (VN) test. Sera of pigs, rats, cows and dogs had VN activities to HEV. On the other hand, sera of mice, rabbits, goats, sheep, horses, cats, chickens, hamsters and human did not have measurable VN activities, although these sera had high HI activities. Our results support the idea that the VN is a more reliable measure of HEV infection than the conventionally used HI test.


title: Viremic co-infections in children with allogeneic haematopoietic stem cell transplantation are predominated by human polyomaviruses.

text: BACKGROUND Viral infections remain the cause of key complications following haematopoietic stem cell transplantation (HSCT). The impact of multiple, concurrent viral reactivations/infections remains to be delineated. METHODS The clinical correlates of single or multiple viremic infections following HSCT and especially the occurrence of respiratory viruses in the bloodstream were investigated. We retrospectively searched for 23 viruses in a total of 184 sera from 53 paediatric patients. The time-points of interest were pre-HSCT, one, two and three months post-HSCT, and at discharge or death. The viruses were analyzed by quantitative or qualitative PCR. RESULTS Of the 53 patients, 13 (25%) had viraemias by multiple viruses and 27 (51%) by a single virus. Thirteen patients (25%) had no viruses detected by PCR during the study period. In the children with viremic co-infections, polyomaviruses predominated over herpes viruses. Nearly half the patients, 24/53 (45%) had a polyomavirus in their serum at one or more time-points. At 12/15 time-points and in 11/13 patients with co-infections polyomaviruses were involved, compared with 6/15 time-points and 6/13 patients for cytomegalovirus. Acute graft-versus-host disease (GvHD) and steroid use were significant risk factors for the viraemias caused by more than one virus. CONCLUSIONS Viral co-detection is a common finding in children undergoing HSCT. With large-scale viral screening also viruses other than CMV could be found as potential pathogens. In this study, BKPyV predominated over CMV as a contributor in viraemias caused by multiple viruses in children receiving HSCT.


title: Clinical nurse specialists: state of the profession and challenges ahead.

text: Clinical nurse specialists (CNSs) are enjoying a rebirth. As health science and healthcare increase in complexity, it is critical that nurse experts provide leadership to improve patient care, advance nursing practice, and strengthen healthcare delivery systems. CNSs with specialty expertise combined with competencies in patient care, nursing practice, and healthcare delivery systems are essential to translating the products of our vast research enterprise into policies and practices that serve the patient. Many challenges loom. New diseases have emerged; treatments change constantly. We are newly aware of the gravity of the perils posed by natural and man-made disasters. Patients use complimentary and alternative health practices but we do not understand the power and risks of these approaches. Information technology makes possible new approaches to educating nurses and patients and tracking clinical outcomes. CNSs are vital to building a healthcare system that is evidence based, patient centered, outcome effective, safe, ethical, interdisciplinary, and cost-effective.


title: Attitudes, concerns, perceived impact and coping strategies for avian influenza among the first year medical students and interns in Tehran University of Medical Sciences.

text: To study and compare the attitudes, concerns, perceived impact and coping strategies for avian influenza (AI) among the first year medical students (FYMS) and interns in Tehran University of Medical Sciences. This was a cross sectional study carried out on FYMS (n=158) and interns (n=158) in 2008. The data collection tool was a questionnaire containing 37 questions in five parts. The three choices including "agree, disagree and unsure" were considered for all questions. We used Chi-square and Fisher's exact tests for analysis. Most of FYMS and interns (78.2%) believed their health would be depended on the care of their selves. Most of them (95.3%) believed that if they knew avian flu better, they could be more prepared for it. The majority were concerned about risk to their health from their work (62.7%). Most (67.7%) accepted the risk and only 5 (1.6%) would consider stopping work. For non-work concerns, 70.9% were concerned about their spouses/sexual partners and 65.8% about their children. For perceived impact, most (66.5%) believed that they would feel stressed at work and the majority (74.4%) expected an increased workload. FYMS and interns have positive attitudes but major concerns about contracting AI and its relation to medical practice.


title: [Environment and occurrence of epidemics].

text: Epidemic diseases are defined as the temporary accumulation of dangerous infections diseases in certain areas. They are based on the principles of monocausality of Henle and Koch and represent the most important group of monocausal infectious diseases. Tight ecological relations exist between epidemic diseases and environment. The ecosystem encloses all living organisms as well as the inanimate environment (e.g. soil, water, air, waste). Some chains of infections are demonstrated with American equine encephalitis, rabies, Aujeszky's disease, salmonellosis and so-called soil-born epidemic diseases as examples. Any change of the environment causes enduring effects on the development and progression of epidemic diseases. Many epidemic diseases correlate with certain geographical zones. The variation of climate for instance led to an alteration of the occurrence of epidemic diseases caused by streptococci and staphylococci. A further evidence for the relation of environment and occurrence of epidemic diseases are the seasonal and secular rhythmics in the progress of epidemic diseases. On the basic of new techniques (finger-printing, hybridisation, sequence analysis) the origin of new types of infectious diseases such as American equine encephalitis and infections with Parvo- and Corona viruses can be explained. Finally medicine has to face this thesis: In contrast to the Darwinian theory the recombination of two different infectious agents in a common host may cause evolutionary jumps.


title: Proliferative growth of SARS coronavirus in Vero E6 cells.

text: An isolate of SARS coronavirus (strain 2003VA2774) was obtained from a patient and used to infect Vero E6 cells. The replication cycle of the virus was followed from 1 to 30 h post-infection (p.i.). It was surprising to observe the swift growth of this human virus in Vero cells. Within the first hour of infection, the most obvious ultrastructural change was the proliferation of the Golgi complexes and related vesicles accompanied by swelling of some of the trans-Golgi sacs. Extracellular virus particles were present by 5 h p.i. in about 5 % of the cells and this increased dramatically to about 30 % of the cell population within an hour (6 h p.i.). Swollen Golgi sacs contained virus nucleocapsids at different stages of maturation. These virus precursors were also in large vacuoles and in close association with membrane whorls. The membrane whorls could be the replication complexes, since they appeared rather early in the replication cycle. As infection progressed from 12 to 21 h p.i., the cytoplasm of the infected cells was filled with numerous large, smooth-membraned vacuoles containing a mixture of mature virus and spherical cores. Several of these vacuoles were close to the cell periphery, ready to export out the mature progeny virus particles via exocytosis. By 24 to 30 h p.i., crystalline arrays of the extracellular virus particles were seen commonly at the cell surface.


title: Severe acute respiratory syndrome can be mild in children.

text: A 13-year-old boy contracted severe acute respiratory syndrome (SARS). The clinical course was mild, and no specific treatment was given. His recovery was spontaneous and complete. SARS in children can be a mild and self-limiting disease. The use of the World Health Organization/Centers for Disease Control and Prevention case definitions may not be adequate for the diagnosis of SARS in children.


title: Immunomodulatory peptide from cystatin, a natural cysteine protease inhibitor, against leishmaniasis as a model macrophage disease.

text: Cystatin, a natural cysteine protease inhibitor, has strong antileishmanial activity, which is due to its potential to induce nitric oxide (NO) generation from macrophages. Cysteine protease-inhibitory activity and NO-up-regulatory activity correspond to different regions, as revealed by the dissection of cystatin cDNA into nonoverlapping fragments. By using synthetic overlapping peptides, the NO-up-regulatory activity was found to be confined to a 10-mer sequence. In addition to having reasonable inhibitory effects on amastigote multiplication within macrophages (50% inhibitory concentration, 5.2 microg/ml), 97 and 93% suppression, respectively, of liver and spleen parasite burdens was achieved with the 10-mer peptide at a dose of 0.5 mg/kg of body weight/day, given consecutively for 4 days along with a suboptimal dose of gamma interferon in a 45-day mouse model of visceral leishmaniasis. Peptide treatment modulated the levels of cytokine secretion by infected splenocytes, with increased levels of interleukin-12 and tumor necrosis factor alpha and increased inducible NO synthase production, and also resulted in resistance to reinfection. The generation of a natural peptide from cystatin with robust immunomodulatory potential may therefore provide a promising therapeutic agent for macrophage-associated diseases.


Dual camera colon capsule endoscopy increases detection of colorectal lesions.


title: High dose intravenous methylprednisolone in the treatment of severe acute respiratory syndrome.

text: The case of a 72-year-old woman with probable severe acute respiratory syndrome is reported. While on treatment with ribavirin and antibiotics (for community-acquired pneumonia), the patient continued to have progressive clinical deterioration and chest radiographic evidence of respiratory deterioration. Pulse dose intravenous corticosteroids were used in an unsuccessful attempt to treat the inflammatory component of this respiratory illness.


title: Mutational analysis of aminopeptidase N, a receptor for several group 1 coronaviruses, identifies key determinants of viral host range.

text: Feline coronavirus (FCoV), porcine transmissible gastroenteritis coronavirus (TGEV), canine coronavirus (CCoV), and human coronavirus HCoV-229E, which belong to the group 1 coronavirus, use aminopeptidase N (APN) of their natural host and feline APN (fAPN) as receptors. Using mouse-feline APN chimeras, we identified three small, discontinuous regions, amino acids (aa) 288 to 290, aa 732 to 746 (called R1), and aa 764 to 788 (called R2) in fAPN that determined the host ranges of these coronaviruses. Blockade of infection with anti-fAPN monoclonal antibody RG4 suggested that these three regions lie close together on the fAPN surface. Different residues in fAPN were required for infection with each coronavirus. HCoV-229E infection was blocked by an N-glycosylation sequon present between aa 288 to 290 in murine APN. TGEV required R1 of fAPN, while FCoV and CCoV required both R1 and R2 for entry. N740 and T742 in fAPN and the homologous R741 in human APN (hAPN) were key determinants of host range for FCoV, TGEV, and CCoV. Residue N740 in fAPN was essential only for CCoV receptor activity. A conservative T742V substitution or a T742R substitution in fAPN destroyed receptor activity for the pig, dog, and cat coronaviruses, while a T742S substitution retained these receptor activities. Thus, the hydroxyl on T742 is required for the coronavirus receptor activity of fAPN. In hAPN an R741T substitution caused a gain of receptor activity for TGEV but not for FCoV or CCoV. Therefore, entry and host range of these group 1 coronaviruses depend on the ability of the viral spike glycoproteins to recognize small, species-specific amino acid differences in the APN proteins of different species.


title: Mid-term follow-up after laparoscopic sleeve gastrectomy in obese adolescents.

text: BACKGROUND Laparoscopic sleeve gastrectomy (LSG) is gaining credibility as a simple and efficient bariatric procedure with low surgical risk. Since surgical treatment for morbid obesity is relatively rare in adolescents, few results have bten accumulated so far. OBJECTIVES To prove the safety and efficacy of LSG turgery in an adolescent population METHODS Data were prospectively collected regarding adolescent patients undergoing LSG. All patients underwent pre- and postoperative medical and professional evaluation by a multidisciplinary team. RESULTS Between the years 2006 and 2011, 32 adolescents underwent LSG in our center (20 females and 12males). Mean age was 16.75 years (range 14-18 years), mean weight was 121.88 kg (83-178 kg), and mean body mass index 43.23 (35-54). Thirty-four comorbid conditions were identified. LSG was the primary bariatric procedure in all the patients. Mean operative time was 60 minutes (range 45-80 min). Tiere were two complications (6.25%): an early staple line leak and a late acute cholecystitis. There were no deaths. Mean percent excess weight loss at 1, 3, 6, 9,12, 24, 36, 48, and 60 months post-surgery was 27.9%, 41.1%, 62.6%, 79.2%, 81.7%, 71%, 75%, 102.9% and 101.6%, respectively. Comorbidities were completely resolved or ameliorated within 1 year folllowing surgery in 82.4% and 17.6%, respectively. CONCLUSIONS LSG is feasible and safe in morbidly obese adolescents, achieving efficient weight loss and impressive resolution of comorbidities. Further studies are required to evaluate the long-term results of this procedure as well as its place among other bariatric options.


747: OPTIMAL THRESHOLDS OF NIRS-BASED CEREBRAL AUTOREGULATION MEASUREMENT TO PREDICT OUTCOME IN COMATOSE.


title: Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures.

text: The interferon (IFN) system is an extremely powerful antiviral response that is capable of controlling most, if not all, virus infections in the absence of adaptive immunity. However, viruses can still replicate and cause disease in vivo, because they have some strategy for at least partially circumventing the IFN response. We reviewed this topic in 2000 [Goodbourn, S., Didcock, L. & Randall, R. E. (2000). J Gen Virol 81, 2341-2364] but, since then, a great deal has been discovered about the molecular mechanisms of the IFN response and how different viruses circumvent it. This information is of fundamental interest, but may also have practical application in the design and manufacture of attenuated virus vaccines and the development of novel antiviral drugs. In the first part of this review, we describe how viruses activate the IFN system, how IFNs induce transcription of their target genes and the mechanism of action of IFN-induced proteins with antiviral action. In the second part, we describe how viruses circumvent the IFN response. Here, we reflect upon possible consequences for both the virus and host of the different strategies that viruses have evolved and discuss whether certain viruses have exploited the IFN response to modulate their life cycle (e.g. to establish and maintain persistent/latent infections), whether perturbation of the IFN response by persistent infections can lead to chronic disease, and the importance of the IFN system as a species barrier to virus infections. Lastly, we briefly describe applied aspects that arise from an increase in our knowledge in this area, including vaccine design and manufacture, the development of novel antiviral drugs and the use of IFN-sensitive oncolytic viruses in the treatment of cancer.


title: Persistent infectivity of a disease-associated herpesvirus in green turtles after exposure to seawater.

text: Herpesviruses are associated with several diseases of marine turtles including lung-eye-trachea disease (LETD) and gray patch disease (GPD) of green turtles (Chelonia mydas) and fibropapillomatosis (FP) of green, loggerhead (Caretta caretta), and olive ridley turtles (Lepidochelys olivacea). The stability of chelonian herpesviruses in the marine environment, which may influence transmission, has not been previously studied. In these experiments, LETD-associated herpesvirus (LETV) was used as a model chelonian herpesvirus to test viral infectivity after exposure to seawater. The LETV virus preparations grown in terrapene heart (TH-1) cells were dialyzed for 24 to 120 hr against aerated artificial or natural seawater or Hank's balanced salt solution (HBBS). Fresh TH-1 cells were inoculated with dialyzed LETV, and on day 10 post-infection cells were scored for cytopathic effect. Virus samples dialyzed up to 120 hr were positive for the herpesvirus DNA polymerase gene by polymerase chain reaction. Electron microscopy revealed intact LETV nucleocapsids after exposure of LETV to artificial seawater or HBSS for 24 hr at 23 C. LETV preparations remained infectious as long as 120 hr in natural and artificial seawater at 23 C. Similar results were obtained with a second culturable chelonian herpesvirus, HV2245. LETV infectivity could not be detected after 48 hr exposure to artificial seawater at 30 C. Since LETV and HV2245 remain infectious for extended periods of time in the marine environment, it is possible that FP-associated and GPD-associated herpesviruses also may be stable. These findings are significant both for researchers studying the epidemiological association of herpesviruses with diseases of marine turtles and for individuals who handle turtles in marine turtle conservation efforts.


Oxygen transport to tissue--IV.


title: Sub-continental Atmosphere and Inherent Immune System may have Impact on Novel Corona Virus' 2019 (nCovid-19) Prevalence in South East Asia.

text: Pandemic enveloped RNA Novel Corona Virus' 2019 (SARS-CoV-2) appears as a beating reed which induce overwhelming outbreak all over the world since November 2019 to till date. Inherent Immunity developed by traditional food habit, exposure to various antigens and vitamin D induced sunlight exposure. Meteorological parameters are the important factors which influencing the severe acute respiratory syndrome (SARS) like infectious disease. Aim of this review to enhance our knowledge and explore the association among build up immunity, weather parameters and Corona virus disease (COVID-19) death. In this review we emphasize role of meteorological factor included degree of sun exposure and effect of temperature on enveloped lipid bi-layer structure of Novel corona virus. These meteorological factors and inherent immunity may have impact on SARS-CoV-2 incidence among South East Asian including Bangladeshi. In summary, this study suggests that temperature-humidity variation, inherent immunity and lower life expectancy of South East Asia may be important.


title: Laparoscopic Experience for Recurrent Inguinal Hernia Repair in a Single Center for 14 Years.

text: Laparoscopic techniques are now well pervading in the treatment of inguinal hernia. This study aims to investigate the laparoscopic strategy for recurrent inguinal hernia repair. Laparoscopic technique was retrospectively applied to 330 patients with 352 recurrent inguinal hernias in the past 14 years. The surgical strategies were further evaluated. There were 22 cases with bilateral recurrent hernias, whereas the rest 308 cases with unilateral disorders. Patients were further categorized by previous repair approaches as high ligation, sclerotherapy, conventional suture repair, Lichtenstein repair, plug and patch repair, and preperitoneal repair. All cases were successfully repaired by laparoscopic approaches including transabdominal preperitoneal (TAPP) (288 cases), totally extraperitoneal (50 cases), and intraperitoneal onlay mesh (14 cases). The median operation duration was 39.5 ± 13.4 minutes. The average Visual Analog Scales score on postoperative day 1 was 2.4 ± 1.1. The median follow-up time was 36 (14-61) months. There was one case of recurrence during the follow-ups. One severe complication, i.e., bowel injury, was observed and cured, whereas other complications were as follows: 22 seroma, 8 urinary retention, 3 transient paresthesia, and 1 ileus. Laparoscopic procedures for recurrence inguinal hernia are safe and applicable. A surgeon can choose to reinforce the myopectineal orifice or only fix the hernia defect accordingly. The strategy of choosing TAPP and/or totally extraperitoneal depends on the type of previous repair, the exact anatomical position of the previous implanted mesh, and more importantly, the surgeon's experience. Moreover, the intraperitoneal onlay mesh technique can be regarded as a backup option for TAPP in certain cases.


title: The epidemiology of severe acute respiratory syndrome in the 2003 Hong Kong epidemic: an analysis of all 1755 patients.

text: BACKGROUND As yet, no one has written a comprehensive epidemiologic account of a severe acute respiratory syndrome (SARS) outbreak from an affected country. OBJECTIVE To provide a comprehensive epidemiologic account of a SARS outbreak from an affected territory. DESIGN Epidemiologic analysis. SETTING The 2003 Hong Kong SARS outbreak. PARTICIPANTS All 1755 cases and 302 deaths. MEASUREMENTS Sociodemographic characteristics; infection clusters by time, occupation, setting, and workplace; and geospatial relationships were determined. The mean and variance in the time from infection to onset (incubation period) were estimated in a small group of patients with known exposure. The mean and variance in time from onset to admission, from admission to discharge, or from admission to death were calculated. Logistic regression was used to identify important predictors of case fatality. RESULTS 49.3% of patients were infected in clinics, hospitals, or elderly or nursing homes, and the Amoy Gardens cluster accounted for 18.8% of cases. The ratio of women to men among infected individuals was 5:4. Health care workers accounted for 23.1% of all reported cases. The estimated mean incubation period was 4.6 days (95% CI, 3.8 to 5.8 days). Mean time from symptom onset to hospitalization varied between 2 and 8 days, decreasing over the course of the epidemic. Mean time from onset to death was 23.7 days (CI, 22.0 to 25.3 days), and mean time from onset to discharge was 26.5 days (CI, 25.8 to 27.2 days). Increasing age, male sex, atypical presenting symptoms, presence of comorbid conditions, and high lactate dehydrogenase level on admission were associated with a greater risk for death. LIMITATIONS Estimates of the incubation period relied on statistical assumptions because few patients had known exposure times. Temporal changes in case management as the epidemic progressed, unavailable treatment information, and several potentially important factors that could not be thoroughly analyzed because of the limited sample size complicate interpretation of factors related to case fatality. CONCLUSIONS This analysis of the complete data on the 2003 SARS epidemic in Hong Kong has revealed key epidemiologic features of the epidemic as it evolved.


title: Application of immunohistochemistry and in situ hybridization for detection of bovine coronavirus in paraffin-embedded, formalin-fixed intestines.

text: A monoclonal antibody (MAb) (Z3A5) against spike protein subunit of bovine coronavirus (BCV) reacted with the virus in formalin-fixed intestines in an immunoperoxidase test. We found an 88% correlation between immunohistochemistry with Z3A5 and in situ hybridization with a BCV nucleoprotein cDNA probe. MAb Z3A5 reacted with 90 BCV isolates from the United States and was an effective reagent for the diagnosis of BCV.


title: Heterologous protein secretion in Lactococcus lactis: a novel antigen delivery system.

text: Lactic acid bacteria (LAB) are Gram-positive bacteria and are generally regarded as safe (GRAS) organisms. Therefore, LAB could be used for heterologous protein secretion and they are good potential candidates as antigen delivery vehicles. To develop such live vaccines, a better control of protein secretion is required. We developed an efficient secretion system in the model LAB, Lactococcus lactis. Staphylococcal nuclease (Nuc) was used as the reporter protein. We first observed that the quantity of secreted Nuc correlated with the copy number of the cloning vector. The nuc gene was cloned on a high-copy number cloning vector and no perturbation of the metabolism of the secreting strain was observed. Replacement of nuc native promoter by a strong lactococcal one led to a significant increase of nuc expression. Secretion efficiency (SE) of Nuc in L. lactis was low, i.e., only 60% of the synthesized Nuc was secreted. Insertion of a synthetic propeptide between the signal peptide and the mature moiety of Nuc increased the SE of Nuc. On the basis of these results, we developed a secretion system and we applied it to the construction of an L. lactis strain which secretes a bovine coronavirus (BCV) epitopeprotein fusion (BCV-Nuc). BCV-Nuc was recognized by both anti-BCV and anti-Nuc antibodies. Secretion of this antigenic fusion is the first step towards the development of a novel antigen delivery system based on LAB-secreting strains.


title: [Emerging and reemerging diseases].

text: Emerging and reemerging diseases are the result of the interaction of multiple factors, such as social determinants of health, climate change, and conditions that prevail and are identifiable in some populations. As a consequence, there may be situations that by their nature are defined as a health emergency, impacting directly on the health of a population, either because they are not known or due to their rapid spread, resulting in a health security problem. Examples of these diseases are described in this article, starting with their origin, their impact on the population, and the response necessary in order to contain or prevent damage of a greater magnitude. The presence of these agents and their consequent damage to the population should lead efforts towards comprehensive prevention and appropriate containment strategies to ensure the protection of public health. Endeavors should be directed not only to a specific agent, but rather to factors that determine their reemergence, such as Ebola, or their permanence, such as the binomial infection of tuberculosis-AIDS. In order to correctly implement strategies, training and availability of supplies play a crucial role in facing the challenges that lie ahead.


title: Severe acute respiratory syndrome-associated coronavirus genotype and its characterization.

text: OBJECTIVE To study the severe acute respiratory syndrome (SARS)-associated coronavirus genotype and its characteristics. METHODS A SARS-associated coronavirus isolate named ZJ01 was obtained from throat swab samples taken from a patient in Hangzhou, Zhejing province. The complete genome sequence of ZJ01 consisted of 29,715 bp (GenBank accession: AY297028, version: gi: 30910859). Seventeen SARS-associated coronavirus genome sequences in GenBank were compared to analyze the common sequence variations and the probability of co-occurrence of multiple polymorphisms or mutations. Phylogenetic analysis of those sequences was done. RESULTS By bioinformatics processing and analysis, the 5 loci nucleotides at ZJ01 genome were found being T, T, G, T and T, respectively. Compared with other SARS-associated coronavirus genomes in the GenBank database, an A/G mutation was detected besides the other 4 mutation loci (C:G:C:C/T:T:T:T) involved in this genetic signature. Therefore a new definition was put forward according to the 5 mutation loci. SARS-associated coronavirus strains would be grouped into two genotypes (C:G:A:C:C/T:T:G:T:T), and abbreviated as SARS coronavirus C genotype and T genotype. On the basis of this new definition, the ZJ01 isolate belongs to SARS-associated coronavirus T genotype, first discovered and reported in mainland China. Phylogenetic analysis of the spike protein gene fragments of these SARS-associated coronavirus strains showed that the GZ01 isolate was phylogenetically distinct from other isolates, and compared with groups F1 and F2 of the T genotype, the isolates of BJ01 and CUHK-W1 were more closely related to the GZ01 isolate. It was interesting to find that two (A/G and C/T) of the five mutation loci occurred in the spike protein gene, which caused changes of Asp to Gly and Thr to Ile in the protein, respectively. CONCLUSION Attention should be paid to whether these genotype and mutation patterns are related to the virus's biological activities,epidemic characteristics and host clinical symptoms.


title: Assessment of knowledge and skills in early diagnosis of leprosy and attitudes towards leprosy amongst doctors working in dermatological services, Shandong Province, People's Republic of China.

text: After the leprosy control programme in Shandong Province, China, had declared elimination in 1994, it was no longer cost effective to rely on rapid surveys, population surveys and contact tracing for case detection, and since then most new cases have been diagnosed by the dermatological services. The dermatological services will continue to play an important role in diagnosis of the few incident leprosy cases scattered in wide geographic areas and in a population of 90 million. In order to better understand the knowledge and skills in early diagnosis of leprosy among doctors working in dermatological services around the province, doctors attending the dermatological annual meeting and a dermatological training workshop were assessed on their knowledge and skills in early diagnosis of leprosy and their attitude towards leprosy with a semi-structured questionnaire. The results showed that continuous training was needed for dermatologists from both general hospitals and the leprosy control programme. In particular, the training methods for the skills in nerve examination including palpation of peripheral nerves and nerve function assessment should be improved.


title: Surgical advantages of reduced-port laparoscopic gastrectomy in gastric cancer.

text: BACKGROUND Although a few studies have reported the use of reduced-port laparoscopic gastrectomy (RPG) in gastric cancer patients, the feasibility of routinely using this technique remains unclear. It is therefore important to evaluate the surgical advantages of this technique in this patient group. METHODS Between August 2010 and July 2015, 165 patients underwent RPGs at our hospital, performed by a single surgeon. Of these patients, 88 underwent reduced-port laparoscopic distal gastrectomy (RPLDG) and 77 underwent reduced-port laparoscopic total gastrectomy (RPLTG). In addition to short-term surgical outcomes after RPG, survival times and the surgical learning curve were also evaluated. RESULTS Blood losses during lymph node dissection in the RPLDG and RPLTG groups were not significantly different (p = 0.160). Conversion to open surgery was necessary in only two patients. Postoperative morbidities were observed in 14.8 % of the RPLDG group and 14.3 % of the RPLTG group, but there were no deaths. Most patients expressed high cosmetic satisfaction in both groups. In the RPLDG group, operation time during reconstruction decreased over the first 50 cases and then plateaued, as the surgeon's experience of the technique increased. In contrast, in the RPLTG group, operation times dropped with surgical experience for both lymph node dissection, plateauing after 40 cases, and for reconstruction, plateauing after 30 cases. Only three patients died of gastric cancer in the follow-up period and three patients died of other diseases. Five-year overall survival and 5-year disease-specific survival were 95.6 and 98.0 %, respectively. CONCLUSIONS We have shown that reduced-port gastrectomy (RPG) could be an acceptable and satisfactory procedure for treating gastric cancer for an experienced laparoscopic gastric surgeon who has sufficient previous experience of conventional laparoscopic gastrectomies.


title: Silencing of natural interferon producing cell activation by porcine circovirus type 2 DNA.

text: Porcine circovirus type 2 (PCV2) infection of natural interferon producing cells (NIPCs) impairs the induction of interferon (IFN)-alpha and tumour necrosis factor (TNF)-alpha by cytosine-phosphorothioate-guanine (CpG) oligodeoxynucleotides (ODNs), thereby preventing both their autocrine maturation and the paracrine maturation of myeloid dendritic cells (DCs). The present study shows that the PCV2-mediated inhibition of NIPCs was mediated by viral DNA, although it was independent of virus replication. The inhibitory effect of PCV2 DNA was more diversified than if it had simply targeted CpG-ODN-induced cytokines (IFN-alpha, TNF-alpha, interleukin-6, IL-12). A broad spectrum inhibition was noted, affecting responses induced by toll-like receptor (TLR)-7 and TLR9 agonists, as well as viruses including pseudorabies virus, transmissible gastroenteritis virus and classical swine fever virus. From these results, it would appear that PCV2 DNA can induce a dominant negative signal influencing independent pattern recognition receptor-induced activation cascades. Despite a concomitant internalization of PCV2 DNA and CpG-ODNs, no colocalization was observed, indicating that PCV2 DNA and CPG-ODNs may not target the same receptor. This study describes a novel modulation of the innate immune response, which would render the host more susceptible to secondary or concomitant microbial infections.


title: Proteolytic processing of a human astrovirus nonstructural protein.

text: To analyse the activity of the putative 3C-like serine protease encoded in open reading frame (ORF)-1a of human astrovirus serotype 1 (HAstV-1), ORF-1a was transcribed and translated in vitro. Translation products, identified by immunoprecipitation with specific antibodies against recombinant C-terminal ORF-1a fragments, include the full-length 101 kDa (p101) protein and a 38 kDa band (p38). In addition, a 64 kDa protein (p64) was immunoprecipitated by an anti-FLAG antibody when a FLAG epitope was inserted at the N terminus of the ORF-1a product. Mutation of the amino acids predicted to form the catalytic triad of the HAstV-1 3C-like serine protease (Ser-551, Asp-489, His-461) resulted in undetectable levels of p38, supporting the involvement of the HAstV-1 3C-like serine protease and the importance of these amino acids in the processing of p101 into p38 and p64. N-terminal deletions of up to 420 aa of p101 that did not involve the predicted 3C-like serine protease motif did not alter levels of p38 compared to wild-type. C-terminal deletion analysis localized p38 to the C terminus of ORF-1a. Mutation of the P1 residue of the predicted cleavage site, which is conserved among known human and sheep astrovirus sequences, resulted in no detectable p38, supporting cleavage at the Gln-567/Thr-568 dipeptide. These results suggest that p101 is cleaved into an N-terminal p64 fragment and a C-terminal p38 product at Gln-567/Thr-568 in a process that is dependent on the viral 3C-like serine protease.


SARS: experience from the emergency department, Tan Tock Seng Hospital, Singapore.


title: Molecular and genetic characterisation of the SARS coronavirus auxiliary protein X1 in Drosophila.

text: 1. We have generated monoclonal antibodies against the SARS coronavirus (SARS-CoV) X1/3a protein (3a), which are suitable for western blotting, immunocytochemistry, and immunohistochemistry. 2. We have established and characterised an in-vivo 3a transgenic Drosophila model, and demonstrated its usefulness in studying SARS-CoV 3a gene function. 3. We validated our in-vivo findings on 3a gene function in mammalian Vero E6 cells. 4. Our findings raise the possibility of using ion channel blockers as a novel approach to suppress SARS-CoV-induced cell death.


[Hematologic Malignancies/Pediatric Malignancies Update on Novel Treatment Strategies in Multiple Myeloma].


title: The post-lockdown period should be used to acquire effective therapies for future resurgence in SARS-Cov-2 infections.

text: COVID-19 will be with us through the remainder of 2020 and almost certainly beyond. New Zealand needs a viable strategy to protect its populace until a vaccine is developed and in wide use. Until that time, it makes sense to protect the population by putting in place treatments that will be safe and effective, such as the use of convalescent sera and the use of direct-acting anti-virals. These treatments should be sourced externally or made locally, but steps in this direction must now begin as the lockdown ends. New Zealand has the scientists, the facilities and the will to make this happen, but the support of the government and the population will be needed if this plan is to succeed.


title: Multiplex reverse transcription-PCR for rapid differential detection of porcine epidemic diarrhea virus, transmissible gastroenteritis virus, and porcine group A rotavirus.

text: A novel multiplex reverse transcription polymerase chain reaction (multiplex RT-PCR) that can detect porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), and porcine group A rotavirus (GAR) was developed. The 3 viruses (PEDV, TGEV, and porcine GAR) are major agents in viral enteric diseases of piglets. As the clinical signs of these diseases are similar, including watery diarrhea, differential detection is required for etiologic diagnosis. A mixture of 3 pairs of published primers was used for amplification of viral nucleic acids, yielding 3 different amplicons with sizes of 859 bp, 651 bp, and 309 bp for TGEV, PEDV, and porcine GAR, respectively. A total of 157 specimens (78 fecal and 79 intestinal samples) from piglets with acute gastroenteritis were collected in Korea between January 2004 and May 2005. They were tested for the presence of 3 viruses by multiplex RT-PCR. Coinfections with PEDV and porcine GAR were identified in 16 farms (43.2%). PEDV, porcine GAR, and TGEV infection were 26.3%, 13.2%, and 2.7% respectively. The relative sensitivity and specificity of multiplex RT-PCR were evaluated, with results suggesting that this assay is equal in quality to conventional single-agent RT-PCR assays (sensitivity:100%, 92.9%, 100% for TGEV, PEDV, GARs; specificity: 100% for all 3 viruses). This multiplex RT-PCR is a simple assay and may be a potentially useful for rapid, sensitive, and cost-effective etiological diagnostic tool for acute viral gastroenteritis in piglets.


title: Risk perception in women: a focus on menopause.

text: OBJECTIVE To investigate risk perceptions in relation to menopausal experiences, comparing premenopausal women's expectations to actual experiences of menopause, including perceptions of symptoms, fears, risks of future illnesses, and side effects of symptomatic treatments. DESIGN This was a cohort study using surveys in a random sample of Australians participating in an Australian Health Report series, supported by Pfizer. This article focuses on perceptions about menopause of 710 women. RESULTS Peri- and postmenopausal women experienced more fatigue, sleeplessness, fluid retention, and bloating than premenopausal women expected to experience. Perimenopausal and postmenopausal women rated menopause as the "first day of the rest of [my] life" significantly more than premenopausal women. All women perceived that menopause had an impact on aging and weight gain, but more premenopausal women feared loss of sexuality (55%), loss of femininity (39%), and the inability to have more children (37%). Perceptions of illnesses differed from actual incidence, with 27% of all women perceiving breast cancer and 11% perceiving heart disease as a health risk, compared with actual female mortality figures of 3% and 41%, respectively. Perceptions of the effects of hormone therapy were inaccurate, with 53% of all women expecting a reduction in hot flushes, 44% expecting that hormone therapy increased breast cancer, and 23% expecting that hormone therapy decreased fractures. CONCLUSIONS This study suggests a difference between perceptions of symptoms, fears, risks of future illnesses, and side effects of symptomatic treatments at menopause and actual experience. Because risk perception influences health-related behaviors, visits to healthcare providers, and treatment decisions and can be modified through education, an understanding of risk perception is clinically important. Further research is needed.


title: Virus Like Particles as Immunogens and Universal Nanocarriers.

text: Over the last two decades virus-like particles (VLPs) have become an important tool in biomedical research and medicine. VLPs are multiprotein structures that resemble viable virus particles in conformation but lack the viral genome. Consequently, they are non-infectious and non-replicative, but retain the ability to penetrate cells, making them useful for a vast spectrum of applications. Above all, VLPs mimicking genuine viruses in antigenic structure provide a safe alternative to attenuated and inactivated viruses in vaccine development. Moreover, due to their transducing proprieties, VLPs may efficiently deliver foreign nucleic acids, proteins, or conjugated compounds to the organism, or even to specific cell types. Additionally, VLPs are versatile nanovectors due to their flexibility in terms of composition and expression systems. In this review, different approaches for of virus-like particle synthesis and manipulation, as well as their potential applications, will be discussed.


title: Development of a 1-step enzyme-linked immunosorbent assay for the rapid diagnosis of bovine respiratory syncytial virus in postmortem specimens.

text: Bovine respiratory syncytial virus (BRSV) is associated with severe respiratory disease in cattle. BRSV infection frequently leads to the death of young infected animals. The presence of BRSV in postmortem specimens is routinely detected using indirect immunofluorescence (IIF). However, this technique requires special equipment and considerable expertise. The present paper describes the development of a 1-step ELISA for rapid (1.5 hours) detection of BRSV antigen in organ homogenates. The performance of the new 1-step ELISA was evaluated using bovine postmortem specimens (n = 108) in comparison with 3 other BRSV diagnostic techniques: indirect immunofluorescence, the Clearview respiratory syncytial virus (RSV) test, and real-time reverse transcriptase polymerase chain reaction (RT-PCR). The relative sensitivity, specificity, and the kappa coefficient of 1-step ELISA, the Clearview RSV electroimmunoassay (EIA), and IIF were calculated, using real-time RT-PCR as the reference test. The new 1-step ELISA was the most sensitive and specific of the 3 tests. Thus, the new 1-step ELISA is a reliable test for detecting BRSV antigen in organ homogenates.


title: Are Non-Tumescent Ablation Procedures Ready to Take Over?

text: Tumescent anesthesia refers to the percutaneous administration of large volume anesthetic to cause the target tissue to become swollen or firm. The use of tumescent anesthesia is essential for the treatment of refluxing truncal veins using endothermal technologies. In order to obviate the use of tumescent anesthesia as an adjunct to treatment, one has to evaluate the technologies that do not employ thermal energy as the modality for treatment. These technologies include foam sclerotherapy, mechanicochemical ablation (MOCA), and the use of glue (Sapheon™ closure system). The following review juxtaposes the literature supporting the use of tumescent-based techniques to the literature supporting the use of tumescent-less techniques.


title: Novel uses of noninvasive ventilation.

text: Noninvasive ventilation (NIV) and continuous positive airway pressure (CPAP) have been used in various unusual settings to assist breathing. NIV is now frequently used to treat exacerbations of chronic obstructive pulmonary disease and chronic respiratory failure in neuromuscular disease. This paper discusses CPAP and NIV for postoperative hypoxemia, preventing intubation in high-risk bronchoscopy, respiratory failure in pandemics, obesity hypoventilation syndrome, and respiratory support during percutaneous endoscopic gastrostomy tube placement.


title: Gross postmortem and histologic examination findings from abortion losses and calf mortalities in western Canadian beef herds.

text: Production losses from abortions, stillbirths, and early calf mortality were described for the 2002 calf crop in 203 beef herds in western Canada. A total of 1689 calves were examined. A summary diagnosis was reported for 64% of aborted calves, 78% of stillborn calves, 88% of neonatal calves, and 94% of the calves > 3 d of age. Diagnoses for aborted calves included: thyroid gland lesions, pneumonia, developmental anomalies, placentitis, and myocardial necrosis or myopathy. For stillborn calves, diagnostic findings included: dystocia, thyroid gland lesions, myocardial necrosis or myopathy, developmental anomalies, and skeletal myopathy or necrosis. The most common diagnoses for neonatal calves (≤ 3 d) were: pneumonia, skeletal myopathy or necrosis, myocardial necrosis or myopathy, accident or trauma, and septicemia. For older calves (3 d to 3 mo), the most common diagnoses included: starvation, abomasal ulcer or perforation, enteritis or colitis, pneumonia, and intestinal volvulus, obstruction, or perforation.


title: Clinical and Radiologic Characteristics of COVID-19 in Patients With CKD.

text: INTRODUCTION In this study, we aimed to evaluate the presentation and outcome of COVID-19 in patients with chronic kidney disease (CKD). METHODS We included 43 patients with a past history of CKD and confirmed diagnosis of COVID-19. Patients were evaluated for demographic characteristics, clinical and laboratory data and findings of initial chest computed tomography (CT) and were followed until either death or discharge occurred. Then, study variables were compared based on final outcome and stage of CKD. RESULTS Mean age ± SD of patients was 60.65 ± 14.36 years; 65.1% were male. Five of 43 patients (11.6%) died on follow-up and the rest were discharged. Disease outcome did not differ across CKD stages (P > .05). More than half of the patients (58.1%) presented with severe disease on admission. Clinical symptoms were similar to those of non-CKD individuals. Mean duration of hospitalization was higher in those who died, although not significant (16.6 ± 8.38 vs. 11 ± 6.26, P > .05). The only hematologic parameter that significantly differed between survivors and non-survivors was lactase dehydrogenase level (P < .05). Ground-glass opacification and reticular pattern were the most frequent patterns on CT and pleural effusion existed in about one-fifth of all patients. A greater lower zone score was noted in deceased patients (P < .05). CONCLUSION Patients with CKD are vulnerable to a more severe form of COVID-19 and experience a higher mortality rate than the general population; however, higher CKD stage is not related to worse prognosis or different imaging manifestation compared with lower stage.


Glycoprotein E1 of coronavirus A59: a new type of viral glycoprotein.


title: Retroviruses pseudotyped with the severe acute respiratory syndrome coronavirus spike protein efficiently infect cells expressing angiotensin-converting enzyme 2.

text: Infection of receptor-bearing cells by coronaviruses is mediated by their spike (S) proteins. The coronavirus (SARS-CoV) that causes severe acute respiratory syndrome (SARS) infects cells expressing the receptor angiotensin-converting enzyme 2 (ACE2). Here we show that codon optimization of the SARS-CoV S-protein gene substantially enhanced S-protein expression. We also found that two retroviruses, simian immunodeficiency virus (SIV) and murine leukemia virus, both expressing green fluorescent protein and pseudotyped with SARS-CoV S protein or S-protein variants, efficiently infected HEK293T cells stably expressing ACE2. Infection mediated by an S-protein variant whose cytoplasmic domain had been truncated and altered to include a fragment of the cytoplasmic tail of the human immunodeficiency virus type 1 envelope glycoprotein was, in both cases, substantially more efficient than that mediated by wild-type S protein. Using S-protein-pseudotyped SIV, we found that the enzymatic activity of ACE2 made no contribution to S-protein-mediated infection. Finally, we show that a soluble and catalytically inactive form of ACE2 potently blocked infection by S-protein-pseudotyped retrovirus and by SARS-CoV. These results permit studies of SARS-CoV entry inhibitors without the use of live virus and suggest a candidate therapy for SARS.


title: Immunohistochemical characterization of a hepatic neuroendocrine carcinoma in a cat.

text: A hepatic mass was identified in a 5-year-old, female mixed-breed cat that died spontaneously after a clinical history of progressive emaciation, ptyalism, and persistent coryza. At necropsy, a 7-cm-diameter, yellow-brown, firm, multilobulated tumor was identified in the liver. Microscopically, the mass consisted of neoplastic cells arranged in small, closely packed nests within a thin fibrovascular stroma. These cells were of medium sized and polygonal, with fine argyrophilic cytoplasmic granules. Nuclei were predominantly round with finely stippled chromatin and indistinct nucleoli. Mitotic figures were numerous. Immunohistochemically, most of the neoplastic cells were immunoreactive for chromogranin A, neuron-specific enolase (NSE), and cytokeratin AE1/AE3 and weakly labeled for synaptophysin. The tumor was negative for glial fibrillary acidic protein (GFAP), vimentin, and cytokeratins 5, 6, 8, and 17. Vascular emboli and intrahepatic micrometastasis were also identified with chromogranin A. All these features were consistent with a hepatic neuroendocrine carcinoma and emphasized the importance of using a panel of antibodies to diagnose such rare tumors.


title: Does electrocardiography at admission predict outcome in Crimean -Congo hemorrhagic fever?

text: BACKGROUND & OBJECTIVES Crimean - Congo hemorrhagic fever is an acute viral hemorrhagic fever with considerable mortality. Despite increasing knowledge about hemorrhagic fever viruses, the pathogenesis of Crimean -Congo hemorrhagic fever and causes of death were not well described. We aimed to evaluate whether there were electrocardiographic parameters designating mortality among these patients. STUDY DESIGN This retrospective study was performed among confirmed Crimean -Congo hemorrhagic fever cases in Turkey. Electrocardiography was available in 49 patients within 24 h of hospitalization. All electrocardiograms were evaluated by two expert cardiologists according to Minnesota coding system. RESULTS Among patients with available electrocardiograms, there were 31 patients who survived, and 18 patients who died of Crimean - Congo hemorrhagic fever. Both groups were similar in terms of age, sex, body temperature, heart rate, and blood parameters. T-wave changes and bundle branch block were more frequently encountered among those who died. Presence of T-wave negativity or bundle branch block in this cohort of patients with Crimean -Congo hemorrhagic fever predicted death with a sensitivity of 72.7%, specificity of 92.6%, positive predictive value of 88.9%, negative predictive value of 80.6%. CONCLUSIONS We think within the light of our findings that simple electrocardiography at admission may help risk stratification among Crimean-Congo hemorrhagic fever cases.


title: Complete genomic sequence of human coronavirus OC43: molecular clock analysis suggests a relatively recent zoonotic coronavirus transmission event.

text: Coronaviruses are enveloped, positive-stranded RNA viruses with a genome of approximately 30 kb. Based on genetic similarities, coronaviruses are classified into three groups. Two group 2 coronaviruses, human coronavirus OC43 (HCoV-OC43) and bovine coronavirus (BCoV), show remarkable antigenic and genetic similarities. In this study, we report the first complete genome sequence (30,738 nucleotides) of the prototype HCoV-OC43 strain (ATCC VR759). Complete genome and open reading frame (ORF) analyses were performed in comparison to the BCoV genome. In the region between the spike and membrane protein genes, a 290-nucleotide deletion is present, corresponding to the absence of BCoV ORFs ns4.9 and ns4.8. Nucleotide and amino acid similarity percentages were determined for the major HCoV-OC43 ORFs and for those of other group 2 coronaviruses. The highest degree of similarity is demonstrated between HCoV-OC43 and BCoV in all ORFs with the exception of the E gene. Molecular clock analysis of the spike gene sequences of BCoV and HCoV-OC43 suggests a relatively recent zoonotic transmission event and dates their most recent common ancestor to around 1890. An evolutionary rate in the order of 4 x 10(-4) nucleotide changes per site per year was estimated. This is the first animal-human zoonotic pair of coronaviruses that can be analyzed in order to gain insights into the processes of adaptation of a nonhuman coronavirus to a human host, which is important for understanding the interspecies transmission events that led to the origin of the severe acute respiratory syndrome outbreak.


title: [Clinical study on treatment of severe acute respiratory syndrome by integrative Chinese and Western medicine].

text: OBJECTIVE To evaluate the effect of integrative Chinese and western medicine (ICWM) in treating severe a cute respiratory syndrome (SARS). METHODS Sixty SARS patients were diagnosed and observed according to the universal standard, and divided into the ICWM group (n = 31, treated with ICWM) and the control group (n = 29, treated by conventional western medicine alone). RESULTS ICWM showed better effect than that of western medicine alone in improving clinical symptoms, promoting the absorption of inflammation in lung, increased oxygen saturation (P < 0.01) and decreased the dosage of corticoid used (P < 0.05). CONCLUSION The effect of ICWM is better than that of simple western medicine in treating SARS.


title: Identification of the catalytic sites of a papain-like cysteine proteinase of murine coronavirus.

text: The murine coronavirus mouse hepatitis virus gene 1 is expressed as a polyprotein, which is cleaved into multiple proteins posttranslationally. One of the proteins is p28, which represents the amino-terminal portion of the polyprotein and is presumably generated by the activity of an autoproteinase domain of the polyprotein (S. C. Baker, C. K. Shieh, L. H. Soe, M.-F. Chang, D. M. Vannier, and M. M. C. Lai, J. Virol. 63:3693-3699, 1989). In this study, the boundaries and the critical amino acid residues of this putative proteinase domain were characterized by deletion analysis and site-directed mutagenesis. Proteinase activity was monitored by examining the generation of p28 during in vitro translation in rabbit reticulocyte lysates. Deletion analysis defined the proteinase domain to be within the sequences encoded from the 3.6- to 4.4-kb region from the 5' end of the genome. A 0.7-kb region between the substrate (p28) and proteinase domain could be deleted without affecting the proteolytic cleavage. However, a larger deletion (1.6 kb) resulted in the loss of proteinase activity, suggesting the importance of spacing sequences between proteinase and substrate. Computer-assisted analysis of the amino acid sequence of the proteinase domain identified potential catalytic cysteine and histidine residues in a stretch of sequence distantly related to papain-like cysteine proteinases. The role of these putative catalytic residues in the proteinase activity was studied by site-specific mutagenesis. Mutations of Cys-1137 or His-1288 led to a complete loss of proteinase activity, implicating these residues as essential for the catalytic activity. In contrast, most mutations of His-1317 or Cys-1172 had no or only minor effects on proteinase activity. This study establishes that mouse hepatitis virus gene 1 encodes a proteinase domain, in the region from 3.6 to 4.4 kb from the 5' end of the genome, which resembles members of the papain family of cysteine proteinases and that this proteinase domain is responsible for the cleavage of the N-terminal peptide.


title: [New infections: myths and reality].

text: New contemporary data about new infectious diseases of XXI century are presented. Data on morbidity and mortality from severe acute respiratory syndrome (SARS, atypical pneumonia) and avian influenza are analyzed and compared with World Health Organization data on human influenza. Biologic characteristics of avian influenza virus A/H5N1 are discussed as well as possibility of its human-to-human transmission. Principles of SARS and avian influenza infections transmission as zoonoses are described as well as mechanisms of transmission impeding their ability to infect humans. It has been argued that SARS should be regarded as contagious infection, whereas avian influenza - as non-contagious. Features of all stages of epidemic process of these infections are analyzed.


title: Respiratory viruses and atypical bacteria triggering severe asthma exacerbation in children.

text: 1. Respiratory viruses and atypical bacteria were detected in 51.0% of Hong Kong children with asthma exacerbations, which was significantly higher than the detection rate of 27.3% in children with chronic stable asthma. 2. Co-infections of two or more respiratory pathogens were more commonly found in children with asthma exacerbations (10.7%) than in patients with stable asthma (2.6%). 3. Human rhinovirus infection was a significant risk factor for asthma exacerbations. 4. There was no significant association between the severity of asthma exacerbations and respiratory viral or atypical bacterial infections. 5. Routine use of macrolide antibiotics in the treatment of childhood asthma exacerbations should be discouraged.


title: A first look at COVID-19 information and misinformation sharing on Twitter.

text: Since December 2019, COVID-19 has been spreading rapidly across the world. Not surprisingly, conversation about COVID-19 is also increasing. This article is a first look at the amount of conversation taking place on social media, specifically Twitter, with respect to COVID-19, the themes of discussion, where the discussion is emerging from, myths shared about the virus, and how much of it is connected to other high and low quality information on the Internet through shared URL links. Our preliminary findings suggest that a meaningful spatio-temporal relationship exists between information flow and new cases of COVID-19, and while discussions about myths and links to poor quality information exist, their presence is less dominant than other crisis specific themes. This research is a first step toward understanding social media conversation about COVID-19.


Survey and evaluation of modified oxygen delivery devices used for suspected severe acute respiratory syndrome and other high-risk patients in Hong Kong.


title: Veterinary vaccines for public health and prevention of viral and bacterial zoonotic diseases.

text: To meet with the increasing demand for food, the scale of world food production is increasing, as is the transport of animals and food products. At the same time, the contact of animals with the environment remains unchanged or, in the case of free-ranging animals, is even increasing. A number of microorganisms have established themselves in farmed animals, which although relatively harmless to animals are pathogenic to man. In this article, the options for reducing the risk of transferring zoonotic agents from animals (particularly farm animals) to man using veterinary vaccines against viral and bacterial diseases are described.


title: Mapping the scope and opportunities for public health law in liberal democracies.

text: The two questions, "What is public health law?" and "How can law improve the public's health?" are perennial ones for public health law scholars. This paper proposes a framework for conceptualizing discussion and debate about the scope and opportunities for public health law within liberal democracies. Part 2 of the paper draws selectively on this framework in order to highlight some areas where law's potential role deserves greater acknowledgment and exploration.


title: Detection of antibodies against SARS-Coronavirus using recombinant truncated nucleocapsid proteins by ELISA.

text: Severe acute respiratory syndrome (SARS) is a lifethreatening emerging respiratory disease caused by the coronavirus, SARS-CoV. The nucleocapsid (N) protein of SARS-CoV is highly antigenic and may be a suitable candidate for diagnostic applications. We constructed truncated recombinant N proteins (N1 [1-422 aa], N2 [1- 109 aa], and N3 [110-422 aa]) and determined their antigenicity by Western blotting using convalescent SARS serum. The recombinants containing N1 and N3 reacted with convalescent SARS serum in Western blotting. However, the recombinant with N2 did not. In ELISA using N1 or N3 as the antigens, positive results were observed in 10 of 10 (100%) SARS-CoV-positive human sera. None of 50 healthy sera gave positive results in either assay. These data indicate that the ELISA using N1 or N3 has high sensitivity and specificity. These results suggest that the middle or C-terminal region of the SARS N protein is important for eliciting antibodies against SARS-CoV during the immune response, and ELISA reactions using N1 or N3 may be a valuable tool for SARS diagnosis.


title: Impact of respiratory viral infections on cystic fibrosis.

text: The life expectancy for patients with cystic fibrosis has improved remarkably over the last 20 years. Progressive deterioration of pulmonary function continues despite the aggressive use of antimicrobials. The absence of fever, neutrophilia, and systemic symptoms suggest that during pulmonary exacerbations other non-bacterial factors may have played a part. Some have suggested respiratory viruses as main suspects. So far, few data have illustrated the relationship of respiratory viruses and cystic fibrosis. By gaining further knowledge of this relationship, one may change future clinical practice and boost the survival of these patients.


title: Comparison of capsid sequences from human and animal astroviruses.

text: We have sequenced the genomic 3'-end, including the structural gene, of human astrovirus (HAstV) serotype 7 and morphologically related viruses infecting pig (PAstV), sheep (OAstV) and turkey (TAstV-1). These sequences were compared with corresponding astrovirus sequences available in the nucleic acid databases, including sequences of the seven other HAstV serotypes, two other avian astroviruses (TAstV-2 and avian nephritis virus) and astrovirus from cat (FAstV). A 35 nt stem-loop motif near the 3'-end of the genome, previously described as being highly conserved, was present in all of the astroviruses except TAstV-2. In the N-terminal half of the capsid precursor protein, there were several short conserved peptide motifs. Otherwise the capsid proteins of astroviruses infecting different hosts were highly divergent. Calculation of genetic distances revealed that the distance between FAstV and HAstV is comparable to the largest distances between different HAstV serotypes. Higher similarities between the HAstV, FAstV and PAstV capsid sequences suggest interspecies transmissions involving humans, cats and pigs relatively recently in the evolutionary history of astroviruses.


title: The cellular and molecular pathogenesis of coronaviruses.

text: Coronaviruses cause a wide spectrum of diseases in humans and animals but generally fall into two classes, with respiratory or enteric tropisms. Mouse hepatitis virus (MHV) and rat coronaviruses are the viruses most frequently encountered in the laboratory animal setting. This review focuses primarily on the cellular and molecular aspects of MHV pathogenesis. The high mutation and recombination rates of coronaviruses lead to a diverse, ever-changing population of MHV strains. The spike (S) protein is the most variable coronavirus protein and is responsible for binding to cell surface receptors, inducing cell fusion and humoral and cellular immunity. Differences within the S protein of different MHV strains have been linked to their variable tropisms. Since immunity to MHV is strain-specific, seropositive mice can be reinfected with different strains of MHV. Natural infections with MHV are acute, with persistence occurring at the population level, not within an individual mouse, unless it is immunocompromised. Age, genotype, immunologic status of the mouse, and MHV strain influence the type and severity of disease caused by MHV. Interference with research by MHV has been reported primarily in the fields of immunology and tumor biology and may be a reflection of MHV's capacity to grow in several types of immune cells. While many methods are available to diagnose coronavirus infection, serologic tests, primarily ELISA and IFA, are the most commonly used. MHV is best managed on a preventive basis. Elimination of MHV from a population requires cessation of breeding and halting the introduction of naive mice into the population.


title: Ribavirin suppresses eIF4E-mediated oncogenic transformation by physical mimicry of the 7-methyl guanosine mRNA cap.

text: The eukaryotic translation initiation factor eIF4E is deregulated in many human cancers, and its overexpression in cells leads to malignant transformation. Oncogenic properties of eIF4E are directly linked to its ability to bind 7-methyl guanosine of the 5' mRNA. Here, we observe that the antiviral guanosine analogue ribavirin binds to eIF4E with micromolar affinity at the functional site used by 7-methyl guanosine mRNA cap, competes with eIF4E:mRNA binding, and, at low micromolar concentrations, selectively disrupts eIF4E subcellular organization and transport and translation of mRNAs posttranscriptionally regulated by eIF4E, thereby reducing levels of oncogenes such as cyclin D1. Ribavirin potently suppresses eIF4E-mediated oncogenic transformation of murine cells in vitro, of tumor growth of a mouse model of eIF4E-dependent human squamous cell carcinoma in vivo, and of colony formation of eIF4E-dependent acute myelogenous leukemia cells derived from human patients. These findings describe a specific, potent, and unforeseen mechanism of action of ribavirin. Quantum mechanical and NMR structural studies offer directions for the development of derivatives with improved cytostatic and antiviral properties. In all, ribavirin's association with eIF4E may provide a pharmacologic means for the interruption of posttranscriptional networks of oncogenes that maintain and enhance neoplasia and malignancy in human cancer.